The Journal of Maternal-Fetal and Neonatal Medicine, 2012; 25(4): 403407

! 2012 Informa UK, Ltd.

ISSN 1476-7058 print/ISSN 1476-4954 online
DOI: 10.3109/14767058.2011.581715

Are we ready for a new look at the diagnosis of premature rupture of

membranes?
FEDERICO G. MARIONA1 & LLUIS CABERO2
1

Division of Maternal Fetal Medicine, Wayne State University School of Medicine, Michigan Perinatal Associates, Dearborn, Michigan,
USA and 2Department of Obstetrics & Gynecology, Hospital Val dHebron, Barcelona, Spain
Abstract
Premature rupture of membranes is a significant contributor to preterm birth with its associated short- and long-term
complications. The absence of a standard approach to its management places a burden on the clinicians ability to promptly and
accurately diagnose premature rupture of membranes. For the last half century, there have been no significant changes in the way
premature ruptured membranes is diagnosed. With the advent of newer, amniotic fluid-specific, noninvasive, and accurate
markers, there is an opportunity to update the diagnosis of premature rupture of membranes.
Keywords: Ruptured fetal membranes, update, diagnosis

Premature rupture of membranes (PROM) is defined as the

spontaneous rupture of fetal membranes prior to the initiation
of labor. It is consistently reported as occurring in approximately 10% of term pregnancies, PROM is associated with
over 60% of preterm births. The etiology of PROM is
multifaceted and appears directly related to the gestational age
at which it occurs or may occur in the absence of any of the
recognizable risk factors. If PROM has occurred preterm, the
accepted risk of recurrence varies between 15 and 30% [1]. In
the absence of current accurate and consistent knowledge of
the etiology of PROM, clinicians are compelled to concentrate
their efforts in the management of the event once it has been
accurately diagnosed.
The existence of membranes surrounding the fetus in
experimental animals and man was reported by Fabricius in
his notable document, The formed fetus, published in 1600
[2]. Thomas Denman in 1801 described the surgical PROM
just to condemn it [3]. He added that the PROM whether
natural or artificial has been often mentioned as the cause of
much mischief and of many tedious and difficult labors.
Further, he wrote, If the membranes containing the waters
were intended to be the medium by which the os uteri and
other tender parts ought to be dilated, some inconvenience
must arise when these are broken and the waters discharged.
To that end, in 1969, some 168 years after Denmans
description, Kuznetsov et al. reported in the American Journal
of Obstetrics and Gynecology in February of 1960 a 15.4%
stillbirth rate after prolonged dry labor.
In 1948, Knox et al. [4] conducted a study of pregnant
women with suspected or proven premature labor followed by
preterm birth. Using methodology that would be considered
unsophisticated today, they demonstrated the existence of

acute and chronic, even severe, histological evidence of

infection in the fetal membranes of the studied population,
while absent in the controls. Sixty-two years later, these
findings have been corroborated in a model of term human
pregnancy, in spontaneous labor with PROM utilizing the
transcriptome of the fetal membranes demonstrating a
weakness zone in the area of maximum exposure close to
the cervix with differential expression of genes allowing for the
diagnosis of local apoptosis and inflammation [5].
The treatment of PROM is closely associated with the need
for prompt and accurate diagnosis once it is suspected.
Management practices continue to present challenges to
obstetricians and neonatologists and show substantial variations among practitioners and institutions. The evaluation
(diagnosis?) of these patients appears significantly different
between practitioners in academic versus nonacademic
institutions when it comes to performing amniocentesis.
Nonacademic practitioners perform amniocentesis in 72% of
these patients, while academic practitioners do it in 61% of
patients (p 0.02) [6].
The critical importance of accurate and prompt diagnosis
of PROM at any gestational age to decrease or avoid its
inherent and potential serious complications for mother and
fetus have been repeatedly emphasized by investigators for the
last 50 years. The medical and lay literature is overpopulated
with such works. Yet, neither a single etiology or physiopathology nor a standardized treatment has yet been agreed
upon. Obstetricians and perinatologists still offer a wide
variety of approaches to the management of PROM. A recent
survey aiming at characterizing variations in the management
of pregnant women with PPROM showed that only 30% of
practitioners in the world had a formal protocol [7].

(Received 18 February 2011; revised 2 April 2011; accepted 5 April 2011)

Correspondence: Federico G. Mariona, Michigan Perinatal Associates, 18181Oakwood Blvd., Suite 302, Dearborn, MI 48124 USA.Tel: 313-593-5957.
Fax: 313-593-8919. E-mail: [email protected]

404

F. G. Mariona & L. Cabero

By the middle of the twentieth century, a number of

processes, procedures, and physical, as well as chemical
markers were used for the diagnosis of PROM (Tables I
and II). All these methods depend on physical properties
inherent to amniotic fluid, however not specific to amniotic
fluid. All methods have been extensively and repeatedly
studied. Either their virtues were extolled or often condemned
as inefficient. False positive and false negative results
compromised the promptness and accuracy of the diagnosis,
creating the scenario for misuse of resources for the treatment
of pregnant women suspected of PROM. Many of the
markers for PROM never passed the stage of a single
publication, many with no validation studies, most are not
available for daily clinical use.
By the mid-1970s, a number of clinical investigators
emphasized the need for an objective method to diagnose
PROM. David Charles in Boston wrote:
it is axiomatic that a definitive diagnosis of PROM is
necessary before therapy is begun. The importance of
accurate diagnosis is obvious if the obstetrician is conversant with the seriousness of the entity. A precise
diagnosis may be obtained only by microscopic examination
of the vaginal discharge demonstrating fetal squames and
other elements such as hair, vernix caseosa and cells which
stain orange with Nile blue [8].
In essence, since the middle of the twentieth century, the
noninvasive recommended clinical methods utilized for the
diagnosis of PROM have not changed. Recently, another
indirect, noninvasive, labor intensive, relatively expensive, and
highly variable method bedside ultrasound was added to
detect the amniotic fluid volume to allow for assumptions
regarding the condition of the fetal membranes.

Table I. Diagnosis of premature ruptured membranes.

Current traditional approach
1. Patient history of sudden gush of clear vaginal discharge
2. Sterile vaginal speculum examination visualize leaking fluid from cervix
or pooling
3. Nitrazine strip pH indicator turns colors (yellow-blue) in contact with
vaginal discharge
4. Microscopic observation of vaginal discharge crystallizing when air dried
for 10 min
5. Ultrasound determination of amniotic fluid volume for gestational
age
6. Intra-amniotic injection of indigo carmine with dye passing into the
vagina

Table II. The search for markers of PROM.

1974
1975
1978
1981
1991
1993
1995
2003
2007
2009
2010

Diamine oxydase in vaginal fluid.

Placenta alpha microglogulin-1 in amniotic fluid
Intra-amniotic sodium fluorescein
Vaginal prolactin
Cervical-vaginal fetal fibronectin
Insulin-like growth factor binding protein
Vaginal alpha fetal protein
Vaginal -chorionic gonadotrophin
Thyroid hormone in vaginal washings
Proteomic technologies
Maternal serum pentraxin 3

In 1975, basic investigators described for the first time

human placenta specific alpha 1 microglobulin (PAMG-1), a
protein with a molecular weight of 20 K/Daltons. Its
concentration in amniotic fluid (200025,000 ng/ml) is
substantially higher than the concentration in cervicovaginal
fluid or maternal serum (0.052.0 ng/ml) and not found in
other tissues of a number of experimental animals, including
humans [9]. Very little information was reported on its
biological or physiological importance in pregnancy (Petrunin
19771980). These findings failed to permeate to the western
world for a long period of time. No publications related to the
presence of PAMG-1 in amniotic fluid are found in peer
reviewed publications involving this marker in the American
literature until 2005 [1013]. PAMG-1 has been observed in
the intervillous fibrin and in the cyto- and syncytiotrophoblastic cells of immature chorion of 812 weeks gestation but
not found in maternal blood. No physiologic explanation is
found to describe the mechanism for PAMG-1 migration into
the amniotic cavity.
Some investigators have proposed that the presence of
PAMG-1 in cervicovaginal fluid without clinical evidence of
PROM may be associated with microleakage of amniotic fluid
[11]. This observation was recently published in association
with term labor and no clinical evidence of PROM. The
definition was based on lack of observation of leakage or
pooling, negative nitrazine and negative ferning. The authors
excluded cases of testing discrepancy [14].
In 1992, Salfelder et al. [15] reported the use of fetal
fibronectin in vaginal secretions for the detection of PROM
using FDC-6. If positive, it would represent an unequivocal
sign of PROM or pre-rupture stretching of the membranes.
Soon after this report Putz et al. [16] reported that fetal
fibronectin was detected in blood samples of nonpregnant
women.
In 1993, Rutanen et al. [17] described the insulin-like
growth factor binding protein-1 (IGFBP-1) as a major protein
in amniotic fluid. They evaluated the measurement of this
marker in cervicovaginal secretions as an indicator of PROM.
They compared their results with those obtained by the
determination of fetal fibronectin in vaginal fluid to diagnose
PROM. They reported a positive predictive value of 95% for
the IGFBP-1 and 79% for fetal fibronectin. IGFBP-1 became
the most commonly used marker for the diagnosis of PROM
in Europe. A recent study from Chen et al. compares the use
of IGFBP-1 and PAMG-1 for the diagnosis of PROM [18]
followed by a comparative study of IGFBP-1, PAMG-1, and
nitrazine by Tagore et al. [19] demonstrating that PAMG-1
had the highest sensitivity and specificity for the diagnosis of
PROM between 17 and 37 weeks gestation.
Silva et al. prospectively compared the use of PAMG1before and after the injection of indigo carmine via
amniocentesis in women with clinical suspicion of PROM
between 24 and 42 weeks gestation. They report the PAMG-1
results correlated 100% with the dye injection procedure [20].
A recent observation was made by Mittal et al. in
symptomatic patients between 16 and 34 weeks gestation
with a sonographic short cervix (525 mm). They reported a
32% PAMG-1 positive tests in pregnant women with a
cervical length of 15 mm associated with rupture of
membranes (ROM) and preterm labor at 34 weeks gestation.
As previously mentioned, these authors also theorized that the
presence of PAMG-1 is due to microperforations in the fetal
membranes [21]. Our experience yet unpublished showed
that women between 19 and 32 weeks gestation with a cervix

New look at the premature rupture

#17 mm and fetal membranes at the level of the external os or
bulging in the vagina, 8% will be PAMG-1 positive. These
patients clinical behavior is similar to those on whom PROM
has been diagnosed.
A provocative analogy regarding the delay in the implementation of new technology into clinical obstetric practice is
the evolution of the pregnancy test. In 1928, Ascheim and
Zondek published their basic research associating pregnant
womens urine injected to virgin mice with enlargement and
congestion of their ovaries for the diagnosis of pregnancy, with
a 2% error. Their basic experiments were followed by the
clinical application of their pregnancy test, embraced in the
US in 1929. Agglutination technology for human chorionic
gonadotropin (HCG) was developed in 1950s and 1960s,
radioimmunoassay in the 1970s, and enzyme immunoassay in
the 1980s. It was not until the full evaluation of the
immunology based serum HCG testing in 1984 34 years
later that this test became routine in clinical practice and was
evaluated for effectiveness, sensitivity, specificity, technical
requirements, and costs. Clinical obstetrics has a long record
of protracted acceptance to change, except for electronic fetal
monitoring.
In April of 1988 on its educational bulletin #115, the
American College of Obstetricians and Gynecologists addressed
PROM for the first time since the inception of its educational
publications in 1963. The paragraph on diagnosis contained
the same indirect methods that had been used for half a century.
This bulletin was replaced in June of 1998 by practice bulletin
#1 and subsequently by practice bulletin #80 in April of 2007.
The bulletins contained the same recommendations for the
diagnosis of PROM with the addition of ultrasound. An expert
series addressing preterm PROM was published in Obstetrics
and Gynecology in January of 2003 containing similar
recommendations. In 2004, the Obstetrical and Gynecological
Survey volume 59 #9 published a continuing medical education
(CME) review article entitled, An evidence based approach to
the evaluation and treatment of PROM, Part 1 on page 671
addresses diagnosis-methods referencing a 1969 article for
background. The article includes several chemical markers as
possible methods when the classical approach has been
equivocal. In March of 2005, the British Journal of Obstetrics
and Gynecology published preterm premature rupture of
membranes: diagnosis, evaluation and management strategies,
reported from a US academic source. The paper states: the
diagnosis is made by clinical suspicion, patient history and
simple testing. Two tests have withstood the test of time,
nitrazine paper and ferning of the vaginal pool. The accuracy of
at least two positive tests will be 93%. No further comments or
updates were offered related to diagnosis.
A traditional source of obstetrical education, Williams
Obstetrics, XXII edition, chapter 17, page 425 addresses the
detection of PROM emphasizing three significant reasons for

405

the importance of proper diagnosis: 1. PROM greatly

increases the possibility of prolapsed or compression of the
umbilical cord, 2. Labor ensues soon if the pregnancy is at
near term, and 3. A delay of 24 h or more after PROM is more
likely to be accompanied by infection. The textbook states that
of several recommended diagnostic tests for PROM, none is
completely reliable and unequivocal. Identification of PROM
comes from the injection of various dyes via amniocentesis
(Table I).
Recently, the European Association of Perinatal Medicine
has submitted an update to their guidelines for the management of spontaneous preterm labor, which includes the
diagnosis of PROM [22].
It is widely recognized in the practice of clinical obstetrics
that the only objective noninvasive method to diagnose PROM
is the direct observation of leakage of amniotic fluid through the
uterine cervix at the time of a sterile speculum examination. The
diagnosis of PROM is accomplished in over 90% of the
suspected cases by a combination of an appropriately obtained
patient history, the observation of leakage through the uterine
cervix, and the use of a spectrum of indirect 70-year-old
methods, neither one of which is specifically related to the
presence of amniotic fluid. All of the sanctioned methods
(Table I) use physical characteristics of the vaginal contents
(pooling, local pH, crystallization on a vaginal discharge dried
smear), bedside ultrasound frequently repeated as an official
ultrasound hours later, and in less than 1% of the population
suspected of PROM by amniocentesis and injection of indigo
carmine with observation of stained vaginal discharge.
Practitioners who provide maternity care are deluged by
new technology described as providing evidence for the use
of recently discovered (not necessarily available for daily use)
and superior methods to improve medical care, properly
utilize increasingly scarcer resources, improve clinical outcomes, and decrease the cost of health care. A number of
these markers are not Federal Drug Administration (FDA)
approved, are unavailable in the United States, are not
available for daily patient care outside of limited research
protocols, have an unduly prolonged turn around time for
report, and are considered experimental and investigational
by third party payers and therefore of very limited daily use by
the practicing clinicians (Table II).
If we recognized the frequency of false positive and false
negative results provided by the traditional indirect tests to
diagnose PROM that we have utilized for more than half a
century, patients and physicians will benefit from considering
the use of certain newer technologies (Table III).
After its first description in 1975, PAMG-1 is now
commercially available (AmnisureTM), approved by the
FDA and European Union for the diagnosis of PROM.
Cervicovaginal fluid testing via PAMG-1 with a diagnostic
threshold set at 5.0 ng/ml, properly performed and

Table III. Clinical performance of traditional techniques to diagnose PROM.

Technique
Vaginal speculum
Vaginal pH
Fern test in labor
Fern test not in labor
US AFV

Sensitivity (%)

Specificity (%)

PPV (%)

NPV (%)

FN (%)

9097
98
51.4
56

1670
88.2
70.8
97

6375
92

8093
96

12
12.9
12.9
40

Amniocentesis dye injection and observation of vaginal tampon staining. Invasive, considered by some as the gold standard.
US AFV, amniotic fluid volume by ultrasound; PPV, positive predictive value; NPV, negative predictive value; FN, false negative.

406

F. G. Mariona & L. Cabero

Table IV. Clinical performance of newer amniotic fluid markers.

Marker
Insulin-like growth Factor binding protein-1
Placenta-specific alpha microglobulin-1

Sensitivity (%)

Specificity (%)

PPV (%)

NPV (%)

74100
9899

48394.7
88100

7392
98100

5687
9199

PPV, positive predictive value; NPV, negative predictive value.

interpreted, has a metric performance of 98.9% sensitivity,

100% specificity, a positive predictive value of 100% for the
FDA approved testing objective, and a negative predictive
value of 99.1% [10,13,18,19; Table IV].
Recently, an in vitro study was conducted on an additional
41 patients. Amniotic fluid was obtained and processed at the
time of a cesarean delivery at term qnd processed utilizing
IGFBP-1 and PAMG-1 in tandem. Sensitivity, response time,
and reproducibility of both tests were compared. PAMG-1
showed a superior performance [23].
There is an important balance between evidence of
effectiveness, clinical practice, and cost when planning to
incorporate this test into maternity care. The test may be
used to completely replace the current diagnostic steps. In
that case, the purchase and environmental protection
(temperature, humidity) of Nitrazine strips will no longer
be necessary, as well as the purchase and maintenance of a
microscope and glass slides and container for discarding of
used slides. The need to purchase, ultrasound equipment,
cost of the maintenance and replacement of damaged
transducers, and update of the equipment will not be
necessary. There will be no need to have a trained
technologist to provide the US examination 24/7 in level I
institutions where the number of obstetrical patients per
year does not warrant the implementation of a fully
equipped obstetrical triage unit. Experienced obstetrical
nursing personnel or certified nurse midwives can provide
the test at the bedside. Periodic quality control and updates
of personnel skills are done according to policies established
in each institution or obstetrical department.
A number of imponderables must enter into this clinical
equation. A pregnant woman who complaints of abnormal
vaginal discharge and whose diagnosis is ambiguous will
greatly benefit from the use of a simple, rapid, accurate,
noninvasive, non-labor intensive test, administered and
reported at the point of care, and rapidly communicated to
her physician, allowing for swift and appropriate disposition.
If appropriate and based on evidence, the test can completely
replace all the other tests currently in use, or conversely be
utilized in ambiguous cases.
A number of steps will be simplified if such a test is made
available for the diagnosis of PROM. Maternal ambulance
transfers to level II or III institutions will decrease, as well as
hospital admissions for observation, repeated exams, and use
of additional therapies (antibiotics, tocolytics, steroids, nonstress testing, repeated amniotic fluid volume determinations,
cervical status evaluation via ultrasound, continuous monitoring, biophysical profiles, pregnancy interruption, or formal
induction of labor). To the above, we may add possible
disruption of family life and employeeemployer relationships
if the diagnosis falsely documents PROM. A prompt and
accurate diagnosis will avoid the womans and familys work
schedule being disrupted; absenteeism and need for a
replacement worker will decrease. Conversely, when the test
is positive, all appropriate management policies will be

instituted in preparation for the possible prolonged hospitalization, delivery planning, and preterm birth, including
neonatal consultation and social worker intervention when
indicated. In this era of medical practice, even the possibility
of litigation due to failure to diagnose PROM promptly and
accurately will be avoided. Long-term personal and family
side effects due to the loss of an extreme premature baby or
complications from sepsis or long-term systemic failures may
decrease.
The above discussion brings us to the question that was the
impetus for this writing: are we ready for a serious new look at
the way we diagnose PROM? Is it time to rethink the
processes and procedures of the last 70 years? Is it time to
replace the old indirect technology with an up-to-date specific
marker to detect the presence of amniotic fluid in the vaginal
discharge in those pregnant women between 16 and 41 weeks
of gestation that present with abnormal leakage? We
encourage extending the clinical database to provide solid
evidence for the updating of the traditional diagnostic
techniques.
Clinical obstetrics has been charged frequently for lacking
adequate applicable basic research that can be translated into
care to provide optimal outcomes to our patients. The use of
PAMG-1 to promptly, accurately, and inexpensively diagnose
PROM may be a relevant change in our practice.
Timely and accurate testing is an important step in medical
care. The discovery of new markers and the development of
new technologies require that we clinicians remain attentive to
remarkable advances to deal with pregnancy complications.
Scientists must be able to provide translational research for
practitioners to incorporate into clinical practice at the
bedside.
Obstetricians carry the extraordinary responsibility to care
for a pregnant woman and her fetus, often considered as a
unique situation in clinical medicine, the duty to respond to
the needs of two patients. As such we must remain alert and
responsive to useful changes and innovations in our field of
practice.
Declaration of interest: The authors report no conflicts of
interest. The authors alone are responsible for the content and
writing of the paper.

References
1. American College of Obstetricians and Gynecologists Practice
Bulletin # 80. April 2007. Lippincott Williams & Wilkins, New
York City, New York. USA.
2. Talbott JH. A biographical history of Medicine. Excerpts and
essays on the men and their work. Grune & Stratton, New York,
New York. USA, 1970.
3. Dunn PM. Perinatal lessons from the past. Arch Dis Child
1992;67:882884.
4. Knox Jr IC, Hoerner JK. The role of infection in premature
rupture of the membranes. Am J Obstet Gynecol 1950;59:190
194.

New look at the premature rupture

5. Nhan-Chang CL, Romero R, Tarca AL, Mittal P, Kusanovic JP,
Erez O, Mazaki-Tovi S, Chaiworapongsa T, Hotra J, Than NG,
et al. Characterization of the transcriptome of chorioamniotic
membranes at the site of rupture in spontaneous labor at term.
Am J Obstet Gynecol 2010;202(5):462. E141.
6. Nuthalapaty FS, Ramin KD, Lu G, Ramin S, Nuthalapaty ES,
Ramsey PS. The relationship between practice setting and
management of preterm premature rupture of membranes.
J Matern Fetal Neonatal Med 2005;18(1):5357.
7. Ramsey PS, Nuthalapaty FS, Lu G, Ramin S, Nuthalapaty ES,
Ramin KD. Contemporary management of preterm premature
rupture of membranes (PROM): a survey of maternal fetal
medicine providers. Am J Obstet Gynecol 2004;191(4):
14971502.
8. Charles D. Controversy in obstetrics and gynecology II. Reid and
Christian. W.B. Saunders Co; 1974. Philadelphia, Pennsylvania
USA. p 34.
9. Petrunin DD, Griaznova IM, Petrunina IuA, Tatarinov IuS.
Immunochemical identification of the human placenta organospecific alpha 2 globulin and its concentration in amniotic fluid.
Moscow Medical Institute, USSR. Biull Eksp Biol Med
1976;82(7):803804.
10. Cousins L, Smok DP, Lovett SM, Poeltler DM. AmnisureTM
placental alpha microglobulin-1 rapid immunoassay versus
standard diagnostic methods for detection of rupture of membranes. Am J Perinatol 2005;22:14.
11. Si Eun Lee, Park JS, Norwitz ER, Kim KW, Park HS, Jun JK.
Measurement of placental alpha-microglobulin-1 in cervicovaginal discharge to diagnose rupture of membranes. Obstet Gynecol
2007;109:634640.
12. Joong Shin Park, Park JS. Non-invasive testing for rupture of the
fetal membranes. In: US Obstetrics and Gynecology, Touch
briefings 2007, 1316.
13. Caughey AB, Robinson JN, Norwitz ER. Contemporary diagnosis and management of preterm premature rupture of
membranes. Rev Obstet Gynecol 2008;1(1):1122.
14. Lee SE, Lee J, Seong HS, Lee SE, Park JS, Romero R, Yoon BH.
The clinical significance of a positive AmnisureTM test in women
with term labor with intact membranes. J Matern Fetal Neonatal
Med 2009;22(4):305310.

407

15. Salfelder A, Kagerah M, Nugent W, Blees M. Detection of

fibronectin for confirming the diagnosis of premature rupture of
fetal membranes. Geburtshilfe Frauenheilkd 1992;52(12):730733.
16. Putz I, Winkler, Rath W. Reliability of the detection of fetal
fibronectin using monoclonal antibody FDC-6. Geburtshilfe
Frauenheilkd 1995;55(12):703706.
17. Rutanen EM, Pekonen F, Karkkainen T. Measurement of
insulin-like growth factor binding protein-1 in cervical vaginal
secretions: comparison with the ROM check membrane immunoassay in the diagnosis of ruptured membranes. Clin Chim Acta
1993:214(1):7381.
18. Chen FC, Dudenhausen JW. Comparison of two rapid strip tests
based on IGFBP-1 and PAMG-1 for the detection of amniotic
fluid. Am J Perinatol 2008;25(4):243246.
19. Tagore S, Kwek K. Comparative analysis of insulin-like growth
factor binding protein-1 (IGFBP-1), placental alpha microglobulin-1 (PAMG-1) and nitrazine test to diagnose premature rupture
of membranes in pregnancy. J Perinat Med 2010;38:609612.
20. Silva E, Martinez JC. Diagnosing ROM: a comparison of the gold
standard, indigo carmine amnioinjection, to the rapid immunoassay, the Amnisure ROMTM test. J Perinat Med
2009;37(S1):956.
21. Mittal P, Romero R, Soto E, Cordoba M, Nhan Chang CL,
Vaisbuch E, Bieda J, Chaiworapongsa T, Kusanovic JP, Yeo L,
et al. A role for placental alpha-microglobulin-1 in the identification of women with a sonographic short cervix at risk for
spontaneous rupture of membranes. Am J Obstet Gynecol
2009(Suppl). Abstract # 528.
22. Di Renzo GC, Cabewro Roura L, Facchinetti F, and the
European Association of Perinatal Medicine-Study group in
preterm birth; Antsaklis A, Breborowicz G, Gratacos E,
Husslein P, Lamont R, Mikhailov A, Montenegro N, et al.
Guidelines for the management of spontaneous preterm labor:
identification of preterm labor, diagnosis of preterm premature
rupture of membranes and preventive tools for preterm birth. J
Matern Fetal Neonatal Med, in press.
23. Pollet-Villard M, Cartier R, Gaucherand P, Doret M. Detection of
placental alpha microglobulin-1 versus insulin-like growth factor
binding protein-1 in amniotic fluid at term: a comparative study.
Perinat 2011 Jan 11 (Epub ahead of print).

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