INTRODUCTION

With the development of affordable, high-resolution, real-time ultrasound equipment, and the introduction
of transvaginal scanning, the indications for pelvic imaging have increased dramatically. The
gynecologist/ultrasonographer now has the capability of visualizing processes in vivo that, only a few years ago,
could only be inferred. The appropriate integration of real-time ultrasonography into the practice of gynecology is a
subject of continuing controversy.1,2,3,4,5,6 Questions regarding its cost-effectiveness and diagnostic utilization
have been raised.7 Other authors support the modality as a means of obtaining a better understanding of gynecologic
pathology as well as enhancing the diagnostic ability of the practicing gynecologist.8,9,10
As health-care reimbursement evolves into a managed care mechanism, it is necessary to reevaluate
management protocols to ensure maximum value. Traditional approaches to the evaluation of common gynecologic
abnormalities, such as abnormal uterine bleeding or asymptomatic ovarian cysts, have to be reassessed.
In selected cases, expectant follow-up with anticipated spontaneous resolution of the process is preferable
to relatively costly surgical management. With this in mind, the modern gynecologist must consider the existing
scientific evidence regarding the diagnostic accuracy, advantages, disadvantages, and pitfalls of gynecologic
ultrasonographic imaging. It is imperative that we explore this modality thoroughly and consider how it can be
integrated into our daily practice to improve patient care in a cost-effective manner.
The practitioner is, therefore, confronted with several important decisions regarding pelvic
ultrasonography, including whether or not to become actively involved as a gynecologic ultrasonographer, whether
or not to refer patients for consultative ultrasonography, and most important, which patients should be evaluated
with real-time ultrasonography in the optimum care setting. As we look toward the twenty-first century, the clinical
settings in which two-dimensional pelvic imaging and, more recently, Doppler imaging of the pelvis are used, will
continue to expand as we strive to gain a more accurate assessment of the anatomic and functional status of the
female pelvis.
Gynecologic processes of interest that are now approachable with ultrasonographic imaging include
localization and characterization of pelvic masses; assessment and evaluation of early pregnancy location and
potential viability; screening for and assessment of adnexal masses; monitoring of follicular development; a more
in-depth assessment of the difficult-to-examine patient; and evaluation of pelvic blood velocity waveforms by
Doppler imaging. All of these areas are discussed in this chapter.

PRINCIPLES OF ULTRASONOGRAPHIC IMAGING

For optimum ultrasonographic visualization, certain mechanical, physical, and ultrasonographic principles
must be understood. The quality of an image ultimately depends on the degree of resolution. In general, the closer
the transducer tip is to the imaging target, the greater the resolution, and therefore the clearer the image will be.
Every effort must be made to avoid interference with transmission of ultrasonographic energy.11 A thorough
understanding of the longitudinal (sagittal), cross-sectional (axial), and coronal anatomy of the pelvis is necessary
for optimal image interpretation. Whereas scanning planes for transabdominal scanning are classically described as
sagittal, axial, and oblique, the transvaginal approach offers the additional coronal scanning plane.12,13 Accurate
orientation is a necessity for the appropriate interpretation of pelvic imaging. Since much of the imaging is
performed with the use of "organ specific" planes, one must always be aware of the actual scanning orientation in
order to achieve an accurate interpretation of the findings noted on the image.13
In addition to the need for close approximation of the imaging target by the transducer, one must also
realize that the quality of the image will be influenced by the frequency of the transducer, pulse repetition frequency,
and image processing. For a more in-depth analysis of these imaging principles, the reader is referred to standard
texts on ultrasonography.

DOPPLER ULTRASONOGRAPHIC SCANNING

The direction, velocity, and variability of blood flow can be evaluated ultrasonographically by using the
principle of the Doppler effect. By displaying the Doppler frequency shifts that result from calculating the difference
between the emitted frequency and the frequency of echoes returning from a moving target, a flow velocity
waveform is created. This can be described in terms of velocity (in centimeters per second), as well as by using
descriptive ratios depicting the difference in the systolic velocity and diastolic velocity.
The S/D ratio (also referred to in some literature as the A/B ratio) is calculated by dividing the systolic
maximum velocity by the diastolic minimum velocity. As the diastolic velocity approaches zero, however, this
relationship becomes less accurate. To avoid this problem, other ratios are also used. The pulsatility index is
1
calculated by dividing the difference between the systolic and diastolic velocities by the mean velocity ([S -
D]/mean velocity). The resistance index divides the same numerator by the systolic velocity.
The velocity of blood flow is influenced by myocardial contractile force, vessel diameter, and downstream
resistance. The interpretation of flow velocity waveforms requires a realization that blood flow velocity and volume
of flow are not synonymous because of the effect of vasoconstriction.
As is addressed later, the ability to visualize small arteries with color Doppler interrogation offers the
potential for further evaluation of the physiology and pathophysiology that may occur in the female genital tract.
When ordering and/or interpreting Doppler studies of the ovary and/or uterus, one must always be cognizant of the
effect of estrogen and progesterone on the blood flow velocity waveform. In general, during the periovulatory and
luteal phases, there is an increasing diastolic velocity (reduced S/D ratio, pulsatility index, or resistance index). This
realization is necessary for the correct interpretation of blood flow velocity waveforms in the premenopausal patient.
Keeping these principles in mind, one can see the potential improvement in diagnostic accuracy in the assessment of
functional, as well as pathologic, conditions in the gynecologic patient.14,15,16

SCANNING TECHNIQUES
At the present time there are two basic scanning approaches applicable to gynecologic ultrasound imaging:
transabdominal and transvaginal. The transabdominal technique refers to insonation of the pelvis through a partially
distended urinary bladder to minimize the acoustic impedance of interposed bowel gas. This scanning technique
may be performed with static scanning or real-time equipment offering sagittal, axial, and oblique planes of pelvic
anatomy for evaluation.
Static scanners produce repetitive still images of pelvic anatomy. Echoes that return from multiple acoustic
interfaces are detected by a manually maneuvered transducer and are electronically combined to produce the final
display. Real-time scanners differ from static scanners in that the image approximates actual motion. The image is
created by displaying multiple returning images at a very rapid frame rate to reflect the actual activity that is
happening.22
The evaluation of blood flow depends on the imaging of a flow velocity waveform depicting an upstroke
(systolic) velocity generated by myocardial systole and interval velocity, which is a function of downstream
resistance. The vessels to be insonated can readily be delineated by color Doppler and studied by specific vessel
insonation to establish the Doppler waveform mentioned above (Fig. 13).
The transvaginal technique, which uses a transducer inserted into the vagina, has emerged as a separate
scanning technique applicable to gynecologic ultrasonography.23 Sagittal, coronal, and oblique images of the pelvic
viscera may be obtained, as demonstrated in Figure 14 and Figure 15. Transvaginal ultrasonography offers a number
of advantages over transabdominal ultrasonography. First, the scanning tip may be placed closer to the scanning
target, thus enhancing resolution. Second, a full urinary bladder is not needed, resulting in a procedure that is much
more acceptable to most patients. Third, transvaginal ultrasonography interfaces nicely with the pelvic examination,
which can be performed at the same sitting. Fourth, the image quality of transvaginal ultrasonography has been
found superior to transabdominal ultrasonography in most instances, although the depth of penetration is
comparatively limited. Finally, the transvaginal approach offers superior tissue characterization of the uterus and
ovaries.24
A complete ultrasonographic evaluation of the pelvis, however, should include transabdominal
ultrasonography if any question exists regarding the possibility of pedunculated masses, ovarian cysts that may be
on long pedicles, or other masses that may not be readily visible by the vaginal route. Similarly, a postvoid
transabdominal scan may allow visualization of previously unapparent masses.25
With either technique, it is imperative that the ultrasonographer employ a deliberate scanning technique
that allows interpretation of echoes in an organized and thorough manner, paying constant attention to orientation.
The entire pelvis should be explored with documentation of the appearance of the adnexa, uterus, cervix, and any
other significant pelvic structures that are noted. Although Doppler insonation is feasible with either technique, most
favor the transvaginal Doppler approach because of its ability to approximate the pelvic vasculature.

MINIMIZING ARTIFACTS
Artifactitious echoes may produce confusing images. Procedures that will minimize artifacts include
avoiding interspersed air between the scanning tip and the imaging target, appropriate sensitivity setting of the
scanning instrument, use of variable bladder distention, and careful integration of ultrasonographic images with
knowledge of the expected pelvic anatomy. Nonetheless, the ultrasonographer should always realize the potential for

2
a certain echo to be artifactitious in nature. The realization of this possibility minimizes the likelihood that an artifact
will be interpreted as a significant pathologic process. A repeat study after bowel evacuation may be helpful.

3
 DIAGNOSTIC ULTRASONOGRAPHY IN
GYNECOLOGY
UTILIZATION OF REAL-TIME ULTRASONOGRAPHY BY THE
GYNECOLOGIST
Real-time ultrasonography, and more specifically, intravaginal or transvaginal real-time ultrasonography,
interfaces well with the pelvic examination and offers the potential for enhanced diagnostic accuracy of gynecologic
conditions. As noted above, the knowledge of sagittal, coronal, and axial anatomy; attention to maximizing image
detail; and correlation with the patient's history and physical examination should offer a comprehensive evaluation
of the gynecologic patient. In all probability, the role of gynecologic scanning will continue to expand. The
correlation of palpable pelvic findings with visual images of tissue texture should enhance the diagnostic acumen of
the clinical gynecologist. It is incumbent on all clinicians, however, to continue to strive to delineate the appropriate
utilization of this modality and to limit its use to those clinical situations when the cost-benefit ratio clearly warrants
its use.
In closing, a word should be mentioned regarding training and experience of the gynecologic
ultrasonographer. At this time, no specific guidelines exist regarding the educational experience necessary for
assurance of competence in gynecologic imaging. Prerequisites to the utilization of this technique are a thorough
knowledge of gynecologic physiology and pathology; the ability to access or obtain a thorough gynecologic history
and physical examination; and experience in acquisition, display, and documentation of ultrasonographic images.
Obviously, attention to continuing education through periodicals and postgraduate courses is necessary if the
physician is to stay abreast of this rapidly expanding field.

NORMAL PELVIC ANATOMY

UTERUS

Regardless of the scanning approach used, a reliable landmark for orientation is the uterus (Fig. 1). For this
reason, it is more difficult to scan posthysterectomy patients than those with a uterus in situ. The uterus should be
readily seen in the midplane of the pelvis and normally exhibits an echo density that is clearly distinguishable from
surrounding pelvic viscera (Fig. 2). The endometrial echo has a variable density, depending on water content and
cellular density, that fluctuates with the hormonal status of the patient (Fig. 3). The changes noted in endometrial
ultrasonographic appearance have been characterized. Progressive echogenicity of the functional zone (compactum
and spongiosum) occurs with completion of the preovulatory phase and during the secretory phase.17 The thickness
of the endometrium correlates with the histologic response to estrogenic stimulation.18 The relative position of the
uterus to the cervix and to the axis of the vagina should be noted. Retrodisplacement of the uterus usually produces a
less clearly defined image on transabdominal scanners, but does not interfere with uterine delineation significantly
using the transvaginal approach.19 The shape or symmetry of the uterus should also be assessed during the scanning
session.

CERVIX. The uterine cervix is visible and may be measured with a great degree of accuracy, especially with
the transvaginal technique. It should be remembered that with the transvaginal approach, the cervix may not be seen
if the scanning tip is placed in either the anterior or posterior fornix. For this reason, careful scanning during
insertion and removal of the scanning transducer is advisable.

URINARY BLADDER

The urinary bladder is usually very clearly seen and represents another landmark for anatomic orientation
in transvaginal and transabdominal scanning. The bladder should be partially distended before attempting
transabdominal scanning. Caution must be used to differentiate a full urinary bladder from a unilocular, anechoic-
type ovarian cyst that may lie anterior to the uterus. If any question regarding this possibility exists, a postvoid scan
is advisable for definitive evaluation.
Excessive filling of the urinary bladder displaces the uterus so posteriorly that not only does the patient
experience undue discomfort, but adequate imaging is difficult. Conversely, in the interpretation of transabdominal
4
images with inadequate bladder filling, significant posterior uterine wall or fundal pathology may be missed. The
appropriate amount of urine in the bladder for optimal visualization varies from patient to patient.
During insonation of unilocular cystic structures, a proximal artifact may occur as a result of near-field
sensitivity, or of the "gain setting" producing near-field reverberation artifact. To the uninitiated, this echo may
appear to represent intracystic echo-dense areas. Variation of the sensitivity (gain setting) of the equipment allows
these areas to be differentiated from more significant findings.
On either side of the urinary bladder in the anterolateral pelvic area are the iliopsoas muscles. These areas
should not be confused with pathologic pelvic masses (Fig. 4).
Frequently the urethra and the urethrovesical junction can be visualized. Transvaginal or perineal (introital)
scanning will enhance this imaging of these structures.

VAGINA

The vagina appears as a collapsed tubular structure lying inferior to the urinary bladder and distal to the
uterine cervix by transabdominal scanning. Transvaginal ultrasonography does not delineate the vagina as well as
the transabdominal or perineal (introital) approach. Anomalies of vaginal development are discussed later in this
text.
Occasionally, with overdistention of the urinary bladder, urine may accumulate in the vagina (Fig. 5).
Likewise, the presence of tampons or menstrual blood may be discerned.

ADNEXA

The adnexa include the ovaries, fallopian tubes, blood vessels, supporting ligaments, and peritoneal folds of
the lateral pelvis. The main structures that are recognizable with ultrasonography include the ovary, fallopian tube,
and vascular anatomy.

OVARY. The position of the ovary is somewhat variable, depending on the length of the infundibulopelvic
ligament, the presence or absence of adhesions, and other anatomic abnormalities that may displace the ovary.
Usually, the ovaries lie in a lateral position to the uterus and are identifiable by scanning in transverse or
longitudinal planes lateral to the uterine corpus. Identification of the internal iliac vessels with transvaginal
ultrasonography is helpful in identifying the appropriate location of the ovary, but manipulation of the scanning
transducer to bring out the full extent of the ovarian echo is frequently necessary. During transvaginal scanning, the
manipulation should be performed slowly, and patient cooperation is helpful. In the absence of pelvic adhesive
disease, the ovary is noted to move in response to transducer manipulation.
With the availability of high-resolution ultrasonography, the ability to monitor follicular development
exists. Follicles are clearly visible in the majority of ovaries in women of reproductive age, and appear as echo-
sparse, well-circumscribed areas within the ovarian stroma, varying between 5 and 20 mm in diameter (Fig. 6).
Ultrasonographic follicular monitoring has become an integral aspect of ovulation induction protocols by allowing
correlation of serum estradiol levels with follicular diameter during gonadotropin stimulation. A follicular diameter
of 18 to 22 mm is characteristic of a periovulatory follicle.20,21
Ovarian blood supply is largely from the ovarian artery coursing through the infundibulopelvic ligament.
Velocity waveform analysis reveals increasing diastolic velocity in the periovulatory and luteal phase (Fig. 7 and
Fig. 8).

FALLOPIAN TUBE. The fallopian tube is difficult to visualize in the normal state. Frequently, in cases of
abnormal tubal morphology, such as after the development of a hydrosalpinx or neoplasm, the tube may be more
clearly defined. Transvaginal ultrasonography results in a higher frequency of tubal visualization. A hydrosalpinx is
typically a convoluted, anechoic tubular structure (Fig. 9). Frequently the tube and ovary form a complex, echo-
dense, adnexal mass in cases of adhesive inflammatory disease of the pelvis or a neoplastic process.

OTHER PELVIC FINDINGS

TRUE AND FALSE LIGAMENTS OF THE UTERUS. The supporting uterine ligaments are rarely
clearly visualized with ultrasonography. The folds of peritoneum covering the vascular and lymphatic supply to the
ovary and uterus (infundibulopelvic and broad ligaments) are not true ligaments and are not seen; the uterosacral
ligaments are also not usually seen. The round ligament, which is actually a tubular structure composed of smooth
muscle, may be seen. Variable echo densities and reflected echoes may result from inflamed peritoneal surfaces
involved in adhesive pelvic disease. In most instances, however, the echo pattern is such that, although a more echo-
dense peritoneal area may be visualized, a definitive diagnosis is usually not possible.
5
 BOWEL CHARACTERISTICS. The presence of gas and feces in the bowel produces a variably dense
echo return. Peristalsis is easily seen. Frequently, gas-filled bowel will have proximal echoes with poor distal echoes
due to gas attenuation of the ultrasound energy. Occasionally, a distended loop of bowel may be confused with a
complex cystic or solid adnexal mass. The possibility of a primary bowel process must always be considered in the
diagnosis of adnexal processes.

URETERS. The ureters are rarely visualized with ultrasonography unless they are specifically searched for
and somewhat dilated. In transverse section, the ureter may be seen juxtaposed near the lateral border of the uterine
cervix. Most ureteral imaging via either the transabdominal or transvaginal route is done in situations where there is
a concern regarding a potential ureteral dilatation, as in patients with parametrial extension of cervical carcinoma.

PELVIC VASCULAR ANATOMY. The internal iliac vessels, as previously noted, serve as landmarks for
ovarian location (Fig. 10). The uterine arteries may be visualized occasionally and are frequently noted to exhibit
prominent pulsations in early pregnancy. Pelvic vessels that are amenable to insonation for Doppler study include
the ovarian and uterine arteries, as well as vascular structures within the stroma of pelvic masses.

CUL-DE-SAC FLUID ACCUMULATION. The presence of fluid in the cul-de-sac is a frequent finding.
Small amounts of peritoneal fluid will accumulate in the inferiormost portion of the cul-de-sac as a result of the
menstrual cycle. Massive accumulations of fluid may exist in cases of ovarian carcinoma (Fig. 11). The
hemoperitoneum of ruptured tubal pregnancy is very apparent during transabdominal or transvaginal scanning (Fig.
12).

CHARACTERIZATION OF PELVIC MASSES

Ultrasonographically detected masses should be classified as predominantly cystic or solid. Cystic masses
produce anechoic or hypoechoic images with excellent through-transmission of sound resulting in a bright, distal
surface (acoustic enhancement). Solid masses attenuate the sound energy and result in poor penetration. Masses
containing gas also demonstrate poor sound transmission, with clear proximal borders and indistinct distal
boundaries.26 Cystic masses containing blood, tissue fragments, or other material are described as complex because
they produce a cystic appearance as judged by sonic transmission, but the echo density of the intracystic material is
greater than that of fluid alone.27 This type of echo pattern is frequently referred to as low-level echo density.
In addition to ultrasound characteristics, masses should be categorized by the suspected site of origin or
location (e.g., uterine, ovarian, adnexal, cul-de-sac). If the site of origin is unclear, then a statement delineating
separate, noninvolved organs is frequently helpful (e.g., an adnexal mass that does not appear to arise from either
ovary).
The size of pelvic masses is usually measured along specified scanning planes in order to allow volume
assessment if desired. In addition, the character of a cyst wall (smooth versus irregular) and intracystic anatomic
appearance (e.g., septated, papillary) also assists in establishing the likelihood of a neoplastic or reactive
(inflammatory or endometriotic) process, as opposed to a functional process.

GYNECOLOGIC ABNORMALITIES

CONGENITAL ABNORMALITIES

MÜLLERIAN (PARAMESONEPHRIC). Müllerian anomalies of the reproductive tract may be divided into
two broad categories:

1.Patients with a normal 46,XX karyotype who exhibit abnormalities of the reproductive tract secondary to
partial or complete failure of müllerian development or fusion.
2.Patients with abnormal karyotypes, including lack of an X chromosome (45,X), presence of a Y
chromosome or portion of a Y, or a mosaic combination of these karyotypes.

Patients with Normal Chromosomes. Anomalous development in patients with a normal 46,XX karyotype
usually involves failure of canalization of the developing müllerian tubercle as it meets the invaginating urogenital
sinus or incomplete fusion of the paired müllerian ducts. Anomalies resulting from abnormal müllerian tubercle
6
fusion with the urogenital sinus and canalization include imperforate hymen and transverse vaginal septum. During
attempted transvaginal scanning, a hematocolpos may be noted as cystic dilatation of the superior vagina with
cephalad displacement of the uterus and other pelvic viscera (Fig. 16 and Fig. 17).28,29,30,31,32,33,34
Ultrasonographic guidance may offer intraoperative assistance in correcting these anomalies.35
Patients with failure of müllerian differentiation to the degree where there is no discernible uterus or cervix
and only small fibromuscular condensations of tissue near the gonad may represent the Mayer-Rokitansky-Küster-
Hauser syndrome (müllerian agenesis).36 Ultrasound evaluation of these patients reveals no apparent uterus, but
gonadal development is noted in the adnexal areas.33
Abnormalities of müllerian fusion in chromosomally normal 46,XX patients may result in a variety of
uterine abnormalities, ranging from a true bicornuate uterus to uterine septation.37,38,39,40 The presence of two
distinct endometrial cavities is discernible by ultrasonography; however, some difficulty may be encountered in
establishing whether or not a septate or bicornuate uterus exists (Fig. 18). The association of müllerian anomalies
with renal anomalies must always be kept in mind.

Patients with Abnormal Chromosomes. Patients with androgen insensitivity syndrome, who manifest a
46,XY karyotype, exhibit no uterine development and have intraabdominal testes. The shallowness of the vagina in
these patients, along with sparse pubic hair, chromosomal constitution, and serum androgen concentration, are
helpful in the differential diagnosis of this syndrome and müllerian agenesis. Gonads containing a Y chromosomal
component or a portion of a Y chromosome should be removed because of the risk of gonadoblastoma development
in the gonad.41
Patients with 45 X gonadal dysgenesis will reveal a sexually infantile body habitus as well as a prepubertal
uterine morphology (Fig. 19).42 Monitoring of the change in uterine morphology secondary to estrogen replacement
therapy reveals a transformation of the uterus into a more adult-type appearance with fundal dominance (Fig. 20).
In summary, transabdominal and transvaginal ultrasonography are excellent additions to the pelvic
examination in patients suspected of anomalous reproductive tract development. The transperineal technique may be
beneficial in the peripubertal patient who is difficult to examine and who has signs and symptoms of possible
cryptomenorrhea.37

WOLFFIAN (MESONEPHRIC). Nonanomalous embryologic remnants of the wolffian ducts may

occasionally be seen. Epoophoron cysts or hydatids of Morgagni produce small anechoic areas adjacent to the ovary.
Gartner's duct cysts are located in the anterolateral areas of the vagina and are also anechoic and unilocular (Fig.
21). These structures are of minimal clinical significance and rarely warrant any significant management.

OTHER ABNORMALITIES OF DEVELOPMENT. Uterine and cervical abnormalities due to in utero

exposure to diethylstilbestrol have been documented. The depiction of this abnormality by ultrasonography has not
been as clear as with hysterosalpingography.43

GYNECOLOGIC CONDITIONS OF THE UTERUS

MYOMETRIUM. Leiomyoma. Uterine enlargement not due to pregnancy is most often due to uterine
leiomyomata. Uterine leiomyomata represent proliferations of smooth muscle and are benign neoplasms.
Leiomyomata are classified by their location as subserous, intramural, or submucous. Ultrasonographically,
leiomyomata exhibit poor sound transmission because much of the sonic energy is attenuated by the solid
consistency of the mass. Uterine contour irregularity is one of the most consistent findings44; however, a variety of
findings may occur.45 Ultrasonography offers the potential of measuring uterine leiomyomata in those patients in
whom a conservative or nonsurgical management plan is initiated (Fig. 22 and Fig. 23).46 In addition,
ultrasonography may detect early signs of degeneration or calcification of uterine leiomyomata. The effect of
gonadotropin-releasing hormone suppression of uterine leiomyomata is easily monitored by ultrasonography.
Occasionally, leiomyomata may undergo degeneration and mimic other cystic pelvic masses.47,48

Leiomyosarcoma. Rarely, a malignant leiomyosarcoma may be found. Leiomyosarcomas present a complex

echo pattern somewhat analogous to uterine leiomyomata with degeneration. Differential diagnosis of these clinical
phenomena requires more extensive analysis. Two-dimensional imaging is rarely diagnostic of this process, but
evidence of increased diastolic velocity with Doppler ultrasound may assist in the diagnosis.49

ENDOMETRIUM. The endometrium is clearly imaged with pelvic ultrasonography, especially the
transvaginal technique. Endometrial thickness correlates well with the endometrial response to estrogen stimulation.
Morcos and associates50 noted that an endometrial echo greater than 1.5 cm had a sensitivity of 94% and specificity
of 93% in predicting a withdrawal bleeding response to progesterone in amenorrheic reproductive-age women.

7
 The instillation of a small quantity of sterile saline into the endometrial cavity (hydrosonography) creates
an ultrasonographic interface between solid tissue and liquid. This results in improved visualization of the
endometrium in general, and the endometrial surface in particular. This procedure has also been termed
hysterosonography or sonohysterography.
A small polyethylene catheter or pediatric Foley catheter is inserted through the cervix into the endometrial
cavity after appropriate cleansing with an antiseptic solution. Concurrent real-time imaging via the transvaginal or
transabdominal technique allows visualization of the separation of the endometrial surfaces as the fluid is instilled
(Fig. 24, Fig. 25, and Fig. 26).
Using this technique, the ultrasonographer can achieve better delineation of endometrial polyps, submucous
leiomyomata, and the configuration of the endometrial cavity. There is a potential for this technique to enhance the
endometrial assessment of patients on tamoxifen therapy as well.
Using this technique to evaluate small endoluminal masses within the endometrium, Dubinsky and
colleagues51 detected 19 endoluminal masses in 48 patients with an endometrial thickness of 5 to 10 mm. These
masses were clearly diagnosed as either endometrial polyps or submucous leiomyomata.
Concurrent transabdominal scanning and transcervical instillation of saline is another technique used to
visualize the endometrial anatomy. Cicinelli and co-workers52 reported a sensitivity of 100% in the diagnosis of
submucous leiomyomata with this technique. An excellent description of a variety of hydrosonograpic findings was
reported by Goldstein.53
Transvaginal ultrasonography offers the opportunity to visualize the endometrium (Fig. 27 and Fig. 28). In
an effort to select patients at an increased risk of endometrial pathology, several authors have evaluated the
reliability of inferring endometrial histology from measuring the width of the endometrial echo (Fig. 29).
Granberg and associates54 evaluated 205 women with postmenopausal bleeding and noted benign
endometrial histology with an endometrial width (thickness) of less than 9 mm. The mean endometrial width in
patients with endometrial cancer was 18.2 ± 6.2 mm compared to 3.4 ± 1.2 mm in those with atrophic histology.
Malpani and co-workers55 reviewed endometrial thickness measurements in patients with endometrial hyperplasia
compared to those with normal histopathology. The mean width of the endometrial echo in patients with hyperplasia
was 18.8 mm compared to 5.4 mm in the benign group. Varner and colleagues56 also noted benign findings in
patients with an endometrial thickness of less than 5 mm.
In an effort to compare the diagnostic accuracy of transvaginal ultrasonography, endometrial cytology, and
histologic assessment of specimens obtained via dilatation and curettage, Karlsson and associates57 performed all
three of these techniques on 105 patients with postmenopausal bleeding. The sensitivity and specificity of these
three modalities were essentially the same (sensitivity 81%, specificity 58%), leading these authors to conclude that
the method of transvaginal scanning and endometrial thickness measurement was a "valuable adjunct" in managing
these patients.
Realizing that false-positives and -negatives exist for virtually all testing schemes, it must be emphasized
that the patient's response to therapy and persistence of concerning symptoms must be addressed with more in-depth
study. To emphasize this point, a study from Norway by Dorum and co-workers58 noted that 3 of 54 patients with
endometrial carcinoma had an endometrial thickness of less than 5 mm. Two patients had stage 1 adenocarcinoma of
the endometrium; the third had endometrial involvement by a malignant lymphoma.
It appears that the likelihood of a malignancy in a patient with a thin endometrium, negative endometrial
biopsy, or normal specimen obtained via dilatation and curettage is very low. Persistent bleeding, failure of expected
response to therapy, development of new symptoms, or persistence of concerning symptoms require further
evaluation. It appears, therefore, that a postmenopausal patient with a very thin (less than 5 mm) endometrial width
may be managed without endometrial sampling or curettage for abnormal bleeding, assuming an appropriate
response to therapy follows.59
The value of ultrasound assessment of endometrial carcinoma, particularly the depth of invasion of the
myometrium, is under investigation. Endometrial carcinoma produces an irregularity of the endometrial cavity in
advanced cases (Fig. 30).60,61,62,63 Of 25 cases of endometrial carcinoma, the correct depth of invasion was
predicted in 21.64 In a separate study, Conte and associates65 confirmed these data, predicting the correct amount of
myometrial invasion in 18 of 20 patients.
The finding of endometrial fluid should heighten the ultrasonographer's suspicion of unapparent
abnormalities of the genital tract. Of 17 postmenopausal patients with endometrial fluid collection, 5 had
malignancies: 2 had ovarian cancer, 1 had tubal carcinoma, 1 had endometrial carcinoma, and 1 had cervical
carcinoma.66

CERVIX. In addition to visualization of the volume of cervical cancer,67 the evaluation of parametrial
involvement has also been performed (Fig. 31). Using a transrectal probe, Yamamoto and Kitao68 evaluated the
accuracy of ultrasonographic prediction of parametrial involvement compared with computed tomography and
Federation of International Gynecology and Obstetrics (FIGO) staging and noted a sensitivity of 83% and specificity
of 97%. The potential also exists to assess Doppler flow characteristics of the uterine arteries in cervical
malignancy.
8
GYNECOLOGIC CONDITIONS OF THE ADNEXA

FUNCTIONAL OVARIAN PROCESSES

FOLLICULAR MATURATION. As noted earlier, in addition to the delineation of specific ovarian masses,
follicular maturation may be monitored by serial transabdominal or transvaginal ultrasonography.69 Preovulatory
follicular development is clearly seen with progression of follicle diameter to the 18 to 22 mm range at midcycle.
Follicular dominance and progression are easily monitored by real-time ultrasonography in correlation with serum
estradiol concentration in efforts to induce ovulatory ovarian function (Fig. 32 and Fig. 33).70,71,72,73,74,75
Transvaginal-directed oocyte retrieval for assisted reproductive techniques is now the preferred method of acquiring
oocytes.

POLYCYSTIC OVARY SYNDROME. Polycystic ovary syndrome produces a wide spectrum of menstrual
disturbances and manifestations of androgen excess. The ovary also may exhibit a variety of appearances, ranging
from multiple cystic follicles (2.5 cm) of varying sizes to only a few follicle cysts (>2.5 cm) (Fig.
34).76,77,78,79,80,81,82 In cases of hyperthecosis, in which fewer follicles are developed, the ovary would be
expected to exhibit a more solid echo pattern. Monitoring of the changes in ovarian volume with suppressive
treatment with gonadotropin-releasing hormone analogs has been described.83

OVARIAN MASSES. The ovary has the capacity of developing many different cystic and solid masses.
Transvaginal and transabdominal ultrasonography can categorize adnexal masses into various echo densities and
morphologies, thereby narrowing the differential diagnosis. The reliability of ovarian size assessment has been
documented to be high, with a correlation coefficient of 0.960 between observers documented by Higgins and co-
workers.84

Ovarian Cysts. Unilocular cystic masses with few intracystic echoes are most likely serous-type cysts of the
ovary (cystic follicles or follicle cysts) or serous cystadenomas (Fig. 35). Cystic masses with complex echogenic
intracystic echoes are more commonly hemorrhagic in origin (hemorrhagic corpus luteum cysts or
endometriomata).85
A more conservative management approach is feasible in patients with reassuring intracystic morphology
(e.g., anechoic, smooth wall, no papillary excrescences). The decreased need for surgery in children was
demonstrated retrospectively in 1989 by Thind and colleagues,86 who reviewed the cases of 64 children with
ovarian cysts. In addition, the potential also exists for therapeutic cyst aspiration using ultrasound guidance of
selected cysts in young women.87,88 In patients for whom expectant management is elected, comparative studies
after subsequent cycles or hormonal therapy is feasible, especially with the transvaginal technique.
The differentiation between endometriomas and nonendometriotic ovarian cysts was investigated by
Guerriero and associates,89 who evaluated 251 premenopausal, nonpregnant patients using transvaginal ultrasound.
Of the 31 diagnosed as ovarian endometriomas, 24 were confirmed as endometriomas by histologic assessment. The
sensitivity of transvaginal ultrasound in differentiating endometriotic cysts from cysts of other etiologies was 83%
and the specificity 89%. The authors noted that this was compatible with the diagnostic accuracy of magnetic
resonance imaging.
Controversy exists regarding the significance of cystic masses in the postmenopausal age group. Fleischer
and associates90 published an excellent correlation of ultrasonographic findings with subsequent histopathology of
67 ovaries in 37 postmenopausal patients. A positive predictive value of 92% and a negative predictive value of
92% were noted in this highly selected population. Luxman and colleagues91 noted that 2 of 29 ovarian cancers
were not detected by transabdominal ultrasonography. Goldstein and co-workers92 and Andolf and Jorgensen93
noted no malignancies in hypoechoic cysts less than 5 cm in more than 190 patients.
Therefore it appears that small, nonsuspicious cystic areas in postmenopausal patients may be followed
conservatively with surgical evaluation for persistent cysts or those that progressively increase in size. The absolute
maximum cystic diameter that may be followed safely is debatable, but appears to be in the 3.5 to 5 cm range. If a
noninterventional posture is selected, the ultrasonographer must realize that a small likelihood of an unapparent
malignancy exists and that close follow-up is mandatory.

Ovarian Neoplasms. Germ Cell Tumors. The most common neoplasms of reproductive-age women are germ
cell tumors. Cystic teratomas are well-circumscribed, complex, cystic masses that are usually unilateral and exhibit a
variably complex, intracystic echo pattern (Fig. 36 and Fig. 37).94,95,96 This type of tissue characterization is
important because these complex cystic masses require surgical evaluation for definitive therapy more often than the
9
smaller, unilocular, serous-type cysts, which may be followed expectantly. Rupture of cystic teratomas during
pregnancy is a major complication that should be avoided.97 Although the specific pathologic diagnosis of an
ovarian mass cannot be made ultrasonographically, ultrasound can be used to categorize and describe these masses
in order to establish a more precise differential diagnosis.98

Stromal Neoplasms. Solid ovarian neoplasms include those arising from ovarian stromal cells (fibroma and
thecoma)99 (Fig. 38) and the Brenner cell tumor.100

Ovarian Carcinoma (Epithelial Ovarian Tumors). Ovarian malignant neoplasms produce a variety of
ultrasonographic patterns that typically produce an image of mixed solid and cystic components, irregular
septations, and coexistent ascites, and they are frequently bilateral (Fig. 39 and Fig. 40).101,102
The role of ultrasonography in screening for ovarian cancer is controversial. An ever-increasing body of
literature continues to question the costeffectiveness of ultrasound as a screening modality. A thorough review of
this controversy is beyond the scope of this chapter. Suffice it to say that as of this writing, ultrasound screening for
ovarian cancer is by no means widely accepted. The combined use of tumor-associated antigens (e.g., CA-125) with
ovarian imaging by two-dimensional technique and Doppler may offer an enhanced potential for diagnosis of
ovarian malignancies in high-risk groups.14,103,104
The salient question that must be answered before recommending universal ovarian cancer screening with
this modality encompasses the reliability and cost-effectiveness of the screening protocol to detect early (stage I or
stage II) disease. The realization that CA-125 levels are not elevated in many cases of early-stage disease raises a
serious question regarding the efficacy of this serum test as a screening component. The question of routine ovarian
cancer screening remains unanswered. The role of ultrasonography in staging and follow-up of ovarian cancer
continues to expand. Conte and co-workers105 described the potential value of ultrasound study in the preoperative
staging of ovarian carcinoma. Although ultrasonography can detect macroscopic residual disease with acceptable
accuracy, its limitation in detecting small residual disease in lieu of second-look laparotomy has been demonstrated
by Murolo and associates.106
Breast cancer and gastrointestinal tract cancer may metastasize to the ovary. Other ovarian neoplasms have
been described ultrasonographically, including Brenner and Krukenberg tumors.107,108 The Krukenberg tumor has
been characterized ultrasonographically as a complex solid mass and a cystic mass, but is unlike the ultrasound
picture of primary ovarian carcinoma.109 Ovarian neoplasms may be imaged more precisely by the vaginal
approach. Figure 41 shows the image quality of an ovarian thecoma by transvaginal ultrasonography.
Many articles have been published further describing the ultrasonographic two-dimensional image
characteristics of ovarian cancer. In addition, Doppler interrogation of small vessels detected by color Doppler
imaging reveals increased diastolic flow velocities and evidence of neovascularization secondary to tumor
angiogenesis. The resultant calculations of waveform flow velocity ratios are therefore decreased.
Multiple scoring systems for two-dimensional findings and two-dimensional and Doppler findings have
also been created. The details of these systems are beyond the scope of this chapter. Suffice it to say that the various
scoring systems offer the potential of assigning numeric values to the well-known findings of ovarian malignancy,
such as thickened cyst walls, septations, papillary excrescences, complex intratumoral echoes, and disorganized
echo texture. The addition of Doppler waveform analysis frequently confirms the concern of nonreassuring two-
dimensional findings, but rarely increases concern in patients with benign-appearing cysts on two-dimensional
findings.
Brown and co-workers110 evaluated 44 masses with two-dimensional and color Doppler imaging. They
noted significant overlap in the resistance index and pulsatility index between benign and malignant masses. This
finding contrasts with that of other investigators.111

FALLOPIAN TUBE CARCINOMA. Although much less common than ovarian carcinoma, cancer of the
fallopian tube exhibits a similar clinical course. The complex echo pattern of tubal carcinoma diagnosed by
transvaginal ultrasonography has been described.112,113,114

PELVIC INFLAMMATORY DISEASE AND ENDOMETRIOSIS

Other adnexal processes exclusive of neoplastic changes include pelvic inflammatory disease and
endometriosis. Pelvic inflammatory disease most often results from a primary salpingo-oophoritis that has
progressed to some degree of hydrosalpinx formation with adhesive pelvic disease. A variety of ultrasonographic
findings with differing types of complex adnexal masses result with frequent visualization of tubal dilatation and
intrafallopian tube fluid (hydrosalpinx formation).115 The ability to diagnose and guide aspiration of tubo-ovarian
abscesses with transvaginal ultrasonography has been documented.116,117,118,119,120
It is frequently extremely difficult to establish the precise etiology of complex adnexal masses on an
endometriotic or inflammatory basis.121,122,123 Endometriosis will also produce complex adnexal masses with
10
distortion of the pelvic anatomy typical of adhesive disease (Fig. 42, Fig. 43, Fig. 44, and Fig. 45). In some
instances, endometriotic involvement of a nongynecologic structure, such as the urinary bladder or liver, has been
noted.124,125,126

INTRAUTERINE DEVICES

Ultrasonographic localization of intrauterine devices (IUDs) has been possible for many years (Fig. 46).
The advent of transvaginal scanning increases the accuracy of IUD localization.127 IUD removal under
transabdominal ultrasound guidance offers a more precise and potentially less traumatic removal in difficult clinical
settings.128,129 The ability to extract an IUD that is juxtaposed, but inferior to, an early intrauterine pregnancy is
also occasionally enhanced by transabdominal ultrasound guidance.

EARLY PREGNANCY

INTRAUTERINE PREGNANCY. The most common cause of uterine enlargement is early pregnancy. The
advent of transvaginal ultrasonography offers the capability of extremely early diagnosis of pregnancy. The
prominent echogenicity of decidualized endometrium is clearly seen on transabdominal or transvaginal scanning
before the visualization of a gestational sac.130,131 With currently available transvaginal imaging techniques, a
gestational sac that is located within the uterine cavity and developing normally should be clearly visible,
concomitant with a serum human chorionic gonadotropin (hCG) concentration of 1000 mIU/mL (Second
International Standard [2nd IS]).132 Using the transabdominal technique, the same author reported the
discriminatory zone to be 1800 mIU/mL (2nd IS).133 It should be noted that the First International Preparation (1st
IRP) standard results in hCG values that are approximately twice the 2nd IS values. Other published analyses of
transvaginal ultrasound have shown lower discriminatory zones of 300 mIU/mL (2nd IS),134 450 to 750 mIU/mL
(presumed 2nd IS),135 and 1100 mIU/mL (1st IRP).136 From a clinical standpoint, if a quantitative hCG exceeds
1000 mIU/mL and an intrauterine gestational sac cannot be seen with transvaginal scanning, the suspicion of an
ectopic pregnancy must increase, and serial follow-up or further evaluation is indicated. Studies of serial scanning of
patients conceiving during in vitro fertilization cycles reveal the presence of a gestational sac at even lower hCG
concentrations.137
The correlation of gestational sac visualization and serum hCG concentration offers the practicing
gynecologist a powerful tool for early diagnosis of extrauterine pregnancy. The principles of management,
evaluation, and diagnosis presuppose knowledge of the rate of increase of hCG concentration in normal pregnancy
and correlation with ultrasonographic findings. As a general rule, hCG should double every 2 to 3 days during the
early first trimester.138,139,140,141 Many ectopic pregnancies exhibit a subnormal rise in hCG.
Early intrauterine pregnancy scanning displays the developing amniotic membrane, chorion, and yolk
sac.130,142 Before visualization of the fetal pole, the assessment of pregnancy status depends on the rate of growth
of the sac and correlation with hCG levels. Early in gestation the mean sac growth is 0.9 to 1.13 mm/day.136 A yolk
sac should be seen when the mean sac diameter exceeds 2 cm, and a fetal pole should be visible after the sac
exceeds 2.5 cm (Fig. 47)143 using the transabdominal approach. Transvaginal scanning allows visualization of the
embryo with a mean sac diameter of 1.2 cm.144 As the first trimester progresses, the fetus can easily be outlined,
and the cephalic pole, caudal pole, limb buds, and umbilical cord can be delineated.135 The presence of fetal cardiac
activity in early pregnancy scanning indicates an excellent prognosis for the pregnancy. Fetal cardiac flicker can be
seen in embryos of at least 5 mm with transvaginal scanning and in embryos of at least 9 mm with the
transabdominal approach.144 In published series, the likelihood of spontaneous abortion of ultrasonographically
normal pregnancies in the 8- to 12-week range approximates 2% to 4%.145 Before cardiac flicker becomes
apparent, correlation of the gestational sac size with quantitative hCG assessment provides important predictive
information. If the hCG concentration is clearly abnormal for the stated gestational sac size, the likelihood of
pregnancy progression is unlikely. The presence of a normal hCG concentration for a specified gestational sac
measurement does not necessarily predict a successful outcome.146
The accuracy of diagnosing pregnancy failure has been enhanced by ultrasonography. Incomplete
spontaneous abortion is characterized by disorganized intrauterine echoes, irregularity of the gestational sac,
frequent eccentric sac location, and the evidence of intradecidual hemorrhage.147 The anembryonic pregnancy
(blighted ovum) is characterized by a visible gestational sac (chorion), but no apparent fetal pole. Frequently the sac
is smaller than expected.143,148,149 When the mean sac diameter minus the crown-rump length is less than 5 mm,
94% of pregnancies were lost.150 Retention of a discernible embryo that has undergone an early demise has been
termed a missed abortion.
First-trimester hydatidiform mole may produce bizarre echoes in early pregnancy or may initially appear as
an unremarkable gestational sac.149 The ultrasound characterization of hydatidiform mole has been well described.
The early diagnosis of molar pregnancy enhances appropriate management and hopefully minimizes the likelihood

11
of malignant sequelae. Although variable, the echo pattern suggestive of a molar pregnancy consists of irregular
solid and cystic interfaces within the endometrial cavity in a patient with signs and symptoms of early pregnancy
(Fig. 48).

EXTRAUTERINE PREGNANCY. Pregnancies located outside the intrauterine cavity are referred to as
extrauterine pregnancies. Although these pregnancies include ovarian pregnancies, abdominal pregnancies, and
cervical pregnancies, the most common location is in the fallopian tube. This section addresses the preclinical
diagnosis of unruptured tubal pregnancies using a combined approach of ultrasonographic findings correlated with
serum hCG concentration.
Currently, as noted earlier, a discriminatory zone of approximately 1000 mIU/mL is being used by means
of transvaginal ultrasonography as the level at which a normal gestational sac should be seen.132 The lack of
visualization of the gestational sac with hCG concentrations greater than 1000 mIU/mL or an inadequate rate of
increase of hCG is suggestive of the diagnosis of extrauterine pregnancy and warrants further evaluation.132,151
Using transvaginal ultrasound and an hCG discriminatory zone of 1500 mIU/mL (1st IRP), Barnhart and
colleagues152 noted that all viable intrauterine pregnancies that were visualized by ultrasound demonstrated hCG
values in excess of 1500 mIU/mL. In a study of 1253 patients, there were 205 ectopic pregnancies diagnosed by the
combined use of serial hCG measurements and transvaginal ultrasound. Fifty-nine percent of ectopic pregnancies
never produced hCG concentrations greater than 1500 mIU/mL. In their experience, the sensitivity of this combined
protocol was 100% and the specificity 99%.
A word of caution is justified. Multifetal pregnancies typically demonstrate a higher discriminatory zone of
hCG. Kadar and co-workers153 noted that a discriminatory zone of 3000 mIU/mL would be required in order not to
misdiagnose early potentially viable multifetal pregnancy.
Since the hCG doubling time is relatively short (2 to 3 days), this difference in discriminatory hCG levels
does not translate into a long period of time, but as noted in the study mentioned earlier,152 most ectopic
pregnancies do not achieve an hCG level of 1500 mIU/mL, much less 3000 mIU/mL. If one wants to minimize the
risk of intervening in a potentially normal intrauterine pregnancy, it seems that a discriminatory zone of 3000
mIU/mL and expected doubling time of 72 hours would be preferable.
If this protocol is adopted, the physician must be assured of the patient's reliability and potential for follow-
up, having the ability to intervene rapidly if concerning symptoms develop. It must be stressed that this diagnostic
protocol applies to patients who are asymptomatic or minimally symptomatic. Patients with an acute abdomen,
vasomotor instability, or evidence of hemoperitoneum on transvaginal scanning should be treated surgically.
Using the transvaginal approach, an extrauterine conceptus is frequently delineated with ultrasonography,
at which time definitive surgical therapy may be instituted.154,155 As noted above, this technique allows
assessment of the cul-de-sac for fluid accumulation. If evidence of a possible hemoperitoneum is seen,
transvaginally directed culdocentesis can be readily accomplished.
Rarely, a combined intrauterine and extrauterine pregnancy (heterotopic pregnancy) may be
seen.156,157,158,159 The incidence of heterotopic pregnancy has been noted to be more frequent in patients
undergoing in vitro fertilization and warrants heightened awareness.160
The role of Doppler assessment to increase diagnostic accuracy is being evaluated. A sensitivity of 73% for
early evaluation was noted in a study of 96 ectopic pregnancies by Taylor and co-workers161 using Doppler
technology. Early diagnosis results in less morbidity, potential tubal salvage, and the possibility of medical
therapy.162
The assessment of eccentric intrauterine implantations is more difficult. The diagnosis of a cornual or
isthmic implantation site is frequently possible, and in these cases the early diagnosis alleviates the potential for
catastrophic uterine rupture.163 Chronic and interstitial ectopic pregnancies producing complex adnexal echogenic
masses have been described.164,165,166,167

12
 DIAGNOSTIC OBSTETRIC IMAGING
The role of ultrasonography in obstetric practice has continuously evolved since its introduction more than 35
years ago. In the past decade, real-time ultrasound has led to significant advances in obstetric care attributable to
improvements in both image resolution and clinical correlation. Using this imaging technique, clinicians can detect
pregnancy as early as 3 weeks after conception, confirm or revise gestational age within 1 week, diagnose multiple
gestation in early pregnancy, confidently diagnose fetal death at any gestational age, assess fetal well-being,
evaluate amniotic fluid volume, and diagnose a broad variety of fetal malformations.

CONTENT OF AN ULTRASOUND EXAMINATION

A basic ultrasound examination should contain a fetal survey, an evaluation of fetal biometry, and
documentation of the anatomic images obtained. The survey includes a confirmation of fetal number, viability,
position, assessment of amniotic fluid volume, and location of the placenta. In assessing fetal biometry, the
applicable standard fetal measurements already discussed, including CRL, BPD, abdominal circumference, and
femur length, should be taken. The estimation of fetal weight is a clinically useful parameter obtained from the fetal
biometric measurements. Several equations have been produced based on fetal biometry that estimate fetal weight.
One or more of these usually is incorporated into the software of ultrasound machines. An estimation is provided
automatically after the biometry is recorded. These weight estimations differ little in accuracy, and most provide an
estimated fetal weight that has a standard deviation of ±8% to 10%. Therefore, 95% (2 standard deviations) of
estimations are within 20% of the actual birth weight.
An ultrasound examination also should include specific documentation of fetal anatomic images obtained.
These images are usually stored in the form of Polaroid pictures, videotape, thermal prints, or digital image files.

USE OF ULTRASOUND AS A SCREENING TEST

Generally recognized indications for obstetric ultrasound imaging are found in Table 2. Although the routine
use of ultrasound in early pregnancy is not considered the standard of care by any public organization in the United
States,10 it is promoted by many practitioners. Some investigators have noted a significant reduction in the
frequency of labor induction for postdate fetuses when routine ultrasound is performed. Routine ultrasound early in
pregnancy can result in a significant revision of the estimated date of delivery in up to 10% of patients with an
accurate, normal last menstrual period. Routine ultrasound use may decrease the incidence of antepartum fetal
assessment and induction of labor for postdate fetuses.
Belfrage and colleagues11 compared the routine use of ultrasound in early pregnancy with the use of
ultrasound for selected indications. Routine ultrasound use resulted in correction of the estimated date of
confinement by more than 2 weeks in 7% of cases. There also was a significant reduction in the incidence of labor
induction for postdate fetuses in the routine ultrasound group. Neonatal outcome was similar in both groups.
The use of ultrasound as a routine screening tool in obstetric patients applies to low-risk patients who have
none of the indications shown in Table 2. The multicenter Routine Antenatal Diagnostic Imaging with UltraSound
(RADIUS) study intended to determine the clinical benefits of routine ultrasound in a low-risk population.12
Patients were recruited from 109 obstetricians and family practitioners from private, academic, and health
maintenance organization practices. Of the initial patient population of some 53,800 patients, in the final analysis,
only 15,530 patients (29%) of the initial registered group were randomized to receive either selected or routine
ultrasound. The study concluded that there was no benefit to routine ultrasound in this low-risk population. The
RADIUS study has been criticized in that the patients selected for final inclusion in this study bear little similarity to
the average obstetric population. Only about one third of fetal anomalies were detected antenatally. If only serious
malformations are considered, the detection rate was significantly improved at 78%. Clearly, the detection of
anomalies in tertiary centers was significantly more accurate than that in primary care ultrasound clinics.
The Helsinki ultrasound trial included 9310 women: half were randomly allocated to ultrasound screening
and half to routine obstetric care.13 In the ultrasound screening group, perinatal mortality was significantly lower by
a factor of about 50%, mainly because of improved early detection of major malformations in the group randomized
to ultrasound, which led to an increased rate of pregnancy termination. It also appeared in this trial that twin
pregnancies detected earlier had a lower perinatal mortality rate.

13
 Clearly, the use of ultrasound as a screening test is a controversial matter. The most likely benefits of
ultrasound screening in low-risk patients are obstetric and include confirmation of dates, early detection of multiple
gestation, location of the placenta, and baseline growth data. In virtually every complication that may occur later in
pregnancy, clinical decisions may be facilitated if the patient had an ultrasound earlier in pregnancy.
To be used as a screening test, ultrasound should be widely available and have a relatively low cost and high
sensitivity and specificity rates. One of the stated intents of the RADIUS study was to determine whether routine
ultrasound screening would improve perinatal outcome. Ultrasound, however, is a diagnostic modality, not a
therapeutic one. Ultrasound alone cannot reduce perinatal mortality, but the information obtained from an ultrasound
can be used to guide the clinician to choose the appropriate therapy. In the final analysis, whether ultrasound is used
as a screening test may depend on its cost.
In the RADIUS study, about two thirds of the subjects were thought to have an obstetric indication for
ultrasound; however, it is only in the small proportion of truly low-risk patients that a screening ultrasound should
be considered. Should every obstetric patient have a routine ultrasound examination? Only if it is adequately
performed, properly recorded, and the patient is counseled regarding appropriate goals and limitations of ultrasound.
Routine screening is best done between 18 and 20 weeks' gestation. At this time, the fetus usually is large
enough that the fetal anatomy can be surveyed well, and yet the gestation is early enough that the accuracy of
biometric measurements is preserved.

CLINICAL APPLICATIONS
Ultrasound estimation of fetal weight can be invaluable in many clinical situations, such as obstetric
management of the patient presenting with labor or ruptured membranes and no previous prenatal care.
Identification of fetal macrosomia also is of particular interest to the clinician because this condition is
associated with an increased risk of a variety of obstetric complications. The accuracy of ultrasound in predicting
macrosomia depends on the clinical situation in which the ultrasound is used.32 In a diabetic patient, if the
ultrasound-estimated fetal weight predicts macrosomia, and the abdominal circumference is at or above the 90th
percentile, then the accuracy of ultrasound in the diagnosis of macrosomia approaches 90%.33 In the diabetic
patient, calculating the fetal chest diameter (at the level of the fetal heart) and subtracting the BPD may allow
predelivery prediction of macrosomia with increased accuracy. A chest diameter more than 1.4 cm larger than the
BPD was 87% accurate in predicting a fetal weight of 4000 g or more in one study.34 The clinical utility of these
observations is limited, however, and any management decisions must take all other clinical features into account,
such as presentation, progress in labor, clinical pelvimetry, and obstetric history.

1. DIAGNOSIS OF PREGNANCY BY ULTRASONOGRAPHY

In the presence of leiomyomas or ovarian cysts, gestational age may be overestimated. The availability of
high resolution abdominal probes and transvaginal probes frequently clarifies the nature of the mass and provides
for more accurate dating (Fig. 1, Fig. 2). The transvaginal probe also allows for high resolution images of the uterine
endometrium and more frequent identification of uterine anomalies (Fig. 3). In the presence of uterine pathology,
the combined use of ultrasound and endoscopy may aid in pregnancy terminations.1
Ultrasonography is also useful in the objective determination of gestational age. Assessment of pregnancy
dates from the menstrual history is imprecise;2,3,4,5 physicians who base their judgments solely on this history may
in some situations make incorrect estimates of gestational age. This can effect the safety of pregnancy termination if
the wrong procedure is used.6 Accurate determination of gestational age is also critical in the management of
preterm labor, postdates pregnancy, and in scheduling elective cesarean sections at the appropriate gestational age.
The impact of the use of ultrasonography on the practice of obstetrics has been profound. Given but one
choice from the many biochemical and biophysical techniques that have been developed in more recent years to try
to improve pregnancy outcome, sonography would seem the best. Methods for evaluating the health of the fetus that
apply pulse-echo ultrasound are now employed widely for many reasons that will be summarized in this chapter and
illustrated frequently throughout the book. Ultrasonic techniques that are now available, when performed carefully
and interpreted accurately, can supply vital information about the status of the fetus, with no confirmed biological
hazards from ultrasound (American College of Obstetricians and Gynecologists, 1993; American Institute of
Ultrasound in Medicine, 1991).
Since the first obstetrical application of ultrasound imaging by Donald and co-workers (1958), ultrasonic
evaluation of the pregnant uterus has become commonplace. For example, by 1989, 45 percent of pregnancies—1.7
million women in the United States— underwent sonographic evaluation (National Center for Health Statistics,
1992). Because of the current impetus for cost-effective medicine and outcomes-based research, the National
Institutes of Health commissioned the Routine Antenatal Diagnostic Imaging with Ultrasound (RADIUS) trial,
which has sparked a lively debate concerning its findings. Indeed, the Office of Medical Applications of Research
14
(1995) of the National Institutes of Health held a workshop in December 1993 to discuss implications of the
RADIUS trial.
First Trimester. Early pregnancy may be evaluated with abdominal or vaginal ultrasonography. Information
listed in Table 44–2 should be obtained. Using abdominal scanning, the gestational sac is reliably seen by 6 weeks
menstrual age and fetal echoes and heart activity by 7 weeks. With transvaginal scanning, these are seen about 1
week earlier (American College of Obstetricians and Gynecologists, 1993).
Early sonography is valuable in confirming blighted ovum or an embryonic pregnancy, missed abortion, and
suspected ectopic pregnancy (see Chap. 27 ). Finally, multifetal gestation can be identified and the number of
amnions and chorions possibly determined.

VAGINAL SONOGRAPHY SECTION

In thin patients, transvaginal ultrasound (TVS) allows for the evaluation of early pregnancy structures
approximately 1 week earlier than transabdominal ultrasound. In markedly obese patients, TVS may visualize early
gestational sacs and embryonic structures weeks before the transabdominal technique. TVS has the added advantage
of being performed with an empty bladder, making the procedure much more comfortable and acceptable to
patients.
By using high-frequency vaginal transducers, Warren and colleagues have shown an orderly appearance of
embryonic and extraembryonic structures (Table 1).7 The early visualization of a chorionic gestational sac, yolk sac,
and fetal pole can be correlated with b-human chorionic gonadotropin (b-hCG) findings to aid in the early diagnosis
of intrauterine pregnancy, ectopic pregnancy, and missed abortion (Table 2).8

EARLY PREGNANCY

As reported by Goldstein and co-workers,9 the high-frequency vaginal transducer allows visualization of a
chorionic gestational sac with a mean diameter of only 4 mm (Fig. 4) and a b-hCG level of 1025 mIU using the First
International Reference Preparation (IRP). This b-hCG level is called the discriminatory zone, or the level at which
an intrauterine pregnancy should be ultrasonically visualized. As shown in Table 2, Fossum and associates8 using
the transvaginal technique reported a slightly higher discriminatory zone of 1400 for the First IRP. By comparison,
an abdominal transducer can only resolve a gestational sac when the mean diameter is approximately 10 mm and the
b-hCG level is either 6500 mIU or 3600 mIU (First IRP), depending on whether static or high-resolution equipment
is used abdominally.10,11
Fossum and associates8 also compared the appearance of early pregnancy structures by the First IRP and the
Second International Standard (see Table 2). Due to the large number of b-hCG assays, each practitioner must be
aware of the assay being used by their lab to establish discriminatory zones. The Second International Standard will
have discriminatory b-hCGs approximately 50% less than the First IRP. Inability to visualize an intrauterine
pregnancy sac using a high-frequency vaginal probe when the b-hCG reaches the discriminatory zone raises the
possibility of abnormal early pregnancy including ectopic gestations. However, the practitioner must realize that
there are limitations to using discriminatory zones in clinical practice. Early gestational sacs may not be visualized
at a given discriminatory b-hCG level in cases of multiple gestation, incomplete abortion, or complete abortion.
Leiomyomata of the uterus may also obscure visualization of early gestational sacs and embryonic structures.9

EARLY PREGNANCY LOSS

Batzer and colleagues12 using transabdominal technique initially proposed that the appearance of the
intrauterine gestational sac, yolk sac, and fetal pole can be correlated with the b-hCG titers to assess risk for early
pregnancy loss. Initially b-hCG titers are expected to double within 36 to 48-hour intervals.12 Bree and co-
workers13 using TVS found that a intrauterine gestational sac, yolk sac, and fetal pole with fetal heart tones should
be visualized at b-hCG titers greater than 1025 mIU, 7200 mIU, and 10,800 mIU, respectively (First IRP). Risk for
early pregnancy loss is also increased when the mean sac diameter is 10 mm and a fetal pole is not seen. Similarly if
the mean sac diameter is 20 mm, a fetal pole with fetal heart tones should be seen.14 Similarly, positive fetal heart
tones should always be demonstrated when the fetal pole measures 5 mm or more.15

ECTOPIC PREGNANCY

The combination of b-hCG quantitative assays and TVS allows for more timely diagnosis of ectopic
pregnancy. Failure to see a gestational sac at 35 days from the last menstrual period or at a b-hCG of 1025 mIU/ml
is associated with an increased risk of ectopic gestation. The clinician must be aware that early gestational sacs can
be confused with pseudogestational sacs. Pseudogestational sacs represent either fluid or blood within thickened
15
endometrium or decidua (Fig. 5)16 By comparison, a true gestational sac is noted eccentrically placed adjacent to
the endometrial stripe (see Fig. 4). The appearance of the yolk sac within an intrauterine sac at 35 to 49 days from
the last menstrual period unquestionably identifies an intrauterine gestational sac (Fig. 6).
Among emergency room patients, Timor-Tritsch and associates17 have shown that TVS is highly accurate in
diagnosing ectopic pregnancies, with a sensitivity of 100%, a specificity of 98%, a positive predictive value of 98%,
and a negative predictive value of 100%. Additionally, these investigators have positively identified fetal heart
motion in 23% of ectopic pregnancies, a much higher frequency than the 5% to 10% rate possible by abdominal
sonography (Fig. 7). Earlier diagnosis of ectopic pregnancy can allow for increased use of operative laparoscopy and
methotrexate therapies.18,19,20

2. DETERMINATION OF GESTATIONAL AGE

In the past gestational age was established by a combination of the historical information and the physical
examination. Reliance was placed on the menstrual history and the maternal sensation of fetal movement
("quickening"). Other factors include assessment of uterine size by bimanual examination in the first trimester,
initial detection of fetal heart tones by Doppler (10-12 weeks) or auscultation (19-21 weeks), and uterine fundal
height measurement. However, both the history and the findings on physical examination are fraught with error,
even in the best of circumstances (Table 1).6,7,8 It has been estimated that 20% to 40% of women cannot relate the
LMP with certainty.6,7 Some of the reasons for this uncertainty include oligomenorrhea, metrorrhagia, bleeding in
the first trimester of pregnancy, pregnancy following use of oral contraceptives or intrauterine devices, and
becoming pregnant in the postpartum period. Hertz and co-workers9 reported that menstrual history was considered
reliable in only 18% of women. In another report, even among women with known LMP, neonatal age assessment
differed markedly from that assigned by certain menstrual dates in 15%.8 Physical examination also tends to be
inaccurate, especially with advancing gestational age.10 Bimanual examination in the first trimester may be accurate
within ±2 weeks; however, fundal height measurement, which is more commonly used to assess gestational age, is
only accurate within ±4 to 6 weeks. Clearly, the inaccuracies of history and physical examination may limit their
usefulness in assessment of gestational age. Methods that assess the time of ovulation or conception can accurately
establish gestational age.11,12,13,14 Timed ovulation, either by basal body temperature recording or
semiquantitative assessment of luteinizing hormone surge, predicts gestational age within ±4 to 6 days. Ovulation
induction with agents such as clomiphene citrate and Pergonal, also accurately predicts gestational age. In vitro
fertilization, with known date of conception, is likely the most accurate means of predicting gestational age (±1
day). However, in most pregnancies, the date of ovulation or conception cannot be as accurately predicted as
outlined above and gestational age must be established by other methods.

The advent of ultrasound has allowed a more direct means of assessing fetal structures and development.
Measurements of a wide variety of parameters have been devised to establish gestational age. Ultrasound assessment
of gestational age is feasible in a majority of pregnancies and may be used to establish gestational age with greater
accuracy than physical examination. In the first trimester, gestational sac mean diameter and crown-rump length
measurements have become the primary means of evaluating gestational age.15,16,17,18,19 In the second and third
trimesters, fetal head, body, and extremity measurements have been commonly used to assess gestational age. Those
parameters most commonly measured include biparietal diameter,20,21,22,23,24,25,26,27,28 head
circumference,29,30 abdominal circumference,31,32,33,34,35 and femur length.36,37,38,39 Although numerous
other parameters have been measured and related to gestational age, few offer any improvement in the accuracy of
gestational age assessment.40,41,42,43,44,45,46 In this chapter, the most widely used and accepted ultrasound-
derived fetal growth parameters are discussed and a review of their accuracies and potential errors is presented.

A number of ultrasonically derived fetal parameters can be used to estimate menstrual gestational age,
including the binocular distance,21 the diameter of the cerebellar bodies,22 fetal foot length and heel ossification
centers,23,24 head circumference,25 abdominal circumference,25 crown-rump length (CRL),26 biparietal diameter
(BPD),27,28,29 and femur length.30,31
In this chapter, we will discuss only the CRL, BPD, and femur length because they are the most accurate
predictors of dates, as well as the most commonly used measurements for estimating menstrual age.

Human pregnancy lasts an average of 280 days from the first day of the last menstrual period in patients with
regular 28-day menstrual cycles. Both clinical and ultrasonographic gestational age are expressed using this
standard.
The earliest ultrasonic evidence of pregnancy is the finding of a fluid-filled gestational sac with an echogenic
border. This finding may be seen with abdominal ultrasound as early as 5 weeks from the last menstrual period, at
16
which time it is about 11 cm in size. By 6 weeks, the sac doubles in size, and in a normal pregnancy, a fetal pole
becomes visible. At 7 weeks' gestation, fetal cardiac activity can be seen. After this time, the presence or absence of
fetal cardiac activity is an accurate method of determining fetal viability.
The use of endovaginal ultrasound has greatly enhanced our ability to detect pregnancy early. Using a
vaginal probe, the gestational sac and fetal pole can be found earlier than with the abdominal approach. A
gestational sac should be visible at 4 weeks and 4 days, and cardiac activity is seen at 6 weeks.1 The endovaginal
transducer eliminates the need for a full bladder before examination and significantly improves resolution in obese
patients.

A single parameter (CRL, BPD, HC, AC, or FL) may be used to assess gestational age. The accuracy of a
single parameter is dependent on the gestational age at the time of ultrasound examination (Table 9). Several
methods have been employed to improve the accuracy of gestational age assessment compared with the use of a
single parameter. Two of these methods, growth-adjusted sonographic age79 and averaging multiple
parameters80,81 are discussed. Several principles are important to remember when assessing gestational age by
ultrasound:

1.When menstrual dates fall within the confidence limits of the ultrasound assessment, the role of ultrasound
is to confirm menstrual dates.
2.When menstrual dates fall outside the confidence limits of ultrasound assessment, assignment of dates
should be based on ultrasound assessment of gestational age.
3.When menstrual dates are unknown, assignment of dates should be based on ultrasound assessment of
gestational age.

Gestational age, synonymous with menstrual age, is defined in weeks beginning from the first day of the
last menstrual period (LMP) prior to conception. Accurate determination of gestational age is fundamental to
obstetric care and is important in a variety of situations. For example, antenatal test interpretation may be dependent
on gestational age. Specifically, the level of a-fetoprotein in both amniotic fluid and maternal serum is related to
gestational age and when dates are inaccurate test results will be incorrect and misleading.1 Similarly, the magnitude
of increased optical density above baseline at 450 nm (delta OD 450) by amniotic fluid spectrophotometric
measurement is used to predict the severity of fetal hemolytic disease in pregnancies complicated by rhesus
isoimmunization.2,3 Test results are interpreted based on Liley's zones relative to gestational age. Again, inaccurate
assessment of gestational age will lead to errors in assessing the severity of fetal sensitization by the delta OD 450.
Fetal growth assessment, either clinically or by ultrasound evaluation, also relies on accurate assessment of
gestational age. Fetal growth retardation or macrosomia may be missed or incorrectly diagnosed owing to errors in
gestational age assignment. Interpretation of antenatal biophysical testing (non-stress tests and biophysical profiles)
may be subject to variation with gestational age as well. Fetal heart rate reactivity and fetal breathing develop with
advancing gestational age; therefore, the absence of these biophysical parameters may be interpreted as abnormal for
fetuses in whom the gestational age has been overestimated. Obstetric management is also dependent on gestational
age. Proper decisions regarding presumed preterm labor or postdate pregnancies are only possible when gestational
age is accurately estimated. Likewise, timing of repeat cesarean section requires accurate assessment of dates.4,5
Ultrasound is a reliable method for establishing the length of pregnancy and in this way can improve obstetric care.

Fetal Measurements. There are many tables and nomograms that describe the normal growth of various
fetal dimensions. Among the most commonly measured dimensions are crown–rump length, biparietal diameter,
abdominal circumference, and femur length. There also are nomograms for other fetal dimensions such as head
circumference, length of the humerus, ulna, tibia, and clavicle, and binocular distance. As emphasized by Jeanty
(1991), deciding which table(s) to use can be difficult. It also is important to emphasize that most predictions of
gestational age are based upon the 50th percentile measurement observed in normal fetuses. However, there is a
wide range of normal percentiles (5th through 95th) for a given fetal dimension. For example, a biparietal diameter
of 40 mm could represent a fetus of 14 weeks (5th percentile) or 20 weeks (95th percentile) as compared with 17
weeks when the 50th percentile is used. Jeanty (1991) reviewed thoroughly the many considerations necessary in the
selection of appropriate nomograms for estimating gestational age and fetal size. A combination of measurements is
superior to a single measurement. Importantly, most ultrasound machines now are available with microcomputers
and software that permit instantaneous calculation of fetal indices such as fetal weight estimates.
Different fetal dimensions have different reliability and ease of measurement at different gestational ages.
Shown in Tables 44–4 and 44–5 are commonly used gestational age nomograms for crown–rump length, biparietal
diameter, head circumference, abdominal circumference, and femur length. Shepard and co-workers (1982) have
reported formulas frequently used for estimation of fetal weight using the biparietal diameter and abdominal
circumference.

17
FIRST-TRIMESTER ASSESSMENT
In the first trimester, the gestational sac mean diameter and crown-rump length are used to establish fetal
age. Both parameters are useful because each measures a different aspect of the first-trimester pregnancy and may
be used at different times during the first trimester.

GESTATIONAL SAC MEAN DIAMETER.

The gestational sac is the first identifiable structure routinely imaged in the first trimester. It is identified by
transabdominal ultrasound as early as 5 weeks' gestation and may be seen as early as 4 weeks' gestation by
transvaginal ultrasound.15,16,47 The gestational sac is an echo-free space containing the fluid, embryo, and
extraembryonic structures. The sac is measured inside the hyperechoic rim, including only the echo-free space (Fig.
1). The gestational sac is imaged first in the longitudinal plane, obtaining long axis and anteroposterior
measurements perpendicular to each other. Then, in the transverse plane at the level of the anteroposterior
measurement, the width measurement is obtained. The three measurements are averaged to obtain the gestational sac
mean diameter. Table 2 compares gestational ages from 5 to 12 weeks with the gestational sac mean diameters.15
The accuracy of gestational sac measurement as a predictor of gestational age has been evaluated in only one report
and was found to be approximately ±1 week.16

CROWN-RUMP LENGTH.
The crown-rump length (CRL) is a measurement of the embryo, usually identified at 6 to 7 weeks'
gestation.17,48 The embryo is measured along its longest axis to obtain the CRL measurement (Fig. 2). Crown-
rump length may be used to accurately date pregnancy between 7 and 13 weeks' gestation. The technique involves
measurement of the fetal length from the tip of the cephalic pole to the tip of the caudal pole. The fetus should be at
rest and assuming its natural curvature. At 5 to 6 weeks' gestation, distinct landmarks cannot always be identified
but heart motion usually can be detected centrally. As the pregnancy continues, the head can be easily identified
from the rest of the body. After 12 weeks' gestation excessive curvature of the fetus may lead to erroneous
shortening of CRL measurement; therefore, other measurements, such as the biparietal diameter, should be used to
estimate gestational age.
The correlation between sonographic CRL values and dates was first reported by Robinson and Fleming,
who obtained CRLs in pregnancies of women with certain menstrual histories.17 Drumm and associates18
performed a similar study; however, their patients fulfilled more stringent dating criteria. These early studies
suggested that gestational age assessment by CRL was extremely accurate, approaching ±3 to 4 days. Subsequent
studies have suggested that the CRL is somewhat less accurate; however, the accuracy is still within ±5 to 7
days.49,50,51,52 Most recently, MacGregor and co-workers19 evaluated CRL measurements in pregnancies of
women with known dates of ovulation and reported data that differed from those of the previous two studies. Table
3 summarizes the results of these three studies evaluating gestational age relative to CRL.
Variations in the measurement of CRL can be attributed to differences in fetal growth patterns. Such
differences are related to factors similar to those that influence birth weight curves, including maternal age and
parity, prepregnancy maternal weight, geographic location, and population characteristics.53,54,55 Indeed, the
existence of subpopulations with altered CRL growth patterns has been suggested by previous reports.56,57
Technical factors can also lead to errors in CRL measurements. These include incorporation of the yolk sac or lower
limbs in the CRL measurement, excessive curling or extension of the fetus, and tangential section of the trunk.17
Despite these potential sources of error, CRL measurement is an accurate and useful method of assessing gestational
age in the first trimester.

Robinson and Fleming first described the methodology of localizing the longitudinal axis of fetuses between
7 and 13 weeks of gestation for the purpose of measuring the fetal CRL.32 He subsequently showed that the fetal
CRL can be used to predict gestational age with an accuracy of ±5 days in 95% of the population. The
reproducibility of the CRL is ±1 mm. MacGregor and colleagues related CRL measurements to a group of women
with known ovulation dates.26 They showed that CRLs derived from menstrually dated pregnancies32
underestimated dates by 5 days in the interval between 7 to 9 weeks, and by an overall average of 3.5 days. Thus,
they recommended use of a chart based on more reliable ovulation dates (Table 3). Other researchers have also
noted a similar discrepancy between CRL and early dates, as follows:
CRL = 1 cm at 49 days (7 weeks), Robinson and Fleming32
CRL = 1 cm at 57 days (8 weeks and 1 day), Selbing and Fjallbrant33
CRL = 1 cm at 56 days (8 weeks), Rossavik and coworkers34
CRL = 1 cm at 54 days (7 weeks and 5 days), MacGregor and colleagues26
An easily remembered formula is gestational age (days) = early embryonic size (mm) + 42.35

18
 The crown–rump length (CRL) of the fetus is an accurate predictor of gestational age.2 A practical
approximation is that fetal CRL in centimeters plus 6.5 equals gestational age in weeks. A 9-week fetus, for
example, would have a CRL of 2.5 cm (Fig. 1). CRL has been promoted as the most accurate method of dating a
pregnancy, but experience has shown that the average of the biparietal diameter (BPD), femur length, and
abdominal circumference obtained before 20 weeks' gestation is comparable in accuracy.3

SECOND- AND THIRD-TRIMESTER ASSESSMENT

BIPARIETAL DIAMETER
In the second trimester of pregnancy, the ultrasonically derived fetal BPD can be used to predict gestational
age. The accuracy of the prediction is such that in relation to a given BPD obtained at 14 to 16 weeks of gestation,
the length of pregnancy varies by ±7 days (2 SD).27 If the BPD is obtained at 17 to 26 weeks' gestation, the
accuracy of predicting dates is within ±11 days in 95% of the population.27

BPD STANDARDIZATION. The first published ultrasonography charts showed a marked variation in the
specific BPD values used to predict mean gestational age.28 The variations were assumed, at least in part, to
represent population differences. Subsequently, however, we showed that the mean BPDs obtained from both black
and white fetuses were almost identical, particularly in the first half of pregnancy.27 Furthermore, careful analysis
of a number of well-designed studies in which BPDs were derived by similar ultrasonographic methodology showed
no statistically significant differences in the cephalic measurements of a heterogeneous population of fetuses.28
These findings led to the development of a composite mean BPD chart (Table 4).28
Although this composite BPD chart can be universally used to predict menstrual age, its applicability to
gravidas residing in geographic areas of high altitude, where mean fetal BPDs may be smaller, remains to be
elucidated.

BPD VERSUS 24-WEEK LIMIT. It is generally accepted that a pregnancy should not be terminated when
menstrual age exceeds 24 weeks because the fetus in question may have attained viability. Thus, it is important to
define the upper limit of the BPD beyond which pregnancy should not be terminated.
A BPD of 6 cm is equivalent to a mean gestational age of 24 weeks (see Table 4), but this prediction varies
by ±11 days (2 SD)—that is, from 22 weeks and 3 days to 25 weeks and 4 days. Fetuses with biologically small
BPDs are more advanced in gestational age than is apparent from the mean BPD chart (Fig. 8). By the same token,
fetuses with biologically large BPDs are less mature than is apparent from the mean BPD chart.29
Because the gestational age in a particular fetus can only be assessed within a margin of ±11 days, the
validity of terminating the pregnancy in gravidas with a fetal BPD of 6 cm may be questioned on the basis that some
fetuses (statistically estimated to represent 20% of the group with a BPD of 6 cm) may be more advanced in
gestational age by 7 to 11 days. Similarly, the duration of pregnancy in 20% of gravidas with a fetal BPD of 6.4 cm
(or 25+ weeks' mean gestation) may, in fact, fall within the 24-week range.
It is apparent that the BPD value predicting the 24th week of gestation or the limit beyond which pregnancy
should not be terminated is difficult to ascertain. Nonetheless, when strict adherence to an upper limit of 24
menstrual weeks is mandatory, the selected BPD should not exceed 5.7 to 5.8 cm.

After the first trimester, CRL determination is not practical because of fetal posturing and size. From 12
weeks onward, the BPD is one of several useful estimators of fetal gestational age. The BPD is the largest transverse
measurement of the fetal skull and usually is measured from an occipitofrontal scan plane at the level of the fetal
thalami and the septum pellucidum cavum (Fig. 2). The fetal head should have an oval shape with clear midline
margination. The measurement is determined, by convention, from the outer edge of the proximal fetal parietal bone
to the inner edge of the distal parietal bone (Fig. 3). The gestational age is estimated by comparing the observed
BPD to tables relating BPD to gestational age.
Because of increasing biologic variation with advancing gestational age, the precision of estimated
gestational age from BPD is greatest early in the second trimester. Between 14 and 20 weeks, the BPD correlates
with gestational age within 1 week in 95% of cases. Late in the third trimester, the measured BPD may predict
gestational age within only 3 to 4 weeks.4,5
In about 5% of cases, BPD cannot be obtained because of fetal position; in a fetus in occipitoanterior or
occipitoposterior presentation, the proper plane of the fetal skull cannot be visualized. Deferring the study for a short
time allows the fetus to assume a more favorable position. If an appropriate BPD cannot be obtained, an alternative
fetal dimension is chosen.
The occipitofrontal diameter is measured in the same plane as the BPD and is a measurement of the
longitudinal axis, by convention taken from outer skull tables on each side. This measurement can be averaged with
the outer-to-outer skull measurement in the transverse plane to provide a basis for estimating head circumference.
The cephalic index is the ratio of the transverse to longitudinal diameters measured in a similar fashion; a normal
19
cephalic index is 0.78 + 0.05. An abnormal cephalic index in not necessarily indicative of fetal pathology, but BPD
measurements may be inaccurate estimators of gestational age if the fetal head is either more oval (dolichocephalic)
or more round (brachycephalic) than average.6 A low cephalic index, for instance, often is seen in breech
presentations.
The biparietal diameter (BPD) is one of the most commonly measured parameters in the fetus. Campbell was
the first investigator to link fetal BPD to gestational age20; however, since this original report, numerous
publications on this subject have appeared in the literature.20,21,22,23,24,25,26,27,28,58,59,60,61,62,63 The BPD
may be rapidly and reproducibly measured by ultrasound examination from 12 weeks' gestation until the end of
pregnancy. The BPD is imaged in the transaxial plane of the fetal head at a level depicting thalami in the midline,
equidistant from the temporoparietal bones and usually the cavum septum pellucidum anteriorly (Fig. 3).58,59
Although several methods have been used to measure BPD, the most commonly accepted method is measurement
from leading edge to leading edge (outer-to-inner) (see Fig. 3).
Gestational age assignment is based on the mean BPD; however, a single BPD encompasses a range of
ages in which most fetuses of that size are most likely to fall (Table 4).23 The accuracy of fetal age assessment
based on BPD is dependent on gestational age.22,23,27,28,51,58 Between 12 and 26 weeks' gestation, the BPD is
accurate to within ±10 to 11 days. After 26 weeks' gestation, the accuracy of BPD measurement progressively
decreases and is ±3 weeks near term. A number of factors may contribute to variation or inaccuracy in the BPD
measurement. Biologic variation, for example, may occur because of differences in maternal age, parity,
prepregnancy weight, geographic location, and specific population characteristics. Technical factors including
interobserver error, different techniques of measurements, and single versus multiple measurements may likewise
influence the accuracy of BPD in assessing gestational age.60,61,62 Although most dating curves show the same
general relationship between BPD and gestational age, there are often significant differences in gestational age
assignment for any particular BPD measurement. Furthermore, BPD measurement is most accurate in assessing
gestational age when the head shape is appropriately ovoid. If the head is unusually rounded (brachycephalic) or
unusually elongated (dolicocephalic), BPD measurements would overestimate or underestimate gestational age,
respectively. To determine whether head shape is appropriate, Hadlock and co-workers64 compared the BPD and
the frontooccipital diameter. The ratio of these diameters is called the cephalic index (CI), with a mean value of 0.78
and a normal range (±2 SD) of 0.70 to 0.86. In the fetus with an abnormal cephalic index (noted in <2% of fetuses
prior to 26 weeks' gestation), dates may be estimated more accurately using other fetal parameters, such as head
circumference.

GROWTH-ADJUSTED SONOGRAPHIC AGE

Gestational age estimation using a single biparietal diameter is accurate within a margin of ±10 to 11 days
in the second trimester. Gestational age can be more accurately predicted by obtaining paired BPD measurements
(the first from 20 to 26 weeks' gestation and the second from 31 to 33 weeks' gestation) and assigning gestational
age by a method developed by Sabbagha and co-workers79 known as growth-adjusted sonographic age (GASA).
In approximately 90% of fetuses, BPD growth from 20 to 33 weeks' gestation tends to progress within
narrow percentile ranks (Table 10).21,25 BPD growth patterns can be subdivided into three types: large (90th
percentile); average (10th to 90th percentile); and small (10th percentile). Paired BPD measurements obtained at
different gestational ages allows categorization of the specific cephalic growth pattern. The first measurement
should be obtained between 20 and 26 weeks' gestation, and the second measurement should be obtained between 30
and 33 weeks' gestation. The first BPD measurement will not distinguish the fetus with large, average, or small BPD
growth, and, therefore, the fetus is assigned a mean gestational age based on an assumed average BPD growth
pattern. The second BPD measurement identifies the specific type of growth pattern. For example, in the fetus with
average growth the second BPD measurement will fall between the 10th and 90th percentiles, confirming the
gestational age assignment from the first BPD measurement. In contrast, BPD growth in the small-for-gestational
age fetus will follow a slow growth pattern and the second BPD measurement will be less than or equal to the 10th
percentile for the gestational age assigned by the first BPD. Since the first BPD measurement failed to recognize the
small growth pattern and, therefore, underestimated gestational age, the second measurement allows the gestational
age assessment to be adjusted based on the BPD growth pattern. Such a fetus with a slowed growth pattern would
have the gestational age advanced by 1 week at the time of the second BPD measurement. Similarly, dates in the
large-for-gestational age fetus may be adjusted by GASA at the time of the second BPD measurement, decreasing
gestational age assignment by 1 week if the BPD measurement is greater than or equal to the 90th percentile (Fig.
6). Use of GASA has been reported to increase the accuracy of gestational age estimation by BPD measurement to
within ±3 to 5 days.79
The method of GASA has not been used when the first BPD measurement is obtained prior to 20 weeks'
gestation; therefore, it is best to confine the use of GASA to pregnancies in which serial ultrasound studies are
contemplated and the first measurement is obtained between 20 and 26 weeks' gestation. Smazal and associates51

20
evaluated the method of GASA and suggested that the accuracy was indeed ±5 days. However, in this report, the
accuracy of a single BPD was also approximately ±5 days.

HEAD CIRCUMFERENCE.
The head circumference (HC) measurement may be used to estimate gestational age in a similar manner to
BPD measurement (Table 5).30 Although tracing of the outer perimeter of the head (by trackball on the ultrasonic
equipment or by digitizer) is the most reliable means of measuring HC, the following formula using biparietal and
fronto-occipital diameters may be used to calculate HC with a maximum error of 6%:63,65

(D1 + D2)/2 3.14

The accuracy of gestational age estimation by HC measurement is comparable with that of BPD
measurement.30 However, in fetuses with abnormal head shape, either brachycephaly or dolicocephaly, HC may be
a more accurate predictor of fetal age than BPD.30,65

MEASUREMENT OF FETAL LONG BONES. FEMUR LENGTH

Measurement of the fetal limb bones also may be used to determine gestational age. The femur length usually
is chosen because of its relative positional stability. The measurement is obtained by aligning the transducer with the
lower end of the fetal spine and rotating toward the ventral aspect of the fetus.7 At first, only part of the femur may
be seen; slight rotation and angulation of the transducer allows the entire length to be imaged. When properly
visualized, the femur should have clear distal margins. Often, the bone casts a shadow to help identify this landmark
(Fig. 4). The ultrasound images typically do not include epiphyses in early gestation; therefore, 8% to 15% of the
palpable bone is not measured. Because the reference tables were derived in this fashion, accuracy is preserved.
As is the case with BPD, the reliability of femur length in prediction of gestational age is best in early
pregnancy. In the third trimester, however, femur length shows less variation than the BPD. Femur length may be
difficult to obtain in a breech presentation, and measurement of the fetal humerus provides a good alternative. The
humerus usually can be identified arising from the lateral upper fetal chest.

The osseous shaft of the femur is one that is an easy fetal bone to image and measure. However, the accuracy
of estimating dates by femur length is quite controversial, and the measurement is subject to a wide interobserver
variability of 4.4 mm.36
O'Brien and colleagues30 showed that in the first part of the second trimester of pregnancy, the femur length
was accurate within a 2 SD range of ±7 days (Table 5). In another study, however, the range in dates relative to
femur length widened with advancing gestation, from ±11 days to ±3 weeks in the second and third trimesters of
pregnancy, respectively.31 On the other hand, Jeanty and colleagues reported a ±2.8 week variation in dates relative
to femur length at any time in pregnancy.37
The controversy in the accuracy of the femur length may stem from a number of variables, including the
following:

1.Differences in the number of patients entered into each study; the biggest group was that studied by Jeanty
and colleagues.37
2.Lack of strict adherence to accepted methodology; only the osseous portion of the femur should be
included in the measurement.38
3.Measuring the femur length in the horizontal rather than the axial plane. Axial values are significantly
smaller than lateral values.39 Pretorius and colleagues found that the absolute error in lateral measurements fell into
the range of 0 to 12 mm, whereas that noted in axial measurements was only between 0 and 4 mm.40

Despite these differences, the femur length is useful in assessing pregnancy dates, particularly in fetuses at
high risk for having an abnormally small or large cephalic size, such as in microcephalus, dolichocephalous (side-to-
side flattening of the fetal head), hydrocephalus, and brachycephalus. By the same token, the femur should not be
used to predict menstrual age in gravidas at high risk for skeletal dysplasia because its length may be abnormally
small.

All the fetal long bones can be adequately examined and measured by ultrasound; however, the femur is the
largest of the long bones, least moveable, and easiest to image. The femur may be adequately visualized from 14
weeks' gestation until delivery.38,39,40,67,68,69,70,71,72,73,74 It is measured along the long axis of the bone; a
straight measurement of the osseous portion is taken from one end to the other, disregarding bone curvature (Fig. 5).
The femoral neck and both proximal and distal epiphyseal cartilages are excluded from the measurement. Femur
length (FL) measurements may be used to accurately predict gestational age between 14 weeks' gestation and term
21
(Table 8).39 Most observers consider the accuracy of the FL and BPD measurements to be similar in the third
trimester. Although there is controversy regarding the accuracy of the FL prior to 26 weeks' gestation,38,39 the
accuracy of gestational age prediction based on FL is greatest in the second trimester and least near term.
Biologic variation may lead to inaccuracies of FL measurements in a manner similar to that of the other
fetal growth parameters. In addition, several technical factors are potential sources of error in the measurement of
the femur.67,70,72 Sector ultrasound imaging may lead to overestimation of FL, particularly when the femur is in
the far field or lateral margins of the image. Linear-array ultrasound imaging provides more accurate measurements
of FL. In addition, FL measurements obtained in the axial plane (parallel to the ultrasonic beam) have less mean
absolute error than those obtained in the lateral plane, perpendicular to the ultrasonic beam (1.7 mm vs. 3.7 mm,
respectively).74 Tangential section of the femur, failing to visualize the entire length of the shaft, leads to
underestimation of FL and, therefore, of gestational age. Artifactual bowing of the femur may also occur on
ultrasound imaging and lead to a shortened FL measurement. The distal femoral epiphysis becomes echogenic in the
third trimester and is separated from the distal end of the diaphysis, the osseous portion of the shaft. Inclusion of the
distal epiphysis will falsely overestimate FL.67,68
Gestational age assessment by FL is particularly useful when head measurement is difficult to obtain due to
fetal position. The femur length may also be compared with the biparietal diameter (FL/BPD) as an age-independent
ratio.73 The FL/BPD ratio (normal values 79 ± 6%) is useful as an internal verification of the measurements
obtained, as well as an indicator of pathologic entities, such as microcephaly (FL/BPD abnormally high) and
hydrocephalus or short-limb dysplasia (FL/BPD abnormally low). Although the femur length and abdominal
circumference (FL/AC) have also been compared in order to diagnose fetal growth abnormalities (macrosomia and
fetal growth retardation),34 there is much overlap between normal and abnormal values of this ratio.75,76,77,78

ABDOMINAL CIRCUMFERENCE
The fetal abdominal circumference, or mean abdominal diameter, also is useful in predicting gestational
age.8 This measurement is obtained in a transverse plane, perpendicular to the fetal spine, at the level of the stomach
and umbilical vein (Fig. 5). The fetal image in this transverse plane is nearly circular; the abdominal circumference
is the average of the anteroposterior and transverse diameters, measured from outer diameter to outer diameter. The
circumference can be obtained by multiplying the mean abdominal diameter by p (about 3.14), or by directly
measuring the circumference using a perimeter system on the ultrasound image, which is provided on most current
ultrasound systems.

Measurement of the fetal abdominal circumference (AC) is obtained in the transaxial view of the fetal
abdomen. The AC is measured at the level of the fetal liver, using the umbilical portion of the left portal vein as a
landmark (Fig. 4). The fetal stomach is at the same level, which is slightly caudad to the fetal heart and cephalad to
the kidneys. The AC measurement is taken from the outermost aspects of the fetal soft tissues. Measurement of the
AC is performed in the same manner as that of the HC, that is, by (1) tracing the outer perimeter of the AC by the
trackball on the ultrasonic equipment or by digitizer or (2) the same equation as for HC using transverse and
anteroposterior diameters of the fetal abdomen. The AC may be used to estimate gestational age (Table 6) but is less
accurate than head measurements (BPD or HC).33 Similar to head measurements, the accuracy of AC in estimating
gestational age is greatest in the second trimester, with decreasing accuracy near term. Biologic variation and
technical factors may contribute to the inaccuracy of AC measurements in a manner similar to that previously
described for bi-parietal diameters. Of particular note, the abdominal circumference is the growth parameter most
commonly affected in pregnancies complicated by abnormal fetal growth patterns.33 A macrosomic fetus will have
increased AC relative to gestational age, and an asymmetrically growth-retarded fetus will have diminished AC
measurements. Variation in AC measurements in macrosomic and growth-retarded fetuses is due to differences in
liver size and width of subcutaneous tissue in these two types of abnormal growth patterns. Thus, estimation of
gestational age by AC will lead to inaccuracies in fetuses displaying either of these growth patterns. However, the
HC/AC ratio may be useful as a predictor of head-to-abdomen symmetry or asymmetry in order to identify the type
of abnormal growth (Table 7).66

MULTIPLE PREDICTORS
The most accurate parameters for dating pregnancy are CRL measurements from 6 to 13 weeks and BPDs
from 14 to 26 weeks. However, when two or more parameters predict the same end point, the probability of the
accuracy of that end point is increased (Bayes' theorem).25 Thus, it is important for a sonographer to measure
different parameters to determine whether there is any similarity in the estimation of dates. The following guidelines
can be followed:

22
 1.When menstrual dates fall within confidence limits of any one or more parameters, the role of
ultrasonography will be to confirm menstrual dates.25
2.If the menstrual age estimates derived from two or more ultrasonic parameters are within 1 week of each
other and the pregnancy is normal (no growth retardation or macrosomia is suspected), it is justifiable to assign
dates from the average of these parameters. This approach is referred to as selective averaging. It involves averaging
the ultrasonographic parameters that predict a similar end point.
3.When menstrual dates fall outside the confidence limits of one or more ultrasonographic parameters, dates
may be assigned by the most accurate ultrasonographic predictors (CRL, BPD between 14 and 26 weeks) if altered
growth can be ruled out.

The relation between ultrasonographically derived fetal dimensions and gestational age is purely empiric.
The older a normal fetus, the larger it is. The reproducible ultrasonographic measurement of any fetal dimension in a
normal reference population of fetuses of known gestational age allows the construction of a regression relation
between that dimension and age. Subsequently, the determination of the gestational age of a pregnancy for which
the conception date is unknown can be made by comparing that dimension with the reference data (Table 1).
Averaging the gestational ages derived from two or more measurements has been shown to be more accurate
than using any single parameter.9 Determinations made early in pregnancy are more accurate than those made later.
Because of the greater accuracy of the early study, ultrasound examinations subsequent to an early study should not
be used to change the estimated date of confinement (EDC), but rather should be used as a measure of the quality of
fetal growth between the two studies. Similarly, it is not appropriate to revise an EDC on the basis of an ultrasound
examination if the patient's menstrual dates are within the range of error of the ultrasound method.
If significant discrepancy is seen between two ultrasonographically measured fetal dimensions (more than a
2-week difference), the ultrasonographer must consider the possibility of an error in measurement technique. If a
critical reevaluation reveals no error, then asymmetry in fetal growth may be present. Growth asymmetry may occur
as a result of physiologic alteration in fetal head shape (brachycephaly or dolichocephaly) or in association with
intrauterine growth restriction (IUGR) or a fetal anomaly.

Hadlock and co-workers80,81 combined several measurements in an effort to increase the accuracy of
gestational age assessment. The rationale for employing multiple parameters for fetal dating is that when two or
more parameters predict the same end point, the probability of correctly predicting that end point is increased. The
BPD, HC, AC, and FL measurements were obtained and the mean gestational ages of combinations of these
parameters were averaged to obtain a mean gestational age. The use of multiple parameters improved the accuracy
of gestational age assessment compared with any single parameter (Table 11).80 If the gestational age estimates
derived from all of the parameters are similar, assignment of gestational age from the average of all the parameters
will improve accuracy. However, if gestational age estimates of the various parameters are quite different, averaging
multiple parameters will decrease the accuracy of the best predictor(s). Averaging of fetal growth parameters should
be avoided when certain conditions are suspected, such as fetal macrosomia, intrauterine growth retardation (both
symmetric and asymmetric), and congenital anomalies (skeletal dysplasias, hydrocephalus, and others).

MULTIPLE GESTATIONS
The detection of multiple gestations is important since multiple gestations are at greater risk for many
complications, particularly fetal growth retardation. Fetal biometric data are available for twin
gestations81,82,83,84,85; however, triplet and quadruplet pregnancies have not been adequately studied owing to
their infrequent occurrence.
In general, ultrasound-derived fetal dating tables obtained for singleton pregnancies can be used accurately
for twin pregnancies until approximately 30 weeks' gestation.82,83,84,85,86 During the last 10 weeks of pregnancy
there is a decrease in the growth rate for twin fetuses compared with singleton fetuses. Grumbach and co-workers86
have suggested that the femur continues to grow normally throughout pregnancy in twin gestations, while the head
(BPD and HC) and abdominal (AC) growth rates decrease in the last 10 weeks of pregnancy. Although further
studies are required to confirm these findings, this study suggests that FL measurement may be a more reliable
parameter to use for gestational age assessment in twin gestations during the third trimester. Gestational age
estimations in twin pregnancies prior to 30 weeks' gestation should be performed in a similar manner to that for
singleton pregnancies.

SUMMARY
A simple, but uniform approach to the evaluation of gestational age should be performed in all fetuses. The
ultrasound assessment of fetal age is based on the earliest ultrasound study, provided the measurement is technically
23
adequate. Early in gestation fetal measurements have the least variability and, therefore, are most likely to predict
fetal age. In the first trimester, the CRL measurement is used to estimate gestational age, whereas in the second and
third trimesters fetal head (BPD and HC), body (AC), and extremity (FL) measurements are used to assess
gestational age. The following guidelines are recommended for the assessment of gestational age:

1.Crown-rump length measurement is used to establish fetal age in pregnancies with unknown menstrual
dates or in pregnancies with discrepancy between menstrual dates and crown-rump length measurement of greater
than ±7 days. If CRL and menstrual dates are within the normal range of error of the measurement (±7 days), the
menstrual dates are used to establish fetal age.
2.In the second trimester, menstrual dates are used if the mean gestational age predicted by (a) a single
parameter (BPD, HC, or FL) or (b) multiple parameters (BPD or HC and FL ± AC) is within the range of error of
these measurements. If menstrual dates are unknown, or the difference between menstrual dates and the mean
gestational age predicted by single or multiple parameters is greater than the range of error of these measurements,
fetal age should be established using the best ultrasound predictors (either single or multiple parameters) or GASA
method.
3.In the third trimester, gestational age assessment is particularly problematic. Menstrual dates should be
used to establish fetal age if the mean gestational age predicted by multiple parameters is within the range of error of
these measurements (±2-3 weeks). In the pregnancy with unknown menstrual dates or a discrepancy between
menstrual dates and mean gestational age predicted by multiple parameters of more than 3 weeks, fetal age should
be estimated by the multiple parameters method. However, the potential error of this method in the third trimester of
pregnancy may not be acceptable. Obstetric management must appreciate this potential for error. For example, a
patient presenting in spontaneous labor at 33 ± 3 weeks' gestation should be managed as if the pregnancy may be as
little as 30 weeks' gestation, rather than as advanced at 36 weeks' gestation. Similarly, the patient presenting for
prenatal care at 39 ± 3 weeks' gestation, should be managed for the potential of postdates pregnancy.

Use of the multiple parameters method of assessing gestational age is valid when the gestational age
estimates of the various ultrasound parameters are similar. If the gestational age estimates of one or several
parameters is greater than 2 weeks different than the estimates of the other parameters, either the abnormal
ultrasound parameters should be excluded or a different method should be used to estimate gestational age. When
the various ultrasound parameters predict different gestational ages the fetus should be further evaluated to explain
these differences. For example, an abnormally small FL measurement may suggest short-limb defects, a large BPD
may be secondary to hydrocephalus, and an abnormally small or large AC measurement may suggest asymmetric
intrauterine growth retardation or macrosomia, respectively. As mentioned previously, the different ultrasound ratios
(CI, HC/AC, and FL/BPD) may be used to identify abnormally small or large parameters. In the instance of an
abnormal cephalic index, the HC should be used to estimate gestational age, rather than the BPD measurement.
In conclusion, assessment of gestational age is fundamental to obstetric care and should be a carefully
thought-out process. Assessment should depend on history and physical examination, as well as ultrasound
evaluation.

3. ASSESSMENT OF FIRST-TRIMESTER COMPLICATIONS

First-trimester ultrasonography can be of significant value in predicting the outcome in patients with bleeding
in early pregnancy. Except in the unusual circumstance of a combined pregnancy (incidence 1 in 30,000), the
finding of a pregnancy within the uterus excludes an ectopic pregnancy. This distinction, however, is not always
clear. The normal gestational sac has a well-defined, echogenic border. In ectopic gestation, decidua and blood may
distend the uterine cavity, and the ultrasound image can mimic a gestational sac, resulting in the so-called
pseudogestational sac.14 These entities often can be distinguished by ultrasound; in a pseudogestational sac, the
echogenic rim usually is absent, ill defined, or not centrally positioned in the uterus.15 In questionable cases, serial
growth of the sac can be assessed. In a normal pregnancy, the gestational sac should grow at least 0.6 mm daily.16
Using a quantitative assay of human chorionic gonadotrophin (hCG) with ultrasound improves diagnostic
accuracy. Even with b-hCG values as low as 750 mIU/mL, a gestational sac can be visualized.17 If the level is
below this value, in a clinically stable patient, serial HCG values can be followed. In a normal early pregnancy, the
b-hCG level should increase at least twofold in 72 hours.
In practice, a clinical problem often faced is differentiation of a threatened abortion from an ectopic
pregnancy. In both these conditions, a subnormal rise in b-hCG usually is seen. Ultrasound findings in a pregnancy
destined to abort include a poorly defined gestational sac, a large yolk sac (6 mm), a low site of sac location in the
uterus, or an empty gestational sac at 8 weeks' gestational age—the blighted ovum.
The only absolute assurance that a pregnancy is intrauterine is the finding of a fetal pole within the uterine
cavity. The endovaginal ultrasound can be useful in this clinical setting because the fetal pole can be seen at 6
weeks. In a normal pregnancy, the fetal pole should be visible if the gestational sac is 25 mm or larger in diameter.
24
 The presence of a fetal pole with demonstrable cardiac activity is reassuring and greatly decreases the
likelihood of spontaneous abortion. In an ultrasonically normal gestation without bleeding at 8 to 9 weeks, there is a
3% chance of subsequent pregnancy loss.18 If bleeding is present, this chance increases to about 13%.19
Also included in the differential diagnosis of vaginal bleeding in pregnancy is the hydatid mole, which has a
characteristic ultrasound appearance (Fig. 6).

4. EVALUATION OF FETAL GROWTH ABNORMALITIES

Fetal growth can be evaluated by comparing individual dimensions to normative data, by comparing various
fetal dimensions to assess symmetry, or by integrating selected measurements to produce an estimation of fetal
weight.
Several investigators have derived equations useful for estimating weight, using fetal dimensions, such as
BPD, mean abdominal diameter, abdominal circumference, and femur length. Warsof and colleagues24 first
provided a clinically useful formula for weight estimation using BPD and AC. Shepard and co-workers25 reported a
second similar equation with slightly improved accuracy. Rose and McCallum26 described a system using the sum
of the BPD, mean abdominal diameter, and femur length in centimeters that is relatively easy to use. The differences
between these and other published methods is small when compared with the overall accuracy of fetal weight
estimation. Generally, the ultrasonic predicted weight is within 10% of the actual weight in two thirds of cases and
within 20% in 95% of cases.
In the preterm fetus in which clinical estimation of fetal weight is notably inaccurate, estimating fetal weight
using ultrasound is useful. In the term fetus, however, because of the greater actual error, ultrasound-estimated fetal
weight may be no more accurate than a clinical weight estimation.27
If the gestational age in a pregnancy is confidently established, ultrasound can provide an accurate diagnosis
of IUGR. IUGR can result from uteroplacental insufficiency, drug exposure, intrauterine infection, or genetic
factors.35 Symmetric IUGR, in which all fetal parameters are small for a given gestational age, occurs with extrinsic
conditions that are active early in pregnancy (e.g., tobacco or alcohol abuse, congenital rubella). Symmetric IUGR
also can result from intrinsic conditions that limit fetal growth potential (e.g., chromosomal abnormalities).
Symmetrically reduced growth also is seen in the constitutionally small, normal fetus.
Fetal growth may be normal until the late second or early third trimester, at which time the limit of
uteroplacental circulation in sustaining fetal growth is reached. This results in asymmetric fetal growth, in which the
fetus adapts to the relative decrease in uteroplacental blood flow by redistributing cardiac output to favor the brain at
the expense of the muscles and abdominal viscera.
For these reasons, the use of BPD alone can detect only half of IUGR cases. When IUGR is suspected,
ultrasound-estimated fetal weight can detect up to 90% of affected infants.36,37 An estimated fetal weight below the
10th percentile for gestational age is predictive of IUGR. When IUGR is suspected, the ultrasonographer should
look critically at amniotic fluid volume. Oligohydramnios, resulting from decreased fetal urine production as blood
is shunted away from the fetal kidneys, commonly is associated with severe IUGR. Manning and associates38 noted
that when a 1-cm pocket of amniotic fluid could not be found, IUGR was present in 90% of cases.38 The amniotic
fluid index also has been described as a useful tool in the evaluation of fluid volume.39
When the gestational age is not precisely known, assessment of fetal growth during a 2-week period is useful
in distinguishing IUGR from incorrectly dated pregnancies. In the third trimester, fetal weight should increase about
300 g in 2 weeks. Another gestational age–independent assessment is the abdominal circumference/fetal length or
mean abdominal diameter/fetal length ratio.40 Reece and co-workers41 reported that the transverse fetal cerebellar
diameter is unaffected by IUGR; this additional parameter may help to discriminate IUGR from incorrectly dated
pregnancies.

5. ASSESSMENT OF THIRD-TRIMESTER BLEEDING

Ultrasound examination is useful in differentiating causes of third-trimester bleeding. The placenta can be
identified easily with the real-time scanner. Placenta previa can be diagnosed with a high degree of accuracy (Fig.
7). In cases of marginal previa, the examination should be done with both an empty and a full bladder for greatest
accuracy. The internal os may be located by identifying the bladder angle in a moderately full bladder.
Apparent placenta previa is an incidental finding in 5% of second-trimester scans done for other indications.
In marginal previa or central previa (central insertion of the placenta over the cervix) seen on a second-trimester
scan, a follow-up scan in the third-trimester is indicated; more than 90% of these cases have spontaneously resolved
on subsequent examination because of asymmetry in uterine growth, not placental migration.28,29
Other causes of third-trimester bleeding include abruptio placentae and vasa previa. Although these
conditions have been diagnosed with ultrasound, they cannot be excluded confidently in most cases. A
retroplacental clot may be seen in some cases of abruptio,30 but ultrasound cannot exclude abruption, and the wise
course in most cases is to treat the patient as clinical circumstances dictate.

25
 With increasing gestational age, the placenta increases in echogenicity because of increased fibrosis and
calcium content. This feature of placental maturation has led to a grading of placentas from immature (grade 0), to
mature (grade 3).31 In a grade 3 placenta, individual cotyledons are outlined by dense fibrotic calcified septa. The
correlation of a grade 3 placenta with fetal pulmonary maturity is high. A grade 3 placenta can be observed in the
third trimester in a variety of high-risk fetal conditions (e.g., IUGR, chronic hypertension) but also can occur in
normal pregnancy. Conversely, a grade 3 placenta may not be seen in many normal patients in labor at term.

6. EVALUATION OF MULTIPLE GESTATIONS

In evaluating multiple gestations, the ultrasonographer should note the number and presentation of the fetuses
and the position and number of placentas. A membrane almost always can be seen between each fetus in early
gestation. Monoamniotic twins, which comprise only 3% of all twin gestations, have no intervening membrane and
are at much greater risk of perinatal mortality than other twins. The thickness of the membrane between twins may
provide a clue about whether both chorion and amnion are present because a thicker membrane is present in
dichorionic-diamniotic twins.42
As is the case with ultrasound diagnosis of IUGR, discordance is better predicted by estimated fetal weight
calculation than by BPD alone.43 Discordance is determined by dividing the observed fetal weight difference by the
weight of the larger twin. Mild discordance (15% to 25% difference in fetal weights) occurs in about 20% of twin
pregnancies, and severe discordance (more than 25% difference) occurs in about 5% of twins.44 Discordant twins
are at increased risk for perinatal mortality; the smaller twin is at greatest risk antenatally. A reasonable approach to
assess growth in twin gestation is to perform serial estimated fetal weight measurements on both twins every 4
weeks beginning at 20 weeks' gestation. If discordance is present, or if intertwin weight differences are increasing,
weight determination is recommended more often.

7. DETECTION OF FETAL MALFORMATIONS

The ability of ultrasound to detect and characterize a broad array of fetal malformations is well known.
Ultrasound is best suited to the detection of obstructive malformations, or major distortions of surface anatomy.
Each ultrasound examination performed should comprise an anatomic survey of the fetus, including cranial and
intracranial structures, spinal anatomy, a four-chamber cardiac view, the abdomen with stomach and umbilicus, the
bladder, and at least one long bone. Any suspicion of abnormality should result in referral for a more detailed
ultrasound examination.
A basic office ultrasound examination is adequate for most patients. A targeted scan, performed by an
ultrasonographer with experience in the evaluation of fetal malformations, is done when there is a suspected fetal
abnormality on a basic ultrasound examination or to evaluate fetal anatomy when the patient is in a high-risk
category based on history, physical findings such as polyhydramnios, or laboratory testing (e.g., AFP).
Determination of fetal karyotype should be considered in any case in which a malformation is
ultrasonographically detected. Aneuploidy is discovered in about 10% of cases of ultrasonographic dysmorphology.
The finding of a lethal karyotype could alter obstetric management because fetal distress during labor often occurs
in this setting, and a cesarean section delivery might otherwise result. Additionally, the finding of one structural
malformation should prompt a more detailed search for other anomalies.45

Fetal Anatomy. Most attempts to survey fetal anatomy using ultrasound take place during the early second
trimester or later. Although some investigators have reported success with imaging various fetal structures during
the first trimester, Green and Hobbins (1988) generally were unable to identify fetal structures transabdominally
before 9 weeks; their success rate improved remarkably, however, as gestation progressed. By 12 weeks, they were
able to visualize the stomach in 95 percent, the anterior abdominal wall in 80 percent, the adrenal glands in 100
percent, the kidneys in 100 percent, and the bladder in 60 percent. Similarly, Timor-Tritsch and associates (1990)
reported consistent success at imaging the skull, brain, spine, limbs, and anterior abdominal wall in 35 fetuses
examined transvaginally between 9 and 14 weeks. By 11 weeks, they were able to visualize the fingers and feet.
Although there are increasing numbers of case reports that describe detection of a variety of fetal anomalies
during the first trimester, and in spite of the obvious potential for identifying congenital fetal malformations at this
point, caution is recommended for several reasons: (1) Normal first-trimester embryological development may
mimic pathological changes in the second and third trimesters; for example, physiological anterior wall herniation
may mimic an omphalocele. (2) Grossly abnormal embryos may appear normal, as with anencephaly. (3) Some
abnormal embryos may manifest only with a crown–rump length that is less than expected for their gestational age
(Levi and associates, 1990).
Caution emphasized by the American College of Obstetricians and Gynecologists (1993) is worth repeating.
Whichever method used, and regardless of the stage of pregnancy evaluated, it is unrealistic and
unreasonable to expect detection of all fetal anomalies even with the most expert and thorough scanning.
Some limitations of the routine 18 to 20 week scan are listed in Table 44–6. Gonçalves and colleagues (1994)

26
reported that the overall sensitivity of sonography in detecting fetal defects was 53 percent. Overall specificity was
99 percent. Although the technique was highly sensitive—89 percent—for detecting lethal malformations, it missed
serious cardiac defects, microcephaly, and many musculoskeletal deformities.

The recent development of high-resolution ultrasound equipment has markedly improved the diagnostic
accuracy of ultrasound. In particular, the introduction of high-frequency vaginal probes has enabled early diagnosis
of certain fetal abnormalities from the 12th to 14th week of pregnancy. Such early testing is of special importance
for women with a history of pregnancies associated with birth defects. The frequency with which different organ
systems can be imaged is shown in Table 1.1 The sequential appearance of fetal neural structures during the first
trimester of pregnancy is shown in Table 2.2
The examination for the detection of congenital anomalies is referred to as either detailed ultrasound study
or targeted imaging for fetal anomalies (TIFFA)3, 4 In such examinations, a variety of fetal anatomic views
("targets"') are specifically sought after and imaged by experienced ultrasonographers. The indications for TIFFA
are listed in Table 3.
Despite these technical advances, ultrasound accuracy remains dependent on gestational age. For example,
if only one ultrasound examination is to be performed in the second trimester of pregnancy, the best time would be
between weeks 19 and 20. Accuracy also depends on the skill of the ultrasonographer in obtaining the correct
anatomic views and in differentiating between normal and abnormal structures.
The ultrasonographer also plays an essential role in 1) interpretation of the pathophysiology of a discovered
defect, and 2) delineating the risk involved. For example, the risk for spina bifida in a woman with elevated maternal
serum alpha-fetoprotein is much lower if a detailed ultrasound study is normal (Table 4).5 Thus, the need for
amniocentesis to evaluate amniotic fluid alpha-fetoprotein (which is a better predictor of spina bifida than maternal
serum alpha-fetoprotein) should be reevaluated in relation to the newly assigned risk (see Table 4).5 Similarly, the
risk for autosomal trisomy is lower than the age-related or maternal triple-screen risk in women with a normal
second trimester fetal ultrasound examination (Table 5, Table 6, Table 7 and Table 8).
TIFFA examinations entail ultrasonic visualization of at least 34 fetal views and measurement of seven
specific sites (Fig. 1). For each of these views, the ultrasonographer should indicate whether the structure is normal,
previously normal, not applicable, suspect, abnormal, or poorly visualized. Poor visualization occurs when (1) fetal
movement or position does not allow adequate imaging of a specific area, or (2) gestational age is less than 19 to 20
weeks.
A normal TIFFA scan takes approximately 1 hour to complete. However, the presence of an anomaly is
likely to extend the study and make it necessary for the mother to undergo a combination of genetic counseling,
amniocentesis, or chorionic villi sampling to define fetal karyotype.
Studies that definitively resolve any possible concern regarding the long-term safety of ultrasound as well
as its cost:benefit analysis are not yet available.6
Ewigman and co-workers7 evaluated the efficacy of routine antenatal diagnostic imaging with ultrasound
(RADIUS) in reducing adverse perinatal outcome. Secondary outcomes included maternal morbidity and diagnostic
accuracy of ultrasound. Study subjects were recruited from 92 obstetric and 17 family medicine practices in six
states. Selection was based on predefined entry criteria that placed all study patients (screened group) in a low-risk
category. Ultrasound screening examinations were performed on 7812 study subjects during two pregnancy
intervals: 15 to 22 weeks, and 31 to 35 weeks. The women (n = 7718) in the control group had an ultrasound
examination performed only if it was clinically indicated. The sensitivity in the detection of congenital anomalies
was significantly higher in the screened versus control groups (34.8% vs 11%, p < 0.01); however, the higher
detection of anomalies did not result in improved perinatal outcome. Romero8 and others9, 10 attribute the lack of
improvement in perinatal outcome to (1) the limited sensitivity in the detection of anomalies in the RADIUS study,
and (2) the low rate of pregnancy termination in women diagnosed with a fetal anomaly.
The low sensitivity (16.6%) in the detection of anomalies in the RADIUS study, particularly before 24
weeks' gestation, is very disturbing because it does not represent the current diagnostic capability of ultrasound.
Specifically, in four studies11, 12 13, 14 published from 1990 to 1992, the sensitivity of ultrasound screening for
congenital anomalies before 24 weeks' gestation was 40%, 60.7%, 74.4%, and 84.3%, respectively. The specificity
and negative predictive values were greater than 98%.11, 12, 13, 14 Except for the Helsinki trial,11 the positive
predictive values in these studies were equal to or greater than 98%.12, 13, 14

HEAD AND SPINE

Central Nervous System Evaluation. Prenatal sonography has proven an excellent method to detect and
characterize fetal central nervous system abnormalities. This is especially important because of the frequency of
these abnormalities as well as their potential for causing severe disability or death. By adopting a systematic
approach to the ultrasound evaluation of the central nervous system, it is possible to identify virtually all fetuses
with major abnormalities (Filly and colleagues, 1989). Such early identification allows timely consideration of
prognosis and therapeutic options, including pregnancy termination.
27
 Three routine transverse (or axial) sonographic views are recommended by Nyberg (1989) to depict the fetal
brain and cranium. The transthalamic view (Fig. 44–1 ), which is used to measure biparietal diameter and head
circumference, includes the thalamus, cavum septi pellucidae, and the frontal horns of the lateral ventricle. Moving
superiorly yields the transventricular view (Fig. 44–2 ), which contains the lateral cerebral ventricles and the
echogenic choroid plexus and also allows visualization of cranial contour. The transcerebellar view (Fig. 44–3 ) is
obtained by angling through the posterior fossa in the suboccipital bregmatic plane, and demonstrates the cerebellum
and cisterna magna. Normal transverse cerebellar diameters for fetuses between 13 and 40 weeks have been reported
by Goldstein and associates (1987).
Filly and colleagues (1989) reported their experiences with 137 fetuses between 15 and 39 weeks who had
sonographically diagnosed central nervous system abnormalities. Of these, 25 had obvious anencephaly and 99 had
a ventricular atrial diameter larger than 10 mm. Seven of the remaining 13 fetuses had cisterna magna either smaller
than 2 mm or larger than 11 mm in size. Using this sequence of evaluation, only 6 of 137 fetuses with abnormal
nervous systems were not identified; however, in three of these fetuses, other grossly apparent abnormalities were
seen. Thus, using a relatively simple sequence of evaluation, 134 of 137 fetuses with central nervous system
abnormalities would have been identified. This same group also studied 150 normal fetuses between 15 and 40
weeks and found that the ventricular atrium could be identified and measured in 99 percent and the cisterna magna
in 90 percent.
Monteagudo and associates (1991) found that transvaginal ultrasonography in the second and third tri-
mesters enhanced findings in fetuses with central nervous system abnormalities. Using this approach, they changed
the diagnosis in 5 of 13 fetuses. We have found transvaginal sonography to be particularly helpful in the 16- to 20-
week fetus to clarify neural-tube defects.
ANOMALIES OF THE CENTRAL NERVOUS SYSTEM

The frequency of central nervous system anomalies varies according to geographic area and race. It is
approximately 2:1000 newborns, and the recurrence risk is 1% to 2%.

ANENCEPHALY

In anencephaly, the cerebral hemispheres and overlying skull and scalp are absent. In exencephalus, the
cranial bones are also absent, but a large amount of disorganized brain tissue is present. The diagnosis can now be
made in the latter part of the first trimester of pregnancy with the use of high-frequency transvaginal ultrasound
(Fig. 19).60

MICROCEPHALY

The diagnosis of microcephaly is more likely to be accurate when the head circumference is 3 SD below
the mean for dates (Table 12).4, 5 A definitive diagnosis is usually difficult to make before 24 weeks' gestation
because the etiology is variable (Table 13), and head size may not become small for gestational age until the third
trimester of pregnancy.
Sonographic measurement of the frontal lobe (i.e., the distance from the posterior wall of the frontal horn to
the inner aspect of the skull) has been proposed as a helpful diagnostic tool because the frontal aspect of the brain is
the area most compromised.61, 62, 63 The normal frontal lobe values ± 2 SD from 16 to 24 weeks' gestation are
shown in Table 14.

MENINGOCELE AND ENCEPHALOCELE

In cranial meningocele, the meninges protrude through a bony defect in the skull. Occipital presentation of
meningocele is most common, occurring in 75% of cases. The differential diagnosis of cranial meningocele includes
(1) scalp edema associated with fetal hydrops, (2) cystic hygroma, (3) teratoma, and (4) encephalocele (Fig. 20).64,
65
Spina bifida is frequently associated with meningocele. The latter represents extrusion of the meninges
through the bony defect. Some cerebrospinal fluid (CSF) is usually contained within the meningocele. As a result,
the area appears cystic, an ultrasound characteristic that enhances visibility of small spina bifida (Fig. 21).

CHOROID PLEXUS CYST

28
 A choroid plexus cyst is visualized in approximately 1% of fetuses scanned at 16 to 22 weeks' gestation
(Fig. 26). In 1% to 2% of such fetuses, fetal trisomy 18 or 21 is noted.71, 72, 73, 74 Parents therefore should be
counseled regarding the assessment of fetal karyotype. They should also be informed that trisomy 18 is a fatal
condition, but that approximately 10% of infants with this defect live beyond 1 year of age. These parents should be
counseled with respect to the emotional and financial cost of caring for an infant with this disorder.75
It has been postulated that the risk for aneuploidy may be small if (1) the cyst is less than 1 cm in diameter,
(2) the cyst decreases in size or disappears as the pregnancy advances to 22 weeks, and (3) no other anomalies are
noted. Whether there is indeed a decreased risk in such pregnancies, however, remains controversial. Kupfermink
and co-workers76 showed that in a fetus with isolated choroid plexus cyst, the risk for aneuploidy is high (1:25) and
thus amniocentesis is warranted.

THE POSTERIOR FOSSA

The posterior fossa shows the cerebellum and the cisterna magna (Fig. 27). Normally, the cisterna magna
measures 1 to 10 mm. The differential diagnoses of an enlarged cisterna magna include trisomy 18, arachnoid cyst,
and obstruction of normal CSF flow at the level of the foramina Luschka and Magendie. CSF obstruction occurs in
the following conditions:

1.Dandy-Walker malformation
2.Abnormalities of the subarachnoid space:
a. Arnold-Chiari II syndrome
b. Cerebral infection
c. Achondroplasia
d. Hurler syndrome.77, 78, 79

In Dandy-Walker malformation, dilation of the posterior fossa results from atretic foramina Luschka and
Magendie, hypoplastic cerebelli, and vermis (roof of the fourth ventricle). As a result, the dilated fourth ventricle
"herniates" into the area of the cisterna magna, ultrasonically appearing as symmetrically dilated cisterna magna (see
Fig. 27). In contrast, an arachnoid cyst in the posterior fossa is less symmetric.77

HYDROCEPHALUS
The incidence of hydrocephalus ranges from 0.3 to 0.8 per 1000 births (Chap. 39 ). Fetuses who are
diagnosed prenatally have other intracranial or extracranial malformations or chromosomal abnormalities in 85
percent of cases, and appear to have a very poor prognosis for normal long-term development (Chervenak, 1983;
Nyberg, 1987; Pretorius, 1985; and their colleagues).
Currently, the most accurate measure of ventriculomegaly is the lateral ventricle atrial measurement. In the
normal fetus, the diameter of the lateral ventricular atrium is relatively constant from 6 to 9 mm between 15 and
35 weeks (Cardoza and colleagues, 1988b). Early in the second trimester, the choroid makes up the majority of the
ventricular volume, but it involutes with increasing gestational age to become only a small portion of the volume by
the third trimester (Fig. 44–4 ). An atrial diameter greater than 10 mm suggests ventriculomegaly. This observation
is especially useful, as dilatation of the ventricular atrium and occipital horns is thought to be an early event in the
development of fetal hydrocephalus.
Cardoza and associates (1988a) examined the relationship between the choroid plexus and the lateral wall of
the dependent lateral ventricle. They compared 50 normal fetuses at 15 to 38 weeks with 25 hydrocephalic fetuses at
18 to 39 weeks. Mahony and colleagues (1988) quantified the anatomical relationship between the choroid plexus
and the medial wall of the dependent lateral ventricle. Their findings suggest that a free-floating or dangling
choroid plexus may facilitate the early diagnosis of fetal hydrocephalus. In the presence of hydrocephalus, the heavy
choroid plexus in the dependent lateral ventricle will separate from the medial ventricular wall through the action of
gravity.
Ventricular enlargement is not always due to hydrocephalus; it is also caused by brain parenchymal
destruction or colpocephaly (poor brain development). The combined use of the three cranial views have led to very
sophisticated antenatal diagnoses, based on their classical findings, including aqueductal stenosis,
holoprosencephaly, hydranencephaly, cerebral atrophy (secondary to intrauterine infection or infarction),
porencephalic cyst, agenesis of the corpus callosum, and intracranial tumors.
Isolated Mild Cerebral Ventriculomegaly
ISOLATED MILD CEREBRAL VENTRICULOMEGALY. In about 25 to 50 percent of cases of
ventriculomegaly, the defect is mild and there are no associated abnormalities. The reports of Brown and colleagues
(1995) and Patel and associates (1994) indicate that about 20 percent of such infants will manifest neurological

29
abnormalities later in life. Those with borderline ventriculomegaly fare better. As expected, those later found to
have other abnormalities such as chromosomal anomalies or evidence for intrauterine infection do poorly.
Hydrocephalus is most sensitively detected by measurement of the width of the lateral ventricle at the
choroid plexus. A value of 10 mm or less before 20 weeks' gestation is normal. In early hydrocephalus, the choroid
plexus may be displaced anteriorly and does not fill the atrium of the ventricle. Early diagnosis is thus made on
morphologic as well as measurement criteria. In later gestation, the diagnosis may be made by comparing the
distance to the lateral aspect of the ventricle width relative to the cranial hemisphere width. The normal ratio of
these measurements is dependent on fetal gestational age.47

Figure 22 depicts the flow of CSF in hydrocephaly. Any lesion preventing normal flow of CSF from the
lateral ventricles to the cisterns results in hydrocephaly.
Obstruction at the level of the aqueduct of Sylvius results in enlargement of the third and lateral ventricles
(Fig. 23). The etiology of such obstruction includes (1) X-linked recessive inheritance, (2) infection with
cytomegalovirus or toxoplasmosis, and (3) other lesions that impinge on the area.
Hydrocephaly plus dilation of the posterior fossa results from obstruction of CSF flow at the level of the
foramina Luschka and Magendie (see Dandy-Walker syndrome, below). Table 15 lists a number of other specific
syndromes that result in hydrocephaly.

In approximately 25% of hydrocephalic fetuses, an abnormal karyotype is found. Of these fetuses,

approximately 85%, have additional anomalies. Thus, the prognosis should be individualized depending on specific
etiology, but this cannot always be determined antenatally.
Hydrocephalic fetuses should not be delivered before pulmonary maturity is attained because there is a
weak correlation between the extent of compression of the cerebral cortex and the severity of mental retardation.

ROUTE OF DELIVERY. In a term fetus with normal chromosomes, isolated hydrocephalus (i.e., no other
abnormality noted), and head circumference less than 90th percentile, vaginal delivery may be a reasonable option.
If head circumference is equal to or greater than 90th percentile at term, cesarean section may be the least traumatic
route. When hydrocephalus is associated with conditions incompatible with life, such as renal agenesis,
thanatophoric dwarfism, or trisomy 18, cephalocentesis may be used to accomplish vaginal delivery. The
combination of hydrocephalus with spina bifida also can determine the mode of delivery (see section on Spina
Bifida. below).
In contrast to simple ventriculomegaly, hydrocephalus usually is more progressive, and it is frequently
associated with compression of the choroid plexus (see Fig. 23).
The progression of hydrocephalus may be gauged by (1) the ventricular:hemispheric ratio, and (2) the
diameter of the ventricular atrium (see Fig. 22 and Fig. 23).66, ,68 Dilation of the ventricular atrium is also a
characteristic finding in agenesis of the corpus callosum. In such cases, the third ventricle is displaced cephalad and
the frontal horns laterally.69

DIFFERENTIAL DIAGNOSES. Differential diagnoses of hydrocephaly include the following:

1.Holoprosencephaly: In this condition, the cerebral hemispheres do not separate; a single ventricle is noted,
and hypotelorism is a characteristic finding. Fetal karyotype is abnormal in 50% of fetuses with holoprosencephaly,
and trisomy 13 is the most frequent chromosomal abnormality. The diagnosis may be made in the latter part of the
first trimester with the use of high-frequency vaginal ultrasound (Fig. 24).
2.Hydranencephaly. In this condition, early bilateral vascular thrombosis of the carotid arteries bilaterally
results in infarcted and atrophic cerebral hemispheres. The cerebellum, midbrain, and basal ganglia are seen,
however. and are characteristically surrounded by a fluid interface.
3.Porencephaly. In contrast to hydranencephaly, the condition results from localized brain atrophy secondary
to a vascular accident.
4.Aneurysm of the vein of Galen (Fig. 25):70 Dilation of the vein of Galen results from an arteriovenous
malformation in which one or more arterioles feed the vein of Galen and distend it. The diagnosis is clarified by
color Doppler velocimetry (see Fig. 25). The distension may result in hydrocephaly, and it may lead to high-output
cardiac failure (see Fig. 25).

NEURAL-TUBE DEFECTS
Neural-tube defects result from failure of tube closure by the sixth gestational week (embryonic age 26 to 28
days). A more detailed account of common neural-tube anomalies is found in Chapter 39 , and their incidence is
cited in Table 39–8.
Anencephaly was the first fetal malformation to be diagnosed prenatally by using sonography. Although its
diagnosis is theoretically possible as early as 8 weeks, it can be missed by experienced sonographers in the first
30
trimester (Levi and associates, 1990). In the second trimester, however, if an adequate ultrasound examination can
be performed, anencephaly is diagnosed with virtually 100 percent accuracy. Sonographically, anencephaly is
characterized by absence of the cranial vault and brain above the base of the skull and orbits. Hydramnios,
secondary to impaired fetal swallowing, commonly accompanies anencephaly but is typically a late finding.
Goldstein and Filly (1988) reported increased amnionic fluid in 85 percent of anencephalic fetuses after 25 weeks,
but in only about 10 percent before. Associated fetal anomalies are common but have not been extensively described
because anencephaly itself is uniformly fatal.
Encephalocele defines the condition in which the meninges and cerebrospinal fluid, usually in association
with brain tissue, herniate through a cranial defect. This lesion most commonly results from an occipital midline
defect. Sonographically, encephaloceles vary in size and are characterized by either a cystic or solid appearance
depending on which fetal structures are involved. Encephaloceles are commonly associated with either
hydrocephaly or microcephaly. The presence of an encephalocele is an important feature of Meckel–Gruber
syndrome and frequently accompanies amnionic band syndrome. An occipital encephalocele can usually be
detected using transthalamic and transcerebellar views.
The incidence of fetal open neural tube defects in the United States is 1 to 2 per 1000 births. Anencephaly, in
which the cranial vault is absent, accounts for about half of these. By locating the fetal spine and moving the
ultrasound transducer cephalad, the absence of a cranial vault can be confirmed. In anencephaly, the fetal orbits
should be visible. The cranium should be visualized by 14 weeks' gestation.

Spina bifida is more difficult to detect; the fetal spine must be meticulously examined in three planes.
Successful ultrasonographic detection of spina bifida requires examination of both spinal and cranial anatomy.
Experience strongly suggests that intracranial abnormalities are present in most all cases of spina bifida.20,46 Five
cranial signs associated with spina bifida are frontoparietal notching (the "lemon" sign; Fig. 8), mild hydrocephalus,
a small-for-date BPD, abnormal cerebellar hemispheres, and obliteration of the cisterna magna. The finding of a
normal fetal cerebellum and cisterna magna virtually excludes spina bifida. This view is obtained by finding the
axial plane of the BPD and rotating the transducer to view the posterior fossa (Fig. 9).
Spina bifida consists of a hiatus, usually in the lumbosacral vertebrae, through which a meningeal sac may
protrude, forming a meningocele. If the sac contains neural elements, as it does in 90 percent of cases, the anomaly
is called a meningomyelocele. Roberts and colleagues (1983) reported their 6-year experience with the ultrasound
diagnosis of spina bifida in a group of women at high risk for an affected fetus. All studies were performed before
20 weeks, and in the first 3 years they correctly diagnosed only 6 of 18 defects while they falsely diagnosed a defect
in 49 of 1243 normal fetuses. In the second 3 years of their study, they correctly diagnosed 16 of 20 defects and
misdiagnosed only 4 of 1171 normal fetuses. The importance of experience is apparent.
The fetal spine should be examined by sonography with sagittal, transverse, and coronal views (Fig. 44–5 )
whenever possible. These provide the best opportunity to detect the presence and extent of defects in the fetal spine
and overlying soft tissues. Fetal movement of the lower extremities and urination may be seen despite the
presence of neurologically significant spina bifida.
Because of the difficulty in detecting small spinal defects, especially during the second trimester, the
association of cranial abnormalities with spina bifida has recently been the subject of intense investigation. For
example, spina bifida is commonly, if not invariably, accompanied by the Arnold–Chiari malformation. Although
the exact cause of this malformation is unclear, its pathology is well characterized: the medulla and fourth ventricle
are elongated and, in combination with a portion of the cerebellum, extend through the foramen magnum into the
upper cervical spinal canal. The Arnold–Chiari malformation is felt to be responsible for sonographically
detectable fetal abnormalities that include cerebral ventriculomegaly, frontal bone scalloping (lemon sign),
abnormal curvature of the cerebellum (banana sign), decreased cerebellar size, and failure to visualize the
cerebellum and obliteration of the cisterna magna.
In spina bifida, splaying of the spine is noted in the longitudinal plane. However, small spinae bifida
located in the lumbosacral area are best visualized by careful cross-sectional imaging (see Fig. 21). The size of
spinae bifida varies from a tiny bone defect to one involving many segments of the spine (myeloschisis).
Importantly, an Arnold-Chiari type II malformation occurs in nearly all cases of spina bifida. This is
characterized by forward scalloping of the frontal aspect of the fetal head (lemon sign; see Fig. 21), and an
abnormal, banana-shaped cerebellum (banana sign). The ultrasonographer should always look for these signs during
the examination; if they are present, the ultrasonographer should extend the examination to search for spina
bifida.80

MODE OF DELIVERY. Currently, there are no controlled prospective studies that indicate whether a fetus
with spina bifida should be delivered vaginally or by cesarean section. In a recent retrospective report, however,
Luthy and associates81 showed that the mean functional level of infants delivered by cesarean section extended to a
lower level than that of infants delivered vaginally (L4 vs L2). This two-segment difference may determine the
prognosis as to whether an infant will be able to walk.81, 82 Thus, obstetricians prefer delivery by cesarean section
because it allows controlled handling of the fetal lumbosacral area.
31
 Cerebral ventriculomegaly has been reported in approximately 80 percent of fetuses with spina bifida.
Although it generally is mild to moderate, it tends to worsen with advancing gestational age (Goldstein and
colleagues, 1989; Nyberg and co-workers, 1988). Benacerraf and co-workers (1989) reported that a cerebellar
banana sign was present in 22 of 23 fetuses diagnosed with spina bifida between 16 and 27 weeks. Van den Hof and
associates (1990) presented findings from 130 fetuses with sonographically diagnosed spina bifida. A banana sign
was found in 70 percent of 107 affected fetuses before 24 weeks, and another 29 had an “absent cerebellum.” After
24 weeks, only 4 of the 23 fetuses with spina bifida demonstrated a banana sign, but another 17 had an absent
cerebellum. When the data from these two studies are combined, a total of 1405 fetuses subsequently proven not to
have spina bifida were examined with ultrasound because of maternal risk factors for neural-tube defects, and none
had an abnormal cerebellum. In a related observation, Goldstein and colleagues (1989) evaluated a group of fetuses
between 17 and 38 weeks who were at risk for neural-tube defects. They obtained an adequate view of the posterior
fossa in 19 of 20 fetuses with spina bifida. In 18 of these fetuses the cisterna magna was completely effaced, and in
one it measured 2 mm. In all 33 of the nonaffected fetuses, the cisterna magna measured 4 to 9 mm.
Normally, when visualized in the transthalamic or transventricular planes, the frontal contour of the fetal
cranium is convex. The presence of a concave or flattened frontal contour has been termed the lemon sign (Fig. 44–
6 ). In the study by Van den Hof and associates (1990), 105 of the 107 fetuses less than 24 weeks old with spina
bifida had this sign compared with only 3 of 23 after 24 weeks. Similarly, Nyberg and associates (1988) found a
lemon sign in 24 of 27 affected fetuses before 24 weeks, compared with 8 of 25 fetuses later in gestation.
Combining the two studies, however, only 12 of 1497 fetuses evaluated because they were at increased risk for
neural-tube defects had a lemon sign in the absence of spina bifida.

CHOROID PLEXUS CYSTS

Choroid plexus cysts have been identified in up to 3 percent of second-trimester fetuses (Benacerraf and co-
workers, 1990; Chinn and associates, 1990). The cysts vary in size from 2 to 20 mm. They are usually transient and
will resolve by 24 weeks (Fig. 44–7 ). They may be associated with chromosomal anomalies; the most common is
trisomy 18, which is found in about 1 percent of these fetuses.
Chitkara and associates (1988) detected choroid plexus cysts measuring 2 to 20 mm in 40 fetuses between 16
and 21 weeks. Approximately half were bilateral. Of the 40 cysts, 33 resolved by 23 to 24 weeks, and another 4 by
26 to 28 weeks. One fetus with large bilateral cysts and additional ultrasound abnormalities had trisomy 18. Chan
and co-workers (1989) prospectively studied 513 women who underwent genetic amniocentesis between 16 and 24
weeks. Thirteen fetuses had choroid plexus cysts between 3 and 10 mm. Approximately one third were bilateral. All
13 fetuses had normal karyotypes. Conversely, of the 500 fetuses without choroid plexus cysts, five had trisomy 21
and two had trisomy 18.
Kupferminc and colleagues (1994) identified 102 fetuses (1.1 percent) with choroid plexus cysts among 9100
pregnant women undergoing ultrasonic evaluation. Four fetuses had obvious associated anomalies; two of these had
trisomy 18 and a third an unbalanced translocation. The remaining 98 fetuses had choroid cysts as an isolated
findings. In 75, amniocentesis was done and there were four abnormal karyotypes—three Down syndromes and one
trisomy 18. Because of a 1 in 25 risk of an associated chromosomal anomaly with an isolated cyst, they recommend
that amniocentesis be offered. Conversely, Benacerraf and co-workers (1990) calculated that if all second-trimester
fetuses with no ultrasound abnormalities except choroid plexus cysts underwent genetic amniocentesis, 478
procedures would have to be done to identify each case of trisomy 18. Gross and colleagues (1995) provided
substantiating data from 74 fetuses with isolated cysts. None of these had associated trisomy 18, and their meta-
analysis identified two cases among 748 such fetuses. They too argued against routine cytogenetic testing in these
cases. More recently, Leonardi and associates (1996) described 149 women with isolated cysts at a mean of 19
weeks. There were 12 percent associated anomalies, including 4 percent aneuploidies. They recommended
karyotype evaluation if there were associated minor or major anomalies seen on sonography. The largest study
comes from a registry of 524 fetal choroid plexus cysts identified over 3 years in the Yorkshire region of the United
Kingdom. Gupta and colleagues (1995) also added cases from published prospective studies as well as 71 cases
from Dundee, Scotland. Their analysis totalled 1361 cases and they found that the risk of chromosomal anomaly
was 1 in 150 when no other fetal anatomical anomalies were seen by ultrasound. Conversely, the risk was 1 in 3 if
any other anomaly was detected. They concluded that it was advisable to regard these cysts as an indication for
detailed ultrasound assessment, rather than invasive testing.

THORAX
Fetal lungs are usually visualized by midpregnancy. There are a variety of thoracic malformations that can
develop. Some of the more common include pulmonary hypoplasia, cystic adenomatoid malformation, and
pulmonary sequestration (Crane and colleagues, 1994; Gonçalves and associates, 1994). Recent data from Treadwell
and associates (1996) support a better prognosis than previously reported.

32
CARDIAC EVALUATION
The four-chamber view of the fetal heart is obtained from a near transverse midchest scan plane at the level
of the heart (Fig. 10). A normal four-chamber view with symmetry and synchronous action of the ventricles
excludes 95% of clinically significant cardiac malformations.48 The normal fetal heart is angled at 45 ± 10ˇ (1
standard deviation) to the left of the anteroposterior midline.49 The anteroposterior midline passes through the left
atrium and the right ventricle. Asymmetry in chamber size, defects in the septum, or displacement of the fetal heart
should lead to referral for a more detailed ultrasonographic evaluation (Fig. 11).

Cardiac Evaluation. Congenital heart disease has been the most commonly recognized birth defect with a
reported frequency of 8 per 1000 live births and 27 to 77 per 1000 stillborns (Hoffman and Christianson, 1978;
Mitchell and associates, 1971). The reported frequency of specific heart defects varies significantly between studies
done on live borns, stillborns, and fetuses in whom heart lesions were identified in utero (Chap. 47 ). Perone (1988)
recommends that women with any of the following risk factors undergo a detailed ultrasound examination of the
fetal heart: nonimmune hydrops, suspected abnormality seen by screening sonogram, teratogen exposure, parental or
sibling heart defects, aneuploidy, extracardiac anomalies, maternal diabetes, and fetal arrhythmias. The recurrence
risk for congenital heart defects if siblings or parents are affected is shown in Table 39–9.
Congenital heart defects are frequently associated with aneuploidy, and Copel and co-workers (1988a)
reported that 11 of 34 fetuses (32 percent) with cardiac anomalies detected prenatally had an abnormal karyotype.
Additionally, associated extracardiac structural abnormalities are present in 25 to 45 percent of such fetuses (Copel
and associates, 1986).
Although heart motion can be visualized sonographically in a 6- to 7-week embryo, detailed cardiac
evaluation is usually not possible until at least 18 weeks. Even at this time, adequate anatomical cardiac assessment
is dependent on factors that include fetal position and activity, maternal size, and amnionic fluid volume. The detail
of such examinations depends on the availability of proper equipment and expertise, and the study may be time
consuming and require pediatric cardiological collaboration.
Visualization of a four-chamber view is central to fetal cardiac assessment (Fig. 44–8 ). This view is obtained
by imaging a transverse plane through the fetal thorax at a level just above the diaphragm, and allows evaluation of
the size, location, and orientation of the fetal heart. Additionally, the atrial and ventricular chambers can be assessed,
the interatrial and interventricular septa viewed, and the atrioventricular valves observed. Normally, the two atria are
similar in size as are the two ventricles. The apex of the heart typically forms a 45-degree angle with the left anterior
chest wall.
The importance of the four-chamber view was demonstrated by Copel and colleagues (1987), who reported
that 71 of 74 fetuses (96 percent) with sono-graphically detectable heart defects had abnormal four-chamber views.
As reviewed by Perone (1988), at times other cross-sectional views may be required, either to demonstrate fetal
heart integrity or to characterize abnormalities. In addition to these, M-mode echocardiography may be required to
measure chamber size, wall thickness, and wall and valve motion, and to facilitate assessment of cardiac
arrhythmias (DeVore and co-workers, 1987). Pulse Doppler and real-time Doppler color-flow mapping are also
used to define normal or abnormal blood flow in the fetal cardiovascular system (DeVore and associates, 1987;
Shenker and colleagues, 1988).
Given these technological considerations, what accuracy should be expected of an ultrasound examination to
detect fetal cardiac disease? Crawford and colleagues (1988) reported their experiences with almost 1000 women at
high risk for having children with cardiac abnormalities. They performed over 1750 fetal echocardiograms and
successfully identified 74 of 91 anomalies (80 percent). In almost half of those with cardiac anomalies,
chromosomal or extracardiac structural defects were also found. They emphasized that heart disease diagnosed
prenatally is usually severe and is associated with a poor long-term prognosis. By contrast, Benacerraf and
associates (1987) studied a group of women who underwent ultrasonic studies for multiple reasons. Although 49
fetuses were subsequently found to have 66 cardiac defects, only 33 (50 percent) of these were detected antenatally.
According to both of these reports, ventricular septal defects, anomalous pulmonary venous return, and aortic or
pulmonic stenosis were especially likely to be missed by fetal ultrasound evaluation. Ott (1995) recently reported a
14-percent sensitivity for detection of congenital heart disease in a low-risk population, compared with 63 percent in
the high-risk group. Lanouette and co-workers (1996) correctly emphasized that routine cardiac views are not
consistently available for each routine ultrasound examination. They calculated the adjusted positive predictive
value to be about 55 percent. Berghella and associates (1996) found that significantly more lesions were detected
when a pediatric cardiologist participated in the evaluation.
CONGENITAL HEART DISEASE

The frequency of congenital heart disease (CHD) is approximately 6 to 8 per 1000 newborns, and the
recurrence risk is 8%. In 25% of cases, the etiology can be related to familial, chromosomal, or environmental
causes (Table 9).15 The prenatal risk factors for CHD are shown in Table 10.16 The overall survival rate of fetuses
with CHD remains poor (17% to 24%).17, 18
33
 The examination of the fetal heart includes evaluation of many views, including the four chambers, the
parasagittal view (also known as the left ventricular outflow tract), the short axis, the great vessels, and the aortic
arch.

THE FOUR-CHAMBER VIEW

The structures that can be visualized in the four-chamber view are as follows:

1.Both ventricles, including the position or' the heart in the chest and the appearance of the pericardial and
pulmonary areas
2.The interventricular septum (IVS)
3.The atrioventricular valves
4.The septum primum and secundum (Fig. 2).

The ultrasonographer should obtain a number of views of the four chambers to gain adequate visualization
of all these structures (Fig. 3).

THE VENTRICLES. Although both ventricles should be similar in thickness and size, the right ventricle is
normally characterized by the appearance of the moderator band, which consists of thickened trabeculae extending
from the septum to the parietal wall of the right ventricle (see Fig. 3A). Absence of the moderator band from its
normal location implies corrected or L-transposition of the great arteries. In this abnormality, the right ventricle
functions as the left chamber, assuming the role of pumping blood into the aorta. Thus, in contrast to D-
transposition, L-transposition allows blood flow to the lungs and body to be maintained normally.
Hyperechogenicity or thickness of the ventricular walls or ventricular septum, or both, is consistent with
cardiomyopathy (Fig. 4).
In dextroversion, the apex of the heart points to the right side of the chest. The main differential diagnoses
of this condition are cystic adenomatoid malformation of the lungs, diaphragmatic hernia, and polysplenia. In
levoversion the apex of the heart points to left side of the chest excessively; the main differential diagnosis of this
condition includes left pulmonary hypoplasia and a right-sided pulmonary mass.

THE INTERVENTRICULAR SEPTUM. Defects in the IVS constitute the most common form of congenital
heart disease and can occur in various locations within the septum. Ultrasonic visualization of small ventricular
septal defects, regardless of location, may not be possible in the four-chamber plane. For example, membranous or
perimembranous defects (located adjacent to the aortic valve) are situated below the anterior portion of the IVS and
are not visualized in the four-chamber plane (Fig. 5). Such defects usually are depicted in the parasagittal plane (Fig.
6).

THE ATRIOVENTRICULAR VALVES. The septal insertion of the tricuspid valve should be visualized
slightly below that of the mitral valve (see Fig. 2 and Fig. 3). If the insertion is lower, Ebstein anomaly should be
considered. Interestingly, hyperechogenicity limited to the area of the mitral valve is usually inconsequential; that is,
cardiomyopathy is not a consideration.

THE SEPTUM PRIMUM AND SECUNDUM. The foramen ovale is the opening between both atrial septi,
allowing blood to flow from the right atrium to the left. In endocardial cushion defect, a single common
atrioventricular valve is noted superior to a large ventricular septal defect.

DIAGNOSTIC UTILITY OF THE FOUR-CHAMBER VIEW

Because the four-chamber view depicts so many cardiac structures and is also the plane used to evaluate
cardiac arrhythmia, it is included in all obstetric studies. Copel and associates19 showed that 92% of cardiac defects
may be discovered by some abnormality in the four-chamber view and proposed routine screening for CHD. After
including the four-chamber view in their examinations, Vergani and colleagues20 improved their CHD diagnosis
sensitivity from 43% to 81%. Subsequently, Sharland and Allan21 showed that after routinely including the four-
chamber view in obstetric studies, 53 fetuses were referred for possible CHD over a period of 32 months;
previously, from 1980 to 1988, only 8 fetuses had been referred. They reported a 77% sensitivity for the four-
chamber view in the diagnosis of CHD. Studies by Bromley and co-workers22 and Wigton and associates,23
however, suggest that the sensitivity of the four-chamber view in detecting CHD is even lower, ranging from 69% to
39%, respectively. This is understandable because the four-chamber view does not allow for assessment of the
pulmonary and aortic arteries-outflow tracts that are evaluated best in the parasagittal, short axis, and great vessel
views.
34
PARASAGITAL VIEW

The parasagittal view encompasses the left ventricle. aortic outflow, a portion of the right ventricle, and the
left atrium (see Fig. 6). This plane is significant for two main reasons:

1.The aorta at the level of the aortic valve can be readily assessed.
2.Membranous IVS defects (located adjacent to the aortic outflow tract and below the plane of the four
chamber view) stand a better chance of being visualized in this view.

SHORT AXIS VIEW

The short axis view (Fig. 7) encompasses the aortic and pulmonary valves as well as the ductus arteriosus
and the right branch of the pulmonary artery. It is used to evaluate the size of the aorta and pulmonary arteries at the
valvular level.

GREAT VESSEL VIEW

The great vessel view depicts the relatively parallel relationship of the superior vena cava, aorta, and
pulmonary arteries after the latter two cross each other (Fig. 8). Clear visualization of this plane indicates that the
crossing of the aorta and pulmonary artery is normal and virtually rules out transposition of the great vessels. Aortic
or pulmonary stenosis also can be recognized in this view.
In truncus arteriosus, the pulmonary artery is not clearly depicted by ultrasound. Instead, the aortic outflow
tract is large and the aorta is overriding.
The great vessel view also allows a comparative measurement of the two arteries a short distance beyond
the valvular level; the measurements should be obtained from the inner aspects of these arteries. Normally the ratio
of pulmonary artery: aorta has a mean value of 1.09 (range = 0.75 to 1.43) and is independent of gestational age.24

AORTIC ARCH

The aortic arch is depicted in Figure 9. Coarctation of the aorta most frequently occurs at the isthmus, the
area of the arch at the insertion site of the ductus arteriosus. The isthmus is normally narrow in the fetus but dilates
in the newborn after the ductus closes. Because narrowing in the isthmus occurs normally, in utero diagnosis of
coarctation of the aorta is difficult.

ESOPHAGEAL ATRESIA

This is a very rare anomaly occurring at a rate of 1:25,000 births. In 10% of cases it can be characterized
ultrasonographically by a dilated proximal esophagus, absence of stomach echo, and polyhydramnios.25 In the
remaining 90% of cases, however, the defect cannot be ultrasonically recognized because of abnormal
communication channels between the proximal aspects of the esophagus, trachea, and stomach, which result in free
flow of amniotic fluid.

PULMONARY CYSTIC ADENOMATOID MALFORMATION

Three types of pulmonary cystic adenomatoid malformation have been characterized26:

Type I: The cysts are large ( 2 cm). The prognosis depends on the size of the tumor and the degree of fetal
hydrops (Fig. 10). If the fetus survives, resection of the affected portion of the lung is usually indicated.
Type II: The cysts are less than 1 cm in diameter, but other anomalies of the renal or gastrointestinal tract
may be present.
Type III: The lesion is microcystic, brightly echogenic, and large, and its presence is associated with a poor
prognosis (see Fig. 10).

A pulmonary cystic adenomatoid malformation can result in a right or left shift of the mediastinum (see
Fig. 10). The differential diagnosis includes pulmonary sequestration and diaphragmatic hernia.27

35
PULMONARY HYPOPLASIA

Pulmonary hypoplasia is associated with a high mortality rate. Lung weight at autopsy is 2 SD below the
mean.49 The etiology of this disease usually is related to (1) compression of the lungs, and (2) oligohydramnios28
(Table 11); however, the disease also can occur as a primary condition.
Although high-resolution equipment has enabled lung tissue to be visualized adjacent to the heart, most
studies dealing with antenatal diagnosis of pulmonary hypoplasia have focused on reduced chest size as a predictor
for the condition.29, 30 More recently, Vintzileos and colleagues31 showed that the highest sensitivity (85%) and
positive predictive value (83%) for the diagnosis of pulmonary hypoplasia could be obtained with the following
ratio:

[chest area - heart area/chest area] x 100

The chest area should be traced at the midpoint of the chest wall. The ratio is independent of gestational age
and is considered abnormal when it is less than or equal to 62 (5th percentile). The ratio can be used when the
abdominal circumference is large (as in ascites or obstructive uropathy) or small (as in omphalocele). It is not
applicable to fetuses with diaphragmatic hernia because chest size is artificially enlarged in this condition.

DIAPHRAGMATIC HERNIA
Congenital diaphragmatic hernia results from incomplete fusion of the pleuroperitoneal membrane, occurs
more frequently on the left, and has a frequency of 1 in 2000 to 3000 births (Romero and associates, 1988). On
ultrasound examination, a cystic structure, usually behind the left atrium, is seen on an axial image at the level of the
four-chamber cardiac view. Associated findings include absence of an intra-abdominal stomach bubble, a
mediastinal shift usually with a normal cardiac axis, and a small abdominal circumference. The most specific
finding is peristalsis in the fetal chest. Associated hydramnios also is common and was identified in 75 percent of
affected fetuses studied by Adzick and co-workers (1985).
Diaphragmatic hernia is associated with other major anomalies in almost half of all cases, and chromosomal
abnormalities are found in up to 20 percent of affected infants (Benacerraf and Adzick, 1987; Romero and
associates, 1988). Importantly, Benacerraf and Adzick (1987) reported an overall survival rate of only 10 percent
despite accurate prenatal diagnosis and optimal neonatal management in a tertiary-care hospital. Adzick and co-
workers (1985) found that survival is related to defect size, and noted that nonsurvivors may have more abdominal
viscera displaced into the chest earlier in gestation. They also reported that survival was 55 percent when there was
normal amnionic fluid volume, compared with 10 percent when hydramnios was present. Neonatal death generally
results from respiratory failure secondary to pulmonary hypoplasia or from associated lethal anomalies. Moya and
colleagues (1996) have documented decreased surfactant components in amnionic fluid. Although diaphragmatic
hernias are usually repaired after delivery, Harrison and associates (1990) have attempted repair in utero.

Congenital defects in the diaphragm result in herniation of bowel, stomach, and possibly parts of the liver
and pancreas, into the chest. The hernia displaces the heart and mediastinum, making antenatal diagnosis possible.
The most common defect (1:3000 births) involves the foramen of Bochdalek, which is situated in the posterolateral
aspect of the diaphragm.32 This condition may be associated with cardiac abnormalities or aneuploidy (trisomy 13,
18, and 21).
In utero corrective surgery is possible in cases of isolated diaphragmatic hernia. The outcome of open in
utero surgery, however, should be weighed against that of extracorporeal oxygen membrane oxygenation in the
neonate, which has been reported to carry a success rate of only 55%. Data on this subject are still evolving.33
Another rare type of diaphragmatic hernia is found through the foramen of Morgagni. This hernia is
associated with a poor prognosis because of its association with other anomalies, such as hydrocephalus,
encephalocele, enlarged cisterna magna, malrotation of the gut, cardiac anomalies, and trisomies.32
The differential diagnosis of diaphragmatic hernia includes (1) eventration or displacement of visceral
contents into the chest secondary to a thin diaphragm; (2) chest mass; and (3) pulmonary tumor.

ABDOMEN
ABDOMINAL WALL DEFECTS
Anterior abdominal wall defects as a group are relatively common malformations. The two most common are
omphalocele and gastroschisis, and each has a frequency of approximately 1 in 5000 live births. Because of
maternal serum alpha-fetoprotein screening programs, these two defects can be ascertained early in pregnancy.
Although these defects have many similarities, it is important to recognize that they differ markedly in

36
developmental pathology, association with other major abnormalities, and prognosis. These are discussed in detail in
Chapter 39.

Fetal bowel normally is located outside the abdomen in the first trimester of pregnancy. This is known as
physiologic herniation, a condition that can be appreciated with the use of high-frequency vaginal transducers.34, 35
Thus, the diagnosis of omphalocele should not be made before the 14th week of pregnancy.
True ventral wall defects occur at a rate of 1:2500 births. Two main forms are described: omphalocele and
gastroschisis. In omphalocele, the fetal gut (and sometimes the liver) is outside the abdomen but is covered by a sac-
like cyst interface (Fig. 11). In gastroschisis, segments of intestine are noted in the peritoneal cavity without any sac-
like cover. In contrast to omphalocele, the umbilical cord in gastroschisis is inserted into the abdominal wall (see
Fig. 11). Gastroschisis is not associated with other fetal abnormalities, but a chromosomal abnormality may be
found in approximately 50% of fetuses with omphalocele, particularly if fetal liver is not part of the hernia.36, 37
Other anomalies involving the cardiac, skeletal, renal, and central nervous systems may also be present. The
Beckwith-Weidman syndrome of organomegaly and hypoglycemia has been described in association with
omphalocele.
In the presence of a ventral wall defect, the mode of delivery (vaginal delivery vs cesarean section) remains
controversial.38, 39 Vaginal delivery appears safe, however, when the hernia is small and the liver is not herniated.

GASTROINTESTINAL ABNORMALITIES
Using high-resolution diagnostic sonography, the integrity of the abdominal wall, umbilical cord insertion,
and intraabdominal anomalies can be assessed with confidence (Fig. 44–9 ). The liver, spleen, gallbladder, and
bowel can be identified in most pregnancies. Normally, the appearance of the fetal bowel changes with gestational
age, and considerable overlap exists between normal and pathological conditions (Hertzberg, 1994). Pretorius and
colleagues (1988) reported successfully visualizing the fetal stomach in 98 percent of fetuses after 14 weeks.
Moreover, nonvisualization was associated with an abnormal outcome in 55 percent of fetuses studied after 14
weeks and 100 percent after 19 weeks. They suggested repeat sonograms for all cases of stomach nonvisualization.

The fetal stomach can be seen as a fluid-filled structure on the left side of the abdomen caudal to the four-
chamber view (see Fig. 5). The normal umbilical cord insertion can be seen in a transverse section below the fetal
stomach (Fig. 12). In this area, ventral wall defects of the fetus are seen, including gastroschisis and omphalocele.
Gastroschisis is an open defect in the abdominal wall with evisceration of the abdominal organs that usually occurs
to the right of a normal cord insertion. There is no membrane covering the eviscerated fetal bowel loops, which can
be seen in the amniotic fluid at the site of the defect (Fig. 13). Omphalocele, a failure of the embryonic gut to return
into the abdomen by 12 weeks' gestation, occurs at the cord insertion (Fig. 14) and usually is covered by a
membrane consisting of peritoneum and amnion.50 Omphalocele is associated with fetal chromosome abnormalities
in one third to one half of cases51 and should prompt a careful search for other fetal anomalies. IUGR commonly is
associated with both gastroschisis and omphalocele.
The "double-bubble" sign, classically associated with duodenal obstruction, is not specific for atresia but also
may be seen with obstruction from malrotation or an annular pancreas.
OBSTRUCTIVE GASTROINTESTINAL LESIONS AND HYPERECHOGENIC BOWEL

Duodenal atresia results from failure of recanalization of the upper gastrointestinal tract at 8 weeks'
gestation. It may be associated with Down syndrome and other anomalies involving the gastrointestinal. cardiac, and
renal systems. This condition is characterized by dilation of the stomach and proximal part of the duodenum
(double-bubble sign). Occasionally the diagnosis can be made before the 20th week of pregnancy, but it is more
likely to be made after the 20th week, when the quantity of swallowed amniotic fluid exceeds the resorptive capacity
of the gut.40
Small bowel obstruction results from in utero avascular necrosis of segments of jejunum and ileum.
Dilation of small bowel proximal to the necrotic segments is ultrasonically recognizable by the presence of valvular
flaps projecting into the lumen.
The pattern of bowel dilation in other obstructive bowel abnormalities is not specific enough to allow for a
precise diagnosis. These abnormalities include malrotation of the bowel, volvulus, intussusception, and Hirschprung
disease (congenital intestinal aganglionosis).
Meconium within normal bowel sometimes appears bright and has been described as hyperechogenic
bowel (Fig. 12). In many fetuses that exhibit this entity, the outcome may be norma141; however, it has been
associated with cystic fibrosis and aneuploidy.42 Prospective couples should be counseled regarding appropriate
antenatal testing.

37
 Differentiation between hyperechogenic bowel and meconium peritonitis may be possible. In the latter
condition, bowel perforation results in extravasation of meconium into the abdominal cavity. Meconium induces an
inflammatory response, formation of adhesions, and calcium deposition in the area.

GASTROINTESTINAL ATRESIA
Gastrointestinal Atresia. Most of these anomalies are caused by obstruction with subsequent proximal
bowel dilatation. In general, the more proximal the obstruction, the more likely it will be associated with
hydramnios. Esophageal atresia is one of the most common gastrointestinal anomalies, and is encountered in about
1 in 3000 births (Robertson and colleagues, 1994). Most cases are associated with a tracheoesophageal fistula and
they cannot be diagnosed reliably in utero, although they may be suspected when hydramnios is found in the
absence of a fluid-filled stomach. About half of fetuses have associated anomalies and cardiac malformations are
most common. Pretorius and colleagues (1987), in a retrospective review, reported that only 7 of 22 infants born
with a tracheoesophageal fistula had both hydramnios and a nonvisualizing stomach. In an additional seven
pregnancies, hydramnios and a fetal stomach were both present sonographically. None of these women developed
hydramnios before 24 weeks, and other abnormalities were present in 12 of the 22 infants.
Duodenal atresia occurs in about 1 in 10,000 live births (Robertson and colleagues, 1994). The lesion is
diagnosed prenatally by the demonstration of the double-bubble sign, which represents the distention of the stomach
and the first part of the duodenum (Fig. 44–10 ). Demonstrating continuity between these two structures will
differentiate duodenal atresia from other cystic structures in the upper abdomen. The diagnosis of duodenal atresia
generally is not possible before 24 weeks, although it has been made as early as 19 weeks (Romero and associates,
1988). More than half of fetuses have associated anomalies and trisomy 21 is encountered in approximately 30
percent of infants. Obstructions in the lower small bowel usually result in multiple dilated loops, and these may
show increased peristaltic activity. Large bowel obstructions and anal atresia are less readily diagnosed in utero
because hydramnios is not a typical feature and the bowel may not be significantly dilated.

EVALUATION OF ABNORMAL A-FETOPROTEIN TESTING

For more than a decade, a-fetoprotein (AFP) testing has been offered to obstetric patients in the United
States. Many practitioners are now using the triple screen, which includes AFP, hCG, and serum estriol. These
biochemical markers are used as a screening test for fetal anatomic abnormalities and Down syndrome. Fetal
abnormalities associated with elevated AFP levels include fetal death, spina bifida, anencephaly, abdominal wall
defects such as omphalocele and gastroschisis, and renal abnormalities. Low AFP levels have been associated with
Down syndrome and other chromosomal abnormalities. Because AFP levels and the other biochemical markers vary
with gestational age, the interpretation of these tests demands accurate clinical dating. The first step in evaluation of
a patient with abnormal serum AFP levels is ultrasound.
Because maternal serum AFP levels normally increase with advancing gestational age, an apparent elevation
might result from an error in dates. Twins also cause an elevation of AFP levels. In a basic ultrasound examination
to evaluate elevated maternal serum AFP levels, as many as one third of patients are shown to have incorrect dates,
multiple gestation, or fetal death. If the dates are correct and the elevated maternal serum AFP level is confirmed,
referral for a high-detail ultrasound examination is appropriate. This should be performed by a sonologist with
experience in diagnosing fetal anomalies by ultrasound. Detection of these anomalies is discussed later in the
sections on clinical applications.
In patients who have elevated AFP levels and normal high-detail ultrasound examinations, determination
must be made about whether amniocentesis is appropriate. The information from the ultrasound can then be used
when counseling the patient. In the past, amniocentesis was recommended for determination of amniotic fluid AFP
and karyotype. High-detail ultrasound now can detect up to 95% of neural tube defects, so the risk of missing spina
bifida is low. It is appropriate to inform the patient regarding the risk of an invasive procedure such as amniocentesis
as well as about the very low risk of a normal high-detail ultrasound missing spina bifida.20
In patients who have low AFP levels or abnormal triple-screen results, ultrasound can play an important role
in interpretation and diagnosis.21 An inaccurate gestational age may explain up to half of cases of apparently low
maternal serum AFP values. Usually, if the ultrasound gestational age is within 2 weeks of that determined by the
last menstrual period, the gestational age used for interpretation should not be changed. Ultrasound is less accurate
for determination of chromosomal abnormalities, such as Down syndrome, than it is for determination of neural tube
defects. Benacerraf and colleagues22 reported the finding of occipital nuchal skin thickening in about half of fetuses
with trisomy 21; these data subsequently were confirmed by other investigators.23 Other abnormalities seen with
increased incidence in fetuses with Down syndrome include short femurs, short humeri, dilation of the fetal renal
pelvis, hydrocephalus, and fetal cardiac abnormalities. Combining multiple minor dysmorphic features into an
aneuploidy scoring system may prove useful both in the detection of abnormal fetuses and in the reduction of risk.

38
GENITOURINARY TRACT
Using transabdominal sonography, the fetal kidneys are visualized as paraspinous masses frequently as
early as 14 weeks, and routinely by 18 weeks (Patten and co-workers, 1990). Normal kidneys appear elliptical in
parasagittal planes (Fig. 44–11 ) and circular in transverse planes (Fig. 44–12 ). Initially, fetal kidneys are uniformly
hypoechoic; however, as pregnancy advances, more detail is visualized. The renal cortex, which is echogenic,
surrounds the hypoechoic medullary pyramids and is outlined by perinephric fat and the renal capsule. The renal
pelvis is centrally located and anechoic.
Nomograms have been developed that describe fetal kidney dimensions throughout pregnancy (Grannum and
colleagues, 1980; Sagi and associates, 1987). Although kidney length increases linearly throughout pregnancy, the
ratio of kidney circumference, measured in a transverse plane, to the corresponding abdominal circumference
remains constant between 0.28 and 0.30. In addition, the anterior-posterior (AP) dimension of the renal pelvis
should be less than half the A-P dimension of the entire kidney A-P dimension.
Urine production normally begins late in the first trimester, and consequently the fetal bladder can be
observed as an anechoic area in the pelvis early in the second trimester. Fetal urine production increases from 5
mL/hr at 20 weeks to about 50 mL/hr at 40 weeks (Rabinowitz and co-workers, 1989). In the normal fetus, the
bladder fills and empties every 20 to 45 minutes.
Assessment of amnionic fluid volume provides important information regarding fetal renal function. Often,
significant fetal urinary tract abnormalities result in oligohydramnios (Chap. 29 ). Conversely, normal amnionic
fluid volume suggests urinary tract patency with at least one functioning kidney, especially in the second half of
pregnancy when fetal urine is an increasingly important component of the amnionic fluid. Sivit and colleagues
(1986) reported 16 women identified to have severe oligohydramnios between 16 and 30 weeks. When studied after
pregnancy termination or delivery, 10 of these infants had urinary tract anomalies. Before 16 to 20 weeks, there may
be normal amnionic fluid volume despite absent renal function, although otherwise unexplained oligohydramnios
still suggests a urinary abnormality.
There have been at least three large prospective antenatal sonographic screening programs from which the
frequency and type of fetal urinary tract abnormalities can be ascertained. Helin and Persson (1986) performed
24,000 ultrasound examinations in nearly 12,000 women at 17 and again at 33 weeks. They identified urinary tract
anomalies in 33 fetuses (0.27 percent), and were able to confirm an abnormality in 23 neonates. Only 3 of 33
anomalies were detected at 17 weeks, and the remainder were identified at 33 weeks. By contrast, Livera and co-
workers (1989) performed sonograms on nearly 6300 women at 28 weeks and diagnosed fetal renal abnormalities in
92 (1.5 percent). Postnatal studies confirmed abnormalities in 42 neonates, and 13 had bilateral disease. There were
4 perinatal deaths, and all of these had bilateral disease. Seven infants (0.11 percent) thought to be normal as
assessed by fetal sonography were diagnosed to have renal abnormalities after they developed urinary infections
during the first year of life. Some of the neonatal abnormalities reported in these two studies are listed in Table 44–
7.
Gunn and co-workers (1995) prospectively screened nearly 17,000 consecutive women at 16 to 18 weeks
over a 5-year period. Of these, 3856 fetuses were again examined after 28 weeks for obstetrical indications. Renal
tract anomalies were identified in 313 (8 percent) and in 55 (1.4 percent), these were significant. Upper urinary tract
dilation was most commonly encountered (298 cases), but it was transient in two thirds of cases. Follow-up of
infants with transient obstruction showed that only 1 developed urinary infections. Other abnormalities included
obstruction in 23 infants and 15 of these required surgical correction. Finally, 8 infants had unilateral multicystic
renal dysplasia and 3 others had posterior urethral valves.
Callan and colleagues (1990) reported findings from 55 fetuses identified to have genitourinary abnormalities
in women referred to Johns Hopkins Hospital for ultrasound evaluation. More than half (57 percent) of these fetuses
had bilateral involvement. They undertook no interventional therapy in utero, and there were 35 survivors (66
percent), of whom 22 underwent surgical therapy postnatally. Factors that portended a poorer prognosis were
bilateral disease, oligohydramnios, and associated anomalies.

The frequency of urinary abnormalities is approximately 7:1000 newborns, and the recurrence risk is 8% to
10%.
The etiology of urinary tract abnormalities should extend beyond the apparent site of the lesion. For
example, dilation of the ureteropelvic junction (UPJ) may result either from obstruction at the upper ureter or from
pathology at a more caudad level. This includes increased intraluminal pressure secondary to reflux at the level of
the vesicoureteral junction resulting in dilation of the UPJ. Similarly, a posterior urethral valve (PUV) will dilate the
UPJ and even produce hydronephrosis. Thus, in discussing urinary tract abnormalities, it is reasonable to start with
the urethra and proceed cephalad.

OBSTRUCTIVE UROPATHY
Fetal urinary tract obstruction may develop at the ureteropelvic junction, the ureterovesical junction, or at the
urethra. The severity and location of the obstruction can be determined by assessing amnionic fluid volume as well
39
as the distribution of any resulting urinary tract dilatation. As a general rule, fetal ureters are not visualized, and thus
their identification indicates hydroureter. By contrast, after 20 weeks the fetal renal pelves may normally have an
anteroposterior diameter of up to 10 mm. The normal ratio of the anteroposterior renal pelvis diameter and kidney
diameter measured in a transverse plane is less than 50 percent (Arger and co-workers, 1985).
Brown and colleagues (1987) described 142 neo-nates evaluated for hydronephrosis over 6 years and
reported that 110 were first identified by antenatal sonography. Of the fetuses diagnosed with hydronephrosis,
almost 50 percent had ureteropelvic junction obstruction, 25 percent distal ureteral obstruction, 15 percent
duplication of the collecting system, and 5 percent had a posterior urethral valve. Ghidini and cohorts (1990)
reported results from 70 fetuses with ureteropelvic junction obstruction. Those with renal pelvis dilatation less than
1 cm uniformly did well, whereas those with dilatation more than 2 cm required postnatal pyeloplasty in three
fourths of the cases. Those with dilatation of 1 to 2 cm—about half of the total—did well if the findings were
bilateral; conversely, about 10 percent with unilateral dilatation of this magnitude eventually required pyeloplasty.
Obstructive uropathy may be caused by posterior urethral valves, urethral atresia, or persistent cloaca
syndrome. Ultrasound findings include a large bladder and enlarged ureters, which are seen as cystic convoluted
structures in the lower abdomen (Fig. 16). Ureteropelvic junction obstruction is suspected when an enlarged fetal
renal pelvis, without an enlarged bladder, is seen.

POSTERIOR URETHRAL VALVE

Most PUVs are partial, such that the resulting bladder dilation is not severe. The ureters may only be
slightly dilated, and if present, hydronephrosis is moderate (Fig. 13). In the severe form, however, the
pathophysiology is severe and may resemble the findings in agenesis of the urethra. In complete PUV, the bladder is
markedly dilated. The ureters also are convoluted and large. Hydronephrosis is severe. Oligohydramnios prevents
appropriate pulmonary development and leads to pulmonary hypoplasia.
Early treatment of this condition (less than 20 weeks' gestation) is important to prevent permanent renal
damage. The indications for therapy include the following:

1.Early diagnosis (18 to 20 weeks' gestation)

2.A fetal urine sample showing sodium concentrations less than 100 mg/dL, chloride < 90 mg/dL, and
osmolality, 210 mOsm/dL—all indirectly pointing to the ability of the kidneys to provide the function of salt
conservation
3.Decreasing amniotic fluid volume but not frank oligohydramnios

A number of treatment options are available:

1.Open fetal surgery to marsupialize the bladder

2.A two-ended curved catheter to drain urine into the amniotic cavity (catheter insertion has been difficult,
however, and is frequently followed by catheter displacement and blockage)
3.Frequent bladder drainage procedures.43

To prevent pulmonary hypoplasia, treatment should be initiated by the 20th pregnancy week, Although
early treatment may prevent development of pulmonary hypoplasia, however, 30% to 50% of these children may
subsequently develop dysplastic kidneys and require renal transplantation.44

RENAL DISORDERS.
The fetal kidneys can be seen on a transverse scan plane just below the level of the stomach, in the dorsal
paraspinal areas (Fig. 15). The fetal bladder is seen as a round, fluid-filled structure in the anterior midline of the
fetal pelvis. The amniotic fluid volume provides a clue to fetal renal function. In the fetus with absent kidneys, renal
obstruction, or nonfunctioning kidneys (renal dysplasia) after 20 weeks' gestation, the amniotic fluid volume is
markedly decreased. Before 20 weeks' gestation, however, the amniotic fluid volume may be normal despite renal
malformations.

HYDRONEPHROSIS

Dilation of the renal calyceal system results from abnormalities at a lower level of the urinary tract. It is
differentiated from multicystic dysplastic disease by (1) ultrasonic visualization of radially placed calyces
communicating with the renal pelvis and (2) preservation of some renocortical tissue (Fig. 16).

40
 In utero diagnosis of pyelectasis, UPJ dilation, and hydronephrosis is significant because it identifies
fetuses who will require postnatal urologic evaluation. As a result, early surgical intervention or medical treatment
with antibiotics will prevent irreversible renal compromise.

RENAL AGENESIS
Bilateral renal agenesis has an incidence of about 1 in 4000 births. No kidneys will be visualized
sonographically at any point during gestation. Because there is no urine production, severe oligohydramnios
ultimately develops. In this situation, the fetal adrenal glands appear to enlarge, and care must be taken to avoid
mistaking them for kidneys. Death invariably follows, either in utero or shortly after birth, and the infant exhibits
pulmonary hypoplasia, limb deformities, loose skin, and typical facies of the Potter syndrome. Associated
anomalies, especially cardiac, are common (Chap. 29 ).

The frequency of this condition is 1:4000 births, and the risk of recurrence is 3%.51 The etiology is
variable and may include chromosomal or genetic disorders (recessive or dominant mode of inheritance). It may
also be part of the VATER association: vertebral defects, anal atresia, tracheoesophageal fistula, and radial and renal
dysplasia. The outcome of fetuses with renal agenesis is poor because of oligohydramnios and associated pulmonary
hypoplasia.
Intravenous administration of furosemide (40 mg IV) has not been helpful in differentiating renal agenesis
from severe intrauterine growth restriction. Further, because of associated oligohydramnios as well as an enlarged
adrenal gland that mimics renal appearance, the diagnosis by gray scale ultrasound is difficult (sensitivity, 50%).51
In suspected cases, however, the use of color Doppler velocimetry may show absence of renal arteries in bilateral
renal agenesis and only one renal artery in the unilateral form of this abnormality (Fig. 17).52

CYSTIC RENAL DISEASE

Cystic renal disease is a complex subject because cystic changes of the kidneys may be present secondary to
multiple etiologies including hereditary diseases (autosomal recessive infantile polycystic kidneys, autosomal
dominant adult polycystic kidneys), dysmorphology (multicystic dysplastic kidney, multilocular cystic nephroma),
or chronic obstructive uropathy (Potter type II). Antenatal differentiation of the underlying etiology of cystic
changes is problematic.
Of the hereditary polycystic diseases, autosomal recessive infantile polycystic kidneys may be seen
antenatally, while the autosomal dominant condition usually becomes manifest in adulthood and would not be
expected to be seen antenatally. Autosomal recessive infantile polycystic kidney disease may present with large,
solid-appearing kidneys, a large abdominal circumference, and severe oligohydramnios. The “polycystic” changes
of these kidneys can only be identified microscopically.
Cystic kidneys secondary to dysmorphology such as multicystic dysplastic kidney have been diagnosed
antenatally. The typical sonographic appearance is multiple peripheral cysts, with a relatively normal-sized renal
pelvis. Differentiating this entity from cystic changes secondary to obstructive uropathy is a challenge.
Most important in discussing renal cystic changes is the determination of whether findings are unilateral or
bilateral and assessment of amnionic fluid. Prognosis is good if findings are unilateral and amnionic fluid volume is
normal, while a bad prognosis secondary to pulmonary hypoplasia may be anticipated if there is severe
oligohydramnios and bilateral involvement.

INFANTILE POLYCYSTIC KIDNEY DISEASE

This is an autosomal recessive disorder. The kidneys are enlarged (ratio of kidney:abdominal
circumference greater than the norm of 30%) and show small multicystic echoes.53 Unfortunately, the diagnosis
cannot always be made before 24 weeks' gestation54 because several subtypes of infantile polycystic kidney disease
exist, and these vary in onset and severity.

MULTICYSTIC-DYSPLASTIC KIDNEY DISEASE

The etiology of this condition may be secondary to a chromosomal abnormality or a mutant gene. It is rare,
occurring at a rate of 1:10,000 births, and has a male-to-female ratio of 2:1. The condition is unilateral in 75% of
cases.
The etiology is related to either (1) poor induction of nephron formation or (2) obstructive uropathy.
Defects in nephron formation occur early in embryogenesis, thus impeding renal development. In such cases, the
kidneys are very small, each weighing as little as 1 g, and cysts are evident only via microscopic examination. This

41
defect is classified as Potter type II-B dysplastic kidney.55 If the defect develops by 9 to 13 postmenstrual weeks,
the fetal kidney assumes a large multicystic appearance (Potter type II-A; Fig. 18).
Megacystis-microcolon-intestinal hypoperistalsis (MMIH) syndrome is a fatal autosomal recessive disorder
believed to result from an end-organ receptor defect confined to the smooth muscle of the urinary and
gastrointestinal tracts.56, 57, 58, 59 It is characterized by a large, thick-walled bladder plus dilation and distention of
the small bowel, including the duodenum.57, 58 The kidneys may also appear hydronephrotic or even multicystic.
Amniotic fluid volume may be either normal or excessive. The condition is differentiated from PUV by the absence
of oligohydramnios and dilation of the proximal urethra. This entity has been described only recently, so it is not
clear whether diagnosis by ultrasound is always possible before 24 weeks' gestation.

PRUNE-BELLY SYNDROME

In prune-belly syndrome, the bladder is dilated, the abdominal wall lax, and testicles undescended
(cryptorchidism). Although this condition may result from a PUV, it is also believed that it may represent a primary
mesoderm defect in the abdominal wall and urinary tract muscles.45 Fortunately in most cases of PUV the urethral
obstruction is incomplete, allowing for fetal urination and maintenance of near-normal amniotic fluid volume.

THE URETEROPELVIC JUNCTION

Dilation of the UPJ (Fig. 14) results from (1) abnormal recanalization of the upper part of the ureter,
resulting in varying degrees of obstruction; or (2) absence of the longitudinal muscle fibers in the upper ureter and
renal pelvis. In the latter dysfunction, there is abnormal forward propulsion of urine, resulting in a dilation of the
UPJ.46 Importantly, dilation of the UPJ may be associated with other anomalies involving the fetal cardiac,
gastrointestinal, and central nervous systems.
Further, male fetuses are more frequently affected than female (5:1). The UPJ dilation also occurs more
frequently on the left side and can be unilateral in 70% of cases.

PYELECTASIS

The etiology of a dilated renal pelvis or pyelectasis is similar to that of a dilated UPJ. Reflux occurring at
the level of the vesicoureteral valves also may result in pyelectasis (Fig. 15).
The definition of mild or minimal pyelectasis in the literature is confusing.47 Further, the outcome of
fetuses with minimal pyelectasis is not all "benign" as suggested in some studies.48 In fact, many such fetuses may
require subsequent medical or surgical intervention. Thus, an anteroposterior diameter equal to or greater than 4 mm
or 7 mm before and after 33 weeks' gestation, respectively, warrants postnatal follow-up.48
Moreover., approximately 3.3% of fetuses with pyelectasis in the range of 3 to 5 mm may also have
chromosomal abnormalities, including Down syndrome.49, 50 Interestingly, 25% of fetuses with Down syndrome
have pyelectasis, whereas only 2.8% of fetuses with a normal karyotype show this condition.49

EXTERNALLY VISIBLE BODY DEFECTS AND SKELETAL

ABNORMALITIES

CLEFT LIP AND PALATE

It is now possible to image the fetal nose area and upper lip to rule out cleft lip (Fig. 28). Cleft lip alone is
genetically different from the combination of a cleft lip and palate and is more likely to occur in female infants (sex
ratio, 2:1). Importantly, both conditions may be components of genetic, chromosomal, or other syndromes.

CYSTIC HYGROMA

Cystic hygroma is a rare (1:6000 pregnancies) disorder and usually occurs as a sporadic event, although in
some cases a recessive mode of inheritance is implicated. Importantly, 75% of cases have an associated
chromosomal abnormality, including 45,X trisomies (two thirds of cases).13, 18, 21
In this disorder, poor development of communication channels between the jugular veins and the cervical
lymph sacs (jugular lymphatic obstruction sequence) results in the formation of cystic hygromas (Fig. 29). These
can vary in size depending on the degree of obstruction. In some cases, cystic hygromas have been noted to regress
42
in utero, implying growth in the communication channels with advancing gestational age.83 In mild cases, the
differential diagnosis includes thickening of the nuchal occipital fold secondary to aneuploidy.84 In severe cases,
massive fetal hydrops develops and intrauterine fetal death occurs in the second trimester of pregnancy.

Cystic hygromas are congenital malformations of the lymphatic system that are usually seen in the nuchal
region. They are visualized in the posterior fetal neck and are sonolucent and may be septated. Although hygromas
are associated with fetal hydrops, they commonly co-exist with chromosomal anomalies. In first-trimester fetuses,
aneuploidies predominate (Johnson and colleagues, 1993; Shulman and associates, 1992). In second—and third-
trimester fetuses, monosomy XO becomes the most commonly associated chromosomal aberration. Even with
spontaneous resolution of hygromas, aneuploidy may be present. However, in fetuses with normal karyotypes in
whom there is spontaneous resolution of the hygroma, Shulman and co-workers (1994) usually found a good
prognosis.
There is evidence that fetuses with septated lesions have a worse prognosis than those without septations.
Brumfield and colleagues (1996) described 61 fetuses with cystic hygroma and classified them according to whether
septae were seen ultrasonically. Those with septated lesions were more likely to have an abnormal karyotype or to
develop hydrops, and their survival was significantly diminished. In either case, however, outcomes were dismal.
FETAL HYDROPS

This term is used to describe accumulation of fluid in some or all serous cavities in conjunction with
massive fetal edema. The etiology is immune in 13% of cases and nonimmune in the remaining 87%. In the latter
group, the etiology is idiopathic in 22%, extrinsic in 1% (i.e., due to infections, such as TORCH or parvovirus B
19), and intrinsic in 64%. The most common intrinsic causes are cystic hygroma and cardiac defects. Other intrinsic
etiologies include: chromosomal abnormality, arteriovenous shunts, twin-to-twin transfusion syndrome,
fetomaternal hemorrhage, pulmonary masses. and inherited diseases, such as -thalassemia, Tay-Sachs disease, and
hemoglobinopathy.85

SACROCOCCYGEAL TERATOMA

Sacrococcygeal tumor appears as a predominantly echogenic mass attached to the sacrococcygeal area. It is
quite rare (1:40,000 births) but has the potential to become malignant. The size is variable, but the majority of
tumors are small (Fig. 30). In approximately 10% of cases, the mass is equal to or greater than 10 cm at term,
requiring delivery by cesarean section.86

SKELETAL DYSPLASIA

Skeletal dysplasia involves a heterogeneous group of abnormalities characterized by variability in the mode
of inheritance, recurrence risk, gene penetrance, and type of limb shortening.87 It is beyond the scope of this chapter
to describe each possible abnormality in detail.
In most skeletal dysplasias, the first noticeable feature is short limbs (Fig. 31). Once this is established, a
detailed survey of fetal anatomy is carried out to identify the specific dysplasia. Attention to the following areas is
helpful: (1) facial abnormality, (2) cephalic size, (3) shortened radius, (4) segment of bone shortened, (5) small or
barrel-shaped chest, (6) cardiac defects, (7) head size, (8) protuberance of abdomen; (9) fetal edema; and (10)
demineralization of bone. The abnormal ultrasound findings in various skeletal dysplasias are listed in Table 16.

8. ASSESSMENT OF CHANGES IN AMNIOTIC FLUID VOLUME

Amniotic fluid is a physiologic extension of the fetus. Abnormalities of amniotic fluid volume are
nonspecific findings that warrant further investigation. Polyhydramnios is defined as an amniotic fluid volume in
excess of 2000 mL. The clinical diagnosis is made by the findings of a large-for-date uterine size, increased fluid,
and a normal-sized fetus. The excess fluid is seen as large anechoic areas on ultrasound. A single pocket of fluid that
is 8 cm or larger suggests polyhydramnios; this occurs in about 1% of pregnancies.52 An excess of fluid may be
found in maternal diabetes, erythroblastosis, or fetal malformation.53 In severe erythroblastosis, fetal hydrops may
be seen at the time of ultrasound study.
In one third of pregnancies complicated by polyhydramnios, no cause is determined.54 Fetal malformations
can complicate up to 40% of cases when twins, diabetes, and blood group incompatibility are excluded.
Oligohydramnios can be associated with fetal renal abnormalities, intrauterine growth retardation, postdate
fetuses, or membrane rupture. The clinical diagnosis is made when the fundal height is small and ultrasound
examination shows little or no amniotic fluid. When amniotic fluid is decreased, the fetal small parts are crowded,
and the fetus is in contact with the uterine wall in most scanning planes.
43
 The amniotic fluid index, a sum of the largest vertical pocket of amniotic fluid in each of four quadrants of
the uterus, is a useful semiquantitative measurement of fluid volume.55
Severe oligohydramnios is present when the largest vertical pocket of amniotic fluid measures less than 1 cm.
Major fetal anomalies were observed in 13% of patients with severe oligohydramnios. In the structurally normal
fetus with intact membranes, severe oligohydramnios may be an indication for delivery.56
Estimation of amnionic fluid volume using ultrasound has emerged as an important method of fetal
assessment (Chap. 29 ). Many different definitions of diminished amnionic fluid volume (oligohydramnios) and
excessive fluid (hydramnios) have been proposed, depending on the method used to quantify the volume of fluid.
Originally, Manning and co-workers (1980) proposed that a “pocket” of fluid measuring 1 cm less in the vertical
dimension signified pathological oligohydramnios. Crowley and co-workers (1984) used a 4-cm pocket dimension
to predict fetal distress in postterm pregnancies. Phelan and co-workers (1987) introduced the now-popular
technique termed the amnionic fluid index. This technique is described in detail in Chapter 29 , and normal values
are shown in Table 29–3 and Figure 29–2.

9. ASSESSMENT OF FETAL WELL-BEING

The biophysical profile is a test used in conjunction with antepartum fetal heart rate testing to evaluate fetal
well-being in high-risk pregnancies.57 The test quantifies fetal breathing and body movements, fetal tone, and
amniotic fluid volume. It also incorporates the nonstress test as a measure of fetal reactivity. Each of these five
parameters are assigned a score of 2 if normal and 0 if abnormal (Table 3). The fetus is observed until all parameters
are seen or until 30 minutes has elapsed.
This observation period helps to distinguish the normal fetus with a physiologic periodic sleep cycle from the
chronically asphyxiated fetus with central nervous system depression. Fetal breathing movements occur about 30%
of the time and, when seen, demonstrate that a complex fetal central nervous system function is intact.58 Fetal
breathing movements are seen in the normal fetus after 24 weeks' gestation.59
A normal biophysical profile (score of 8 to 10) is associated with a corrected perinatal mortality rate of 1 to 2
per 1000.60 A test score of 6 indicates the need to repeat testing within 24 hours. Scores of 4 or less are highly
predictive of intrauterine fetal jeopardy and, in a term fetus, are an indication for delivery. Low scores are associated
with fetal distress in labor as well as low Apgar scores. Vintzileos and colleagues61 observed a good correlation
between a low biophysical profile and fetal acidosis.
In the extremely preterm fetus, a low score may not necessarily indicate the need for immediate delivery. The
clinician must weigh the risk of fetal distress or demise with the risks of prematurity. In this clinical situation,
stabilizing any adverse maternal condition (such as elevated blood glucose in a diabetic patient or high blood
pressure in a hypertensive patient) and repeating the biophysical test a short time later may be indicated.

10. ASSESSMENT OF THE RISK OF PRETERM LABOR

There has been considerable interest in ultrasonographic evaluation of the cervix as a marker for assessing
the risk of preterm birth (Fig. 17). Iams and colleagues62 published a large multicenter study confirming that
patients with a short cervix, as determined by endovaginal ultrasonography, are at increased risk of preterm birth. It
is clear that the length of the cervix decreases with advancing gestational age and that there is no cervical length at
which the risk of preterm birth is zero. A cervical length of less than 30 mm, however, does appear to indicate an
increased risk of preterm birth. Cervical length may provide a more objective and clinically effective means of
assessing the cervix in patients with cervical cerclage.

11. GUIDING INVASIVE PROCEDURES

Ultrasound can be used to localize a favorable pocket of amniotic fluid before performing amniocentesis.63
The needle can be inserted under direct visualization using the real-time scanner.64 A needle guide is available to
aid the obstetrician with needle placement, but this can limit the operator's ability to move the needle in three
dimensions. It is preferable to insert the needle in a co-planar fashion (i.e., in the same longitudinal plane as the
ultrasound transducer), so that the entire length of the needle track can be seen. Transplanar placement (i.e.,
perpendicular to the ultrasound plane) limits ultrasound view of the needle.
In chorionic villus sampling, the catheter is inserted into the placental bed under ultrasound guidance.65
Similarly, simultaneous real-time ultrasound guidance is used in percutaneous umbilical blood sampling or
cordocentesis.66

44
DOPLLER

FETAL CIRCULATION
ANATOMY OF FETAL CIRCULATION
In an adult, blood circulates from the left ventricle to the systemic circulation and is returned to the right
side of the heart. From there it circulates through the lungs for reoxygenation. This serial circulatory design is
inappropriate for a fetus because oxygenation occurs in the placenta, and a pair of parallel circulations is present.
This is made possible by anatomical shunts, which normally close rapidly at birth when circulation independent of
the mother is required.1
The fetal circulation is illustrated in Figure 1, which shows approximate values of the percent saturation of
blood with oxygen in various areas. Most of the physiological data presented here are from chronically catheterized,
unanesthetized sheep fetuses, because it is not possible to obtain such data from humans. Although species
differences may occur, it is likely that some general trends and mechanisms also apply to humans.
Well-oxygenated blood returns to the fetus from the placenta by way of the umbilical vein. The umbilical
vein enters the liver, where it joins with the portal venous system. Some of this blood is shunted directly to the
inferior vena cava through the ductus venosus, while some traverses the hepatic parenchyma. An average of 50%
takes the latter path, but the proportion is quite variable.
The saturation of blood in the inferior vena cava is lower than that in the ductus venosus, because it has
mixed with poorly oxygenated blood returning from the lower body. However, this mixture is not complete, and a
streaming of blood within the proximal inferior vena cava has been described. The inferior vena cava blood enters
the right atrium, and approximately 40% is diverted to the left atrium through the foramen ovale. Most of the blood
crossing the foramen ovale corresponds to the stream of well-oxygenated blood in the inferior vena cava coming
from the ductus venosus. In the left atrium, this blood mixes with a relatively small quantity of pulmonary venous
blood, enters the left ventricle, and then proceeds to the coronary circulation and vessels supplying the head, neck,
and upper extremities. Blood entering the right atrium from the superior vena cava joins with the remaining (60%)
blood in the inferior vena cava, which corresponds mainly to the less-oxygenated bloodstream from the distal
inferior vena cava (fetal lower body). This blood enters the right ventricle. From here a small proportion enters the
pulmonary circulation, but most is shunted from this bed through the ductus arteriosus, which joins the descending
aorta. This blood supplies the gut, kidneys, lower body, and also the umbilical circulation.2
Following the route just described, the blood perfusing the fetal lower body is ejected from both the right
and left ventricles, while blood perfusing the upper body is ejected from the left ventricle. The differential streaming
and the fact that inferior vena cava blood crosses the foramen ovale accounts for the about 5% to 10% higher
oxygen saturation observed in the ascending aorta (blood perfusing "vital" organs such as the brain and heart) than
in the descending aorta.

DISTRIBUTION OF BLOOD FLOW

The distribution of blood flow in a fetus is generally described as a percentage of the cardiac output. This is
a simple concept in an adult, who has two essentially equal serial circulations: systemic and pulmonary. In a fetus,
which has two unequal parallel circulations, distribution is described as the percentage of combined ventricular
output (CVO), the combined output of left and right ventricles.
The percentage of CVO in various areas of the heart and other vessels is shown in Figure 2.3 For obvious
reasons, little of this information is available in term infants, and the values are obtained from unanesthetized
chronically catheterized term sheep fetuses.
The human fetal cardiac output at term has been estimated to be about 500 ml/minute/kg, according to data
obtained from noninvasive measurements.4 A term sheep fetus is similar in weight to a human fetus (approximately
7 pounds [3.2 kg]), but species differences may occur (e.g., in the proportion of blood flow to the brain). Values of
central blood flow in milliliters per minute per kilogram fetal body weight are shown in Figure 3. Note that the CVO
is 450 ml/minute/kg, with twice as much from the right as the left ventricle. About 40% of the CVO is umbilical
blood flow (i.e., about 200 ml/minute/kg). The remaining 60% of CVO distribution to the fetal organs has been
determined in fetal sheep. With minor variations among studies, typical values of organ blood flow expressed as
percent of the CVO and as ml/minute x 100 g are shown in Table 1.5

45
FETAL BLOOD PRESSURES
The fetus is surrounded by the fluid-filled amniotic cavity, so pressures must be related to that of amniotic
fluid. In the absence of uterine contractions, this latter pressure is generally stable.
Fetal systemic arterial blood pressure is considerably lower than that in an adult, averaging 55 mm Hg
(systolic/diastolic, approximately 70/45 mm Hg) at term. Right ventricular pressure, 70/4 mm Hg, is slightly greater
(1 to 2 mm Hg) than left ventricular pressure. Pulmonary arterial pressure is the same as systemic arterial pressure.
There is a slightly greater pressure in the right atrium (3 mm Hg) than in the left atrium (2 mm Hg), thus ensuring
right-to-left blood flow across the foramen ovale. Pressure in the systemic venous bed is similar to that of the right
atrium, with the exception of the umbilical vein, where pressure is about 8 to 10 mm Hg.
Systemic blood pressures are somewhat lower earlier in gestation. This is reflected in the fact that
premature newborns have lower blood pressure than term infants. Thus, at 30 weeks gestation the mean arterial
blood pressure is only 35 mm Hg.

FETAL HEART RATE

Fetal heart rate analysis is the prime means by which a fetus is evaluated for adequacy of oxygenation, so
knowledge of its rate and regulation are of great importance to an obstetrician.
The average heart rate in a nonmedicated term fetus before labor is 140 beats/minute (bpm). Earlier in
pregnancy it is higher than this, although not substantially so. At 20 weeks gestation, the average fetal heart rate is
155 bpm, and at 30 weeks gestation, it is 144 bpm. Variations of 20 bpm above or below these values are
encountered in normal fetuses.
A fetal heart is similar to that of an adult in that it has its own intrinsic pacemaker activity that results in
rhythmic contractions. The sinoatrial (SA) node, which is found in one wall of the right atrium, has the fastest rate
of contraction, and it sets the rate in a normal heart (Fig. 4). The next fastest pacemaker rate is found in the atrium,
and finally, the ventricle has a slower rate of beating than either the SA node or atrium. In various cases of complete
or partial heart block in a fetus, variations in rate below normal can be encountered. A fetus with complete heart
block typically has a rate of about 60 bpm.
The mean fetal heart rate is a result of many physiological factors that modulate the intrinsic rate of the
heart.

CARDIAC OUTPUT REGULATION

In adults, the beat-to-beat amount of blood pumped by the heart is determined by the amount of blood
returning to the heart. In accordance with the Frank-Starling mechanism, when the cardiac muscle is stretched
before contraction by an increased inflow of blood, it contracts with a greater force than before and is able to pump
out more blood. In other words, the heart pumps all the blood that flows into it without excessive damming of blood
in the veins. This mechanism has been studied in unanesthetized fetal lambs and has been shown to be less
developed than in adult sheep. The imperfect mechanism in the fetal lamb is probably due to the fact that the heart
muscle is not as well developed as in the adult sheep. It is likely that the same is true of a human fetus, as it is
generally more immature than a fetal lamb when born. As a consequence, increases in the filling pressure or preload
produce minor if any changes in CVO, suggesting that the fetal heart normally operates near the top of its function
curve.
The output of the fetal heart is also related to the heart rate. Some researchers have shown that spontaneous
variations of heart rate relate directly to cardiac outputthat is, as rate increases, output increases. However, different
responses have been observed during right or left atrial pacing studies. No changes were observed in left ventricular
output when the right atrium was paced, whereas the output decreased during left atrial pacing.6 Clearly, additional
factors are operating to explain such differences. The relationship between fetal heart rate and cardiac output has not
been confirmed in human fetuses under physiologic conditions, because the spontaneous increase in heart rate has
been found to be associated with a decrease in stroke volume, maintaining the cardiac output unchanged.7
In addition to heart rate and preload, cardiac output depends on afterload and intrinsic contractility. The
fetal heart appears to be very sensitive to changes in the afterload, represented by the fetal blood pressure. In this
way, increases in after-load dramatically reduce the stroke volume or cardiac output. As has already been stated, the
fetal heart is incompletely developed compared to that of adults. Many ultrastructural differences between the fetal
and adult heart account for a lower intrinsic capacity of the fetal heart to contract. Each of these four determinants of
cardiac output do not work separately, but rather they interact dynamically to modulate the fetal cardiac output
during physiologic conditions. Cardiac output responses during hypoxic bradycardia are described later.

46
REGULATION OF FETAL CIRCULATION

PARASYMPATHETIC NERVOUS SYSTEM

The parasympathetic nervous system consists primarily of the vagus nerve (tenth cranial nerve), which
originates in the medulla oblongata. Fibers from this nerve supply the SA node and also the atrioventricular node
(AV) (see Fig. 4). Stimulation of the vagus nerve or injection of its mediator, acetylcholine, results in a decrease in
heart rate in a normal fetus due to vagal influence on the SA node, decreasing its rate of firing and decreasing the
rate of transmission of impulses from atrium to ventricle. In a similar fashion, blocking of this nerve in a normal
fetus with a substance that blocks the effects of acetylcholine (e.g., atropine) causes an increase in the fetal heart rate
of approximately 20 bpm at term. This demonstrates that there is normally a constant vagal tone on the fetal heart
rate, tending to decrease it from its normal intrinsic rate.
The vagus nerve is also responsible for transmission of impulses causing beat-to-beat variability of fetal
heart rate. Blocking the vagus nerve with atropine results in a disappearance of this variability. Hence, it has been
postulated that two vagal influences impinge on the heart: a tonic influence tending to decrease its rate and an
oscillatory influence that results in fetal heart rate variability.

SYMPATHETIC NERVOUS SYSTEM

Sympathetic nerves are widely distributed in the myocardium at term (see Fig. 4). Stimulation of the
sympathetic nerves will release norepinephrine and cause an increase in fetal heart rate and also an increase in the
vigor of cardiac contractions. These result in an increase in cardiac output. The sympathetic nerves are a reserve
mechanism to improve the pumping activity of the heart during intermittent stressful situations. There is normally a
tonic sympathetic influence on the heart.
When the b-adrenergic receptor blocker propranolol is administered to a normal fetus, the fetal heart rate
will decrease approximately 10 bpm. There is, however, only a small decrease in fetal heart rate variability after
blocking the sympathetic nerves.
a-Adrenergic receptors also are found in a fetus at term. When they are stimulated with methoxamine, there
is an increase in blood pressure and a decrease in the kidney and carcass blood flow. The opposite is observed after
a-adrenergic blockers as phentolamine or phenoxybenzamine.8
Several factors cause the parasympathetic and sympathetic nervous systems to increase their activity.

BARORECEPTORS

In the walls of the arch of the aorta and in the carotid sinus at the junction of the internal and external
carotid arteries are found small stretch receptors that are sensitive to increases in blood pressure (Fig. 5). When
blood pressure rises, impulses are sent from these receptors by way of the vagus and glossopharyngeal nerve to the
midbrain, resulting in further impulses through the vagus nerve to the heart, tending to slow it. This is an extremely
rapid response, being noted with almost the first increase of blood pressure. It is a protective, stabilizing function by
the body attempting to lower blood pressure by decreasing heart rate and cardiac output when blood pressure is
increasing.

CHEMORECEPTORS

Chemoreceptors are found in both the peripheral and central nervous systems. They have their most
dramatic effects on the regulation of respiration, but they are still important in the control of the circulation. The
peripheral chemoreceptors are found in the carotid and aortic bodies (see Fig. 5). Like the pressoreceptors, they are
found in the arch of the aorta and in the area of the carotid sinus. The central chemoreceptors, found in the medulla
oblongata, respond to changes in the oxygen and carbon dioxide tensions in blood or cerebrospinal fluid perfusing
this area.
In adults, when oxygen in the arterial blood perfusing the central chemoreceptors is decreased or the carbon
dioxide content is increased, there is ordinarily a reflex tachycardia. There is also a substantial arterial blood
pressure increase, which is extremely pronounced with increases in carbon dioxide concentration. Both of these
effectsthat is, tachycardia and an increase in blood pressureare thought to be protective in attempting to circulate
more blood through the affected areas in order to bring about a decrease in carbon dioxide tension or an increase in
oxygen. Effects in the fetus are not known.

47
 The peripheral chemoreceptors seem to be highly important in the cardiovascular responses to hypoxia. The
interaction of baroreceptor and chemoreceptor systems in a fetus is not well understood, although the net result of
hypoxia in a fetus is bradycardia and hypertension. During basal conditions, they seem to contribute to stabilize
heart rate and blood pressure.9

CENTRAL NERVOUS SYSTEM

It has been established that in adults there are influences on heart rate from the higher centers of the brain
(Fig. 6). Heart rate can be increased by various emotional stimuli such as fear or sexual arousal. Observations of
fetal lambs and monkeys have shown that the electroencephalogram or electro-oculogram shows increased activity
at times in association with variability of the heart rate and body movements. At other times, apparently when the
fetus is sleeping, activity slows and the fetal heart rate variability decreases, suggesting an association between these
two factors and central nervous system activity.
The hypothalamus is thought to be the area of dispatch of nerve impulses produced by physical expressions
of emotion, including acceleration of the heart rate and elevation of the blood pressure. It has been shown in fetal
lambs that stimulating an electrode in the hypothalamus causes the fetal heart rate to increase, at least initially,
followed by a decrease, probably because of the baroflex mentioned earlier. The increase in blood pressure and heart
rate appears to be mediated by the sympathetic nerves.
The medulla oblongata contains the vasomotor center, an integrative center where the net input results in
either cardioacceleration or cardiodeceleration.

HUMORAL REGULATION

ADRENAL MEDULLA. The fetal adrenal medulla produces epinephrine and norepinephrine in response to
stressful situations (e.g., hypoxia). Both of these substances act on the heart and cardiovascular system in a way
similar to sympathetic stimulation. That is, they produce a faster heart rate, greater force of contraction of the heart,
and an increased arterial blood pressure. However, it is not clear whether catecholamines exert a regulatory function
in a resting fetus, at least in sheep.10

RENIN-ANGIOTENSIN SYSTEM. Angiotensin II seems to play a role in fetal circulatory regulation at rest,
but its main activity is observed during hemorrhagic stress on a fetus.

VASOPRESSIN. Vasopressin has been shown to affect the distribution of blood flow in fetal sheep.
However, this is probably only operative during hypoxia and possibly other stressful situations.

PROSTAGLANDINS. Arachidonic acid metabolites are found in high concentrations in the fetal circulation
and in many tissues. Their main role seems to be in the regulation of umbilical blood flow as well as in maintaining
the patency of the ductus arteriosus during fetal life.
Other hormones such as a-melanocyte-stimulating hormone (a-MSH), atrial natriuretic hormone,
neuropeptide Y, thyrotropin-releasing hormone (TRH), and metabolites such as adenosine have also been described
to be present in the fetus and to participate in the circulatory function regulation, but their importance is still not
determined.

BLOOD VOLUME CONTROL

CAPILLARY FLUID SHIFT. In adults, when the blood pressure of the body is elevated by excessive blood
volume, some fluid moves out of the capillaries into interstitial spaces, thereby decreasing the blood volume back
toward normal. Conversely, if an adult loses blood through hemorrhage, some fluid shifts out of the interstitial
spaces into the circulation, thereby increasing the blood volume back toward normal. There is normally a delicate
balance between the pressure inside and outside the capillaries. This mechanism to regulate blood pressure is slower
than the almost instantaneous regulation found with the reflex mechanisms discussed earlier. Its role in a fetus is
imperfectly understood, but studies performed on sheep show that a fetus appears to be able to keep its blood
volume closer to normal than an adult after reductions or expansions of volume.11

INTRAPLACENTAL PRESSURES. Fluid moves down hydrostatic pressure gradients and also in response
to osmotic pressure gradients. The actual values of these factors within the placental site where fetal and maternal
blood closely approximate are controversial. It seems likely, however, that some delicate balancing mechanisms
within the placental site prevent rapid fluid shifts between mother and fetus. As noted earlier, maternal arterial blood
pressure is much higher (approximately 100 mm Hg) than that of a fetus (approximately 55 mm Hg); hence, some
48
compensatory mechanism must be present to equalize the effective pressures at the exchange points. Imbalances
may be responsible for the hydrops encountered in some cases of Rh isoimmunization and extreme fetal tachycardia.

OXYGEN TRANSFER TO THE FETUS

It is likely that most stillbirths and cases of fetal depression are the result of inadequate exchange of the
respiratory gases. Oxygen has the lowest storage-to-utilization ratio of all nutrients in a fetus. From animal
experimentation it can be calculated that in a term fetus the quantity of oxygen is approximately 50 ml and the
normal oxygen consumption is approximately 21 ml/minute. This means that in theory, a fetus has a 2- to 3-minute
supply of oxygen. Fetuses do not, however, consume the total quantity of oxygen in their bodies within 3 minutes,
nor do they expire after this time. In fact, irreversible brain damage does not occur until about 10 minutes have
elapsed. This is because a fetus has a number of important compensatory mechanisms that enable it to survive on a
lesser quantity of oxygen for longer periods. This is discussed in a later section. The clinical situations in which
there is total cessation of oxygen delivery are rare. These include sudden total abruption of the placenta or complete
umbilical cord compression, generally after prolapse of the cord.
It is of value to examine the factors that determine oxygen transfer from mother to fetus (Table 2).12
Because the transfer of oxygen to a fetus is dependent on rates of blood flow and not limitations of diffusion, the
blood flow on each side of the placenta assumes major importance for maintenance of fetal oxygenation. Studies of
animals suggest that in the normal placenta there is a safety factor of approximately 50% in the uterine blood flow.
That is, the uterine blood flow can drop to half its normal value before fetal acidosis becomes evident. This applies
only to the normal situation with normal placental reserve and is unlikely to be so in pathologic situations, such as
an infant of a hypertensive mother. In this situation, placental function may be adequate for oxygenation but not for
fetal growth, and a growth-retarded infant may result from such a pregnancy. Furthermore, with superimposition of
uterine contractions on such a fetus, there may be transient inadequacy of uterine blood flow (and hence fetal
oxygenation) during the uterine contractions; this may be recognized by responses of the fetal heart ratenamely, late
decelerations.
Additional important determinants of fetal oxygenation include oxygen tension in maternal arterial and
fetal arterial blood. In general, maternal arterial oxygen tension depends on adequate ventilation and pulmonary
integrity. Disruptions of this function are relatively rare in obstetrics, although they can occur with pulmonary
disease such as asthma, with congestive heart failure, or in mothers with congenital cardiac defects. The oxygen
affinity and oxygen capacity of maternal and fetal blood are also important determinants of fetal oxygen transfer.
At a given oxygen tension, the quantity of oxygen carried by blood depends on the oxygen capacity (which
is dependent on the hemoglobin concentration) and the oxygen affinity. The oxygen affinity of fetal blood is greater
than that of maternal blood. That is, the oxygen dissociation curve of a fetus is to the left of that of the mother. In
addition, the hemoglobin concentration of fetal blood is approximately 15 g/100 ml in a term fetus, whereas that of
the mother is approximately 12 g/100 ml. Both of these factorsan increased oxygen affinity and higher oxygen
capacityconfer advantages to a fetus for oxygen uptake across the placenta. Probable values of the oxygen content
and oxygen tension in umbilical vessels and maternal uterine artery and vein are illustrated in Figure 7.
Because most measurements have been made in a human fetus during or after labor and delivery, the values
of oxygen saturation and pH are generally depressed compared with those of an adult. In fact, investigations on
chronically instrumented animals and data obtained from human fetuses by cordocentesis13 have shown that the
oxygen saturation and content of fetal blood and acid-base status are very close to that of maternal blood. Only the
oxygen tension is lower. The arteriovenous oxygen differences across each side of the placenta are also illustrated in
Figure 7. Notice that the quantity of oxygen delivered or taken up by each 100 ml of circulating blood in the
placenta is approximately equal in the mother and fetus. This suggests approximate equality of blood flow on each
side of the placenta. A number of additional miscellaneous factors determine the rate of oxygen transfer across the
placenta; they are listed in Table 2 as the last six determinants. They appear to be relatively minor compared with
the major factors already outlined.

CARBON DIOXIDE AND ACID-BASE BALANCE

Carbon dioxide crosses the placenta even more readily than does oxygen. In general, the determinants for
oxygen transfer also apply to carbon dioxide. It is limited by rate of blood flow and not by resistance to diffusion.
The carbon dioxide tension in fetal blood in the undisturbed state is close to 40 mm Hg. It is well known that
maternal arterial carbon dioxide tension is approximately 34 mm Hg and that a pregnant woman is in a state of
compensated respiratory alkalosis. The pH of fetal blood under undisturbed conditions is probably close to 7.4, and
the bicarbonate concentration is close to that in maternal blood.
49
 Bicarbonate and the fixed acids cross the placenta much more slowly than does carbon dioxide, (i.e.,
equilibration takes a matter of hours rather than seconds). A situation analogous to respiratory acidosis occurs in the
fetus when blood flow, either uterine or umbilical, is acutely compromised. In such cases, the pH drops and carbon
dioxide tension is elevated, but the metabolic acid-base status remains unchanged. This occurs during severe
variable decelerations in association with uterine contractions, especially during the second stage of labor. These
acid-base changes are generally rapidly resolved with cessation of the contraction and the deceleration. However, if
significant oxygen lack is unrelieved, the fetus will decrease its oxygen consumption, redistribute blood flow, and
depend partly on anaerobic metabolism to supply its energy needs, albeit with decreased efficiency. Under these
conditions, lactate (an end product of anaerobic metabolism) is produced, resulting in metabolic acidosis. The
acidosis may also be aggravated by a combined respiratory acidosis because of retained carbon dioxide. Unlike
carbon dioxide, lactate is lost rather slowly from a fetus.

UTERINE BLOOD FLOW

Because uterine blood flow is one of the prime determinants of passage of the respiratory gases across the
placenta, its characteristics and the factors affecting it will be discussed.14 This subject is reviewed in more detail
elsewhere in this book.
Uterine blood flow in a term fetus is approximately 700 ml/minute. This represents about 10% of the
cardiac output. Approximately 70% to 90% of the uterine blood flow passes through the intervillous space, and the
remainder largely supplies the myometrium.
The uterine vascular bed is thought to be almost maximally dilated under normal conditions, with little
capacity to dilate further. It is not autoregulated, so flow is proportional to the mean perfusion pressure. However, it
is capable of marked vasoconstriction by a-adrenergic action. It is not responsive to changes in respiratory gas
tensions. The uterine blood flow is determined by the following relationship:

Uterine blood flow =

uterine arterial pressure - uterine venous pressure

uterine vascular resistance

Hence, any factor affecting either of the three values on the right-hand side of the above relationship will
alter uterine blood flow. A number of causes of decreased uterine blood flow are shown in Table 3.
Uterine contractions decrease uterine blood flow as a result of increased uterine venous pressure brought
about by increased intramural pressure of the uterus. There may also be a decrease in uterine arterial pressure with
contractions. Uterine hypertonus causes decreased uterine blood flow through the same mechanism.
In sheep, it has been shown that if uterine arterial perfusion pressure is altered without changing the
resistance of the uterine vascular bed, there is a direct relationship between uterine blood flow and the pressure.
Hence, hypotension due to any of the mechanisms noted in Table 3 will cause a decrease in blood flow.
In the case of maternal arterial hypertension, it is likely that there is a concomitant increased vascular
resistance that is shared by the uterine vascular bed. This, therefore, results in a decrease in uterine blood flow.
Either endogenous or exogenous vasoconstrictors result in decreased blood flow because of increased uterine
vascular resistance.
There are few useful means of increasing uterine blood flow in cases in which it is known to be less than
optimal. The most important clinical considerations are the avoidance or correction of factors responsible for an
acute decrease in blood flow, such as excessive uterine activity or maternal hypotension.
Clinically it has been known for many years that maternal bed rest may improve the outcome in suspected
fetal growth retardation. There is now some evidence that bed rest does improve fetal growth, as evidenced by
increasing estriol excretion.
Some of the b-mimetic agents that are used as uterine relaxants for premature labor may increase uterine
blood flow, but this effect is still under investigation. There are a number of experimental means of increasing
uterine blood flow, sometimes transiently, but these have no place clinically. Examples of such treatments include
estrogens, acetylcholine, nitroglycerin, cyanide, ischemia, and chronic hypoxia.

UMBILICAL BLOOD FLOW

Umbilical blood flow measured by ultrasonographic techniques is about 360 ml/minute, or 120
ml/minute/kg in an undisturbed fetus15 at term. This figure is considerably less than that of a sheep, where it is
50
approximately 200 ml/minute/ kg. The differences may be explained by the somewhat higher metabolic rate (body
temperature 39°C) and lower hemoglobin concentration (10 g/dl) in a fetal sheep. It is important to recognize this
species difference, because most of our information on fetal circulatory physiology comes from fetal sheep. The
umbilical blood flow is approximately 40% of the combined ventricular output, and about 20% of this blood flow is
shuntedthat is, it does not exchange with maternal blood in sheep. It is either carried through actual vascular shunts
within the fetal side of the placenta or else it does not approach maternal blood closely enough to exchange with it.
Umbilical blood flow is unaffected by acute moderate hypoxia but is decreased by severe hypoxia.
Innervation of the umbilical cord is still questionable, but umbilical blood flow decreases with the administration of
catecholamines. It is also decreased by acute cord occlusion. There are no known means of increasing umbilical
flow in cases in which it is thought to be decreased chronically. However, certain fetal heart rate patternsnamely,
variable decelerationshave been ascribed to transient umbilical cord compression in a fetus during labor.
Manipulation of maternal position either to the lateral or Trendelenburg's position can sometimes abolish these
patterns; the implication is that cord compression has been relieved.

HYPOXIA

FETAL RESPONSES

Studies of chronically prepared animals have shown that a number of responses occur during acute hypoxia
or asphyxia in a previously normoxic fetus. There is little or no change in combined cardiac output and umbilical
(placental) blood flow, but there is a redistribution of blood flow favoring certain vital organsnamely, heart, brain,
and adrenal glandsand a decrease in the blood flow to the gut, spleen, kidneys, and carcass.16 This initial response is
presumed to be advantageous to a fetus in the same way as the diving reflex is in an adult seal, in that the blood
containing the available oxygen and other nutrients is supplied preferentially to vital organs.
Fetal oxygen consumption decreases to values as low as 60% of control (from approximately 8 to 5
ml/minute/kg) during fetal hypoxia in a chronically instrumented fetus with arterial oxygen tension of 10 mm Hg.
This decrease is rapidly instituted, stable for periods up to 45 minutes, proportional to the degree of hypoxia, and
rapidly reversible on cessation of maternal hypoxia. It is accompanied by a fetal bradycardia of about 30 bpm below
control (approximately 170 bpm control to 140 bpm hypoxia in fetal sheep) and an increase in fetal arterial blood
pressure (approximately 54 mm Hg control to 61 mm Hg hypoxia mean pressure). There is also progressive fetal
acidosis during fetal hypoxia (fetal arterial pH 7.38 control to 7.33 after 25 minutes hypoxia). This is an exclusively
metabolic acidosis and is likely to be a lactic acidosis as a result of anaerobic metabolism, presumably in those
partially vasoconstricted beds where oxygenation is inadequate for normal basic needs. During fetal asphyxia, the
increase in carbon dioxide tension superimposes a respiratory component on the acidosis.
The series of responses just describedthat is, redistribution of blood flow favoring vital organs, decreased
total oxygen consumption, and anaerobic glycolysismay be thought of as temporary compensatory mechanisms that
enable a fetus to survive moderately long periods (e.g., up to 30 minutes) of limited oxygen supply without
decompensation of vital organs, particularly the brain and heart. The close matching of blood flow to oxygen
availability to achieve a constancy of oxygen consumption has been demonstrated in the fetal cerebral circulation. In
studies on hypoxic lamb fetuses, cerebral oxygen consumption was constant over a wide range of arterial oxygen
contents because the decrease in arteriovenous oxygen content accompanying hypoxia was compensated for by an
increase in cerebral blood flow.
However, during more severe asphyxia or sustained hypoxemia, these responses are no longer maintained,
and a decrease in the cardiac output, arterial blood pressure, and blood flow to the brain and heart have been
described (Fig. 8). These changes may be considered to be a stage of decompensation, after which tissue damage
and even fetal death may follow.17

METABOLIC EFFECTS

It is known that a fetus depends partially on anaerobic metabolism for its energy needs during oxygen
insufficiency.18 It has also been shown in experimental animals that a newborn's ability to tolerate asphyxia
depends on cardiac carbohydrate reserves. Whether this also applies to a human fetus is unknown, but clinical
observations support the view that carbohydrate-depleted fetuses succumb more readily than those with normal
reserves. A nutritionally growth-retarded fetus also is more susceptible to intrauterine asphyxia and depression than
a normal fetus.19

51
 It has been stated that the prime aim of compensatory responses in hypoxia is maintenance of the
circulation, and maintenance of the integrity of cardiac function is paramount in this regard. It is likely that
carbohydrate availability is critical in supplying substrates for glycolysis at more severe degrees of hypoxia.

MECHANISMS OF RESPONSES

The cardiovascular responses to hypoxia are instituted rapidly and are mediated by neural and hormonal
mechanisms (Fig. 9). As it has been previously mentioned, the tonic influence of the autonomic nervous system on
heart rate, blood pressure, and the umbilical circulation in a normoxic fetus is quantitatively minor. This is in
marked contrast to autonomic activity during hypoxia.
In studies using total pharmacologic blockade, it has been shown that parasympathetic activity is
augmented three to five times and b-adrenergic activity doubles when measured by heart rate response. The net
result of these changes is a decrease in fetal heart rate during hypoxia. Augmented b-adrenergic activity also may be
important in maintaining cardiac output and umbilical blood flow during hypoxia, probably by increased inotropic
effect on the heart.
a-Adrenergic activity is important in determining regional distribution of blood flow in hypoxic fetal sheep
by selective vasoconstriction. As noted earlier, during hypoxia there is preferential blood flow to the brain, heart,
and adrenals and decreased supply to the carcass, lungs, kidneys, and gut. a-Adrenergic blockade reversed the
hypertension and increased peripheral resistance observed during fetal hypoxia. These changes are due to a decrease
in the resistance in the gut, spleen, lungs, and probably carcass, indicating a participation of the a-adrenergic system
in their vasoconstriction.
Plasma concentrations of catecholamines, vasopressin, b-endorphin, and atrial natriuretic factor increase
during hypoxia in a fetus. The contributions of catecholamines to the circulatory responses to hypoxia were
described earlier. Vasopressin contributes to the increase in blood pressure observed during hypoxia by decreasing
umbilical and gut blood flows. b-Endorphin and probably other endogenous opioids also participate in the response
to hypoxia. The blockade of its receptors with naloxone further increases the hypertensive response by increasing
the vasoconstriction in the kidneys and carcass. During hypoxia, a decrease in the fetal blood volume has been
described. Atrial natriuretic factor may play a role in this response. Most of these results have been obtained from
the chronically catheterized fetal sheep model. The relative contribution of these and other mediators to the
cardiovascular response to hypoxia in a human fetus and their potential use as therapeutic tools are being explored.

UTERINE AND PLACENTAL BLOOD FLOW

It should be obvious to any student of maternal-fetal medicine that a multiplicity of factors contribute to
that intrauterine environment which permits normal growth and development of the fetus and also provides a safety
factor for survival under stressful conditions. Aberrations of this environment are often referred to by such terms as
uteroplacental insufficiency and placental dysfunction, which are no more than vague approximations of a less than
optimal fetal environment. If, however, one considers those elements that must have a significant impact on the fetal
environment, placental blood flow (PBF) is a critical factor. This is so not only because maternal blood carries
necessary foodstuffs to the fetus and removes waste products throughout pregnancy but also because the quantity of
oxygen delivered to the placenta is limited directly by the rate of PBF. Thus, since oxygen deprivation is such a
critical determinant of fetal well-being, knowledge of that most important factor controlling oxygen delivery, PBF,
is crucial irrespective of other compensatory responses.
In the half century since Barcroft and associates first quantitated uterine blood flow (UBF) in the pregnant
rabbit, a significant body of knowledge has developed.1 Although we know the most about UBF and PBF in lower
animals, primarily the ovine species, correlative data in subhuman primates and a paucity of observations in women
indicate that despite obvious species variations in placentation, general principles of uterine vascular control are
quite comparable.

DEVELOPMENT OF THE PLACENTAL CIRCULATION AND

HOMEOSTASIS
The uterine circulation is exquisitely sensitive to estrogen stimulation, responding with a degree of
vasodilatation unparalleled by any other organ of the body to any other stimulus.2 During the ovarian cycle,
repetitive patterns of UBF occur reflecting the effect of estrogen secretion and the modulating effects of
progesterone. These cyclic patterns are demonstrated most dramatically in animals with short preovulatory cycle
phases, such as the cow, sow, and ewe, and are illustrated in Figure 1 with peripheral levels of estrogen and
progesterone.3, 4, 5 Following conception in these species, UBF patterns are similar to those in nonpregnant animals
52
until interdigitation of maternal and fetal tissues occurs 17 to 28 days later; then, there is a definitive and progressive
increase in UBF that continues until term pregnancy. Since erosion of endometrium by fetal trophoblast occurs
much earlier after conception in the primate, it is reasonable to presume that UBF increases earlier in these species,
although such responses have never been observed. The overall patterns of total UBF, UBF per unit weight of uterus
and its contents, fraction of UBF supplying the placenta, and fetal weight throughout ovine pregnancy are illustrated
in Figure 2. The period between 17 and 70 days of gestation is associated with the most rapid changes in UBF and
PBF and corresponds with the time of definitive placentation in this species. By mechanisms incompletely
understood, blood vessels supplying the placenta progressively dilate during this time, simultaneously causing an
absolute increase in total UBF and shunting of this blood from nonplacental to placental tissues.* With subsequent
placental maturation, the fraction of UBF supplying the placenta and the absolute amount of PBF increase, but at
rates more similar to that of fetal growth; thus, during the last half of pregnancy, UBF per unit weight of uterus and
its contents is essentially constant. During this same time, the amount of oxygen extracted from each milliliter of
blood is constant and therefore the amount of oxygen delivered per given weight of gravid uterus is also constant.6
Correlative studies in women indicate similar homeostatic patterns from 10 to 40 weeks of gestation and similar
oxygen consumption (approximately 10 ml/kg).7 Since women deliver the same amount of oxygen at lower UBF
rates than the ewe (~150 versus ~270 ml/kg), it follows that the human placenta is more efficient in this regard.
Thus, for fetuses of similar weight, less absolute UBF is required and the pregnancy load on the heart is diminished.
Changes in PBF are accomplished by an ever-increasing vasodilatation of the blood vessels supplying the
placenta throughout the course of gestation. However, at any given moment during the second and third trimesters,
essentially no further acute vasodilatation of these vessels can occur. Therefore, to maintain constant oxygen
delivery during episodes of reduced PBF, increased oxygen extraction must occur (Fig. 3). Based on reported data, it
would appear that the limit of increased extraction is twofold. Thus, PBF has to be reduced more than 50% before
oxygen delivery is diminished. These considerations assume that the rate of homeostatic PBF was optimal prior to
the flow reduction. We know, however, that homeostatic levels may be suboptimal either sub-acutely, as in toxemia,
or chronically, as in nephropathies. In such cases, the safety factor, that is, the percent that PBF can be reduced
before oxygen delivery is compromised, is lowered. This must always be considered when one evaluates the effect
of an acute stimulus on the fetus.

*In man and subhuman primates, the spiral arterioles that will supply the intervillous space (approximately
one per placental cotyledon) lose their capillary connections and dilate about tenfold as the result of replacement of
the vessel walls by trophoblast. This process may extend to or below the myoendometrial junction, literally turning
the spiral arterioles into spiral arteries. Blood flowing through these modified blood vessels into the intervillous
space comprises PBF.
In the ovine species, multiple discrete areas of endometrium called caruncles are present in the nonpregnant
state. During pregnancy, interdigitation of fetal and maternal tissues occurs in these caruncles, which enlarge to
become individual placental cotyledons. Blood flowing to these areas collectively comprises PBF. Although the
cotyledonary arterial blood vessels dilate significantly, they contain no trophoblastic elements, maternal-fetal
transfer is by a capillary-capillary interface, and no intervillous space is present.

DYNAMIC RESPONSES OF THE UTERINE CIRCULATION

The blood vessels of the nonpregnant uterus respond similarly to those of any other muscular organ with
the exception of their unique reactivity to estrogenic stimulation, their response to local anesthetic agents, and,
possibly, their response to prostaglandins (Table 1). During pregnancy, the blood vessels supplying the placenta
progressively dilate, achieving a state in which minimal or no further acute dilatation can occur.24 Therefore,
stimuli which evoke vasodilatation in the nonpregnant uterus are ineffective after definitive placentation has
occurred. However, the placental vessels retain their ability to vasoconstrict as in the nonpregnant state. Since PBF
approximates 80% to 90% of total UBF at term pregnancy, total uterine vascular responses will appear as those of
the placental vessels. This point is often misinterpreted, and one must remember that the responses of the
nonplacental vessels are the same whether pregnancy is present or not.
The hemochorial structure of the human placenta adds a unique factor to those that normally control blood
flow in other vascular beds. That is, blood traverses the spiral arteries to enter the swamplike intervillous space,
perfuses the fetal villi, and then returns to the general circulation by many collecting veins in the basal plate.
Effectively, blood leaves normal vascular channels to circulate in a new extravascular space grafted onto the uterus
for the duration of pregnancy. Since the intervillous space lies within the uterine cavity and since the placenta is a
flexible structure, pressure generated by the contracting myometrium will be transmitted equally to the amniotic
cavity and the intervillous space. Thus, a factor extraneous to usual vascular control, myometrial activity, can
change intervillous space pressure and influence PBF by its effects on perfusion pressure. A schematic
representation of blood flow to the non-placental tissues and to a single cotyledon is shown in Figure 4, along with

53
the formulas pertinent to the control of each. It should be noted that these formulas are only applications of Ohm's
law to these individual cardiovascular situations.

I (Flow) = E (Perfusion Pressure)

R (Vascular Resistance)

The perfusion pressure delivering blood to nonplacental tissues is the difference between uterine arterial and
venous blood pressures. However, the perfusion pressure delivering blood to the intervillous space is the difference
between uterine arterial blood pressure and the intervillous space pressure. The latter is best approximated by
amniotic fluid pressure (IUP). In a muscular organ, resistance factors will include resistance from reactivity of
vascular smooth muscle, or intrinsic resistance (Ri), and the squeeze imparted to blood vessels as they traverse the
contracting myometrium, or extrinsic resistance (Re). It should be evident then that uterine contractions can affect
PBF by two mechanisms: by increasing Re and by reducing placental perfusion pressure.
In clinical practice, three major characteristics of placental vascular control are important. These include
the relationship between perfusion pressure and flow, the responses of the spiral arteries to vasoactive stimuli, and
the effects of myometrial contractions. In addition, the unique effects of local anesthetic agents must be appreciated.

PRESSURE-FLOW RELATIONSHIP

When one observes changes in UBF secondary to reductions in perfusion pressure during myome-trial
quiescence, a straight-line relationship with a slope of one can be developed (Fig. 5). This reflects the widely dilated
nature of the placental vasculature and indicates that PBF will decrease almost in identical proportion to the
decrease in perfusion pressure. Since uterine venous pressure is quite constant under most circumstances, changes in
systemic blood pressure (MBP) may be used to approximate PBF changes. That is, a 25% decrease in mean arterial
pressure would be expected to cause a 25% decrease in PBF. Such measurements should be made in the lateral
decubitus position, however, since pressure of the gravid uterus on the aorta alone has been shown to decrease blood
pressure in the pelvic area below that observed in the brachial artery.

RESPONSES TO VASOACTIVE STIMULI

Since the spiral arteries approach maximum dilatation in the resting state, vasodilator agents or stimuli have
little or no effect even though receptors for such agents are present. However, the smooth muscles of these vessels
are exquisitely sensitive to vasoconstrictor agents or stimuli, more so than most other peripheral vascular beds (Fig.
6). This means that although MPB may increase in response to stimulation by a peripherally acting vasopressor drug
such as phenylephrine, the proportionate increase in placental vascular resistance (Ri) is SO much greater that the
net effect is a marked decrease in PBF. Such differences in vasoconstrictor sensitivity must be considered whenever
a vasopressor drug is indicated. Use of a more centrally acting drug such as ephedrine, although causing a small
amount of placental vasoconstriction, will result in a proportionately greater improvement in MBP with an absolute
increase in PBF.

MYOMETRIAL CONTRACTIONS

Acting by the two mechanisms discussed above, increasing Re and decreasing perfusion pressure,
myometrial contractions decrease PBF in direct proportion to the intensity and duration of each contraction. The
relationship is so precise that a tracing of intrauterine pressure is almost an exact inverse image of PBF (Fig. 7).
Increasing the frequency of contractions decreases PBF during a given unit of time by decreasing the duration of
myometrial diastole, that time when PBF is at homeostatic levels. In addition, should intercontraction tonus be
elevated, as in a placental abruption, intercontraction PBF will be proportionately reduced. Radioangiographic
studies in subhuman primates and women show that during the acme of myometrial contractions of average
intensity, PBF ceases.25 It is evident then that labor is inherently stressful to the fetus, since the mean amount of
PBF perfusing the fetal villi per given period of time progressively decreases as the frequency and intensity of
uterine contractions increase.

LOCAL ANESTHETIC AGENTS

These drugs may exert effects on a vascular bed directly, as after inadvertent intravascular injection, and
indirectly, as a result of paralysis of autonomic nerves that maintain normal vascular tonus. In most organs,
intravascular injections have no significant effects on vascular resistance. However, the uterine and placental
54
vasculatures respond to such stimuli with significant vasoconstriction. In addition, the myometrium is variably
stimulated by such drugs (Fig. 8). Alone or together, these responses diminish PBF. Following paracervical block
anesthesia administered during labor, a delayed fetal bradycardia may occur. The best hypothesis to explain the fetal
response is that local anesthetic agents are injected close to the uterine arteries and that because of their excellent
penetrance, they cross the arterial walls to cause their uterine effects decreasing PBF and causing fetal hypoxia.

CLINICAL APPLICATIONS
We have seen that all physiologic, pathologic, and iatrogenic stimuli usually decrease PBF and that we
have no practical means of increasing PBF above homeostatic levels. Therefore, to optimize the fetal environment,
the clinical goal must be to prevent, minimize, or reverse these adverse effects. In addition, the effects of any
dynamic stimulus must always be interpreted on the background of the adequacy of the homeostatic levels of PBF
prior to the stimulus. A theoretical depiction of this background based primarily on oxygen delivery is shown in
Figure 9 and will serve to illustrate the interplay of homeostatic and dynamic factors.

LABOR

The effects of labor on PBF at three different levels of prelabor homeostasis are illustrated in Figure 10.
This shows mean PBF at four levels of uterine activity and assumes cessation of intervillous space flow for 30
seconds of a 45-second contraction and 45 seconds of a 60-second contraction. Whereas a fetus beginning labor at
optimal maternal PBF levels is never jeopardized with respect to oxygen delivery even during a tumultuous labor,
that fetus whose mother had suboptimal prelabor PBF could withstand average labor patterns but would have been
depressed at birth or possibly stillborn had tumultuous labor occurred. It should be obvious in the third case that
without any prelabor safety factor, even the mildest of uterine contractions would be sufficient to cause fetal
compromise. This latter category probably describes the circumstances when a positive contraction stress test is
evoked.

REGIONAL ANESTHESIA

Epidural or spinal anesthesia may cause maternal hypotension by paralysis of sympathetic nerves,
peripheral vasodilatation, peripheral pooling, and reduced cardiac return of blood. Since the placental vasculature is
normally widely dilated, sympathetic nerve paralysis would have no effect on these vessels. We have then a clinical
example of the pressure-flow experiment, and an x percent decrease in MBP would cause an x percent reduction in
PBF. This response is illustrated in Figure 11, along with two methods of treating the hypotension: vasopressor
drugs and volume replacement. While each restores normotension, their effects on PBF are radically different.
Predictably from the preceding discussion, the peripherally acting agent phenylephrine caused no sustained increase
in UBF since the degree of induced placental vasoconstriction far exceeded the rise in MBP. Treatment of the
underlying pathophysiology, a discrepancy between the capacity and the volume of the vascular system, with
volume replacement simultaneously restored MBP and UBF to normal. Sometimes, however, volume replacement is
ineffective and a vasopressor agent must be used. Figure 12 illustrates the more favorable PBF effects that can be
obtained by the use of centrally acting agents and the critical difference this choice may make depending on the
amount of pre-existing reserve PBF.

HEMORRHAGE

Following a bleed of 10% to 15% of circulating blood volume, MBP usually is maintained within normal
limits primarily by peripheral vasoconstriction. The placental vasculature will participate in this generalized
vasoconstriction with a reduction in PBF. With further blood loss, the limits of compensation are exceeded and
hypotension occurs, adding an additional factor to reduce PBF. If mean blood pressure is decreased 25%, then PBF
will be decreased 25% by the pressure-flow mechanism alone plus an additional decrease from the increased
intrinsic vascular resistance. These predictable responses are confirmed experimentally in Figure 13. As with
hypotension induced by a regional anesthetic block, therapy directed at the underlying problem, volume loss, will
improve MBP and PBF simultaneously, and vasopressor agents should be used only as a last resort.

INHIBITION OF LABOR

55
 The b-adrenergic drugs used to inhibit labor act by their relaxing effect on myometrial contractility. The
central and peripheral effects of these agents cause varying degrees of maternal tachycardia, peripheral
vasodilatation, and hypotension. Since the placental vessels are widely dilated normally, no further vasodilatation
can occur and we have another clinical example of the pressure-flow experiment, PBF varying in direct proportion
to changes in MBP. An example of the interplay of the myometrial and systemic effects of isoxsuprine on PBF in a
patient in active labor is shown in Figure 14. During isoxsuprine therapy, uterine contractions almost ceased and
systemic blood pressure progressively decreased, causing a similar baseline reduction in PBF (Fig. 14A). Prudently,
isoxsuprine was stopped when MBP was halved although the fetal heart rate was still normal. While MBP and PBF
were still at low levels, occurrence of a strong uterine contraction further decreased PBF, causing fetal bradycardia
(Fig. 14B). The wrong decision for proper management was made at this point due to a failure to recognize that
hypotension alone was not stressing the fetus. Rather it was the additional PBF decreases associated with uterine
contractions. Proper management would have been to allow normal uterine contractions to recur gradually,
anticipating that by that time, MBP and PBF would be back to homeostatic levels. As it occurred, oxytocic
stimulation initially caused a sustained contraction that although of low intensity was sufficient to keep PBF at
jeopardy levels despite the progressive increase in MBP. As a more normal myome-trial contractile pattern evolved,
the cessation of PBF during contractions continued to evoke deceleration patterns (Fig. 14C) until MBP and PBF
rose to normal intercontraction levels (Fig. 14D). Fortunately in this patient, homeostatic PBF was within the normal
range, so while transient fetal hypoxemic episodes occurred, the safety factor was adequate to permit normal fetal
survival.

HYPERTENSIVE STATES

There is considerable evidence that toxemia of pregnancy and chronic cardiovascular-renal diseases are
associated with suboptimal levels of homeostatic PBF.26 Presumably, mechanisms responsible for the normal
dilatation of spiral arteries supplying the placenta are compromised or inhibited during the definitive placentation
process and its subsequent maturation. This could result in spiral arteries with a capacity for further acute dilation or
in vessels with walls immobilized by an atherotic process so that further dilation could not occur. In both instances,
one would expect that the slope of the pressure-flow curve would be lowered, decreasing progressively as the
severity of disease increases. Therefore, an x percent reduction in perfusion pressure would cause a less than x
percent decrease in PBF (Fig. 15). Theoretically, an autoregulatory curve is possible that would further minimize
PBF decreases during reductions in MBP, but most morphologic studies augur against such vascular reactivity.
Irrespective of these considerations, hydralazine, a nonspecific vascular smooth muscle relaxant, is frequently used
to control life-threatening maternal hypertension. Since we cannot measure homeostatic PBF and since the effect of
hydralazine on the toxemic placental vasculature is unknown at present, prudent clinical management dictates that
we must assume the least favorable effects. Those would be a decrease in PBF as MBP decreases according to the
pressure-flow relationship and no vasodilatation of the spiral arteries. The end point of therapy should be a tolerable
MBP of 150/90 and normal fetal heart rate patterns. This implies constant fetal monitoring during therapy and a
gradual MBP reduction to prevent undesirable blood pressure and therefore PBF levels. Failure to observe these
tenets may cause fetal compromise as illustrated in Figure 16. In both patients, intrauterine growth retardation was
present, presupposing significant reductions in homeostatic PBF. In both patients, maternal hypertension was
overtreated sufficiently to lower PBF to levels that evoked severe fetal distress and necessitated cesarean section. It
should be noted in the first illustration that the reduction in MBP alone compromised the fetus. In the second
illustration, MBP was reduced less but the added presence of uterine contractions reduced PBF to fetal jeopardy
levels.

UNUSUAL PROBLEMS

The physician must cope constantly with human errors. Figure 17 illustrates one such problem occurring in
a normal laboring woman who accidentally received an injection of methylergonovine maleate (Methergine)
prescribed for a post-partum patient. Ergotrates cause a sustained increase in myometrial tonus plus or minus
superimposed rhythmic contractile patterns. Following the Methergine injection, intercontraction tonus
progressively rose with an obligatory inverse PBF response, and fetal bradycardia ensued. Recalling the relaxing
effect of epinephrine on the myometrium from b-adrenergic stimulation, the physician prescribed such therapy.
Uterine hypercontractility was reduced, but the placental vasculature responded with vasoconstriction. The net effect
of therapy was a decrease in PBF and persistence of fetal bradycardia. To properly manipulate PBF, the physician
must assess the pathophysiology of each given circumstance and then apply the principles of placental vascular
control to optimize fetal environment. As one reviews this record, the status of the fetus appeared to be improving
and only close observation was indicated. Had the fetus evidenced a deteriorating condition, specific therapy in the
form of a myometrial-relaxing general anesthetic agent such as halothane would have been indicated. The use of a

56
b-adrenergic agonist such as ritodrine has been recommended in this situation but is theoretically a less optimal
choice. Halothane should be a more predictable myometrial relaxant, and therapeutic levels would be achieved more
rapidly without the development of confounding variables such as maternal hypotension.

SOCIOLOGIC CONSIDERATIONS
With increased public awareness of physical fitness and the effects of environmental stimuli on well-being,
the obstetrician must broaden his awareness to fetomaternal responses as well. Since the effects on PBF of only a
few such stimuli have been studied, most comments in this area must be speculative. Two of these stimuli, cigarette
smoking and exercise, are addressed in this chapter.
Cigarette smoking increases blood levels of nicotine and carbon monoxide. The latter decreases the
oxygen-carrying capacity of maternal blood, limiting the amount of oxygen available for placental transfer.
Nicotine, a stimulant of autonomic ganglia, apparently mediates its effects by the release of catecholamines, since
maternal blood epinephrine and norepinephrine levels are increased and since direct infusions of nicotine into the
uterine artery cause no change in UBF.15 When nicotine is administered intravenously to gravid sheep, low doses
(125mg/min) cause no effect on UBF,27 while relatively high doses (1.0 to 1.5 mg/min) evoke significant UBF
reductions.15 Presumably, at a given threshold level of nicotine, sufficient catecholamines are released to increase
placental vascular resistance and decrease PBF. One must be cautious in applying such data from sheep to women
since the effects of intravenous nicotine rather than smoking per se have been measured and since factors such as
habituation and tolerance to chronic stimulation have not been evaluated. However, observations of pregnancy
outcome in smoking mothers suggest a subtle, long-term, dose-related reduction in fetal growth. Therefore, it is
reasonable to presume that smoking causes a qualitative long-term reduction in PBF and that smoking should be
stopped or decreased during pregnancy, especially if high-risk conditions exist.
The effects of maternal exercise on UBF and the fetus have been observed only in the ovine species. In
general, these studies indicate that mild to moderate exercise for up to 60 minutes is well tolerated by the fetus.
When exercise was continued to the point of extreme fatigue or exhaustion, maternal respiratory alkalosis and
decreased UBF occurred with reductions in fetal arterial oxygen tensions. In one study, fetal oxygen uptake was
maintained during a 28% decrease in UBF by a 56% increase in oxygen extraction across the uterus.28 In another
study on only four ewes, moderate to heavy daily exercise for 30 minutes during the last half of gestation resulted in
lambs of low birth weight.29
Although the data are fragmentary, they support a fairly consistent response pattern. Cardiac output
increases during exercise in response to the increasing metabolic demands of contracting muscles. The splanchnic
and presumably the uterine circulations continue at only slightly reduced levels as long as this need can be met
adequately. If peripheral demands exceed the cardiac capability, further splanchnic vasoconstriction and peripheral
shunting will occur. During moderate to heavy exercise, the data suggest a degree of PBF reduction that is offset by
increased oxygen extraction. During pregnancy, PBF will be affected by pre-pregnancy conditioning, the increased
pregnancy load on the heart, and the degree of exercise. In addition, the effect on the fetus will be determined by the
adequacy of homeostatic PBF. Recommendations regarding exercise during pregnancy must take all of these factors
into consideration. It would be unwise for a nonjogger to begin such activity during pregnancy. Continuation of an
established exercise program during early pregnancy with a gradual reduction in activity as the pregnancy load on
the heart increases is logical. In the presence of conditions thought to reduce homeostatic PBF, perhaps all but mild
exercise should be prohibited.

OVERVIEW
Uterine vascular adaptations to pregnancy require local blood vessels to dilate some tenfold to 20-fold to
meet the requirements of the fetoplacental unit and the enlarging myometrial mass. While the spiral arterioles that
perfuse the intervillous space probably undergo the greatest morphologic changes during this process, dilatation of
supply arteries from the major uterine vessels down through the radial arteries is also critical to meet the
downstream demand. For example, the middle uterine artery of a yearling ewe prior to conception is thin walled to
the point of translucency and is no greater than 2 mm in diameter. At term pregnancy, the arterial walls are much
thickened, with diameters between 8 and 10 mm. After the first pregnancy, the nonpregnant uterine artery retains its
thickened wall with diameters of approximately 3 mm, and an experienced observer can easily tell from the
appearance of the artery alone whether the ewe has been pregnant previously or not. Similar changes must occur in
arteries within the uterus as well. There is increasing evidence that inadequate development of the uterine
vasculatures to meet pregnancy requirements may be determined primarily during the definitive placentation process
and that PBF so compromised may lead to the development of toxemia of pregnancy.30 The high frequency of
toxemia during the initial pregnancy, that requiring the greatest uterine vascular adaptations, is consistent. If this
theory is correct, then an improved understanding of the placentation process becomes critical to subsequent
57
pregnancy performance and management. Our knowledge of the dynamic factors controlling PBF, although by no
means complete, is adequate to guide rational management. However, we desperately need methods to evaluate
precisely the adequacy of homeostatic PBF. Optimally these would be noninvasive techniques; therefore,
application of ultrasonic methods seems to offer the most fruitful area for research. Development of such technology
would permit increased understanding of PBF changes throughout pregnancy, knowledge that may delineate critical
developmental times and an appreciation of normal as well as pathologic mechanisms.

DOPPLER VELOCIMETRY
Ultrasound technology has evolved from only producing images of the pregnancy to now include methods
for measurement of both maternal and fetal circulatory functions. The phenomenon of Doppler shift of ultrasonic
echoes forms the technical basis for acquisition of information on the maternal–fetal hemodynamic circulations.
Johann Christian Doppler was an Austrian physicist who taught in Prague during the mid-1800s (White,
1982). He suggested that when a sound source (for example, red blood cells in fetal umbilical circulation) is moving
relative to an observer (for example, an ultrasound transducer), the perceived pitch will vary from the true pitch. In
accordance with the Doppler shift principle, echoes returning from moving structures are altered in frequency and
the amount of shift is directly proportional to the velocity of the moving structure. The frequencies of echoes
returning from structures moving toward the transducer are higher than the frequency originally transmitted by the
transducer. In contrast, the frequencies of echoes returning from structures moving away from the transducer are
lower. The primary uses of these Doppler echo shifts in obstetrics have been to detect and measure blood flow. The
sound of moving blood cells within the vasculature generates an effective Doppler shift, which serves as the basis of
Doppler velocimetry studies of maternal and fetal circulations. There are two methods of estimating circulatory
hemodynamics: (1) direct measurement of the volume of blood flow and (2) indirect estimation of flow velocity
using waveform analysis.

DETERMINATION OF BLOOD VOLUME FLOW

Doppler-shifted sound frequencies depend on a number of factors (Fig. 44–13 ):

In this equation, fo is the original frequency of the ultrasound beam (in obstetrical imaging this is usually 3 to
5 MHz), v is the velocity of blood cells in the vessel studied, q is the incident angle (angle of insonance) between the
ultrasound beam and the vessel, and c is the speed of sound (in tissue, equal to 1540 m/sec). The cosine remains
close to 1 as long as the angle is kept low, but at higher angles of insonance, especially those more than 60 degrees,
considerable error in measurement is introduced.
The equation in Figure 44–13 includes a factor (v) for the velocity of blood in the vessel studied. To solve
for v, and to thus estimate the velocity of red blood cells, the following equation is used:

Because volume flow (mL/min) is simply velocity times cross-sectional area of the blood vessel (area equals
pi times the square of the radius), it is possible to calculate volume flow by measuring the blood vessel diameter
using ultrasound. However, there are several technical difficulties with measurement of vessel diameters. For
example, the vessels are dynamic with changing diameters during the cardiac cycle. The many technical difficulties
inherent in Doppler blood volume flow measurements result in high error rates for this methodology. Estimates of
error up to 15 percent have been reported with the most careful attention to methodology (Gill, 1985) and errors up
to 50 percent are not uncommon (Burns, 1987). Because of these methodological problems, blood volume flow
measurements have been largely abandoned in clinical applications (Low, 1991).
WAVEFORM ANALYSIS OF BLOOD VELOCITY
Waveform Analysis of Blood Velocity. From the foregoing, the errors encountered in volume flow
estimation may be profound. Thus indirect indices of flow have been developed that might provide useful
information about flow without engendering excessive errors. These indices are independent of the angle of
insonation and do not require measurement of the diameter of the vessel.
Perhaps the most simple of these indices to compute is the systolic–diastolic ratio, or S–D ratio (Fig. 44–14 ).
The maximal systolic shift is divided by the end-diastolic shift. This may be measured from the maternal uterine or
fetal umbilical artery. In both vessels, the index gradually decreases as gestation progresses. Because of the low
diastolic velocities seen in more central fetal vessels, such as the descending aorta, the S–D ratio is not useful
elsewhere in the fetal circulation.
Similar in ease of calculation is the Pourcelot index, or the resistance index (Fig. 44–14 ). To calculate this
index, the difference in systolic and diastolic shifts is divided by the systolic value ([S - D]/S, also expressed as 1 -
[D/S]). This ratio is also applicable only to the umbilical and the uterine arteries, and low diastolic values limit its
usefulness in the fetal aorta or other central vessels.

58
 Of the widely used indices, the most complicated to measure is the pulsatility index (Fig. 44–14 ). It requires
a digitized waveform for calculating the mean of the maximal frequencies represented. Because of the mean value in
the denominator, this index can be computed using flow data from the fetal descending aorta without encountering
excessive variation caused with division by small numbers as with the other two indices. Doppler arterial waveforms
in nonpregnant humans are characterized by high systolic velocity and little or no diastolic velocity. Exceptions are
the carotid and cerebral vessels, which have continuous diastolic blood flow seen on waveform analysis. During
pregnancy, maternal and fetal vessels perfusing the placenta assume waveforms indicative of continuous diastolic
flow.
Doppler waveforms of vessels have been described in a variety of ways, but all are based upon the
relationship between systole and diastole. The most common measurements are some variation of the S–D ratio.
These measurements are intended to relate peak flow at systole to that at end-diastole, and the ratio is calculated
from the height of the systolic and diastolic peaks.
Waveforms with a high flow in diastole accompany low downstream vessel impedance. In contrast,
waveforms with little diastolic flow, or reversed flow, are seen when vascular impedance downstream is abnormally
high (e.g., placental insufficiency). Figure 44–15 illustrates several of the vessels in which S–D ratios have been
studied, as well as the corresponding S–D waveforms for blood velocity in these vessels. Blood flow velocity has
also been studied in the umbilical vein and fetal cerebral circulation.

TECHNIQUES FOR SPECIFIC VESSELS

UTERINE AND ARCUATE ARTERIES
Placental circulation is characterized by high volume flow, with an extensive diastolic component. Uterine
blood flow increases from 50 mL/min shortly after conception, to 500 to 750 mL/min by term. Its Doppler
waveform shape is unique, characterized by high diastolic velocities similar to those in systole and highly turbulent
flow, with many different velocities apparent (Fig. 44–15 ). With this degree of diastolic flow, indices decrease as
term approaches—that is, diastolic velocity increases with advancing gestation. A failure of this pattern to appear or
the presence of a notch in the waveform at end-systole has been reported with fetal growth retardation (Schulman
and associates, 1986).
The external iliac arteries are easily identified because they do not have diastolic flow (Fig. 46–15 ). For
other vessels, any absence of late-diastolic flow, or reversal of flow, is considered abnormal. As mentioned, the
various indices applied to umbilical artery analysis decrease during the latter phases of normal pregnancy
(Hendricks and co-workers, 1989).
UMBILICAL VEIN
The intra-abdominal portion of the umbilical vein is relatively straight and the flow tends to be constant
rather than pulsating. Therefore, the umbilical vein is a reasonable vessel for measuring volume flow rather than
indexed flow. Umbilical vein blood-flow measurements range from 108 to 153 mL/kg per minute with decreasing
flows as gestation advances (Gerson and co-workers, 1987).
FETAL DESCENDING AORTA
The fetal descending aorta receives the majority of right-ventricular output via the ductus arteriosus, while
the majority of left-ventricular output supplies the fetal head and upper arms. Flow in the descending aorta is highly
pulsatile, with little diastolic flow. The straight course of the aorta also makes it amenable to volume flow studies.
Waveform flow measurement is limited to the pulsatility index because of the lack of diastolic flow. Measurements
of fetal descending aorta blood flow range from 185 to 246 mL/kg per minute (Eik-Nes and co-workers, 1982;
Griffin and associates, 1985).
CAROTID ARTERY AND CEREBRAL BLOOD FLOW
Attempts have been made to measure fetal cerebral blood flow to explain why fetal head growth is spared in
some forms of fetal growth retardation. If there is preferential blood flow to the brain, there should be maintenance,
or even augmentation, of cerebral blood flow. Currently, the carotid arteries are the only cerebral vessels that can be
identified reliably, but they are too narrow to measure accurately. Thus, preliminary findings are interpreted with
caution since it is not always possible to be sure that comparable vessels are studied.

FETAL CARDIAC FUNCTION

The measurement of fetal cardiac function may have immediate clinical importance as well as research
implications.
CARDIAC OUTPUT
Doppler techniques that measure fetal cardiac output are extremely difficult to apply because of fetal
movement and technical factors discussed above. However, with combined use of two-dimensional ultrasound and
Doppler echocardiography, initial results appear promising. Reed and colleagues (1986a, 1986b) reported that mean
59
right-ventricular output was 307 mL/kg per minute and left-ventricular output was 232 mL/kg per minute (right to
left ventricular output ratio 55:45). DeSmedt and associates (1987) reported a slightly higher value for combined
ventricular output.
DUCTUS ARTERIOSUS
Functional applications of fetal Doppler echocardiography have been reported by Huhta and colleagues
(1987). They assessed ductus arteriosus constriction in both lamb and human fetuses. Reversible ductal constriction
was observed in three fetuses whose mothers received indomethacin for treatment of preterm labor. Such changes
were not observed in 25 normal pregnancies.
FETAL ARRHYTHMIAS
Using a variety of techniques, fetal cardiac arrhythmias can be diagnosed and appropriately treated. In most
instances these diagnostic techniques consist of two-dimensional real-time ultrasound examinations to identify
cardiac anatomy and accurate placement of M-mode echocardiographic beams. M-mode echocardiography appears
to be useful, especially in diagnosing fetal cardiac arrhythmias and in assessing ventricular wall function. Functional
outputs by atria and ventricles as well as timing of these events can be measured using pulsed-Doppler methods.
Reed and associates (1987) presented evidence of improved (ventricular) cardiac output after conversion of
supraventricular tachycardias to normal sinus rhythms. They also were able to confirm that the Frank–Starling
mechanism (increased diastolic volume results in increased stroke volume) is operative even in the fetus!

FETAL WELL-BEING
A recurring theme in the potential practical applications of Doppler ultrasound is the search to distinguish
normal from abnormal pregnancies. Of particular interest have been predictions of growth retardation, fetal hypoxia,
and fetal distress. It has also been proposed that abnormal uteroplacental waveforms may identify women at risk for
pregnancy-induced hypertension.
Applications of this technology are discussed in relation to its use in the diagnosis and management of a
variety of pregnancy complications and their management is presented throughout this book. Doppler velocimetry
has been proposed as a method of fetal surveillance, as discussed in Chapter 43. According to the American College
of Obstetricians and Gynecologists (1994), such surveillance is never required and is regarded as investigational.

TABLE 44–1. SOME INDICATIONS FOR OBSTETRICAL ULTRASONIC EXAMINATIONSa

Evaluation of fetal growth
Vaginal bleeding of undetermined etiology
Determination of fetal presentation
Suspected multiple gestation
Adjunct to amniocentesis
Significant uterine size/clinical dates discrepancy
Pelvic mass
Suspected ectopic pregnancy
Adjunct to special procedures
Suspected fetal death
Suspected uterine abnormality
Intrauterine contraceptive device localization
Biophysical evaluation of fetal well-being
Observation of intrapartum events
Suspected polyhydramnios or oligohydramnios
Suspected abruptio placentae
Adjunct to external version from breech to vertex presentation
Estimation of fetal weight and/or presentation in preterm prematurely ruptured
membranes and/or preterm labor
Abnormal serum alpha-fetoprotein value
Follow-up observation of identified fetal anomaly
Follow-up evaluation of placental location for identified placenta previa
History of previous congenital anomaly
Serial evaluation of fetal growth in multifetal gestation
Evaluation of fetal condition in late registrants for prenatal care

aEstimation of gestational age for women with uncertain clinical dates, or verification of dates for women
who are to undergo scheduled elective repeat cesarean delivery, indicated induction of labor, or other
elective pregnancy termination.
Adapted from National Institutes of Health (1984).

60
TABLE 44–2. COMPONENTS OF BASIC ULTRASOUND EXAMINATION ACCORDING TO TRIMESTER
OF PREGNANCY
First Trimester Second and Third Trimester
1. Gestational sac location 1. Fetal number
2. Embryo identification 2. Presentation
3. Crown–rump length 3. Fetal heart motion
4. Fetal heart motion 4. Placental location
5. Fetal number 5. Amnionic fluid volume
6. Uterus and adnexal evaluation 6. Gestational age
7. Survey of fetal anatomy
8. Evaluation for maternal pelvic masses

Modified from American College of Obstetricians and Gynecologists (1993).

TABLE 44–4. PREDICTED MENSTRUAL AGE (MA) IN WEEKS FROM CROWN–RUMP LENGTH (CRL)
MEASUREMENTS (IN CENTIMETERS)a

CRL MA CRL MA CRL MA CRL MA CRL MA CRL MA

0.2 5.7 2.2 8.9 4.2 11.1 6.2 12.6 8.2 14.2 10.2 16.1
0.3 5.9 2.3 9.0 4.3 11.2 6.3 12.7 8.3 14.2 10.3 16.2
0.4 6.1 2.4 9.1 4.4 11.2 6.4 12.8 8.4 14.3 10.4 16.3
0.5 6.2 2.5 9.2 4.5 11.3 6.5 12.8 8.5 14.4 10.5 16.4
0.6 6.4 2.6 9.4 4.6 11.4 6.6 12.9 8.6 14.5 10.6 16.5
0.7 6.6 2.7 9.5 4.7 11.5 6.7 13.0 8.7 14.6 10.7 16.6
0.8 6.7 2.8 9.6 4.8 11.6 6.8 13.1 8.8 14.7 10.8 16.7
0.9 6.9 2.9 9.7 4.9 11.7 6.9 13.1 8.9 14.8 10.9 16.8
1.0 7.2 3.0 9.9 5.0 11.7 7.0 13.2 9.0 14.9 11.0 16.9
1.1 7.2 3.1 10.0 5.1 11.8 7.1 13.3 9.1 15.0 11.1 17.0
1.2 7.4 3.2 10.1 5.2 11.9 7.2 13.4 9.2 15.1 11.2 17.1
1.3 7.5 3.3 10.2 5.3 12.0 7.3 13.4 9.3 15.2 11.3 17.2
1.4 7.7 3.4 10.3 5.4 12.0 7.4 13.5 9.4 15.3 11.4 17.3
1.5 7.9 3.5 10.4 5.5 12.1 7.5 13.6 9.5 15.3 11.5 17.4
1.6 8.0 3.6 10.5 5.6 12.2 7.6 13.7 9.6 15.4 11.6 17.5
1.7 8.1 3.7 10.6 5.7 12.3 7.7 13.8 9.7 15.5 11.7 17.6
1.8 8.3 3.8 10.7 5.8 12.3 7.8 13.8 9.8 15.6 11.8 17.7
1.9 8.4 3.9 10.8 5.9 12.4 7.9 13.9 9.9 15.7 11.9 17.8
2.0 8.6 4.0 10.9 6.0 12.5 8.0 14.0 10.0 15.9 12.0 17.9
2.1 8.7 4.1 11.0 6.1 12.6 8.1 14.1 10.1 16.0 12.1 18.0
aThe 95% interval is ±8% of the predicted age.
Reproduced, with permission, from Hadlock FP, Shah YP, Kanon DJ, Lindsey JF. Fetal crown-rump length:
reevaluation of relation to menstrual age (5–18 weeks) with high-resolution real-time US. Radiology. 182:501,
1992.

TABLE 44–5. AVERAGE PREDICTED FETAL MEASUREMENTS AT SPECIFIC MENSTRUAL AGES

Menstrual Age (wk) Biparietal Diameter (cm) Head Circumference (cm) Abdominal Circumference (cm)
Femur Length (cm)
12.0 1.7 6.8 4.6 0.7
12.5 1.9 7.5 5.3 0.9
13.0 2.1 8.2 6.0 1.1
13.5 2.3 8.9 6.7 1.2
14.0 2.5 9.7 7.3 1.4
14.5 2.7 10.4 8.0 1.6
15.0 2.9 11.0 8.6 1.7
15.5 3.1 11.7 9.3 1.9
16.0 3.2 12.4 9.9 2.0
16.5 3.4 13.1 10.6 2.2
61
17.0 3.5 13.8 11.2 2.4
17.5 3.8 14.4 11.9 2.5
18.0 3.9 15.1 12.5 2.7
18.5 4.1 15.8 13.1 2.8
19.0 4.3 16.4 13.7 3.0
19.5 4.5 17.0 14.4 3.1
20.0 4.6 17.7 15.0 3.3
20.5 4.8 18.3 15.6 3.4
21.0 5.0 18.9 16.2 3.5
21.5 5.1 19.5 16.8 3.7
22.0 5.3 20.1 17.4 3.8
22.5 5.5 20.7 17.9 4.0
23.0 5.6 21.3 18.5 4.1
23.5 5.8 21.9 19.1 4.2
24.0 5.9 22.4 19.7 4.4
24.5 6.1 23.0 20.2 4.5
25.0 6.2 23.5 20.8 4.6
25.5 6.4 24.1 21.3 4.7
26.0 6.5 24.6 21.9 4.9
26.5 6.7 25.1 22.4 5.0
27.0 6.8 25.6 23.0 5.1
27.5 6.9 26.1 23.5 5.2
28.0 7.1 26.6 24.0 5.4
28.5 7.2 27.1 24.6 5.5
29.0 7.3 27.5 25.1 5.6
29.5 7.5 28.0 25.6 5.7
30.0 7.6 28.4 26.1 5.8
30.5 7.7 28.8 26.6 5.9
31.0 7.8 29.3 27.1 6.0
31.5 7.9 29.7 27.6 6.1
32.0 8.1 30.1 28.1 6.2
32.5 8.2 30.4 28.6 6.3
33.0 8.3 30.8 29.1 6.4
33.5 8.4 31.2 29.5 6.5
34.0 8.5 31.5 30.0 6.6
34.5 8.6 31.8 30.5 6.7
35.0 8.7 32.2 30.9 6.8
35.5 8.8 32.5 31.4 6.9
36.0 8.9 32.8 31.8 7.0
36.5 8.9 33.0 32.3 7.1
37.0 9.0 33.3 32.7 7.2
37.5 9.1 33.5 33.2 7.3
38.0 9.2 33.8 33.6 7.4
38.5 9.2 34.0 34.0 7.4
39.0 9.3 34.2 34.4 7.5
39.5 9.4 34.4 34.8 7.6
40.0 9.4 34.6 35.3 7.7
Reproduced, with permission, from Hadlock FP, Deter RL, Harrist RB, Park SK. Estimating fetal age: Computer-
assisted analysis of multiple fetal growth parameters. Radiology. 152:497, 1984.

TABLE 44–6. SOME LIMITATIONS OF THE 18- TO 20-WEEK ULTRASONIC STUDY

Structural review incomplete

Face—lips
Heart—ventricular development, leaflets
Genitalia—some fetuses
Peripheral vessels—too small
Uncertain significance
Umbilical artery velocimetry
Subjectively decreased amnionic fluid
62
 Low-lying placenta
Unusual placental anatomy
Deficit not yet manifest
Late obstructive defects—hydrocephaly, hydronephrosis, gastrointestinal atresia
Intermittent/incomplete anomaly
Fetal growth disturbances
Fetal behavior disorders
Evolution of maternal status
Therapy limited to extrauterine regimens
Reprinted from Harman C. The routine 18 to 20 week ultrasound scan. In James DK, Steer PJ Weiner CP, Gonik B,
eds. High Risk Pregnancy Management and Options. 1994:664, by permission of the publisher WB Saunders
Company Limited, London.

63
 ULTRASOUND BIOEFFECTS FOR THE
PERINATOLOGIST
SAFETY
Safety. Although there is a theoretical risk for tissue damage at high intensities from the effects of heat and
cavitation, no independently confirmed biological effects in mammalian tissue have been demonstrated in the
frequency range of medical ultrasound (American Institute of Ultrasound in Medicine, 1991). In the low-intensity
range of gray-scale imaging, no fetal risks have been demonstrated in over 25 years of use.
Recent advances in technology have introduced Doppler shift imaging coupled to gray-scale imaging in order
to localize spectral wave forms and superimpose color or intensity mapping. Higher-energy intensities are used with
duplex Doppler imaging. For this reason, the Food and Drug Administration (FDA) arbitrarily limited ultrasound
energy exposure to less than 94 mW/cm2 during fetal imaging. Currently, the preferred measures of ultrasound
output are the mechanical index (MI) and thermal index (TI), rather than intensity in mW/cm2. In the case of fetal
evaluation, Doppler has been approved for use in the evaluation of the cardiac anomalies and in the setting of fetal
growth restriction (Scoutt and associates, 1990).

In the past few decades, ultrasound has become the primary imaging procedure for an increasing number of
conditions. Ultrasound imaging is an integral part of the practice of obstetrics, gynecology, radiology, cardiology,
neurology and neurosurgery, pediatrics, gastroenterology, urology, angiology, surgery, and internal medicine. In
obstetrics, ultrasound is increasingly used for applications such as the assessment of gestational age and the
diagnosis of placenta previa, multiple gestations, fetal growth retardation, and certain fetal structural abnormalities
such as spina bifida and hydrocephalus. Diagnostic ultrasound has also proved useful in antenatal surgery for fetal
diseases.

There is no doubt that a spectacular improvement in ultrasound imaging quality contributed to the rapid
increase in its use as a diagnostic tool. Also, the introduction of the linear array real-time scanner in the 1970s led to
a significant increase in the amount of ultrasound imaging performed during pregnancy. Recent advances in real-
time scanners include the introduction of duplex systems, which combine real-time imaging with pulsed (including
color) Doppler ultrasound. These systems made possible the measurement of fetal and uteroplacental blood flow.
Information on that flow may become one of the most important obstetric applications of diagnostic ultrasound.

As a result of these advances, a rapidly increasing number of pregnant women have been exposed to
ultrasound. Over a decade ago, about 40% of all pregnant women in the United States had undergone routine
scanning.1 However, there are reasons to believe that today this number is significantly higher: the corresponding
rate of ultrasound exposure in most western European countries is now about 80%; in West Germany, virtually all
babies are exposed to ultrasound in utero.

Because there is potential for the fetus to have long-term adverse effects from exposure to ultrasound,2 it is
more than relevant to ask, "How safe is ultrasound?" It is well established that under certain conditions ultrasound
can lead to undesirable side effects.3,4,5,6,7 Therefore, it is unrealistic to expect that the answer to this question can
be a simple "yes" or "no." Rather, the question to be answered should be, "Is diagnostic ultrasound safe as presently
used in clinical practice?"

The main goal of this chapter is to summarize the available knowledge regarding whether ultrasound
energy produces bioeffects at the levels currently used with commercial diagnostic equipment.

It must be stressed at the outset of this review that, to date, no evidence has been found of harmful effects
of ultrasound in humans at clinically used exposure levels. However, new applications of and new advances in
diagnostic imaging regularly prompt discussions on its safety and prudent use. Common to these discussions is that
they call for avoidance of unnecessary exposure.7,8,9,10 Also of concern is that although there is no reason to
believe that there are risks related to ultrasonic exposure, there are many inexpensive ultrasonic scanners throughout
the world. Therefore, there is an ongoing need to disseminate the knowledge of interactions between ultrasound
energy and biologic tissue and to identify the potential conditions for bioeffects.7,9,11

It is appropriate to note that any modern literature search on ultrasonically induced bioeffects will result in
a list containing hundreds of papers and reports on the topic. Because the literature on this subject is enormous, only
64
those papers that are considered to be relevant for this review are discussed here. In particular, attention is focused
on data pertaining to mammalian tissue. Those readers who are interested in reviewing all data available are referred
to excellent textbooks12,13 or to several comprehensive reports.3,4,5,6,7,11,14,15,16,17

Any informed discussion on bioeffects requires a basic understanding of the physical parameters involved
and their relation to the observed effect. More specifically, the relation between the magnitude of the effect and the
magnitude of the characteristic parameters of the ultrasound agent should be known. In addition, it is important to
determine whether the effect will give rise to any concern. Otherwise, the significance of the experimental outcome
can be misinterpreted easily and may lead to meaningless conclusions regarding the outcome's relevance to clinical
practice.

To facilitate an understanding of these relations and to judge the significance of the findings reported in the
literature properly, it is appropriate to start with a brief review of the relevant ultrasound parameters and the physical
mechanisms of interaction between ultrasound and biologic tissue. This is followed by a summary of the range of
acoustic output levels produced by the currently used clinical diagnostic machines and a succinct discussion of
recent developments in the regulatory area. Briefly, these developments permit manufacturers to introduce a real-
time on-screen display involving Thermal and Mechanical or Cavitational Index (TI and MI, respectively). These
indices inform the user of the potential for ultrasonically induced bioeffects. Understanding the implications of such
an on-system display is of vital importance for practitioners, including physicians, sonographers, and other allied
health personnel applying ultrasound energy to patients. This is because the displayed information about the
potential of bioeffects requires practitioners to make a direct decision as to the risks and benefits associated with the
given clinical examination.7,8,9,10,11,12,13,14,15,16,17,18

Next, a survey of the literature on biologic effects is given. As already noted, the biologic experiments that
are discussed were carefully selected and limited to those that bear the closest resemblance to clinical exposure
conditions. Special attention is given to human epidemiology studies; limitations and deficiencies of the current
research on ultrasonically induced bioeffects are also discussed.

The conclusions focus on a critical summary of the current evidence on risks associated with ultrasonic
exposure in diagnostic clinical examinations, including several relevant statements on in vivo mammalian bioeffects
and safety by the American Institute of Ultrasound in Medicine (AIUM) Bioeffects Committee.17

PHYSICAL MECHANISMS OF INTERACTION BETWEEN

ULTRASOUND AND BIOLOGIC TISSUE BIOLOGIC TISSUE
It is widely accepted that there are two basic mechanisms, namely, thermal and nonthermal, by which
ultrasound is known to affect biologic materials.3,12,13,14,17,18,19,20 Nonthermal mechanisms include
cavitational and noncavitational effects, which are associated with certain mechanical aspects of the acoustic or
ultrasonic field. These aspects can be described in terms of second-order phenomena, such as radiation pressure,
radiation force, radiation torque, and acoustic streaming, and are comprehensively reviewed in other sources.19,20

Because the data on second-order phenomena were obtained primarily by studying in vitro systems, and
because their biologic significance is not immediately clear, attention is focused on thermal and cavitational
phenomena. The following succinct description of these mechanisms should be satisfactory for the purpose of this
chapter.

THERMAL MECHANISM

This mechanism is associated with the absorption of acoustic energy by tissue and the generation of heat.
The thermal mechanism appears to be the best understood, and analytic models have been developed to predict the
possible temperature elevation in tissue.18 These models relate acoustic energy to the associated temperature
increase, provided that absorption coefficients for the tissues considered are known. A brief description of the
physical and physiologic variables that play a role in the generation of this temperature elevation follows.

As an ultrasound beam traverses tissue layers, the rate of energy deposition is determined by the factors
defined by the operational characteristics of the imaging system and the physical parameters of the tissue being
imaged. The system's operating characteristics are functions of the imaging and/or Doppler mode being used, as well
as of the focal characteristics of the transducer and its frequency. As an example of the way these characteristics
influence energy transfer, one can note the difference in energy distribution between scanned modes such as B-mode
65
and the pulsed-wave (PW) Doppler. More specifically, B-mode energy is distributed over a large volume, whereas
in unscanned modes, such as PW Doppler, the acoustic energy is aimed along a single line. Similarly, a highly
focused transducer has the potential for a highly concentrated energy deposition, whereas weakly focused
transducers tend to spread the energy over larger volumes. Whether or not energy is deposited in a given tissue
volume is determined by that tissue's absorption characteristics, which may vary significantly depending on the
organ considered. For example, there is almost no absorption in liquids such as amniotic fluid, blood, and urine.
However, an adult bone absorbs about 60% to 80% of the acoustic energy impinging on it.18 With fetal bone, there
is a wide variation in absorptive behavior, depending on the degree of ossification. The clinical situation of greatest
interest as far as thermal effects are concerned is a fetus in utero with an ossified bone structure and a mother with a
thin abdominal wall. In such a case there is little attenuation of acoustic energy because of the thin layer of
intervening maternal tissue, yet there is a high degree of absorption associated with the fetal bone.18

Local generation of heat per second in a volume of 1 cm3 can be calculated from the following expression:

W = 0.23 · a(f) · I

where a(f) is the absorption coefficient in dB/cm (in most tissues this coefficient is proportional to the
frequency), and I is the local average intensity per time unit in W/cm2 (a more rigorous definition of intensity is
given in the next section). The absorption coefficient is defined by the tissue characteristics, whereas the in situ
intensity is determined by both the imaging system and the attenuation of the overlying tissues. The relation between
the intensity in a given tissue layer and its absorption deserves a brief discussion here. A highly focused beam whose
focal point is in amniotic fluid will not cause significant heating of the fluid simply because the absorption level of
the fluid is low. In this situation, the a(f) of the above equation is relatively low, whereas the I has a relatively high
value. The same beam with its very high focal intensity will cause a significant temperature rise if it impinges on
ossified bone, which has an a(f) value that is significantly higher than that of amniotic fluid.

Another important determinant of local heating involves the degree of attenuation in tissue layers in front
of the point of interest. An increased amount of attenuation in the overlying tissues decreases the energy available
for conversion into heat. Thus, the use of fetal Doppler through a thick abdominal wall is less likely to cause a
significant temperature increase than are examinations involving patients with thin abdominal walls.

Although the above discussion has concentrated on heat sources, there are at least two mechanisms of heat
loss. Blood perfusion is an efficient mechanism for heat removal. In fact, the designers of hyperthermia systems
have significant difficulties with it.21 The degree of blood perfusion varies between the tissue types: among the best
perfused organs are the kidneys, heart, and brain, whereas bone and resting muscle are among the least perfused.22
Another cooling mechanism is due to heat conduction. The degree of thermal conductivity is relatively uniform
among the tissues and is fairly close to that of water, with the exception of bone, which is highly conductive, and fat,
which is a poor thermal conductor.22

There seems to be an agreement that an in situ temperature rise to or above 41°C is considered hazardous in
fetal exposures because it may lead to undesired effects. A more detailed discussion of the recent AIUM
recommendations concerning possible thermal mechanism -related bioeffects is given in the closing section of this
chapter.17

Experimental studies indicate that intact mammalian systems (in vivo) do not show a significant rise in
temperature when exposed to pulsed imaging equipment.3,12,17 However, the recently developed peripheral vessel
pulsed and continuous-wave (CW) Doppler equipment, when used for a relatively long time (1 -10 min), may be an
exception.17,23 Therefore, the Doppler system should be used with care, especially during the recently developed
applications in which Doppler is used for the study of blood velocities in the umbilical cord and the fetus.

CAVITATIONAL MECHANISM

The term cavitation refers to phenomena associated with the vibration and motion dynamics of small
gaseous bodies when exposed to an ultrasound field.12,17,20 In the first approximation, these gaseous bodies are
treated as spherical cavities (microbubbles) about 1 mm in diameter. Such gaseous bodies may expand because of
"rectified diffusion"24,25 until their radius grows to the magnitude at which mechanical resonance takes place.

Near the frequency of mechanical resonance, the vibration amplitude of the bubble wall is large and may
range up to 100 times the value of the radius at equilibrium (i.e., when the sound field is turned off).26 If the bubble
does not collapse during the ultrasound exposure, the condition is referred to as stable cavitation, in contrast to
66
inertial (collapse) cavitation (formerly known as transient cavitation5), during which the vibration amplitude of the
bubble wall increases so much that the bubble implodes. This implosion generates highly localized shock waves and
is also associated with extremely high local temperatures (up to 10,000°K).27 In addition to the temperature
elevation, the implosion results in the generation of free radicals such as hydroxyl radicals and hydrogen. These
radicals are very active and may lead to some undesired biologic changes, such as spontaneous biochemical
reactions within the tissue.

In this context it is worthwhile to point out that lung hemorrhage has been observed in mice after exposure
to ultrasound waves with relatively low peak pressures of 1 to 2 MPa. More specifically, cavitation-related events
were reported as a mechanism leading to lesions in the lung tissue of adult mice.28 The hemorrhage of lung tissue in
mice occurred as a result of exposure to 1-MHz, 10-ms pulses of about 1 MPa pressure amplitude. Also, the lung
tissue damage was observed in the lungs of monkeys exposed to 3.7 MPa using a commercial diagnostic ultrasound
imaging device operating at the maximum output in combined pulsed and color Doppler mode.29 This is of interest
because monkey represents a biologic model closely resembling human. This suggests that the alveoli may act as
cavitation nuclei and that caution should be exercised in cases in which the ultrasound interacts with lung tissue.
Although only a limited number of primates were used in the study, these results are important because lung
hemorrhage was observed at clinically relevant exposure conditions. Also, although these results have not yet been
independently confirmed, this study suggests an increased potential risk when frequent cardiac examinations are
performed in the neonates. It is appropriate to point out here that certain tissues may be more prone to cavitation-like
events than others. Thus, no kidney hemorrhage in mice was observed at peak positive pressures of 9 to 10 MPa and
negative peak pressure amplitudes of 4 to 5 MPa at frequencies of 1.2 and 3.8 MHz.30 Thus, it appears that in
kidney tissue there are no nuclei to sustain a gas body.

The bioeffects observed in the study by Tarrantal and Canfield29 and the study by Carstensen and
colleagues30 are also relevant to the situation in which the fetus undergoes prolonged exposure to ultrasound in an
early stage of pregnancy. Therefore, the ultrasound examination time should be minimized, consistent with the
requested diagnostic information.

Inertial cavitation leading to severe tissue hemorrhage also has been experimentally observed during
therapeutic treatment of the kidney using an extracorporeal shock-wave lithotriptor.31

Although of only peripheral interest to the present discussion, it should be recognized that a sufficiently
high negative peak amplitude of the ultrasonic wave can cause severe damage to the tissue. A typical pulse
generated by a lithotriptor is shown in Figure 1. The negative pressure amplitude of the typical lithotriptor pulse (see
Fig. 1) may be of the same order of magnitude as the corresponding pressure amplitude of the pulses used in
diagnostic ultrasound (see Acoustic Output Levels).

During stable cavitation, the vibration amplitude of the bubble wall may set up microflow
(microstreaming). The theory of microstreaming is well developed and is well described by Nyborg.32 The theory
predicts that the microstreaming can generate shear stress that acts on adjacent bodies such as cell
membranes.5,32,33 If the shear stress is sufficiently large, it may cause breakage of the cell membrane.32,33 It may
be argued that cell membrane breakage can also happen during exercise such as jogging. Nevertheless, the breakage,
even if unimportant from a biologic point of view, occurs because of the body's response to an external agent, and
therefore it should not be totally dismissed. Although phenomena resembling stable cavitation have been reported in
in vivo experiments, it appears that they occurred under exposure conditions not directly relevant to diagnostic
imaging.28

ULTRASOUND FIELD PARAMETERS

As already mentioned, interpreting the data on the safety of ultrasound requires some knowledge of the
basic terminology of key ultrasound field parameters, such as acoustic pressure or intensity. Thus, before the review
of bioeffects observed, it is essential to briefly clarify the nomenclature used in ultrasonic exposimetry and to
introduce acoustic field parameters relevant to ultrasound bioeffects.34

It is common practice to relate the bioeffects of ultrasound to intensity. Therefore, it is important to

distinguish between spatial peak, spatial average, temporal (or time) peak, and temporal average intensities (Fig. 2).
In addition, spatial peak, pulse average intensity (ISpPa) is often used. In fact, an ISpPa intensity of 190 W/cm2
constitutes a limit for temporal peak output levels of diagnostic ultrasound equipment.35

67
 Spatial peak (Sp) intensity is defined as the maximum point intensity measured in the field of a radiating
transducer; spatial average (Sa) intensity is the average of the intensity across a given area; temporal peak (Tp)
intensity is the maximum intensity for a given time interval; and time average (Ta) intensity is the average of the
intensity for a given time interval. Rigorous definitions of these parameters can be found in several
publications.34,35

It should be pointed out that a combination of spatial and temporal intensities is needed to relate an
observed bioeffect to ultrasound field parameters. Thus, the widely known AIUM publication17 refers to the spatial
peak, temporal average (SpTa) intensity. Also, it should be noted that although bioeffects are conventionally related
to the acoustic intensity or I (units: W/cm2), the field parameter currently gaining attention is acoustic pressure P
(units: pascals or Pa; 105 Pa = 1 bar ~ 1 atmosphere), because it is often the primary parameter measured. Moreover,
knowledge of peak negative pressure amplitude is needed to determine the value of the MI (see The Output Display
Standard).

All intensities are found by analyzing the pressure -time waveform recorded at the prescribed position in
the ultrasound field in water, the beam profile taken at this position, and the measurements of focal distance and
imaging frequency.35 The acoustic pressure -time waveform (Fig. 3), if measured with a calibrated receiver,
contains the information required to determine most of the ultrasound exposure parameters. Thus, the waveform
contains information about the working frequency of the imaging transducer, positive and negative peak pressures,
the pressure gradient, and possible nonlinear propagation phenomena.36,37

From the analysis of the waveform, characteristic times (such as effective pulse duration time) and
ultrasound field intensity parameters (such as Im [instantaneous maximum],35 SpTp [spatial peak, temporal peak],
SpTa [spatial peak, temporal average], SaTa [spatial average, temporal average], and SpPa [spatial peak, pulse
average] intensities) can be determined.3,34,35

In addition to these intensities, the beam pattern distribution, total acoustic power (W), pulse repetition rate
(PRR), and imaging frequency are needed to adequately determine ultrasound field parameters. All of these
parameters can be determined by using calibrated miniature ultrasonic hydrophone probes. The probes are made of
piezoelectric polymer such as polyvinylidene fluoride (PVDF) and exhibit excellent acoustic properties. The most
common designs use either the original hoop membrane approach or the needle-type construction.38 When properly
designed, the probes have proved suitable as reference hydrophones with good spatial and temporal resolution. With
their flat (to within ± 1.5 dB) frequency response and uniformity of voltage sensitivity to beyond 15 MHz, they are
uniquely suited to the measurement and characterization of ultrasound fields and acoustic sources. In addition, the
characteristic features of the probes, such as well behaved, generally predictable directivity patterns, excellent
linearity over a wide range of pressures (up to 100 MPa in the biomedical ultrasonics range of frequencies), and
long-term stability, make them suitable for the comprehensive characterization of both pulsed and continuous-wave
ultrasonic fields. These hydrophones are pressure-sensitive devices; therefore, conversion of the pressure into
intensity units is usually done under the tacit assumption that the plane wave approximation holds (i.e., that intensity
is proportional to the square of the pressure amplitude and inversely proportional to the product of density and sound
velocity).

Calculation of different intensities is fairly complex and involves squaring and integration of the pressure -
time waveform. The steps needed to determine intensities and other relevant exposure parameters from the analysis
of the waveform are shown in Figure 3. Detailed algorithms that allow SpPa, SpTa, and Im intensities to be
calculated in water and in situ can be found in the 510(k) Guide for Measuring and Reporting the Acoustic Output of
Diagnostic Ultrasound Medical Devices.35

An additional ultrasound field parameter to be determined is the total acoustic power generated by the
imaging transducer. Calculation of the total power requires knowledge of the beam profile taken in the plane
corresponding to the focal distance at which the waveform of Figure 3A was recorded.

Complete ultrasound dosimetry also requires information on exposure time, including dwell time. The
dwell time is defined as the time during which the ultrasound beam (more specifically its focal zone) remains at the
same site of the body in usual clinical practice.

Each expression of intensity mentioned above serves a different purpose.34 Briefly, the ISpPa is a measure
of the ultrasound energy associated with a single pulse, and Im intensity characterizes the maximum instantaneous
energy in the period of the pulse duration. The ISpTa corresponds to the energy averaged over a period of time and
is proportional to the PRR. Although a typical imaging system has a PRR (also referred to as pulse repetition
frequency) on the order of 1 kHz, a PRR as high as 20 kHz may be used in blood flow velocity measurements using
68
Doppler devices. The rationale for determining peak negative and peak positive pressure amplitudes and the
intensity parameters shown in Figure 3 is their potential for producing bioeffects. A comprehensive discussion of
this issue is given in the article by Nyborg and Wu.34

ACOUSTIC OUTPUT LEVELS

Once the definitions of the different acoustic intensities are known, the data available on the acoustic output
of ultrasonic equipment for imaging and Doppler applications can be summarized. The acoustic output levels of the
diagnostic devices quoted here were compiled from recently published data and are listed in Table 1, Table 2 and
Table 3.39 The Doppler instruments measured included CW Doppler units for cardiovascular investigations, fetal
monitors, stand-alone pulsed Doppler equipment, color Doppler, and duplex scanners working in Doppler mode, all
in the frequency range of 2 to 8 MHz. Measurements were carried out in water and revealed that pulsed Doppler
equipment could generate SpTa intensities that exceeded 100 mW/cm2, with a maximum of 4520 mW/cm2.39 (The
maximum SpPa intensity for pulsed Doppler equipment was about 770 W/cm2).39

The output of some CW cardiovascular Doppler devices produced intensity levels on the order of 850
mW/cm2, whereas fetal monitoring equipment intensities were on the order of 30 mW/cm2. Table 1 and Table 2
compile the highest intensities measured at the output of pulsed and CW Doppler equipment, respectively. Table 3
summarizes maximum output levels encountered at the output of clinical pulsed echo equipment.

THE OUTPUT DISPLAY STANDARD

Before a review of the clinical evidence for ultrasonically induced bioeffects can take place, it is important
to briefly discuss the clinical implications of the recently implemented Output Display Standard (ODS).7,17,35 As a
result of discussions that involved the Food and Drug Administration (FDA), the AIUM, and the National Electrical
Manufacturers Association (NEMA), in 1994 the FDA revised its guidance on diagnostic ultrasound 510(k)
submissions to allow the use of the MI in place of the ISpPa in determining substantial equivalence of devices. This
revision assumes that on-system displays17 of numerical indices, including MI and TI, will inform the user about
the potential for either thermal or nonthermal bioeffects associated with the actual examination settings of the
imaging system. This enables the clinician to increase acoustic power output beyond the existing FDA guidelines
when clinically warranted. Before the 1994 FDA revision, such an increase was not possible. The maximum
available acoustic output was limited by the manufacturer's software, which would not allow the output to exceed
FDA guidelines for maximum exposure. It must be stressed that with the implementation of the ODS, diagnostic
ultrasound systems can have a higher output limit. With the higher limits comes the potential for increased risk to
the patient, so the clinician must make a careful risk/benefit analysis. Therefore, the purpose of the ODS is to help
the clinician implement the ALARA (as low as reasonably achievable) principle and minimize the potential for
bioeffects.

In the following pages, the thermal and mechanical indices are defined and the potential for added
diagnostic and clinical benefits is briefly discussed. Additional comments on the indices are given in the
Conclusions section. A more comprehensive treatment of the different tissue models (including homogeneous tissue,
soft tissue, and bone tissue) used in the development of the indices is found in Medical Ultrasound Safety,7
Bioeffects and Safety of Diagnostic Ultrasound,17 and the article by Thomenius.18

The TI, which should be displayed during all unscanning equipment operations (i.e., M-mode, CW, and
PW Doppler, as well as color Doppler), is considered to be best suited as a predictor of possible thermal effects. The
MI has been developed as an indicator of the potential cavitation-like phenomena related to B-mode operation. The
TI is defined as: TI = W0/Wdeg, where W0 is the acoustic power output of the probe under a given operating
condition and Wdeg is the estimated acoustic power output necessary to raise the target tissue temperature by 1°C.

The MI is considered to be a suitable predictor of possible cavitation-like phenomena. MI is equal to

(rr.3/f0)1/2, where rr.3 is the maximum derated value of peak rarefactional or negative pressure amplitude and f0 is
the center transducer frequency. It should be noted that whereas the rr.3 values associated with lithotriptors (see Fig.
1) and diagnostic ultrasound instruments often are of the same order of magnitude, the increased potential for the
occurrence of cavitation with lithotriptors is associated with their lower frequency content of the shock waves (about
0.5 -2 MHz).

69
BIOEFFECTS
In general, the bioeffects literature can be divided into two classes: one based on the epidemiology of the
large number of ultrasound examinations performed both clinically and as laboratory experiments, and another in
which a causal relation between bioeffects and the applied acoustic energy is developed. Both classes are discussed
below.

EFFECTS OF ULTRASOUND ON MAMMALIAN TISSUES IN VIVO

Simple in vitro models, such as cells, are often used in the search for biologic effects to gain an
understanding of the possible mechanisms of interaction between ultrasound and biologic tissue. The results of the
research on biologic effects in nonmammalian species, such as insects, amphibians, and avians, indicate that studies
on these relatively simple organisms are helpful in understanding the mechanisms of interaction between ultrasound
and biologic systems.15 However, from the point of view of this work, studies of mammalian species are of more
relevance. The examples chosen for the present discussion pertain mainly to in vivo insonation of mammalian tissue
and include exposure conditions at clinically relevant frequencies. Most of the bioeffects studies were performed on
small rodents, such as mice or rats. Although these animals constitute a fairly inexpensive model for in vivo
bioeffects studies, the extrapolation of experimental results to humans is not immediately obvious. A very
comprehensive review of the effects of ultrasound on mammalian development was prepared by Sikov.16 He
evaluated bioeffects depending on gestational age and thus attempted to extract information on the relation between
exposure parameters and stage of development at exposure.

Because this approach seems useful for drawing some conclusions about the adverse effects of diagnostic
ultrasound in prenatal practice, it was adapted in the following discussion of bioeffects findings.

EARLY STAGE. Several researchers studied the influence of ultrasound exposure in the period before
implantation. In the CW studies, Takeuchi and co-workers40 used pregnant rats exposed to a 2.5-MHz ultrasound
field on the second and third day of gestation, at spatial average intensities of 150 mW/cm2. No increase in prenatal
mortality was found. Similarly, no increase in the rate of postnatal malformation was found after 20-minute
exposures. These results are not surprising in view of the fact that absorption in the embryonic tissue is lower than
that of the surrounding tissue. Therefore, it is likely that more heat was generated in the vicinity of the embryo than
in the embryo tissue itself.

Stolzenberg and associates41 exposed pregnant mice to 2-MHz of CW ultrasound in the first 3 days of
gestation. A 1-inch (about 25 mm) planar source transducer was used, and the spatial average intensity was
determined to be 1 W/cm2. A decreased uninterrupted pregnancy rate was noted after exposure for 5 minutes on the
third day and after exposure for 200 seconds on day zero. Also, a reduction in fetal weight after delivery was
observed at thresholds corresponding to exposure for 100 and 200 seconds on day zero and 200 and 400 seconds on
the first day. In another series of studies,42 ultrasound exposure led to damage of maternal tissue, which was
reflected in increased mortality, decreased weight gain, and paralysis of the pups.

Thus, it appears that in vivo exposure to CW ultrasound at spatial average intensities below 1 W/cm2 does
not affect embryos at the early stage of gestation. However, limited data suggest that levels of ultrasound of 1
W/cm2 may lead to undesirable changes in maternal tissue.

The application of ultrasound in guided oocyte aspiration for in vitro fertilization and embryo transfer is
rapidly growing. Therefore, the recent studies aimed at determining the interaction between ultrasound exposure and
successful fertilization are included in this discussion.43,44 In general, the clinically available data on ultrasound
exposure of oocytes during meiosis are confusing. Although some researchers reported a deleterious effect on the
fertility of patients undergoing artificial insemination (they claimed a reduction in the cumulative rate of
pregnancy),45 others claimed an increase in the success rate, allowing ultrasound monitoring of follicular growth.46

An attempt to clarify this ambiguity was described by Mahadevan and colleagues.47 Their study sought to
determine how oocytes obtained under ultrasound guidance affected the pregnancy rate. The results obtained at 3.5
MHz suggest that exposure of human oocytes to ultrasonic waves during the different phases of meiosis does not
significantly influence the developmental potential of the in vitro fertilized embryos. Unfortunately, except for
ultrasound frequency, these researchers did not give any of the relevant exposure parameters discussed earlier.

70
 ORGANOGENESIS. McClain and associates48 exposed rats to 10 mW/cm2 CW Doppler ultrasound for up
to 2 hours at frequencies of 2.25 and 2.5 MHz. The fetuses were examined on day 20, and no consistent increase in
mortality was observed, nor did the authors detect any other abnormalities.

Stolzenberg and co-workers41 reported a decrease in the uninterrupted pregnancy rate of mice exposed
between days 6 and 8 to a spatial average intensity of 1 W/cm2. They reported statistically significant fetal weight
reductions for exposures longer than 140 seconds. More evidence of the possibility of ultrasonically producing
embryolethal effects during organogenesis has been described.49,50,51,52 Sikov and colleagues49,50,51,52
exposed an exteriorized rat uterus to three frequencies (0.8, 2, and 3.2 MHz) at day 9 and evaluated the offspring at
day 20. The exposure was performed at different intensity levels, with exposure times at 5 or 15 minutes. No effect
on fetal weight was observed, even at spatial average intensities as high as 30 W/cm2, but prenatal mortality at 15 to
20 W/cm2 (spatial average) clearly increased with increasing exposure time. The cause of this was ascribed to a
thermal mechanism.

FETAL BONE HEATING. Several researchers have investigated exposure conditions in which the
ultrasound energy was impinging on a bone embedded in tissue with relatively little absorption or attenuation. This
situation is particularly relevant in obstetrics, because the developing fetus is exposed to diagnostic ultrasound.
Carstensen and associates53 insonified exposed mouse skulls that had thermocouples implanted. Both adult and
young mice were used. The results were reproducible, with the older mice yielding a steady temperature rise of 5.6 ±
0.3°C with a focal intensity of 1.5 W/cm2. In the first 15 seconds of ultrasound application, the temperature rose to
about 75% of the final value. Comparison of these results with the theoretic predictions obtained from an
appropriate tissue model18 indicated an agreement to within 20%; however, the theoretic transient response
indicated the possibility of a considerably faster rate of temperature increase--the 75% was predicted to be achieved
within 5 seconds of exposure. These results indicate that there may be a reason for concern, especially with the rate
of temperature increase. Also, at this rate of heating, the exposure time should be limited to about 1 minute.18 If the
temperature increase had been, for example, 7°C, the exposure time necessary for a bioeffect to occur would have
been 15 seconds. It cannot be ruled out that during an actual examination, the acoustic beam might be held
stationary for such a period.

POSTNATAL DEVELOPMENT. Equally important in determining the safety of diagnostic ultrasound is

knowing the influence of prenatal ultrasound exposure on postnatal development. In a carefully devised study,54
pregnant rodents were exposed to 500 mW/cm2 spatial average intensity at 2-MHz ultrasound for 1 to 3 minutes, or
to 1 W/cm2 spatial average intensity for 40 to 60 seconds. No fetal mortality was observed; however, a weight
decrease in the pups delivered was observed after exposure to 0.5 W/cm2 for 180 seconds.

In another study, the effects of prenatal ultrasound exposure on adult offspring behavior in the Wistar rat
were investigated.55 The animals were exposed on days 15 through 17 and on 19 of gestation to a 5-MHz, 1-kHz
pulse repetition rate and intensities (ISpTp) of 500 and 1500 W/cm2. The total exposure time was 35 minutes. Two
hundred seventy-eight offspring were subjected on postnatal day 60 to two of four well-established behavioral tests.
The animals were tested in random order within sexes. The results showed no consistent dose-related alterations in
adult behavior due to prenatal fetal exposure.

Vorhees and co-workers56 used a unique approach to study the possible teratogenic effects of ultrasound
exposure. They eliminated the need for anesthesia (and therefore the possible complications caused by forced
restraint) by training the rats to remain immobile during the ultrasound exposure. The animals were exposed to 0.1,
2, or 30.0 W/cm2 (ISpTa), 3 MHz CW, for about 15 min/day on days 4 through 19 of gestation. No dose-dependent
changes in various maternal parameters, the incidence of malformation, or fetal weight were observed. In a follow-
up study, Vorhees and colleagues57 exposed rats to these levels of ultrasound for 10 minutes on gestational days 4
through 20. Although they did not observe exposure-related alterations in maternal parameters, offspring survival
and growth, or neonatal psychophysiologic parameters, changes did occur in offspring adult behavior, in locomotor
activity, and in two measures of the multiple-T water maze test performance at the highest dosage level.

In the studies aimed at determining the effects of ultrasound exposure on uteroplacental function, ter Haar
and co-workers58 found that a spatial peak intensity of 2 W/cm2 at 3 MHz caused an exteriorized uterus to increase
in frequency of contraction, which lasted for about 4 minutes after the ultrasound was turned off. They reported no
increase in temperature and thus ascribed the increased rate of contractions to an unspecified nonthermal
mechanism.

Placental function during ultrasound exposure was investigated by Kelman and associates.59,60,61 In their
experiments they insonified the placenta of a guinea pig with 2.5 MHz of ultrasound at different intensity levels and
in both pulsed and CW modes. Functional changes were observed after 10 minutes of exposure at SpTp intensities
71
of 30 W/cm2 in pulsed mode (pulse length, 10 ms; PRR, 1 kHz) and SpTa intensities of 28 to 46 W/cm2 in the CW
mode.

Again, it appears that at sufficiently high intensity levels, ultrasound can affect vitelline blood flow and
lead to increased uterine contractility and changes in placental function. However, the exposure levels far exceed
those present in the clinical environment. Murrils and associates62 found that fetal Doppler monitoring did not
influence fetal activity, which would be an indication of ultrasound effects on the perinatal nervous system.

BIOEFFECTS RELATED TO HYPERTHERMIA

The evidence above indicates that there is a teratogenic effect of heat on the prenatal development of
mammalian tissues. Experiments with cultured rat embryos stressed the importance of ambient temperature; no
bioeffects were observed when embryos were exposed to pulsed ultrasound for 15 minutes at ISpTa levels of 1.2
W/cm2.63 However, the same experiment repeated with the temperature elevated 1.5°C above normal (40°C)
resulted in retardation of head growth. Although the outcome of this experiment cannot immediately be extrapolated
to humans, it indicates that ultrasound exposure of a febrile pregnant patient under certain conditions might
constitute an increased risk for potential bioeffects.

There are relatively few papers containing diagnostically relevant information on this subject; therefore, it
is appropriate to draw attention here to a recent survey.64 This survey established that no thermal bioeffects were
observed at temperature elevations of 39°C, regardless of how long the ultrasound exposure lasts. However, for each
increasing degree of temperature elevation, to stay within safety limits, the duration of ultrasound examination must
be reduced by a factor of four. More specifically, the review indicated that the maximum safe duration for a
temperature of 43°C is 1 minute, and for 42°C it is 4 minutes. Similarly, at 41°C the exposure time may be increased
to 16 minutes, and at 40°C the duration of examination may be as long as 64 minutes. Based on the data available,
the survey concluded that if the maximum temperature rise during the ultrasound exposure is kept less than 2°C, any
biologic effect (in a febrile patient) is highly unlikely. It is possible to express the relation between the exposure
time required for a bioeffect to occur and the associated TI, namely, t = 4 < (6 -TI). Thus, for a TI of 6, the exposure
time should be limited to 1 minute. Similarly, a TI of 4 means that the exposure time should be less than 16 minutes
(see Appendix).

Recent findings indicating that the ultrasound imaging transducer may act as a substantial heat source
(Duck FA, unpublished observations) are also of interest. The temperature at a clinically operated Doppler
transducer was reported to increase by 10°C when the Doppler was applied to skin with a standard coupling gel.
Although tissue heating from the transducer is most likely limited to the tissue volume in the immediate vicinity of
the transducer, this effect should be kept in mind for ultrasound examinations in which an endocavity (e.g.,
endovaginal) transducer is used, or when performing contact scanning of the neonatal brain or in ophthalmologic
applications.

BIOEFFECTS RELATED TO CAVITATION

A few relevant papers reporting lung hemorrhage in mice and in monkeys caused by cavitation-like
phenomena have already been discussed under Cavitational Mechanism.28,29 These papers describe significant
biologic effects associated with gas body activation. The effects were produced in vivo in mammalian lung tissue in
small rodents (mice) and in primates (monkeys). The bioeffects were observed at pressure amplitudes and pulse
durations representative of those currently encountered at the output of diagnostic ultrasound equipment, particularly
when used in pulsed Doppler mode. As previously noted, the results described in those papers are important for the
present discussion because they led to a modification of the AIUM statement on "In Vivo Mammalian Bioeffects."
The statement, which was renamed "Non-Human Mammalian In Vivo Biological Effects," emphasizes the
importance of the MI.17

Recent data presented in the article by Dalecki and colleagues65 indicate that, in general, threshold
pressures increase with increasing frequency. The thresholds for hemorrhage in the intestine of adult mice ranged
from about 1 MPa at 1 MHz to 3 MPa at 3 MHz (10-ms pulse duration, 100-Hz repetition rate).

To date there is no evidence that flowing cardiovascular blood will permit cavitation in vivo. Although
there is some indication that microscopic gas bodies may exist in biologic tissue, there is no evidence that exposure
of these bodies to the ultrasound levels similar to those used in clinical diagnostic practice will cause any significant
bioeffects. However, it is conceivable that vibration of those bodies may introduce cell membrane stresses that can

72
lead to extravasation of blood in lung tissue.5 This may indicate a need for appropriate modification during
cardiovascular examinations and transesophageal echocardiography.

The above findings indicate that the body regions containing gas volumes are very sensitive to the potential
side effects of ultrasound exposure and that biologic effects can be introduced by using a commercially available
diagnostic imaging system in tissues containing gas volumes. Carefully designed studies are needed to assess any
potential hazards with conditions that are typical for diagnostic ultrasound. Such hazards may also be associated
with ultrasonic contrast agents injected into the vascular system.

To summarize, the thresholds for confirmed cavitation-induced biologic effects in mammalian tissues in the
diagnostic frequency range of 2 to 8 MHz are above 1 MPa.17 All of the biologic effects that have been confirmed
under diagnostically relevant exposure conditions involve tissues that are known to contain microscopic gas bodies.
For tissues not containing gas (such as the kidney), no damage was observed at peak positive pressures on the order
of 10 MPa.30 Lung hemorrhage has been observed in neonatal and adult mice, rabbits, monkeys, and neonatal swine
with diagnostically relevant ultrasound pressures ranging from 1 to 3 MPa. No damage was observed in the lungs of
adult swine at pressures on the order of 5 MPa (see Appendix).28,29

EPIDEMIOLOGIC STUDIES

The evidence of ultrasonically induced bioeffects in humans is perhaps the most important information
from the clinician's point of view. As pointed out by Ziskin and Petitti,2 "No matter how many laboratory
experiments show a lack of effect from diagnostic ultrasound, it will always be necessary to study directly its effect
in human populations before any definitive statement regarding risk can be made."

There are extensive reviews of the literature on the epidemiology of human exposure to ultrasound.1,3,6 As
would be expected, the major thrust of these reviews is the assessment of the possible side effects of ultrasound
exposure in utero. This is mainly because most pregnant women are exposed to ultrasound examination in the early
stages of pregnancy and because any harmful effects to the fetus may last for years to come.

In general, few data pertaining to human ultrasound exposure are available. Some of the published data are
reviewed briefly here. The experiments of O'Brien,66 who observed that in utero exposure to ultrasound resulted in
reduced birthweight in mice, prompted similar studies in humans. Bakketeig and associates,67 in their randomized,
controlled trial, reported that they were unable to find any effect of ultrasound on birthweight in humans. A similar
conclusion was drawn from the earlier studies on the relation between ultrasound exposure and birthweight.68

Although no fetal structural anomalies were observed in the recent studies performed by Stark and co-
workers68 and Bakketeig and colleagues,67 Stark and associates reported somewhat disturbing findings in their
retrospective follow-up examinations of 425 children exposed to ultrasound in utero and 381 unexposed children.
They reported an increased risk of dyslexia; however, their study suffers from the fact that the subjects were not
selected at random. No evidence has been found that ultrasound exposure in utero may lead to an increased rate of
childhood cancer.69,70 Likewise, no relation between in utero exposure and children with hearing deficiencies has
been determined.68

DEFICIENCIES OF THE BIOEFFECTS STUDIES

The data presented earlier indicate that the exposure of pregnant rodents to CW ultrasound at sufficiently
high intensities during organogenesis can lead to undesirable biologic changes in the developing fetus. Also, recent
evidence has emerged indicating that the body regions containing gas volumes may be particularly prone to potential
side effects when exposed to sufficiently high pressure amplitudes.28,29 Although the data were carefully selected
to include only those studies that can be readily related to diagnostically relevant exposure conditions, it should be
stressed that in most cases the bioeffects were observed at exposure conditions that were different from those typical
of clinical diagnostic practice. Before 1990, most of the bioeffects observed were ascribed to the thermal mechanism
of interaction between the ultrasound and biologic tissue, but in the past half decade it has been demonstrated that
exposure to ultrasound produced by commercially available diagnostic imaging equipment can produce nonthermal,
cavitation-like bioeffects in the lung tissue of primates.29

Many bioeffects studies describe the effects of whole-body heating, which most likely acts through a
mechanism that is not immediately comparable to ultrasound-induced hyperthermia. Few studies have been
specifically designed to determine threshold values for abnormal embryonic or fetal development.64 On the basis of

73
the thermal criterion, a diagnostic exposure that produces a maximum temperature rise of 1.5°C above normal
physiologic levels can be used without reservation in clinical examinations (see Appendix). However, a diagnostic
exposure that produces an in situ temperature elevation to or above 41°C for 15 minutes should be considered
hazardous to embryonic or fetal development. Any increase in the tissue temperature will act as a potentiating
factor. Therefore, ultrasound examination in a febrile patient may constitute an additional embryonic and fetal risk.5

The reviews on human exposure clearly indicate that epidemiologic studies and surveys yield no evidence
of adverse effects from diagnostic ultrasound, but they also point out several serious deficiencies of all the data
available. These deficiencies are carefully discussed by Ziskin and Petitti.2

Ziskin and Petitti point out that the available results of epidemiologic studies are based on about 500,000
patient examinations that were collected from 179 users of clinical ultrasound. However, the results allow only a
fairly cautious statement to be made, namely, that the users overwhelmingly believe that their experience with
diagnostic ultrasound had been safe.

Ziskin and Petitti also note that all clinical studies on the possible harmful effects of ultrasound exposure to
the fetus produced negative results. However, the acoustic outputs of the diagnostic instruments used were generally
not known. In addition, the sample sizes (the number of patients included in the studies) were limited to a few
hundred. In their careful assessment of the limitations of the epidemiologic studies, Ziskin and Petitti focus on the
lack of information or simply inadequate ultrasound dosimetry. Also, the reasons for the examinations were not
clearly stated, and sparse information is available on the number of examinations and the gestational age at the time
of exposure. In addition, most studies were performed with pulsed ultrasound. As shown in Table 1, Doppler
ultrasound results, in general, in higher values of ISpTa. Ziskin and Petitti suggest that the existing data on exposure
of the fetus in utero are inadequate to conclude that diagnostic ultrasound is safe at all combinations of dose and
period of exposure for both imaging and Doppler devices.

Another point addressed by these researchers is the importance of statistical considerations, including
sample size and statistical level of significance. Because a more thorough treatment of statistics is beyond the scope
of this chapter, it can be simply stated that the larger the sample, the higher the statistical level of significance that
can be achieved. The usefulness of small samples is extremely limited; studies that use small samples usually have
inconclusive results.

In summary, the human studies that have been performed do not preclude the possibility that adverse
effects may be found under certain conditions. The limited data available indicate that no relation has been found
between prenatal exposure to ultrasound and subsequent postnatal changes in children, but statistical considerations
show that minor chemical and behavioral changes, long-term delayed effects, and certain genetic effects could easily
escape detection.2 There is still a need for a well-designed, randomized clinical study addressing the risk for the
fetus exposed in utero.

CONCLUSIONS
In general, the literature describing clinically relevant exposure conditions is rather limited, and few results,
if any (even of experiments in vivo), can be immediately applied or extrapolated to discussions of clinical safety.
The reason for this is the large number of variables that must be considered, which makes bioeffects experiments
difficult to design and perform free from artifacts. Also, the number of subjects exposed to the ultrasound field is
often limited, so the data obtained cannot be considered statistically significant.2,3 It is worth reiterating that lung
hemorrhage was produced in the lung of a macaque monkey whose chest was exposed to the maximum output level
produced by a commercially available diagnostic scanner.29 The mechanism of injury was determined to be a
nonthermal one; the tissue damage appeared to be caused by gas volumes existing in the lung tissue. Although these
findings were not confirmed by an independent laboratory, they indicate that caution should be used in diagnostic
examinations related to echocardiographic and esophageal applications.

Results of experiments performed at exposure levels and durations higher than those used in diagnostic
examinations are difficult to extrapolate to human examination conditions. In addition, reproducibility of the results
presents a further limitation: often the bioeffects observed cannot be confirmed by an independent laboratory. It is
conceivable that more uniform requirements regarding the determination of acoustic output parameters would
facilitate comparison of the experiments between different laboratories.

74
 The current evidence on ultrasonically induced bioeffects in the laboratory setting (with the possible
exception of the results published in the article by Tarrantal and Canfield29 and those pointed out in the article by
Barnett and colleagues5) is not immediately applicable to the clinical situation. However, it is important to keep in
mind that the uncertainties experienced in determining the intensity levels and the associated exposure conditions do
not permit a categorical statement to be made regarding the unconditional safety of diagnostic ultrasound. It is also
important to reiterate that the available data from both empirical and epidemiologic studies indicate that there is no
verified evidence of adverse effects in patients caused by exposure to diagnostic levels of ultrasound (see
Appendix).

Although these findings are consistent with almost three decades of clinical experience, it is also important
to realize that the acoustic exposure levels in the available data may not be representative of the full range of current
fetal exposure (see Table 1, Table 2 and Table 3). As already indicated, the acoustic outputs of diagnostic
instruments have been increasing,17,39 and recent laboratory studies indicate that tissue damage can occur at the
exposure levels produced by commercially available equipment.5

Acoustic output measurements indicate that the peak rarefactional pressure amplitudes of some Doppler
systems can exceed 4 MPa. Although such pressure amplitudes appear to be sufficient to cause adverse effects,29 so
far no evidence has been presented indicating any pulmonary extravasation after ultrasound exposure. However,
these data indicate that appropriate caution should be exerted during neonatal examination, because even small
amounts of extravasation can be of concern. In practice, this would require operators to follow the ALARA principle
and to use the minimum transmitting acoustic power necessary to obtain adequate diagnostic data. The continuously
updated display of the TI and MI should be of significant assistance here. As already mentioned, these indices
provide information on the likelihood of an adverse biologic effect occurring from the ultrasound examination that is
currently performed in clinical practice.7 The TI index provides real-time information indicating the worst-case
temperature rise at the actual operating conditions of the imaging equipment. The MI index indicates the potential
for cavitation phenomena to occur. If the predefined set value is exceeded, indicating the potential for harm, the
clinician will be able to make an informed decision regarding the benefit/risk ratio of the given ultrasound
examination. The decision may be influenced by factors that are not covered in the indices. These factors include
consideration of the imaging site perfusion, patient obesity (which may severely restrict penetration depth), and a
possible reduction in the exposure time by minimizing the duration of examination. A continuously updated on-
screen display of the MI and TI indices is incorporated in recent designs of diagnostic ultrasound imaging
equipment. It is appropriate to note that an output display is not required if the transducer and the system are not
capable of exceeding an MI or TI of 1. However, if the transducer and system are capable of exceeding an MI or TI
of 1, then the system must display values as low as 0.4 to assist the operator to implement the ALARA principle (see
Appendix).7 It should be noted that the MI, which is defined as a derated (0.3 dB/cm/MHz) peak rarefactional
pressure in MPa (rr.3) divided by the square root of the center frequency in MHz, is not a perfect indicator.
Although it simplifies the description of thresholds for bioeffects in tissues containing stabilized gas bodies, it may
underestimate conditions in situ. Another limitation of the MI is that it describes conditions only at the focus. This
may not be the primary point of interest, for instance in cardiological examinations. In this case, the most common
way for the lung to be exposed during a diagnostic procedure is where the transducer is applied directly to the chest
of the patient. Here, the focal region of the transducer is not within the lung tissue. An in-depth discussion of which
index is most appropriate for a given examination, as well as a careful discussion of the limitations involved in
implementing the ALARA principle with the use of these indices, is given in the article titled Medical Ultrasound
Safety (also see Appendix).7

Overall, the clinical data are reassuring in that no established adverse effects on human patients exposed to
diagnostic ultrasound examinations have been reported. However, the deficiencies of the data available and the
tendency to increase the acoustic output power indicate the need for carefully planned experiments to provide safety
information relevant to medical practice. Knowledge of the relevant ultrasound field parameters, such as the
maximum peak pressure (with regard to both space and time), working or center frequency, pulse waveform, beam
profile, and pulse repetition frequency, is essential for proper comparison of the experimental results. This
knowledge, along with the actual exposure time, should be included in papers reporting on the biologic effects of
ultrasound.

Analysis of the acoustic output data given in the previous sections indicates that the diagnostic procedure
that introduces the greatest concern for thermal bioeffects is the use of PW Doppler in a fetal examination.
Similarly, cavitation or a gas body -related mechanism is associated with B-scan imaging of the developing fetus.

This chapter concludes with a brief review of official AIUM statements (see Appendix). These statements
were prepared by the AIUM Bioeffects Committee, whose expertise in the field is widely recognized in the
ultrasound community throughout the world. The statements summarize the current knowledge on the physical
75
mechanisms of interaction between ultrasound and biologic tissue and are based on both empirical and clinical data.
The empirical data were scrutinized to detect possible dose - response relations regardless of the underlying
mechanisms.

The data in the literature allow a fairly comprehensive statement on "Non-Human In Vivo Biologic
Effects," which covers both thermal and nonthermal mechanisms and provides guidelines to estimate potentially
hazardous pressure amplitudes or intensity levels and exposure times.

In conclusion, diagnostic ultrasound has an excellent safety record. The clinical data are reassuring in that
there is no report of damage to human patients from diagnostic ultrasound. However, it must be emphasized that
neither theoretic calculations nor experimental results can yield unambiguous and definite evidence that fully
guarantees the safety of ultrasound diagnostics. Because diagnostic ultrasound is an extremely powerful tool in the
hands of experienced physicians and sonographers, the final decision regarding the risks and benefits can be made
only by the individual responsible for applying the ultrasound to the patient.

APPENDIX
The American Institute of Ultrasound in Medicine (AIUM) Official Statements

CLINICAL SAFETY
Official Statement
Approved
March 1993
October 1982

Diagnostic ultrasound has been in use since the late 1950s. Given its known benefits and recognized
efficacy for medical diagnosis, including use during human pregnancy, the American Institute of Ultrasound in
Medicine herein addresses the clinical safety of such use:

No confirmed biological effects on patients or instrument operators caused by exposure at intensities

typical of present diagnostic ultrasound instruments have ever been reported. Although the possibility exists that
such biological effects may be identified in the future, current data indicate that the benefits to patients of the
prudent use of diagnostic ultrasound outweigh the risks, if any, that may be present.

MAMMALIAN IN VIVO ULTRASONIC BIOLOGICAL EFFECTS

Official Statement
Approved
October 1992
August 1976

Information from experiments utilizing laboratory mammals has contributed significantly to our
understanding of ultrasonically induced biological effects and the mechanisms that are most likely responsible. The
following statement summarizes observations relative to specific ultrasound parameters and indices. The history and
rationale for this statement are provided in Bioeffects and Safety of Diagnostic Ultrasound (AIUM, 1993).

In the low megahertz frequency range there have been no independently confirmed adverse biological
effects in mammalian tissues exposed in vivo under experimental ultrasound conditions, as follows.

a. When a thermal mechanism is involved, these conditions are unfocused-beam intensities* below
100 mW/cm2, focused-beam† intensities below 1 W/cm2, or thermal index values less than 2. Furthermore, such
effects have not been reported for higher values of thermal index when it is less than

log10t
6 - ———
0.6

where t is exposure time ranging from 1 to 250 minutes, including off-time for pulsed exposure.

76
 b. When a nonthermal mechanism is involved,# in tissues that contain well-defined gas bodies, these
conditions are in situ peak rarefactional pressures below approximately 0.3 MPa or mechanical index values less
than approximately 0.3. Furthermore, for other tissues no such effects have been reported.

CONCLUSIONS REGARDING GAS BODIES

Official Statement
Approved
March 1993
October 1987

1. The temporal peak outputs of some currently available diagnostic ultrasound devices can exceed
the threshold for cavitation in vitro and can generate levels that produce extravasation of blood cells in the lungs of
laboratory animals.

2. A Mechanical Index (MI)* has been formulated to assist users in evaluating the likelihood of
cavitation-related adverse biological effects for diagnostically relevant exposures. The MI is a better indicator than
derated spatial peak, pulse average intensity (ISppA.3) or derated peak rarefactional pressure (rr.3) for known
adverse nonthermal biological effects of ultrasound.

3. Thresholds for adverse nonthermal effects depend upon tissue characteristics and ultrasound
parameters such as pressure amplitude, pulse duration and frequency. Thus far, biologically significant, adverse,
nonthermal effects have only been identified with certainty for diagnostically relevant exposures in tissues that have
well-defined populations of stabilized gas bodies. For extravasation of blood cells in postnatal mouse lung, the
threshold values of MI increase with decreasing pulse duration in the 1-100 ms range, increase with decreasing
exposure time and are weakly dependent upon pulse repetition frequency. The threshold value of MI for
extravasation of blood cells in mouse lung is approximately 0.3. The implications of these observations for human
exposure are yet to be determined.

4. No extravasation of blood cells was found in mouse kidneys exposed to peak pressures in situ
corresponding to an MI of 4. Furthermore, for diagnostically relevant exposures, no independently confirmed,
biologically significant adverse nonthermal effects have been reported in mammalian tissues that do not contain
well-defined gas bodies.

CONCLUSIONS REGARDING EPIDEMIOLOGY

Official Statement
Approved
March 1995

Based on the epidemiologic evidence to date and on current knowledge of interactive mechanisms, there is
insufficient justification to warrant a conclusion that there is a causal relationship between diagnostic ultrasound and
adverse effects.

CONCLUSIONS REGARDING HEAT

Official Statement
Approved
March 1993,
October 1987

1. Excessive temperature increase can result in toxic effects in mammalian systems. The biological
effects observed depend on many factors, such as the exposure duration, the type of tissue exposed, its cellular
proliferation rate, and its potential for regeneration. Age and stage of development are important factors when
considering fetal and neonatal safety. Temperature increases of several degrees Celsius above the normal core range
can occur naturally; there have been no significant biological effects observed resulting from such temperature
increases except when they were sustained for extended time periods.

a. For exposure durations up to 50 hours, there have been no significant biological effects observed
due to temperature increases less than or equal to 2°C above normal.

77
 b. For temperature increases greater than 2°C above normal, there have been no significant
biological effects observed due to temperature increases less than or equal to

log 10t
6 - ———
0.6

where t is the exposure duration ranging from 1 to 250 minutes. For example, for temperature
increases of 4°C and 6°C, the corresponding limits for the exposure duration t are 16 min and 1 min, respectively.

c. In general, adult tissues are more tolerant of temperature increases than fetal and neonatal tissues.
Therefore, higher temperatures and/or longer exposure durations would be required for thermal damage.

2. The temperature increase during exposure of tissues to diagnostic ultrasound fields is dependent
upon (a) output characteristics of the acoustic source such as frequency, source dimensions, scan rate, power, pulse
repetition frequency, pulse duration, transducer self heating, exposure time and wave shape and (b) tissue properties
such as attenuation, absorption, speed of sound, acoustic impedance, perfusion, thermal conductivity, thermal
diffusivity, anatomical structure and nonlinearity parameter.

3. For similar exposure conditions, the expected temperature increase in bone is significantly greater
than in soft tissues. For this reason, conditions where an acoustic beam impinges on ossifying fetal bone deserve
special attention due to its close proximity to other developing tissues.

4. Calculations of the maximum temperature increase resulting from ultrasound exposure in vivo
should not be assumed to be exact because of the uncertainties and approximations associated with the thermal,
acoustic and structural characteristics of the tissues involved. However, experimental evidence shows that
calculations are capable of predicting measured values within a factor of two. Thus, it appears reasonable to use
calculations to obtain safety guidelines for clinical exposures where temperature measurements are not feasible. To
provide a display of real-time estimates of tissue temperature increases as part of a diagnostic system, simplifying
approximations are used to yield values called Thermal Indices.* Under most clinically relevant conditions, the soft-
tissue thermal index, TIS, and the bone thermal index, TIB, either overestimate or closely approximate the best
available estimate of the maximum temperature increase (DTmax). For example, if TIS = 2, then DTmax 2°C.

5. The current FDA regulatory limit for ISPTA.3 is 720 mW/cm2. For this, and lesser intensities, the
best available estimate of the maximum temperature increase in the conceptus can exceed 2°C.

6. The soft-tissue thermal index, TIS, and the bone thermal index, TIB, are useful for estimating the
temperature increase in vivo. For this purpose, these thermal indices are superior to any single ultrasonic field
quantity such as the derated spatial-peak, temporal-average intensity, ISPTA.3. That is, TIS and TIB track changes
in the maximum temperature increases, DTmax, thus allowing for implementation of the ALARA principle, whereas
ISPTA.3 does not. For example,

a. At a constant value of ISPTA.3, TIS increases with increasing frequency and with increasing
source diameter.
b. At a constant value of ISPTA.3, TIB increases with increasing focal beam diameter.

(Reprinted with permission of AIUM, 14750 Sweitzer Lane, Suite 100, Laurel, MD 20707-5906)

NOTIUNI INTRODUCTIVE
Ecografia obstetricala- instrument eficace
Examenul ecografic obstetrical standard
“Ecografistii”
Scopuri- ecografie obstetricala
Continutul- ecografie obstetricala
Scopurile cursului
“Tipuri” de ecografie obstetricala
Determinarea varstei gestationale
Ecografia in T I
uter, anexe (CL)

78
morfologie embrio-fetala
diagnosticul sarcinii
Determinarea varstei gestationale
anomalii

Ecografia in T II-III
stabilirea varstei gestationale-BPC
-HC
-AC
-FL
aprecierea cresterii fetale
morfologia fetala * generalitati- momentul examenului
- examinator/ examinare
- acuratete
* cap
- sectiune transtalamica
- sectiune transventriculara
- sectiune transcerebrala
- anomalii
* coloana
* Cord
* torace
* abdomen- stomac
- ficat, splina, vezica urinara, intestin.
- perete
* aparat urinar- vezica
- rinichi
* aspect exterior, schelet
LA
Placenta
Aprecierea ..... fetale
Uter, anexe
Sarcina multipla
Ecografia interventionala
Doppler
Securitate
screening- controversat
Ecografia obstetricala- instrument eficace
Dg. de curatete al varstei gestationale
Dg. sarcinei multiple precoce
Dg. anomalii morfologice precoce
Aprecierea LA
Cresterea fetala
Bunastarea fetala
Localizarea placentei
In orice complicatie ulterioara – decizie facilitata de o ecografie precoce (α Fp, HLG, cezariana iterativa)
18-20 SA- suficient de devreme – biometrii ....
tarziu - anomalie fetala
Examenul ecografic obstetrical “standard”
( nivelul I biometrii/ nivelul II anatimie- depasit
 consult in echipa
 consult tentit
Ecografia obstetricala:
Scopuri
 evidentierea sarcinei, fatului, anexelor in II-III, diminsiuni
 recunoasterea normalului/ anormalului anatomic
 realizarea de masuratori
Continutul ex. US baza:
 apreciere fetala( nr., viabilitate, pozitie

79
  biometrii fetale, greutate(FW)
 apreciere LA
 localiz. placentei
Scopul cursului:
 familializarea cu notiunile de baza( dg. de sarcina, biometrie fetala)
 recunoasterea anatomiei fetale
 facilitarea practicii
 ajutor in decizia de cunsult in echipa/ trimitere
 ajutor pentru studiul ulterior( teoretic, practic)
ecografia:
 transvaginala Tr. I
 transabdominala- Tr. II-III
 transperineala- col uterin
Determinarea varstei gestationale:
 multitudine de parametrii
 varietate individuala
 diferite sisteme de referinta
Tr. I:
 gestational sac (GS)
 crown-rump length (CRL)
Tr. II-III:
 biparietal diameter(BPD)
 head circuference(HC)
 abdominal circumference (AC)
 femur length (FL)
acuratetea determinarii varstei gestationale bazata pe diferite biometrii
Dg. s. ( deficil FU, CO)
 sac gestational fara elemente E, nedeosebit de o colectie lichidiana ( NU dg. s.)
 din momentul sacului vetilin (6 SA)
 E 6 SA – activ. cardiaca
Morfologia E-fetala Tr. I:
 sacul gestational ( chorionic) prima structura vizibila, celum extraembrionar
 creste 1 mm/ zi
Caracteristici sac N.:
 localiz. fund uterin
 rotund
 incorpurat de o coroana hiperecogena (chorion, vilozitati)
 embrion 6 SA ( la inceput pol embrionar)
 activ. cardiaca ( trebuie sa fie vizibila in E > 5mm CRL(± mod M) la E~ 1mm, SG 20mm
 progresiv- alte structuri (cap, corp)
Vezicula vetilina (yolk sac):
 la 6 SA vizibil
 in afara sacului amniotic- < 6mm
 rotund
 unic (exceptie S. multipla)
 membrana amniotica nelipita 7 SA
 8 SA vizibil clar
Varsta gestationala:-(SG )
 vizibil la 5 SA (4mm)
 masurat-mediu MSD φ (lungime+inaltime+grosime)/3
2 imagini sau 3D
 varsta gestationala (zile) = MSD(mm) +30± 4
CRL:
 E vizibil la 6SA
 masuratul la 7 SA
 adecvat la 7- 13 SA
 varsta gestationala (SA) = CRL+6.5
BPD:
80
  nivel plan transversal (axial)- talamus, cavum sptum, pellciudum,cerebel
 nivel plan transversal (cranial)- sus venriculi- (caudal) jos orbita, fosa post. (cu emisfere
cerebrale)
 conventional- leading edge(margine ext., margine int.)
 6cm= 24SA ± 11 zile .... viabilitate
 in 5% nevizualizate ( pozitie fetala)
 index cefalic BPD/OFD=0.78± 0.05
HC:
 traseu
 calculata automat din 2 diam. sau manual ( BPD+OFD)+II/2(1.57)
 BPD ( biparietal diameter)
 OFD ( occiputofrontal diameter- coventional- extern – extern
 in caz de bradi/dolicocefalie
AC:
 c. m. complexa
 marker fetal variabil
 miscari respiratori fetale(locatie, forma abdomen)
 umbra- coloana, membre→ identificare cutanata dificila
 plan :
 normal pe axul lung al corpului
 nivel- stomac
 nivel- jonctiune v. ombilicala/ sinus portal
 HC/AC= parametru in FG
FL:
 trohantero-extremitatii distale
 excludere: epifide, alte ecouri periostale
 imagine variabila dependent de 9 varsta gestationala, ecouri epifizare)
 sonde sectoriale- ↑ daca departe, lateral
 preferabil axial> lateral
Aprecierea cresterii fetale:
 avantajul unei determinari precoce a varstei gestationale
 masuratori multiple in timp per parametru→ inscrierea pe un grafic BPD, FL, HC, AC,
HC/AC=Fetal weight)
 combinatii, formule
 simetrica/ asimetrica
 reevaluare la 2 SA
 macrosomie (1.4cm+φ abd→ 87%>4000g.
 unul din aspectele c. m. incarcate de responsabilitate
 2-3 % anomalii congenitale majore→ neidentificate
 responsabilitate justificata a N. congenitale → implicatii majore asupra momentului, caii, locului
nasterii si medicolegal
SNC:
Anomalii observate intotdeauna:
 anencefalie
 hidrocefalie
 ventriculomegalie>15mm
 chiste de fosa posterioara
 holoprosencefalie alobar
Anomalii de obicei neobservate:
 spina bifida
 agenezie parietala de corp calos
 chiste mici paraencefalice
 hemivetebre
 scolioza fixata
Corp:
Anomalii observate:
 perete, membre

81
  obstructie intestinala proximala
 hidrotorax cu deplasare mediastinala
 ascita importanta
 omfalocefal continand ficatul sau intestin
 agenezie renala bilaterala
Anomalii de obicei neobservate:
 majoritatea anomaliilor craniofaciale
 intersexualitatea
 agenezie renala unilaterala
 gastroschizis<1cm
 ciste abdominale sau tumori toracice
 hernia diafragmatica cu stomacul in abdomen
 majoritatea anomaliilor de schelet
Momentul examenului:
 normalul mimeaza anormalului (hrnierea fiziologica a pretelui abdominal ant. → omfalocel)
 anormalul mimeaza normalului(anencefalia)
 daca stomac, rinichi, splina, creier, craniu, coloana, membre, perete abdominal anterior) intre 9-
14 SA
Acuratete:
 sensibilitate totala 53%
 specialitate totala 99%
Examenator/ examinare: rolul examinatorului
 interpretatrea fiziopatologica, risc implicat.
 examen detaliat:
 34 sectiuni + masuratori specifice
 pentru fiecare str. normala, suspec., anormal, slab viz., inaplicabila
 1 h- daca este anormal
Morfologie fetala:
Sectiune transtalamica
8. Cap:
 imposibilitate masurare- anencefalie
 forma – 0.71<BPD?OFD<0.87
 Bradicefalic > 0.87
 Dolicocefaic<0.7
 forma de “lamaie” – anomalii
 ventriculi cerebrali:
 < 20 SA pliuri de plexurile coroide( hiperecogene)
 > 20 SA ( plexurile coroide ↓ ) – zone anecogene
 diminsiuni - sfarsitul T I- 90% din sp. i. cranial
 26-40 SA ~ 33%
 separati de o suprafata, hiperecogena = falx cerebri
 Hidrocefalie + craniu, forma rotunda
Sectiune traventriculara
Sectiune transcerebrala
 fosa posterioara
 emisfere cerebeloase- hiperecogene, rotunde
 cisterna magna- anecogena
 anormal- cerebel aplatizat, alungit→ semnul bauanci
anormal:
 anencefalie
 microcefalie
 meningocefal, encefalocel
 chist plixuri coroide
 fosa post. - ↑ cisterna magna
 hidrocefalie- ventricullateral> 10mm
 colpocefalie
 holo[rosencefalie

82
  parencefalie
 agenezie corp calos
 t. i. craniene
 hidroanencefalie
 poencefalie
 anevrisme(v. Galen)
9. coloana:
 planuri:
 sagitale:
• linie cutanata intacta
• lamele post.
• corpii vertebrali
pe intreaga lungime- baza craniului- extremit. caudala
 cronar:
• lamele post. paralele
 transversal:
• piela intacta
• lamele post.
• corp vertebral
anormal spina bifide, meningocel, mielomeningocel
3. Cord:
 examen pretentios
 necesita timp ecipament corespunzator experienta
 standard –imaginea tetracamerala
Confirma date anatomice majore
-inima este in parte stanga a toracelui
-deasupra diafragmului. (Nu exista structuri anormale in torace-stomac).
-1/3 din φ toracelui
-2 ventriculi prezenti aproximativi egali
- sept interventricular prezent
-2 atrii, aprox. egali
- valvele atrioventriculare- septul se intersecteaza in mijlocul inimii
- nu exista lichid percardiac
- nu exista lichid pleural
Examen detaliat cardiac fetal:
 imagine tetracamerala
 orice anormal fetal
 antecedente fam. b. cardiaca
 fact. de risc matern:
 DZ in momentul conceptiei
 b. de colagen
 varsta inaintata
 expunere la droguri teratogene ( dilatin, alcool, isotretinoin)
 inf. virala (rubeola) in sarcina
 IUGR
 anomalii cromosomiale cunoscute
 aritmie fetala
 hidrops nonimun
Defecte observate:
 ectopia cardiaca
 ventricul hipoplazic(unic)
 lichid in pericord(hidrops)
 cardiomegalie, hipertrofie ( cardiomiopatie)
 defecte septale interatriale si interventriculare mari
 tumori cardiace
 atrezia valvulara atrioventriculara
sectiune parasagitala- prin VL, A< o parte VD, AS,
ax scurt- Valve A, P, ram D-AP
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 marile vase- vena cava, A, P (dupa incrucisare)
O sectiune sagitala cu cord, stomac, vezica- elimina numeroase anomalii.

1. prezentare generală
2. anatomie normală
3. ecografia în patologia pelvină
4. ecografia sânului

scopul examenului ecografic ginecologic:

 diagnosticul, localizarea / caracterizarea formaţiunilor pelvine
 diagnosticul, localizarea precisă a sarcinii
 evaluarea conţinutului uterin
 aprecierea zonelor dificil de examinat
 evaluarea lichidului intraperitoneal
 flux sanguin pelvin
 evidenţierea fiziologiei:
 identificarea normalului (+ diagnostic diferenţial)
 monitorizarea foliculilor
 aspect, grosime endometrială

obiectivele cursului:
 prezentarea imaginilor normale
 evidenţierea normalului prin contrastul cu imaginile anormale
 diagnostic diferenţial cu alte organe, formaţiuni abdominale pelvine
 discuţia situaţiilor frecvent întălnite
 ajutor pt. - practica asistată / individuală
- solicitarea / realizarea unui consult ecografic detaliat ginecologic

tehnica standard de examinare

 acoperire în totalitate
 documentaţie
 secţiuni – longitudinală
- transversală
- oblice
- coronară (vaginală)
- vezică în semirepleţie pt. ecografie abdominală

tipuri de ecografie: - abdominală

- transvaginală:
 secţiune coronară
 vezică în depleţie
 rezoluţie > (apropiere, frecvenţă, îndepărtarea formaţiunilor interferente)
 caracterizarea superioară a uterului, ovarelor, tumorilor pelvine
 interferează bine cu examinarea ginecologică
- transperineală
- cu substanţă de contrast

necesar pentru ecografia ginecologică

1. cunoştinţe aprofundate de fiziologie / fiziopatologie
2. posibilitatea + anamneză, examen ginecologic
3. experienţă ecografică
4. aparat

II. anatomie normală

1. uter
2. vezică urinară
3. uretra, joncţiunea uretro-vezicală
4. vagin
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 5. anexă – ovar
- trompă
6. alte imagini pelvine

6. uter – reper ecografic

- în plan median pelvic
- ecogenitate diferită de restul organelor
- endometru – ecogenitatea variabilă (apă, densitate celulară)
pe parcursul ciclului (>preovulator, luteal)
sarcină – decidualizare
menopauză <3 – 5 mm
grosime - > sub stimul E (1-5 mm)
SoHSG, HyCoSy – principiu
- poziţie faţă de axul – cervical
vaginal
- col

7. vezică urinară – reper ecografic

! umplere exagerată
! artefact: near field reverberation
lateral: m. iliopsoas (nu tumori)
8. uretră – eco vaginal, perineal
9. vagin – structură tubulară
cavitate virtuală
caudal de vezică / col
10. ovar – poziţie variabilă – lungime ligament lombo-ovarian
aderenţe
alte variante / anomalii anatomice
lateral de uter
mobilă (eco vaginal, fără aderenţa)
utilă identificarea vaselor iliace
dezvoltare foliculară
Doppler - > flux diastolic în faza postovulatorie / luteală
trompe – normale – dificil de vizualizat
- HyCoSy
11. alte imagini pelvine
- ligamente - nu / rar, ligamente rotunde
- intesrtine - heterogenitate (gaze, conţinut)
peristaltism
- uretere - rar dacă nu special căutate
- secţiune transversală lângă marginea colului
- vascularizaţie - vase iliace
- a. uterine – ocazional P1 > în S. precoce
- Doppler – a. ovariene / uterine
- lichid FDS Douglas - puţin – menstruaţie, ovulaţie

III. ecografia în patologia pelvină

A. noţiuni generale – tumorile abdominopelvine
caracterizarea tumorilor
posibilităţi
protocolul analizelor ecografice
diagnosticul diferenţial
B. patologia organelor genitale – uter
ovare
trompe
alte organe, imagini asociate

tumorile abdominopelvine:
 piatră de încercare pt. examinator (diagnostic diferenţial)
 nu există o ierarhizare a metodelor de investigaţie
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  nu trebuie inversată ordinea normală la examinare
 indicaţii de conduită – observaţie / supraveghere
completare imagistică, investigaţii
terapie
 abilitate de – detecţie
recunoaştere
apreciere
decizie

caracterizare:
 localizare (toate, + meta)
 dimensiuni (detecţie cât mai precoce)
 extindere
 caracter benign / malign
 iatrogenitate
 posibilităţi de ameliorare a imaginii:
- focalizarea fascicolului ( > rezoluţiei în adâncime)
- armonice superioare
- SoHSG, HyCoSy
- Doppler
- 3D
- ecografie intervenţională

protocolul analizei ecografice:

1. localizare, origine
2. relaţii anatomice cu alte structuri
3. dimensiuni
4. extindere
5. contur
6. grosime perete
7. conţinut – lichid - anecogene / hipoecogene
bună transmisie US
margine suprafaţă distală strălucitoare (accentuare distală)
- solid - > ecogenitate
atenuarea transmisiei us
margine – proximală distală
distală neclară
- complex
- septuri
8. semne asociate (meta, ascită)

diagnosticul diferenţial al tumorilor pelvine după conţinut

B.patologia organelor genitale

uter – poziţie
miometru
endometru, cavitate uterină
col
anomalii congenitale

poziţie – deviat de formaţiuni tumorale

- fixat de proces aderenţial
miometru – leiomiom - subseros / intramural / submucos
unic / multiplu
hiperecogen
contur uterin neregulat
semne de degenerare (+ calcificare)
! importanţă – terapeutică
- supraveghere
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 - sarcom – ecogenitate complexă, asemănătoare miomului degenerat
> flux diastolic (Doppler)
endometru
- polipi (+ SoHSG, HyCoSy), hipertrofie / plazie
- urmărire, tratament cu Tamoxifen
- carcinom +_: - cavitate neregulată
interes – invazie miometrială

cavitate uterină:
 lichid – sânge, sarcină
suspiciune infecţii, neoplasm (ovarian, tubar, endometrial, cervical)
 conţinut mixt
sânge
sarcină – normală
implantaţie cornuală, istmică (!ruptură uterină catastrofică)
avort – ecouri neorganizate
SG neregulat
hemoragie intradeciduală
S. anembrionică (ou clar)
molă
 DIU – localizare
ghidaj pt. extracţie (migrat + s. iu)

col: - volum cancer cervical

invazie parametrială (!TR) endorectală
Doppler a. uterină
S. cervicală (diagnostic diferenţial avort incomplet)

anomalii congenitale
 imperforaţie himenală, sept vaginal transversal
 hematocolpos, hematometrie (+ ex. transperineal)
 agenezie mulleriană Mayer – Rokitansky – Kustner – Hauser
 variate anomalii – bicorn, dublu, septat (complet, incomplet) dianostic dificil: septat / dublu (! anomalii
renale asociate)
 sindromul rezistenţei la E; nu există uter, ovare / există testicole
 disgenezii ovariene 45x -> uter hipoplazic
monitorizare E , tratament

ovare:
 procese funcţionale
 tumori
 anomalii congenitale (agenezie, anomalii genetice)

procese funcţionale:
1. folicul
monitorizare foliculară HSO
prelevare ovocitară
2. PCO – imagini variabile
+ hipertecoză - < nr. foliculi
ecogenitate
monitorizarea tratamentului
tumori:
 varietate mare
 clasificarea complexă
 limită benign / malign
 exemple
 diagnostic diferenţial – anse intestinale, cec secţiune transversală
varicozităţi pelviene
rinichi ectopic

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 abcese, tumori apendiculare

diferenţiere tumori benigne/ maligne ovariene

contur neted, regulat neregulat, vegetaţii
pereţi subţiri groşi
conţinut omogen complex, septuri, vegetaţii, mase
solide
vacularizaţie R1<o.4, P1<0.8 (> flux diastolic)
tumoră – vase neregulate
semne asociate ascită, metastaze

chist complexe solide

limite interne netede 1 1 -
neregulate 2 2 -
vegetaţii suspicionate 2 0 -
clare 3 2 -
septuri <3mm 0 1 -
>3mm 2 2 -
ecogenitatea părţii omogenă - 1 2
solide
neomogenă - 2 4
lichid în faza 0 0 0
intraperitoneal preovulatorie
prezent 1 1 1

Scor <4– tumoră benignă

>4 – sispiciune malignitate
Vascularizaţie – în sept, vegetaţii, în partea solidă, vase neregulate
!R1<0.4
P1<0.8

folicul matur – chist unilocular

Φ = 20 –25 mm
conţinut anecogen
perete subţire, perfect regulat
corp galben – formaţiune chistică uniloculară, anecogenă / mixtă, uneori cu septuri fine
Φ = 15 – 30 mm
corp folicular – unilocular
anecogen
Φ = 50– 100mm
perete subţire, regulat
întărire acustică posterioară

corp galben de sarcină – cu septuri fine

perete subţire
conţinut mixt cu zone solide şi lichidiene care nu respectă regulile gravitaţiei

chist seros de indiviziune – unilocular ! semnificaţie deosebită în menopauză

anecogen >3,5 – 5 cm, persistent
perete subţire

chist endometrial – unic / multiplu

conţinut cu multiple ecouri de amplitudine scăzută
Φ = 30-100mm
perete gros ?

chist dermoid – conţinut complex (predominant solid, componente ecogenice, nivel fluid / solid, uretră posterioară)
chisat unilocular, în contact cu peretele unuia sau mai multor noduli cu aspect ecogenic
(patognomonic, rar, nodulul Rokitansky )
chist septat
88
 solid

chistadenom seros – chist unilocular / uneori vegetaţii

conţinut anecogen
întărire acustică posterioară
dimensiuni variabile
uneori septate, multiloculare, multiple

chistadenocarcinom seros – conţinut complex, arii solide

vegetaţii intrachistice
septuri groase, neregulate
ascită (! Sdr. Demon – Meygs)
screening
detecţie tumorală reziduală

chistadenom mucinos – septat

ecouri fine, diseminate

chistadenocarcinom mucinos – conţinut complex

arii solide, vegetaţii

carcinom endometrioid – tumoră chistică

vegetaţii multiple
tumoră solidă
bilaterală 50%

trompe – BIP
endometrioză
SE
carcinom
anomalii congenitale

BIP – hidrosalpinx
piosalpinx
abces tubo-ovarian
imagini complexe (+ aderenţe, implicare ovariană)

endometrioză – imagini complexe – greu de diferenţiat de BIP

SE – cavitate uterină virtuală > 1500 mUI/ml (3000 mUI/ml pentru elimina s. multiplă)
formaţiune anexială – complexă
rar SG
foarte rar E, activitate cardiacă
lichid în Douglas (foarte rar S. heterotipică)

carcinom – imagini complexe

anomalii congenitale – hidatide (Morgagni)

alte organe pelvine, imagini asociate

A. peritoneu – BIP - > ecogenitate, aderenţe
B. lichid în Douglas – sânge
puroi
ascită
C. intestine – distensie – diagnostic diferenţial cu tumoră chistică / mixtă anexială
D. uretere – dilatate
E. vascularizaţie – neovascularizaţie
flux diastolic
F. adenopatii

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