This copy is for personal use only. To order printed copies, contact reprints@rsna.

org
1

WOMEN’S IMAGING
Imaging Review of Obstetric Sequelae
of Maternal Diabetes Mellitus

Hassan Aboughalia, MBBCh

Priya Pathak, MD Diabetes mellitus, whether preexisting or gestational, poses signifi-
Deepashri Basavalingu, MD cant risk to both the mother and the developing fetus. A myriad
Teresa Chapman, MD, MA of potential fetal complications in the setting of diabetic pregnan-
Margarita V. Revzin, MD, MS cies include, among others, congenital anomalies, delayed fetal
Laura E. Sienas, MD lung maturity, macrosomia, and increased perinatal morbidity and
Gail H. Deutsch, MD mortality. Congenital anomalies most commonly involve the ner-
Douglas S. Katz, MD vous, cardiovascular, genitourinary, and musculoskeletal systems.
Mariam Moshiri, MD Delayed fetal lung maturity, probably secondary to hyperglycemia
suppressing surfactant secretion, is a major determinant of peri-
Abbreviations: ACOG = American College of natal morbidity and mortality. Besides the potential complications
Obstetricians and Gynecologists, DM = diabe-
tes mellitus, EFW = estimated fetal body weight, encountered during cesarean delivery in macrosomic fetuses,
FGR = fetal growth restriction, GA = gestational vaginal delivery is also associated with increased risks of shoulder
age, GDM = gestational DM, HbA1c = hemo-
globin A1c, HELLP = hemolysis, elevated liver
dystocia, clavicular and humeral fractures, and brachial plexus
function, and low platelets, MFM = maternal palsy. Maternal complications are related to the increased risk of
fetal medicine, SUA = single umbilical artery, hypertensive diseases of pregnancy and associated preeclampsia
UTD = urinary tract dilatation
and hemolysis, elevated liver function, and low platelets (HELLP)
RadioGraphics 2022; 42:0000–0000
syndrome, as well as complications encountered at the time of
https://doi.org/10.1148/rg.210164 delivery secondary to fetal macrosomia and cesarean delivery.
Content Codes: Additional conditions encountered in the setting of maternal dia-
From the Departments of Radiology (H.A.,
betes include polyhydramnios, placental thickening, and two-ves-
P.P., D.B., T.C.) and Laboratory Medicine and sel umbilical cord, each of which is associated with adverse fetal
Pathology (G.H.D.), University of Washington, and maternal outcomes including fetal growth restriction, preterm
1959 NE Pacific St, Seattle, WA 98195; De-
partments of Radiology (T.C.) and Laboratory labor, placental abruption, and premature rupture of membranes.
Medicine and Pathology (G.H.D.), Seattle Chil- Imaging plays a vital role in the evaluation of the mother and the
dren’s Hospital, Seattle, Wash; Department of
Radiology and Biomedical Imaging, Yale School fetus and can provide invaluable information that can be used
of Medicine, New Haven, Conn (M.V.R.); by maternal fetal medicine to manage this patient population ef-
Departments of Obstetrics and Gynecology
(L.E.S.) and Radiology (M.M.), University of
fectively. The authors review the pathophysiologic alterations in-
Washington Medical Center, Seattle, Wash; and duced by diabetes in pregnancy, discuss the imaging spectrum of
Department of Radiology, NYU Langone Hos- diabetic embryopathy, and provide a detailed review of potential
pital–Long Island and NYU Long Island School
of Medicine, Mineola, NY (D.S.K.). Presented associated maternal complications.
as an education exhibit at the 2020 RSNA An-
nual Meeting. Received May 3, 2021; revision Online supplemental material is available for this article.
requested June 25 and received July 11; ac-
©
cepted July 15. For this journal-based SA-CME RSNA, 2021 • radiographics.rsna.org
activity, the authors M.V.R., G.H.D., D.S.K.,
and M.M. have provided disclosures (see end of
article); all other authors, the editor, and the re-
viewers have disclosed no relevant relationships. SA-CME LEARNING OBJECTIVES
Address correspondence to H.A. (e-mail:
[email protected]; [email protected]). After completing this journal-based SA-CME activity, participants will be able to:
©
RSNA, 2021 List those fetal organ systems most impacted in mothers with DM.
„
Describe the diabetes-specific maternal disease processes that occur during pregnancy.
„
Recognize specific US features of the placenta, amniotic fluid volume, and umbilical
„
cord that may be associated with maternal DM.
See rsna.org/learning-center-rg.

Introduction
Diabetes mellitus (DM) is due to impaired carbohydrate metabo-
lism secondary to defective insulin secretion or function and is one
of the most prevalent endocrine disorders worldwide. DM is classi-
cally categorized into type 1 and type 2 on the basis of epidemiology,
2  January-February 2022 radiographics.rsna.org

Screening for and Diagnosis of GDM

TEACHING POINTS The U.S. Preventive Services Task Force rec-
„ The underlying pathophysiologic alteration in the majority of
patients with GDM is similar to that observed in patients with
ommends laboratory screening for GDM in
type 2 DM and involves pancreatic β-cell dysfunction, lead- all women at or beyond 24 weeks of gestation
ing to poor insulin production, and this is superimposed on a given that medical history alone is inadequate
background of insulin resistance in the muscles, liver, and fat. in identifying women with GDM (3). According
Although GDM usually resolves following pregnancy, both to the American College of Obstetricians and
the affected mother and child are at increased risk of develop-
ing diabetes and cardiovascular diseases in the future.
Gynecologists (ACOG), the most commonly
used method of screening for GDM is the 50-g,
„ Routine inclusion of fetal echocardiography is recommended
only in patients with preexisting DM, according to the most
1-hour oral glucose tolerance test (OGTT).
recent AIUM guidelines. Abnormal screening test results are further con-
„ Infants of women with pregestational DM have a two to five firmed by using the 100-g, 3-hour OGTT (Fig
times increased risk of congenital heart disease, the most 1) (4). In certain situations, screening for GDM
common of which is atrioventricular septal defects according can be done during the initiation of prenatal care,
to a systematic review by Simeone et al. This risk is highest in particularly in patients with high risk for GDM
women who receive insulin therapy at the time of conception
and lower in women who develop gestational diabetes later
including those with obesity, history of GDM in
in pregnancy. a prior pregnancy, family history of type 2 DM,
„ DM is associated with increased risk for preeclampsia, most and prior history of poor obstetric outcomes (4).
commonly in patients with type 1 DM, with a reported inci-
dence of 18% and a lesser incidence in pregnancies with type Pathogenesis of Diabetic
2 DM and GDM. Embryopathy
„ A thick placenta is independently associated with adverse Diabetic embryopathy refers to the spectrum
perinatal outcome including FGR and need for emergency of fetal malformations linked to DM during
cesarean delivery. DM is among the most common causes of
placental thickening, in addition to toxoplasmosis, other infec-
pregnancy. Both type 1 and 2 DM demonstrate
tions, rubella, cytomegalovirus, and herpes simplex (TORCH) overlapping rates of fetal malformations that
infection; triploidy; and fetal hydrops. correlate with diabetic control, with an occur-
rence risk of 5% in patients with a hemoglobin
A1c (HbA1c) level less than 8%. This risk rises
clinical presentation, and underlying metabolic to 25% in patients with HbA1c levels higher
aberration. Type 2 DM accounts for more than than 10% (5). The etiopathogenesis of diabetes-
85% of the overall cases, with type 1 diabetes induced teratogenesis is complex and is still
accounting for 5%–10% (1). Other less com- incompletely understood. Maternal hyperglyce-
mon subtypes of DM exist, including gestational mia is a major factor implicated in teratogenesis
diabetes, a distinct entity that requires special based on elevated HbA1c and glucose levels
attention as it carries significant maternal, fetal, directly correlating with increased risks of fetal
and neonatal health risks. During pregnancy, the congenital malformations. Hyperglycemia results
mother can either present with preexisting DM in increased formation of oxygen free radicals
(type 1 or 2) or can develop pregnancy-related through various metabolic pathways, including
gestational diabetes. Recognized during the sec- glycolysis, the citric acid cycle, and the hexose
ond or third trimester of pregnancy, gestational monophosphate shunt pathway. In addition, there
DM (GDM) is known to affect approximately is increased expression of nitric oxide synthase,
14% of pregnant patients worldwide. The under- which produces reactive nitrogen species, alter-
lying pathophysiologic alteration in the majority ing signaling pathways of arachidonic acid (an
of patients with GDM is similar to that observed ω-6 fatty acid), inositol, and prostaglandins, and
in patients with type 2 DM and involves pancre- increased intracellular concentration of advanced
atic β-cell dysfunction, leading to poor insulin glycosylation end products.
production, and this is superimposed on a back- These metabolic derangements result in gene
ground of insulin resistance in the muscles, liver, dysregulation and apoptosis. Ketone bodies,
and fat. Although GDM usually resolves fol- which are synthesized in higher amounts in ma-
lowing pregnancy, both the affected mother and ternal diabetes, are additional potential terato-
child are at increased risk of developing diabetes gens, acting in synergy with hyperglycemia. Gene
and cardiovascular diseases in the future (1,2). expression and epigenetic processes are affected
Recognized risk factors for developing GDM in diabetes as well, although no single gene that
include obesity, advanced maternal age, eth- correlates to increased risk of subsequent em-
nic group, micronutrient deficiencies, positive bryopathy has been identified to our knowledge
family history of insulin resistance, and other (6,7). Higher placental growth factors produced
diseases of insulin resistance including polycys- by the diabetic environment lead to endothelial
tic ovarian syndrome (1). proliferation, neovascularization, villous malfor-
RG  •  Volume 42  Number 1 Aboughalia et al  3

Figure 1.  Chart shows the diagnostic algorithm for GDM.

Figure 2.  Chart shows that complex pathogenic mechanisms initiated by diabetes induce hyperglycemia
in pregnancy and are involved in causing diabetic embryopathy, fetopathy, and pregnancy complications.
AGE = advanced glycosylation end product, IUGR = intrauterine growth restriction.

mations, and thickening of the basal trophoblast tion of the fetal weight, diagnosis of congenital
membrane, which cumulatively result in fetal malformations, and monitoring of pregnancy in
hypoxia (Fig 2). general. Since maternal diabetes is considered
The timing during which the previously de- a high-risk condition, the American Institute of
scribed sequences are initiated is highly correlated Ultrasound in Medicine (AIUM) recommends
with different maternal and fetal complications. performing detailed diagnostic obstetric second-
Metabolic derangements in early pregnancy, trimester anatomy US in a referral center where
typically before the 7th week of gestation, lead to personnel have expertise in obstetric US. Fetal
blastogenic malformations, spontaneous abor- structures evaluated during a detailed second-
tions, and multiorgan and syndromic malforma- trimester US examination in high-risk pregnancy
tions. On the other hand, the development of compared with those in a standard examination
such metabolic alterations later in pregnancy is are detailed in Table 1 (10). Fetal evaluation
associated with increased risk of macrosomia and should also be tailored further on the basis of any
isolated fetal anomalies (8). In addition, abnor- findings on the anatomic image. For example,
malities of organogenesis and placentation play a fetal echocardiography may be warranted if a
major role in second-trimester pregnancy loss (9). cardiac defect is suspected. Routine inclusion of
fetal echocardiography is recommended only in
Role of US patients with preexisting DM, according to the
The role of US in the management of diabetic most recent AIUM guidelines (11). Some authors
pregnancies is well established. US is routinely advocate for serial US follow-up for assessment of
used for assessment of fetal biometry and estima- fetal growth and amniotic fluid volume, especially
4  January-February 2022 radiographics.rsna.org

Table 1: Fetal Structures Evaluated at Standard and Detailed Second-Trimester US Examinations

Structures at Standard Additional Structures at Detailed

Region Second-Trimester US Second-Trimester US
Head and neck Lateral ventricles and choroid plexus, mid- Third and fourth ventricles, lateral ven-
line falx, cavum septum pellucidi, cerebel- tricular wall and integrity; cerebellar
lum, and cisterna magna lobes, vermis, and cisterna magna; cor-
pus callosum; brain parenchyma, cranial
vault, and neck
Face Upper lip Profile and nasal bones, coronal face
(nose, lips, and lens), mandible and
maxilla, orbits and ear position
Heart Cardiac activity, four-chamber view, right Situs; aortic arch, superior and inferior
and left ventricular outflow tracts vena cava view; three-vessel view, three-
vessel and trachea view; interventricular
septum
Lungs Not mandatory Lung, ribs, and diaphragm
Abdomen Stomach, kidneys and urinary bladder, Abdominal wall integrity, bowel, solid
umbilical cord insertion and vessel organs
number
Spine Cervical, thoracic, lumbar, and sacral spine Shape, curvature, and conus medullaris;
integrity of the spine and overlying soft
tissue; integrity of the spine and overly-
ing skin
Extremities and Legs and arms, hands and feet Number and position of the extremities
external genitalia and digits
Placenta Location and relationship to internal os, Implantation site for adherent placenta,
appearance placental thickness and any masses,
accessory placenta

during the third trimester when macrosomia can Congenital Anomalies

dictate the route of delivery (12).
A major potential limitation of US is obscura- Central Nervous System Anomalies.—Caudal
tion of fetal structures and associated congenital dysgenesis is 200 times more common in infants
anomalies secondary to maternal obesity related of mothers with diabetes and is considered one
to diabetes. In this setting, there should be a low of the hallmarks of diabetic pregnancy (14). Ac-
threshold to perform follow-up US for a more cording to the Torotori classification for spinal
favorable fetal position or pursue fetal MRI if dysraphism, caudal dysgenesis is described as a
suspicion for an abnormality is high. US with closed spinal dysraphism of a complex nature
a transvaginal approach may also be preferable without an associated subcutaneous mass (15).
in this patient population. Although maternal Frequent other associated anomalies include
diabetes does not increase the risk of chromo- anorectal, genitourinary, and gastrointestinal
somal aneuploidy, maternal obesity related to malformations (16). Mutations in the MNX1
diabetes can impact aneuploidy screening. For (HLXB9) homeobox gene are implicated in
example, the nuchal translucency US examina- Currarino syndrome, characterized by sacral de-
tion in pregnant women with diabetes tends to fect, anal atresia, and anterior meningocele (17).
be longer in duration, and there is a reported Caudal dysgenesis is classified into two types.
increased frequency of nonvisualization of the Type 1 describes spinal column termination at
fetal nasal bone resulting in an increased need the level of the S1 vertebral body or above. In
for transvaginal US examination (13). this type, there is abrupt and blunted termina-
tion of the spinal cord, with the conus medul-
Fetal Abnormalities laris level higher than normal. In type 2, the
The spectrum of fetal abnormalities observed osseous termination ends at the level of the
in diabetic pregnancies includes fetal congenital S2 vertebral body or below and is frequently
anomalies, delayed lung maturity, and altered associated with cord tethering by a tight filum,
fetal weight, as well as perinatal morbidity and lipoma, lipomeningocele, and/or a terminal
mortality (Table 2). myelocystocele (18).
RG  •  Volume 42  Number 1 Aboughalia et al  5

Table 2: Spectrum of Complications Encountered in Diabetic Pregnancies

Complication Description
Fetal complications
Congenital anomalies Nervous system: NTDs, holoprosencephaly-caudal dysgenesis
Heart and great vessels: VSD, conotruncal abnormalities
Genitourinary system: renal agenesis, UTD, MCDK, duplex kidney
Skeletal system: preaxial polydactyly, syndactyly, and radial ray anomalies
Fetal lung maturity Maternal hyperglycemia interferes with corticosteroid therapy, delaying lung matura-
tion
Fetal growth Accelerated growth is usually apparent by the late second trimester, with a dispro-
portionate increase in abdominal and head circumferences; in addition, there is
subcutaneous fat deposition
Miscellaneous Spontaneous abortion increases with poor glycemic control
Stillbirth is four times more common
Metabolic derangements and respiratory distress syndrome are more frequent in
infants of diabetic mothers
Maternal complications
Preeclampsia Diabetes increases the risk of preeclampsia, which correlates with the extent of gly-
cemic control (up to 18%); this in turn might be associated with severe obstetric
complications, including HELLP syndrome
Placental abruption: placental detachment before delivery of the fetus
Cesarean delivery The main indication for cesarean delivery is macrosomia to avoid shoulder dystocia
Long-term sequelae of cesarean delivery include increased risk of abnormal placen-
tation, as well as uterine dehiscence and rupture in subsequent pregnancies
Other complications
Placental thickening Thick placenta independently associated with adverse pregnancy outcomes
and early maturation
Amniotic fluid volume Second most common cause of polyhydramnios
Oligohydramnios might be seen if there is long-standing diabetes or associated ma-
ternal hypertension
  Umbilical cord SUA affects up to 6% of infants of diabetic mothers
Associated with increased frequency of growth retardation and preterm delivery
Note.— MCDK = multicyclic dysplastic kidney, NTD = neural tube defect, SUA = single umbilical artery,
TA = truncus arteriosus, TGA = transposition of the great vessels, UTD = urinary tract dilatation, VSD = ven-
tricular septal defect.

At first-trimester US, caudal dysgenesis is sug- lies. In 2008, Correa et al (22) published a large
gested when small crown-rump length, increased U.S.-based multicenter study with 13 030 patients
nuchal translucency, and lower spine protuber- that focused on analysis of the frequency of birth
ance are detected (19). The definitive diagnosis defects in diabetes (22). The authors highlighted
is made at second-trimester US with demon- the increased risk for congenital CNS anomalies
stration of abrupt termination of the spine. The in diabetic pregnancies, particularly anencephaly,
fetal lower extremities may show characteristic encephalocele, and holoprosencephaly. The odds
positioning with hip abduction and knee flexion, ratio was higher in mothers with pregestational
called the cross-leg tailor position or Buddha DM in comparison with those with GDM. For
pose. The iliac wings may be fused, yielding a example, the odds ratio for the presence of anen-
shieldlike appearance of the pelvic bones (Fig cephaly in pregestational DM versus GDM was
3, Movie 1) (20). MRI can better delineate the 3.39 versus 1.33, and for encephalocele was 2.09
level of caudal dysgenesis, associated spinal cord versus 1.82, respectively (22). Another large-popu-
abnormalities, and other accompanying anoma- lation European study by Garne et al (23) in 2012
lies. US follow-up is recommend for evaluation of confirmed the increased risk of CNS anomalies
interval fetal growth and amniotic fluid volume. in the context of pregestational diabetes, with an
Predelivery US is recommended to assess fetal overall odds ratio of 1.23 for any CNS anomaly,
presentation, as malpresentations are common in particularly for encephalocele (odds ratio, 3.22)
caudal dysgenesis (21). and anencephaly (odds ratio, 1.9).
Infants of diabetic mothers are at increased risk Anencephaly is a lethal anomaly describing ab-
for other central nervous system (CNS) anoma- sent major portions of the brain, skull, and scalp
6  January-February 2022 radiographics.rsna.org

Figure 3.  Caudal dysgenesis. (A) Longitudinal gray-scale US image (sagittal orientation) shows a fetus at 23 weeks gestational age
(GA) with absence of caudal spinal elements in the lumbosacral region (arrow). (B) Transverse gray-scale US image of the same fetus
as in A shows associated abnormal approximation of the iliac bones (arrows). (C) Frontal radiograph of a different aborted fetus
shows premature truncation of the vertebral column at the L3 level (*). Note the shieldlike appearance of the pelvic bones (arrow).
(D) Sagittal T2-weighted MR image of the lumbosacral region in a different 1-day-old neonate shows premature truncation of the
spinal column with agenesis of the distal sacral elements (arrow). (E) Photograph of an aborted fetus with caudal dysgenesis shows
a foreshortened left leg with contracture of the ankle joint (arrow), highlighting the frequent association of caudal dysgenesis with
developmental abnormalities of the lower extremities. (F) Clinical photograph of a different aborted fetus with caudal dysgenesis
shows absence of an external anal opening in an imperforate anus (arrow).

above the orbits (Fig 4). Exencephaly describes prosencephalon (forebrain), characterized by
abnormally formed brain tissue without the pres- varying degrees of failed cleavage of the cerebral
ence of a calvarium and can be diagnosed with hemispheres and deep gray matter nuclei. Three
100% confidence at the time of nuchal trans- classic subtypes are described: alobar, semilobar,
lucency screening. This is considered an earlier and lobar holoprosencephaly (Fig 7, Table 3). No
stage of anencephaly, with further destruction of fetal intervention is indicated, and termination
the brain tissue due to absence of the protective can be offered given the grave sequelae of the
calvarium, eventually leading to anencephaly (Fig disease and the high mortality observed in severe
5, Movie 2) (24). cases of holoprosencephaly (26).
Encephalocele refers to protrusion of intracra-
nial structures through a defect in the skull, most Cardiac Anomalies.—Infants of women with pre-
commonly occurring in the occipital or frontal gestational DM have a two to five times increased
regions (Fig 6, Movie 3). On the basis of the con- risk of congenital heart disease, the most com-
tents, a protrusion containing only meninges and mon of which is atrioventricular septal defects
cerebrospinal fluid is called a meningocele, while according to a systematic review by Simeone et
the presence of brain tissue in the sac content is al (27). This risk is highest in women who receive
known as an encephalomeningocele. Encephalo- insulin therapy at the time of conception and
cele outcome depends on its content and loca- lower in women who develop gestational diabetes
tion, and cesarean delivery is often pursued to later in pregnancy (27). The risk for conotruncal
avoid injury of the intracranial structure at the cardiac anomalies, including truncus arteriosus,
time of delivery (24,25). double-outlet right ventricle, transposition of the
Holoprosencephaly refers to a spectrum of great vessels, and tetralogy of Fallot, is statisti-
brain malformations that affect the developing cally significantly higher when compared with
RG  •  Volume 42  Number 1 Aboughalia et al  7

Figure 4.  Anencephaly. (A) Longitudinal gray-scale US image (sagittal orientation) of a fetus at 11 weeks 6 days GA shows lack
of brain development, with only a small amount of tissue above the orbits (arrow). (B) Coronal gray-scale US image of the face
of another fetus shows the characteristic “frog eye” appearance of the fetal head due to lack of brain matter development above
the orbits (arrows). (C) Clinical photograph of an aborted fetus shows total absence of the calvarium superior to the orbits with a
diminutive misshaped skull.

Figure 5.  Exencephaly. (A) Lon-

gitudinal transabdominal gray-scale
US image (sagittal orientation) of a
fetus at 12 weeks 5 days GA shows
disorganized fetal brain tissue with-
out a calvarium (arrow). (B) Sagit-
tal T2-weighted image of another
fetus at 21 weeks 4 days GA shows
absence of supratentorial brain with
abnormal exophytic neuronal tissue
in the posterior fossa and region of
the brainstem along the inferior cal-
varium (arrow).

that for other cardiac anomalies. The proposed hypertrophy. In truncus arteriosus, there is a
theory for this difference is hyperglycemia- common arterial trunk instead of a separate
induced neural crest cell death affecting the aorta and pulmonary artery (Fig 8). On the other
morphogenesis of the developing heart (28). hand, transposition of the great vessels describes
Understanding the sonographic relationship reversed relationship between the pulmonary ar-
among the pulmonary and aortic arteries at fetal tery and aorta with secondary ventriculo-arterial
US assessment is key to diagnose conotruncal discordance (Fig 9). Double-outlet right ventricle
anomalies. Normally, the main pulmonary artery is another anomaly in which a major portion of
lies to the left of the ascending aorta, and the right the aorta arises from the right ventricle, in addi-
pulmonary artery courses posterior to the ascend- tion to the pulmonary artery (29).
ing aorta and below the aortic arch. This relation- Finally, it is also important to highlight that
ship is best evaluated by using the outflow tract these infants are prone to develop hypertrophic
projections, highlighting the origin and orientation cardiomyopathy, which is noted in up to 30% of
of the great vessels. Thus, they are of great value in infants of diabetic mothers at echocardiography.
the assessment of the conotruncal anomalies (29). This condition manifests postnatally with respi-
The essential underlying abnormality in ratory distress, and in up to 12% of cases it can
patients with tetralogy of Fallot is underdevel- manifest as heart failure, requiring supportive
opment of the pulmonary infundibulum with a therapy (30).
resultant constellation of abnormalities includ-
ing right ventricular outflow stenosis, ventricu- Renal Anomalies.—Congenital abnormalities of
lar septal defect with an overriding aorta, and the kidney and urinary tract (CAKUT) account
later development of secondary right ventricular for up to 20% of all prenatally detected birth
8  January-February 2022 radiographics.rsna.org

Figure 6.  Meningoencephalocele. (A) Transabdominal transverse gray-scale US image shows an ex-
tracranial complex cystic structure consisting of herniating meninges and cerebrospinal fluid commu-
nicating with the skull cavity through a calvarial defect (arrow). The complex nature of the cystic lesion
suggests the presence of brain parenchyma within the hernia sac. (B) Clinical photograph of a different
neonate shows a large skin-covered circumscribed bulge in the occipital region, compatible with an
encephalocele.

Figure 7.  Alobar holoprosencephaly in a fetus at 23 weeks 3 days GA. (A) Transabdominal transverse gray-scale US image shows
fused thalami (arrow) and an enlarged posterior midline fluid space (*). (B) Axial T2-weighted MR image shows the enlarged pos-
terior midline fluid space (*). (C) Axial T2-weighted MR image at the level of the orbits shows thalamic fusion (arrow). Fetal hypo-
telorism is additionally noted (*).

Table 3: Subtypes of Holoprosencephaly

Structure

Subtype/Region Interhemispheric Fissure Deep Gray Matter Nuclei Ventricular System

Lobar Present anteriorly and posteriorly Almost completely separated Attempt at third ventricle
and temporal horn for-
mation
Frontal horns present
Semilobar Absent anteriorly but present Varying degrees of separation Attempt at third ventricle
posteriorly Fused thalami and temporal horn for-
mation
Frontal horns absent
Alobar Absent anteriorly and posteriorly Fused Large monoventricle
Absent third ventricle
RG  •  Volume 42  Number 1 Aboughalia et al  9

Figure 8.  Truncus arteriosus in a

fetus at 26 weeks GA. (A) Transab-
dominal transverse gray-scale US
image shows cardiomegaly with
a common outflow tract (arrow)
on the three-vessel view. (B) Color
Doppler US image shows the com-
mon outflow tract (arrow).

Figure 9. Transposition of the

great arteries in a fetus at 34 weeks
GA. (A) Transabdominal transverse
gray-scale US image shows an ante-
riorly located left ventricular outflow
tract (arrow) arising from the right
ventricle (RV). (B) Note the abnor-
mal parallel configuration of the
aortic outflow tract (AO) and pulmo-
nary outflow tract (PA) on the aortic
arch view.

defects and 50% of pediatric chronic kidney chymal abnormalities, ureteral dilatation, and
disease cases (31,32). CAKUT are commonly bladder abnormalities (37). Based on the UTD
subdivided into three categories according to classification, fetuses with a dilated ureter in the
their embryologic origin: renal parenchymal context of collecting system dilatation are at in-
malformations, anomalies of renal embryonic creased risk for developing postnatal uropathies,
migration, and outflow abnormalities (33). The and hence the anomaly is classified as UTD
risk of CAKUT increases by 50% in diabetic A2–3. These patients require follow-up prenatal
pregnancies regardless of diabetes subtype, with imaging as well as postnatal US and consulta-
a higher risk in pregestational DM (34). It is tion by a pediatric urologist. A full discussion
suggested that the teratogenic effect of hypergly- of the UTD classifications and guidelines are
cemia on renal development mainly affects the beyond the scope of this article, and we refer the
ureteric branching during morphogenesis and reader to the review article by Nguyen et al (37).
nephrogenesis (35).
The most commonly encountered CAKUT Musculoskeletal Anomalies.—Polydactyly
in infants of diabetic mothers include renal (supernumerary digits) is an uncommon find-
agenesis (Fig 10), urinary tract dilatation ing during fetal evaluation. It can be isolated
(UTD) (Fig 11), multicystic dysplastic kidneys or syndromic, such as with Ellis-van Creveld
(Fig 12), and duplicated collecting system (Fig syndrome or trisomy 13. Adam et al (38) evalu-
13) (36). Prenatal US plays an important role ated 18 fetuses with diabetic embryopathy and
in the assessment of fetal kidneys and collect- polydactyly in an attempt to establish any asso-
ing system dilatation. The Society for Pedi- ciation between polydactyly and diabetic embry-
atric Urology, in consensus with the AIUM opathy and found that proximally placed preaxial
and ACOG, published guidelines for a UTD hallucal polydactyly (an additional digit along
classification system, which aims to unify the the radial side of the hand) is linked to diabetic
sonographic nomenclature and classification for embryopathy. This relationship is stronger if there
UTD while standardizing imaging evaluation are associated spine segmentation anomalies and
and postnatal follow-up. Factors governing this tibial hemimelia (partial or complete absence
classification include anterior-posterior renal of the tibia) (38). In the literature, a radial ray
pelvic diameter, calyceal dilatation, renal paren- spectrum of anomalies involving the radius, radial
10  January-February 2022 radiographics.rsna.org

Figures 10–13.  (10) Unilateral renal agenesis in a fetus at 20 weeks 4 days GA. (10A) Transabdominal transverse gray-scale US im-
age at the level of the renal fossa shows absence of the left kidney (*). (10B) Longitudinal gray-scale US image (coronal orientation)
shows again an empty renal fossa with an elongated adrenal gland (arrow). (10C) Coronal color Doppler US image shows absence
of the left renal artery (*), the expected location of the origin of the renal artery from the aorta. (11) UTD in a fetus at 33 weeks 3
days GA. Longitudinal gray-scale US image (coronal orientation) shows dilatation of the right renal pelvis (measuring up to 16 mm)
and of the central and peripheral calyces (arrow), corresponding to UTD A2–3. (12) Multicystic dysplastic kidney. (12A) Transverse
gray-scale US image of a fetus at 32 weeks 1 day GA shows bilateral enlarged cystic kidneys with an echogenic cortex, multiple small
cysts (arrows), and a dilated renal pelvis (P). (12B) Gross pathology photograph of the kidney from a different 22-week-old aborted
fetus shows a multicystic appearance with lack of corticomedullary differentiation. (13) Duplicated renal collecting system in a
fetus at 29 weeks 6 days GA. (13A) Longitudinal gray-scale US image (coronal orientation) shows left renal duplication with renal
pelvis dilatation, parenchymal thinning, and ureteral dilatation (calipers) of the upper moiety (UM), as well as dilatation of the lower
moiety (LM). (13B) Longitudinal gray-scale US image (coronal orientation) of the bladder shows an associated ureterocele (arrow).

carpal bones, or thumb is also described in the Delayed Lung Maturity

context of diabetic pregnancies (Fig 14, Movie 4) Lung immaturity is a major determinant of
(39). The oculoauriculovertebral sequence, previ- perinatal morbidity and mortality. In diabetic
ously known as Goldenhar syndrome, defined as pregnancies, lung maturity is delayed, thought
defects in anatomic structures arising from the to be linked to inhibition of surfactant secretion
first and second branchial arches, with variable by type 2 pneumocytes secondary to hypergly-
abnormalities of the eyes, ears, and vertebral col- cemia (41). Lung maturity is primarily assessed
umn, is also known to be associated with radial by measurement of the concentration of vari-
ray anomalies and diabetic embryopathy (40). ous surfactant by-products, including lecithin,
RG  •  Volume 42  Number 1 Aboughalia et al  11

Figure 14.  Radial ray

anomaly. Longitudinal
gray-scale US images
of a fetus at 19 weeks
GA show absence of
the right radius and ab-
sence of the thumb, with
a fixed severely flexed
wrist position.

sphingomyelin, and phosphatidylglycerol within Thus, the ACOG guidelines suggest offering
the amniotic fluid. However, amniocentesis also cesarean delivery to mothers with diabetes when
carries the risk of membrane rupture, direct the estimated fetal weight is more than 4500 g, in
fetal injury, infection, and fetal loss (42). The comparison with mothers without diabetes where
use of MRI has been investigated as a means cesarean delivery is offered when the estimated
for lung maturity assessment. Fetal lung sig- fetal weight is greater than 5000 g. In addition to
nal intensity gradually changes over gestation shoulder dystocia, fetuses of diabetic women are
and is a potential marker for lung maturity. also at increased risk for clavicular and humeral
Several groups have reported on the validity of fractures and brachial plexus palsy regardless of
the lung-to-liver signal intensity ratio (LLSIR), fetal weight at birth (Fig 16) (47).
which has a linear relationship to GA in normal Several studies have investigated the accuracy
fetuses. However, the exact LLSIRs at different of various imaging modalities in fetal weight
gestational ages are still to be validated in large assessment. A systematic review by Cooma-
normative studies (42,43). rasamy et al (48) showed that the fetal biometric
measurements such as abdominal circumference
Fetal Growth Disorders and EFW obtained at two-dimensional US are
Macrosomic and large for GA fetuses are fre- not adequate predictors for increased postna-
quently encountered in diabetic pregnancies. Fe- tal weight. Other literature suggests a relatively
tal macrosomia is diagnosed when the estimated higher sensitivity of MRI for predicting large
fetal body weight (EFW) is more than 4000 g fetal weight at birth compared with that of US
(Fig 15). On the other hand, large for GA gener- (49), although the ACOG recommends further
ally implies a birth weight greater than or equal research to justify performing MRI in this set-
to the 90th percentile for a given GA according ting (44).
to the ACOG practice bulletin on macrosomia Diabetic pregnancy can be also associated with
(44). Uncontrolled diabetes during pregnancy fetal growth restriction (FGR), where EFW is
resulting in maternal hyperglycemia causes fetal lower than the 10th percentile for GA, and is an
hyperglycemia and stimulates fetal insulin release established risk factor for perinatal morbidity and
and increases fetal fat deposition. This effect can mortality (50). FGR is primarily seen in mothers
be noted as early as in the second trimester of with long-standing pregestational diabetes and
pregnancy, with a disproportionate increase in is attributed to vasculopathy resulting in placen-
the fetal abdominal and head circumferences, tal dysfunction and impairment of fetal growth
and associated subcutaneous fat deposition. (51). FGR can also be noted as a consequence of
Both maternal and fetal morbidity increase diabetes-associated congenital malformation and/
with increasing EFW (45). According to the or maternal hypertensive disease (52). Thus, it is
ACOG practice bulletin summary, the risk of recommended to pursue US surveillance every
developing a large for GA fetus is 29% in women 3–4 weeks once a diagnosis of FGR is estab-
with diet-controlled GDM, 30% in women with lished. Serial EFW measurements over time can
medication-controlled GDM, and 38% in women provide an overall picture of growth trajectory,
with preexisting diabetes (44). Disproportion- allowing appropriate follow-up and interven-
ate deposition of fat around the fetal shoulders tion. Furthermore, Doppler US of the umbilical
is responsible for the higher incidence of shoul- artery can be performed to distinguish high-risk
der dystocia in infants of diabetic mothers (46). FGR and to assess for deterioration over time. A
12  January-February 2022 radiographics.rsna.org

Figure 15.  Large for GA fetus at 31 weeks GA. (A) Transverse gray-scale US image shows increased
abdominal circumference and EFW, with an EFW of 2413 g. (B) Graphs show that both abdominal cir-
cumference (left) and EFW (right) are greater than the 99th percentile for GA.

full discussion of fetal Doppler US evaluation is contribute to perinatal asphyxia include neo-
beyond the scope of this article. However, lack or natal cardiomyopathy and nephropathy. These
reversal of diastolic flow in the umbilical artery is infants are also prone to metabolic disturbances
associated with adverse prenatal outcomes (53). including hypoglycemia, hypocalcemia, and
hypomagnesemia (57). Given these increased
Perinatal Morbidity and Mortality risks of complication, neonates of women with
Diabetic pregnancies are associated with in- diabetes have increased risk of neonatal inten-
creased perinatal morbidity and mortality. sive care unit admissions.
Patients with pregestational DM are at increased
risk for spontaneous abortion, especially in the Maternal Abnormalities
context of poor glycemic control evidenced by
elevated HbA1c levels, which can also manifest Hypertensive Diseases
as associated fetal congenital anomalies (Figs Based on the ACOG guidelines, hyperten-
17, 18) (54). Infants of diabetic mothers are at sive disorders of pregnancy are classified into
increased risk of preterm delivery (either spon- four subtypes: preeclampsia and/or eclampsia,
taneous or medically indicated), as well as still- chronic hypertension, chronic hypertension
birth (relative risk [RR] = 1.34) (55,56). Given with superimposed preeclampsia, and gesta-
the increased risk of stillbirth in this population, tional hypertension. Preeclampsia is defined as
antenatal testing with nonstress test or biophysi- elevated blood pressure during the second half
cal profile is recommended in the third trimes- of pregnancy in association with other physi-
ter. This, together with hyperglycemia-induced ologic disturbances including proteinuria, new
delayed lung maturation, contributes to surfac- thrombocytopenia, disturbed kidney function,
tant deficiency disease, manifesting at neonatal abnormal liver enzymes, or cerebral or visual
imaging as low lung volumes and diffuse granu- symptoms (58,59). DM is associated with in-
lar opacities (Fig 19) (57). Other factors that creased risk for preeclampsia, most commonly
RG  •  Volume 42  Number 1 Aboughalia et al  13

Figure 18.  Spontaneous abortion. Longitudinal transvagi-

nal gray-scale US image (sagittal orientation) in a 31-year-
old woman with vaginal bleeding and severe cramps at 8
weeks gestation shows the presence of a gestational sac
containing a fetal pole within the cervix. The fetus and ges-
tational sac were subsequently expelled.
Figure 16.  Shoulder dystocia. Frontal radiograph
in a 3-day-old neonate shows a displaced angulated
fracture of the proximal left humerus (arrow) follow-
ing delivery.

Figure 19.  Respiratory distress syndrome. Frontal chest

radiograph of a neonate a few hours after delivery shows
low lung volumes and diffuse granular ground-glass opac-
ities bilaterally. The endotracheal tube and enteric tubes
are in situ.

Figure 17.  Early failure of intrauterine pregnancy.

Transverse M-mode transvaginal US image centered
over the fetal pole obtained at 7 weeks and 3 days subcapsular hematoma and capsular rupture
GA (crown-rump length, 12 mm) shows absence of (63). Also, preeclampsia is a strong predispos-
fetal heart activity. ing factor for placental abruption and premature
placenta separation, which are associated with
high maternal and fetal morbidity and mortality
in patients with type 1 DM, with a reported (Fig 21). Reported maternal complications of
incidence of 18% and a lesser incidence in placental abruption include hemorrhage, dis-
pregnancies with type 2 DM and GDM (60,61). seminated intravascular coagulation, and renal
Preeclampsia is a spectrum of a disease com- failure, while fetal complications include FGR
prising abnormal blood pressure and laboratory and preterm delivery (64).
values and can progress to eclampsia (seizures)
or hemolysis, elevated liver enzymes, and low Complications Related to Delivery
platelets (HELLP) syndrome (62). HELLP DM is independently associated with an in-
syndrome has a grave prognosis with a myriad creased need for cesarean delivery. In a study by
of consequences including rupture of a hepatic Ehrenberg et al (65), the odds ratio of cesarean
subcapsular hematoma and hepatic necrosis (Fig delivery is 1.8 in women with diet-controlled
20), disseminated intravascular coagulation, and GDM, 3.2 in women with medication-con-
maternal mortality (62). HELLP syndrome is trolled GDM, and 4.5 in women with pregesta-
diagnosed on the basis of clinical symptoms and tional DM (65). Although cesarean delivery is
laboratory markers. Imaging is reserved to help considered a relatively safe procedure, there is
evaluate complications, particularity hepatic increased risk for the development of subsequent
14  January-February 2022 radiographics.rsna.org

Figure 20.  HELLP syndrome in a

31-year-old woman who presented
with severe abdominal pain at 37
weeks of gestation. (A) Transverse
gray-scale US image of the right
upper abdomen shows a hetero-
geneous subcapsular collection or
hematoma along the right hepatic
lobe (arrow). (B) Axial intravenous
contrast-enhanced CT image of
the abdomen obtained 4 days later
shows an evolving subcapsular he-
patic hematoma (arrow).

complications, adding to the burden to any future

pregnancy (Table 4, Figs 22–24). On the other
hand, attempted vaginal delivery, when ap-
propriate by institutional guidelines, might be
complicated with cephalopelvic disproportion,
resulting in need for cesarean delivery; maternal
vaginal and perineal lacerations; and fetal shoul-
der dystocia (66).

Other Abnormalities

Placental Thickening
A thick placenta is independently associated with
adverse perinatal outcome including FGR and
need for emergency cesarean delivery (67). DM
is among the most common causes of placental Figure 21.  Marginal placental abruption. Trans-
verse gray-scale US image of the uterus in a 26-week
thickening, in addition to toxoplasmosis, other pregnancy shows a large heterogeneous retropla-
infections, rubella, cytomegalovirus, and herpes cental hemorrhage at the uterine fundus (calipers).
simplex (TORCH) infection; triploidy; and fetal FH = fetal head.
hydrops. At US, placental thickness is obtained
through a perpendicular measurement at the mid
placenta, excluding the myometrium, from the details of which are beyond the scope of this ar-
subplacental veins to the amniotic fluid surface of ticle. Prenatal normalization of hyperglycemia and
the placenta (Fig 25). It is important to recognize symptomatic management decrease the incidence
that myometrial contraction and placental abrup- of polyhydramnios and can be used as a marker
tion are important pitfalls to be avoided during for glycemic control during pregnancy. Research
placental thickness assessment. The reported by Dashe et al (71) has suggested that the amni-
thresholds for a thickened placenta, measured as otic fluid index parallels the amniotic fluid glucose
a perpendicular line extending from the subpla- level. Less commonly, oligohydramnios in diabetic
cental veins to the amniotic fluid at the midpor- pregnancies is multifactorial and reflects long-
tion of the placenta while excluding the myome- standing DM, fetal renal abnormality, or presence
trium, are 33 mm for an anterior placenta and 40 of maternal hypertension.
mm for a posterior placenta (68).
Abnormalities of the Umbilical Cord
Polyhydramnios GDM is a known risk factor for the develop-
DM accounts for up to 20%–25% of pregnancies ment of a single umbilical artery (SUA). Other
diagnosed with polyhydramnios, defined as am- implicated risk factors include advanced mater-
niotic fluid index greater than 25 or a maximum nal age, smoking, pregestational diabetes, hyper-
vertical pocket greater than 8 cm (Fig 26) (69). tension, preeclampsia, and epilepsy (72). The
Polyhydramnios is independently associated with risk for congenital anomalies (the most common
an increased risk of adverse pregnancy outcomes, of which are genitourinary and cardiovascular)
including preterm labor, placental abruption, and and chromosomal abnormalities is eight and
premature rupture of membranes (70). In selected 16 times higher in fetuses with an SUA, respec-
patients, amnioreduction might be pursued in tively. In addition, an SUA is associated with an
light of amniotic fluid index and clinical status, the increased risk for prematurity, growth restric-
RG  •  Volume 42  Number 1 Aboughalia et al  15

Table 4: Short- and Long-term Complications of Cesarean Delivery

Duration Type Complications

Short-term Maternal Infection, bleeding, thromboembolism, visceral injury, anesthesia
complications, maternal mortality
Neonatal Infection, psychologic, maldevelopment, allergies
Long-term Nongravid uterus Cesarean scar complications (eg, dysmenorrhea, endometriosis, fistula)
Gravid uterus Placental adhesion disorder, cesarean ectopic pregnancy, uterine
dehiscence and rupture, repeat cesarean delivery

Figures 22–24.  (22) Isthmocele. Longitudinal transvaginal gray-scale US image

(sagittal orientation) in a 37-year-old woman with a history of cesarean delivery
and vaginal bleeding shows a focal deficiency containing fluid in the lower ante-
rior uterine wall at the site of the cesarean scar (arrow). (23) Cesarean scar–associ-
ated ectopic pregnancy. Longitudinal transvaginal gray-scale US image (sagittal
orientation) in a 37-year-old woman with a history of prior cesarean delivery at 8
weeks and 5 days gestation shows the presence of a gestational sac containing a
fetal pole embedded in the cesarean delivery scar. (24) Placenta accreta spectrum
in a patient with a history of multiple cesarean deliveries. (24A) Longitudinal
gray-scale US image of the placenta shows an anterior placenta (P) in the lower
uterine segment. Note the progressive thinning of the overlying myometrium
(calipers) toward the lower uterine segment, with no perceptible retroplacental
clear space just posterior to the bladder wall (arrow). (24B) Color Doppler US
image shows multiple prominent myometrial vessels (arrow) extending into the
posterior bladder wall, indicating bladder invasion. Placenta percreta was con-
firmed at pathologic analysis.

tion, and adverse neonatal outcomes (73). A tion in this population necessitates regular fetal
suggested cause for SUA is decreased amount growth monitoring (75).
of Wharton jelly, a gelatinous substance within
the umbilical cord that surrounds the vessels Conclusion
(74). SUA can be identified at both fetal US A pregnancy complicated by preexisting DM or
and MRI. A transverse US image near the fetal GDM is associated with significant health risk to
insertion of the cord can better demonstrate an the mother and developing fetus. The fetus is at
SUA since the umbilical arteries commonly fuse risk for congenital anomalies, delayed lung ma-
near the placental insertion site. In addition, a turity, macrosomia, and perinatal morbidity and
longitudinal image at the level of the urinary mortality. The mother is at risk for developing
bladder shows an SUA lateral to the urinary hypertensive diseases of pregnancy, as well as a
bladder (Fig 27). Doppler US can further con- spectrum of complications in relation to delivery.
firm this finding (72). In such cases, detailed Understanding the role of imaging in diabetic
fetal anatomy evaluation is recommended. Fetal pregnancies serves to improve communications
echocardiography and karyotype analysis can be between the provider and the radiologist and
pursued in cases that display associated congeni- allows appropriate imaging follow-up, pregnancy
tal anomalies. Increased risk of growth retarda- management, and delivery planning.
16  January-February 2022 radiographics.rsna.org

Figure 25.  Thickened

placenta. (A) Transverse
gray-scale US image of a
gravid uterus at 28 weeks
GA shows placental thick-
ness measuring up to 5.4
cm (calipers). (B) Axial
T2-weighted MR image
in a different patient at 19
weeks GA shows a thick-
ened anterior placenta
measuring up to 5.1 cm
(calipers).

Figures 26–27.  (26) Polyhydramnios. (26A) Transverse transabdominal US image shows a maximum vertical pocket of the amni-
otic fluid measuring up to 10.1 cm (calipers). The amniotic fluid index measured 27.1 cm (not shown). (26B) Sagittal T2-weighted
MR image in a different patient at 34 weeks gestation shows polyhydramnios as a large amount of fluid surrounding the fetus.
(27) Two-vessel umbilical cord. Transverse color Doppler US image of a fetus at 20 weeks GA at the level of the urinary bladder
shows a two-vessel umbilical cord with an SUA (arrow) in the left perivesical region.

Disclosures of conflicts of interest.—M.V.R. Editorial board 9. Bhandari J, Thada PK, Khattar D. Diabetic Embryopa-
member of RadioGraphics (not involved in the handling of thy. Treasure Island, FL: StatPearls Publishing, 2020.
this article); royalties from Elsevier for Diagnostic Radiology. 10. AIUM practice parameter for the performance of
G.H.D. Consultant to Boehringer Ingelheim to determine detailed second- and third-trimester diagnostic ob-
patient eligibility for a drug study; money to institution from stetric ultrasound examinations. J Ultrasound Med
NIH-NHLBI for LungMAP grant. D.S.K. Editorial board 2019;38(12):3093–3100.
member of RadioGraphics (not involved in the handling of this 11. AIUM practice parameter for the performance of fetal
article). M.M. Editor of RSNA Case Collection. echocardiography. J Ultrasound Med 2020;39(1):E5–E16.
12. Ahmed B, Abushama M, Khraisheh M, Duden-
References hausen J. Role of ultrasound in the management of
diabetes in pregnancy. J Matern Fetal Neonatal Med
1. Forouhi NG, Wareham NJ. Epidemiology of diabetes. 2015;28(15):1856–1863.
Medicine (Abingdon) 2014;42(12):698–702. 13. Hopkins MK, Dugoff L. Screening for aneuploidy in the
2. Plows JF, Stanley JL, Baker PN, Reynolds CM, Vickers patient with diabesity: Pearls and pitfalls. Clin Obstet
MH. The pathophysiology of gestational diabetes mellitus. Gynecol 2021;64(1):136–143.
Int J Mol Sci 2018;19(11):3342. 14. Kucera J. Rate and type of congenital anomalies among off-
3. U.S. Preventive Services Task Force. Gestational Diabetes: spring of diabetic women. J Reprod Med 1971;7(2):73–82.
Screening. https://www.uspreventiveservicestaskforce.org/ 15. Tortori-Donati P, Rossi A, Cama A. Spinal dysraphism:
uspstf/recommendation/gestational-diabetes-screening. a review of neuroradiological features with embryological
4. ACOG Practice Bulletin No. 190: Gestational Diabetes correlations and proposal for a new classification. Neu-
Mellitus. Obstet Gynecol 2018;131(2):e49–e64. roradiology 2000;42(7):471–491.
5. Kitzmiller JL, Buchanan TA, Kjos S, Combs CA, Ratner 16. Warner T, Scullen TA, Iwanaga J, et al. Caudal regression
RE. Pre-conception care of diabetes, congenital mal- syndrome—A review focusing on genetic associations.
formations, and spontaneous abortions. Diabetes Care World Neurosurg 2020;138:461–467.
1996;19(5):514–541. 17. Hagan DM, Ross AJ, Strachan T, et al. Mutation analysis
6. Ornoy A. Embryonic oxidative stress as a mechanism of and embryonic expression of the HLXB9 Currarino syn-
teratogenesis with special emphasis on diabetic embryopa- drome gene. Am J Hum Genet 2000;66(5):1504–1515.
thy. Reprod Toxicol 2007;24(1):31–41. 18. Pang D. Sacral agenesis and caudal spinal cord malformations.
7. Eriksson UJ, Wentzel P. The status of diabetic embryopathy. Neurosurgery 1993;32(5):755–778; discussion 778–779.
Ups J Med Sci 2016;121(2):96–112. 19. González-Quintero VH, Tolaymat L, Martin D, Roma-
8. Castori M. Diabetic embryopathy: a developmental per- guera RL, Rodríguez MM, Izquierdo LA. Sonographic
spective from fertilization to adulthood. Mol Syndromol diagnosis of caudal regression in the first trimester of
2013;4(1-2):74–86. pregnancy. J Ultrasound Med 2002;21(10):1175–1178.
RG  •  Volume 42  Number 1 Aboughalia et al  17

20. Heuser CC, Hulinsky RS, Jackson GM. Caudal regression 43. Brewerton LJ, Chari RS, Liang Y, Bhargava R. Fetal lung-
syndrome. In: Copel JA, D’Alton ME, Feltovich H, et al, to-liver signal intensity ratio at MR imaging: development
eds. Obstetric Imaging: Fetal Diagnosis and Care. 2nd of a normal scale and possible role in predicting pulmonary
ed. Philadelphia, Pa: Elsevier, 2017; 291–294. hypoplasia in utero. Radiology 2005;235(3):1005–1010.
21. Negrete LM, Chung M, Carr SR, Tung GA. In utero 44. Macrosomia: ACOG Practice Bulletin Summary, Number
diagnosis of caudal regression syndrome. Radiol Case 216. Obstet Gynecol 2020;135(1):246–248.
Rep 2015;10(1):1049. 45. Boulet SL, Alexander GR, Salihu HM, Pass M. Mac-
22. Correa A, Gilboa SM, Besser LM, et al. Diabetes mellitus rosomic births in the united states: determinants, out-
and birth defects. Am J Obstet Gynecol 2008;199(3):237. comes, and proposed grades of risk. Am J Obstet Gynecol
e1–237.e9. 2003;188(5):1372–1378.
23. Garne E, Loane M, Dolk H, et al. Spectrum of congenital 46. McFarland MB, Trylovich CG, Langer O. Anthropometric
anomalies in pregnancies with pregestational diabetes. Birth differences in macrosomic infants of diabetic and nondia-
Defects Res A Clin Mol Teratol 2012;94(3):134–140. betic mothers. J Matern Fetal Med 1998;7(6):292–295.
24. Bromley B. Diagnostic imaging of fetal anomalies. J 47. Bahar AM. Risk factors and fetal outcome in cases of shoul-
Ultrasound Med 2003;22(8):850. der dystocia compared with normal deliveries of a similar
25. Aboughalia H, Bastawrous S, Revzin MVMV, Delaney birthweight. Br J Obstet Gynaecol 1996;103(9):868–872.
SS, Katz DS, Moshiri M. Imaging findings in associa- 48. Coomarasamy A, Connock M, Thornton J, Khan KS.
tion with altered maternal alpha-fetoprotein levels during Accuracy of ultrasound biometry in the prediction of
pregnancy. Abdom Radiol (NY) 2020;45(10):3239–3257. macrosomia: a systematic quantitative review. BJOG
26. Griffiths PD, Jarvis D. In utero MR imaging of fetal 2005;112(11):1461–1466.
holoprosencephaly: A structured approach to diag- 49. Malin GL, Bugg GJ, Takwoingi Y, Thornton JG, Jones NW.
nosis and classification. AJNR Am J Neuroradiol Antenatal magnetic resonance imaging versus ultrasound
2016;37(3):536–543. for predicting neonatal macrosomia: a systematic review
27. Simeone RM, Devine OJ, Marcinkevage JA, et al. Dia- and meta-analysis. BJOG 2016;123(1):77–88.
betes and congenital heart defects: a systematic review, 50. American College of Obstetricians and Gynecologists’
meta-analysis, and modeling project. Am J Prev Med Committee on Practice Bulletins—Obstetrics and the
2015;48(2):195–204. Society for Maternal-Fetal Medicine. ACOG Practice
28. Øyen N, Diaz LJ, Leirgul E, et al. Prepregnancy diabetes Bulletin No. 204: Fetal growth restriction. Obstet Gynecol
and offspring risk of congenital heart disease: A nationwide 2019;133(2):e97–e109.
cohort study. Circulation 2016;133(23):2243–2253. 51. Gutaj P, Wender-Ozegowska E. Diagnosis and manage-
29. Revels JW, Wang SS, Itani M, et al. Radiologist’s guide to ment of IUGR in pregnancy complicated by type 1 diabetes
diagnosis of fetal cardiac anomalies on prenatal ultrasound mellitus. Curr Diab Rep 2016;16(5):39.
imaging. Ultrasound Q 2019;35(1):3–15. 52. Suhag A, Berghella V. Intrauterine growth restriction
30. Narchi H, Kulaylat N. Heart disease in infants of diabetic (IUGR): Etiology and diagnosis. Curr Obstet Gynecol
mothers. Images Paediatr Cardiol 2000;2(2):17–23. Rep 2013;2(2):102–111.
31. Dias T, Sairam S, Kumarasiri S. Ultrasound diagnosis 53. Debbink MP, Son SL, Woodward PJ, Kennedy AM.
of fetal renal abnormalities. Best Pract Res Clin Obstet Sonographic assessment of fetal growth abnormalities.
Gynaecol 2014;28(3):403–415. RadioGraphics 2021;41(1):268–288.
32. Saran R, Robinson B, Abbott KC, et al. US renal data 54. Greene MF, Hare JW, Cloherty JP, Benacerraf BR,
system 2016 annual data report: epidemiology of kidney Soeldner JS. First-trimester hemoglobin A1 and risk for
disease in the United States. Am J Kidney Dis 2017;69(3 major malformation and spontaneous abortion in diabetic
Suppl 1):A7–A8 [Published correction appears in Am J pregnancy. Teratology 1989;39(3):225–231.
Kidney Dis 2017;69(5):712.]. 55. Rosenstein MG, Cheng YW, Snowden JM, Nicholson JM,
33. Ramanathan S, Kumar D, Khanna M, et al. Multi- Doss AE, Caughey AB. The risk of stillbirth and infant death
modality imaging review of congenital abnormalities stratified by gestational age in women with gestational dia-
of kidney and upper urinary tract. World J Radiol betes. Am J Obstet Gynecol 2012;206(4):309.e1–309.e7.
2016;8(2):132–141. 56. Melamed N, Chen R, Soiberman U, Ben-Haroush A, Hod
34. Parimi M, Nitsch D. A systematic review and meta-analysis M, Yogev Y. Spontaneous and indicated preterm delivery
of diabetes during pregnancy and congenital genitouri- in pregestational diabetes mellitus: etiology and risk factors.
nary abnormalities. Kidney Int Rep 2020;5(5):678–693. Arch Gynecol Obstet 2008;278(2):129–134
35. Hokke SN, Armitage JA, Puelles VG, et al. Altered ure- 57. Michael Weindling A. Offspring of diabetic pregnancy:
teric branching morphogenesis and nephron endowment short-term outcomes. Semin Fetal Neonatal Med
in offspring of diabetic and insulin-treated pregnancy. 2009;14(2):111–118.
PLoS One 2013;8(3):e58243. 58. Hypertension in Pregnancy: Executive Summary. Obstet
36. Dunn V, Nixon GW, Jaffe RB, Condon VR. Infants of Gynecol 2013;122(5):1122–1131.
diabetic mothers: radiographic manifestations. AJR Am 59. Duley L. The global impact of pre-eclampsia and eclampsia.
J Roentgenol 1981;137(1):123–128. Semin Perinatol 2009;33(3):130–137.
37. Nguyen HT, Benson CB, Bromley B, et al. Multidisci- 60. Schneider S, Freerksen N, Röhrig S, Hoeft B, Maul H.
plinary consensus on the classification of prenatal and Gestational diabetes and preeclampsia: similar risk factor
postnatal urinary tract dilation (UTD classification profiles? Early Hum Dev 2012;88(3):179–184.
system). J Pediatr Urol 2014;10(6):982–998. 61. Weissgerber TL, Mudd LM. Preeclampsia and diabetes.
38. Adam MP, Hudgins L, Carey JC, et al. Preaxial hallucal Curr Diab Rep 2015;15(3):9.
polydactyly as a marker for diabetic embryopathy. Birth 62. 62 Nunes JO, Turner MA, Fulcher AS. Abdominal imag-
Defects Res A Clin Mol Teratol 2009;85(1):13–19. ing features of HELLP syndrome: a 10-year retrospective
39. Society for Maternal-Fetal Medicine (SMFM); Gandhi review. 2005;185:1205-1210.
M, Rac MWF, McKinney J. Radial ray malformation. 63. Chan AD, Gerscovich EO. Imaging of subcapsular hepatic
Am J Obstet Gynecol 2019;221(6):B16–B18. and renal hematomas in pregnancy complicated by pre-
40. Wang R, Martínez-Frías ML, Graham JM Jr. Infants of eclampsia and the HELLP syndrome. J Clin Ultrasound
diabetic mothers are at increased risk for the oculo-auri- 1999;27(1):35–40.
culo-vertebral sequence: A case-based and case-control 64. Tikkanen M. Placental abruption: epidemiology, risk
approach. J Pediatr 2002;141(5):611–617. factors and consequences. Acta Obstet Gynecol Scand
41. Gewolb IH, O’Brien J. Surfactant secretion by type II 2011;90(2):140–149.
pneumocytes is inhibited by high glucose concentrations. 65. Ehrenberg HM, Durnwald CP, Catalano P, Mercer BM.
Exp Lung Res 1997;23(3):245–255. The influence of obesity and diabetes on the risk of cesarean
42. Moshiri M, Mannelli L, Richardson ML, et al. Fetal lung delivery. Am J Obstet Gynecol 2004;191(3):969–974.
maturity assessment with MRI fetal lung-to-liver signal-in- 66. Ramos SZ, Waring ME, Leung K, Amir NS, Bannon AL,
tensity ratio. AJR Am J Roentgenol 2013;201(6):1386–1390. Moore Simas TA. Attempted and successful vacuum-
18  January-February 2022 radiographics.rsna.org

assisted vaginal delivery by prepregnancy body mass index. and amniotic fluid volume in pregnancy complicated by
Obstet Gynecol 2017;129(2):311–320. diabetes. Am J Obstet Gynecol 2000;182(4):901–904.
67. Miwa I, Sase M, Torii M, Sanai H, Nakamura Y, Ueda 72. Moshiri M, Zaidi SF, Robinson TJ, et al. Comprehensive
K. A thick placenta: a predictor of adverse pregnancy imaging review of abnormalities of the Umbilical Cord.
outcomes. Springerplus 2014;3(1):353. RadioGraphics 2014;34(1):179–196.
68. Fadl S, Moshiri M, Fligner CL, Katz DS, Dighe M. 73. Murphy-Kaulbeck L, Dodds L, Joseph KS, Van den Hof
Placental imaging: normal appearance with review of M. Single umbilical artery risk factors and pregnancy
pathologic findings. RadioGraphics 2017;37(3):979–998. outcomes. Obstet Gynecol 2010;116(4):843–850.
69. Moore LE. Amount of polyhydramnios attributable to 74. Raio L, Ghezzi F, Di Naro E, Franchi M, Brühwiler H,
diabetes may be less than previously reported. World J Lüscher KP. Prenatal assessment of Wharton’s jelly in
Diabetes 2017;8(1):7–10. umbilical cords with single artery. Ultrasound Obstet
70. Ross MG, Brace RA; National Institute of Child Health Gynecol 1999;14(1):42–46.
and Development Workshop Participants. National 75. Lubusky M, Dhaifalah I, Prochazka M, et al. Single
Institute of Child Health and Development Conference umbilical artery and its siding in the second trimester
summary: amniotic fluid biology—basic and clinical of pregnancy: relation to chromosomal defects. Prenat
aspects. J Matern Fetal Med 2001;10(1):2–19. Diagn 2007;27(4):327–331.
71. Dashe JS, Nathan L, McIntire DD, Leveno KJ. Cor-
relation between amniotic fluid glucose concentration

TM
This journal-based SA-CME activity has been approved for AMA PRA Category 1 Credit . See rsna.org/learning-center-rg.