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39 (2015) 495500

Available online at www.sciencedirect.com

www.elsevier.com/locate/semperi

Labor induction in the patient with preterm


premature rupture of membranes
Roger Everett Packard, DO, FACOOG, and
Awathif Dhanya Mackeen, MD, MPH, FACOGn
Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, Geisinger Health System, 100 N.
Academy Ave, Danville, PA 17822

article info

abstra ct

Keywords:

Preterm premature rupture of membranes (PPROM) affects up to one-third of all preterm

Induction of labor

births and confers serious maternal risks, including intra-amniotic infection, and an

Preterm premature rupture of

increased risk of neonatal complications, including respiratory distress and intraventric-

membranes

ular hemorrhage. Management of PPROM is a highly individualized process that requires

Preterm delivery

an accurate determination of gestational age and causal factors, as well as the balancing of

Early PPROM, late PPROM

maternal and fetal risks. In this review of the existing literature on induction of labor in

Management around periviability

PPROM, we examine the differences in appropriate management of patients with early


(32 weeks 0 days to 33 weeks 6 days) and near term (34 weeks 0 days to 36 weeks 6 days)
PPROM, and compare the safety and efcacy of available treatment options. This review of
previous research ndings provides general guidelines for clinical decision making and
highlights the need for future research on management of PPROM.
& 2015 Elsevier Inc. All rights reserved.

Introduction
Preterm premature rupture of membranes (PPROM) dened as
rupture of membranes prior to the 37th week of gestation
complicates approximately 3% of all pregnancies and 2533% of
all preterm births.1 In over 50% of patients diagnosed with
PPROM, delivery occurs within a week of membrane rupture.2
Latency of pregnancy following rupture of membranes is inversely associated with the gestational age at the time of membrane
rupture.3 Intra-amniotic infection (1360%) and placental abruption (412%) are often associated with PPROM. These complications occur more frequently at earlier gestational age of rupture.2
As the gestational age at diagnosis decreases, the severity
and frequency of associated neonatal complications
increases. Respiratory distress syndrome is the most common serious complication observed in the neonate born after
n

Corresponding author.
E-mail address: admackeen@geisinger.edu (A.D. Mackeen).

http://dx.doi.org/10.1053/j.semperi.2015.07.015
0146-0005/& 2015 Elsevier Inc. All rights reserved.

a pregnancy complicated by PPROM.4 Other signicant neonatal


complications associated with PPROM include intraventricular
hemorrhage, necrotizing enterocolitis, sepsis, contractures
(associated with long-standing oligohydramnios/anhydramnios), umbilical cord prolapse (especially when the fetal
presentation is non-vertex) and cesarean delivery for malpresentation.4 Severe oligohydramnios or anhydramnios leads to
an increased incidence of umbilical cord compression and nonreassuring fetal testing, which may increase the chance of
cesarean delivery. The presence of intra-amniotic infection or
inammation in the setting of PPROM has been associated with
an increased incidence of neurodevelopmental delay.5,6
Maternal complications are typically secondary to the
increased likelihood of infection associated with PPROM.
Intra-amniotic infection in patients with PROM is signicantly higher for those with preterm PROM (1360%)

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compared to those with PROM at term (1%).4 Additionally,


intra-amniotic infection is noted more frequently in women
with prolonged PPROM, severe oligohydramnios and multiple
digital vaginal examinations.
Accurate diagnosis as well as adequate estimation of gestational age is of the utmost importance in determining the
appropriate management of pregnancies complicated by
PPROM. Diagnosis is traditionally a clinical one, conrmed
when a suspicious history or sonographic nding of oligohydramnios is accompanied by a pooling of uid in the posterior fornix of the vagina or visual leakage of uid from the
cervical os. If no pooling or visual leakage is appreciated, then
a positive nitrazine test (where the vaginal uid demonstrates an alkaline pH) and the microscopic appearance of a
fern pattern when examining dried vaginal discharge is
highly suggestive of ROM. In the absence of these ndings
despite a highly suspicious history, the tampon (amnio dye)
test may be used: indigo carmine dye is injected into the
amniotic uid via amniocentesisblue coloring noted on the
vaginally inserted tampon within 30 min of intrauterine dye
instillation is considered conrmatory of rupture. At this
time, pharmaceutical companies are no longer producing
indigo carmine dye, so this test may not be an option in the
near future. In the presence of a high degree of suspicion for
ROM without the evidence of pooling, ferning, nitrazine and
without the ability to perform an amnio dye test, consideration may be given to placental alpha-microglobulin-1
(PAMG-1) testing (also known as Amnisures). This test
measures placental alpha-microglobulin-1 (PAMG-1) which
is found in higher concentrations within the amniotic uid
than in vaginal secretions.7 However, PAMG-1 is not considered a rst-line diagnostic test as studies have shown a false
positive rate of up to 31% in laboring patients without clinical
evidence of ROM.8,9 Current management of early PPROM at
or beyond viability favors measures to maintain the pregnancy in the absence of overt intra-amniotic infection, active
labor, or non-reassuring fetal assessment. Management of
late PPROM (after 34 weeks) focuses on expedited delivery.
These differences accentuate the necessity of appropriate
estimation of gestational age, which is a benchmark of sound
prenatal care, either through well-documented menstrual
dates, early sonographic dating or a combination of both.

Management
Causes of PPROM are numerous and subsequent management is heavily inuenced by the pathophysiologic culprit,
when it is known or suspected (Fig). Infection is commonly
linked to PPROM with amniotic uid cultures noted to be
positive in 2535% of samples.2,1012 Clinically diagnosed
intra-amniotic infection is a contraindication to expectant
management of pregnancy and warrants expedited delivery,
reserving cesarean delivery for the typical obstetrical
indications.
Initial evaluation of the patient with PPROM should include
an assessment of intra-amniotic infection (e.g., presence of
fever, uterine tenderness, purulent lochia and maternal, or
fetal tachycardia), evaluation for active labor, fetal position,
and fetal well-being are necessary for determining an

39 (2015) 495500

appropriate management plan. Each of these potential issues


needs to be assessed within the context of estimated gestational age, as this is often the guidepost for PPROM management. A thorough evaluation will allow the provider to assess
for additional contraindications to expectant management.

Late PPROM 34 weeks 0 days36 weeks 6 days


The risk of fetal complications associated with preterm
delivery has an inverse relationship with regard to gestational age, as risks of severe complications are greatest near
the limits of fetal viability and decrease as the pregnancy
progresses. The risks of serious complications are low when a
preterm delivery approaches term. Adjunctive treatments to
prolong pregnancy are not part of current obstetric practice at
this gestational age. Tocolysis may be considered in the
preterm labor patient in order to administer antenatal corticosteroids prior to achieving 34 weeks. However, in the
setting of late PPROM, this practice has not been shown to
be as benecial.2,4,13 Antenatal corticosteroids are not currently recommended beyond 34 weeks 0 days for the
improvement in fetal pulmonary maturity.
Delaying delivery in the patient with late PPROM has been
associated with increased intra-amniotic infection, lower
mean umbilical cord pH, and longer maternal hospitalization
without demonstration of a signicant decrease in perinatal
complications.14,15 Therefore, the current practice is delivery
in this group. More recent research has suggested that
expeditious delivery in late PPROM may not reduce the risk
of neonatal sepsis as compared to expectant management,
although the authors noted that the sample size may have
been too small to demonstrate a difference given the low
incidence of neonatal sepsis.16 In addition, a recent Cochrane
Review reported that planned delivery in the PPROM patient
prior to 37 weeks was not associated with an improvement in
perinatal morbidity or a reduction in perinatal mortality.17
However, this meta-analysis does include a wide range of
gestational ages as well as multiple studies with varied
methodological quality. Current recommendations from the
American Congress of Obstetricians and Gynecologists support the expeditious delivery of the patient with PPROM who
has attained 34 weeks of gestation, as the risk for ascending
infection is increased, the complications of prematurity are
relatively low and the efcacy of antenatal corticosteroids to
improve perinatal outcomes has not been established.4

Early PPROM: 23 weeks 0 days33 weeks 6 days


Individualization of management is a hallmark of obstetrical
care, but most particularly at the periviable gestational age.
The care delivered to such patients should weigh the risk of
ascending infection versus the risks of prematurity, including
severe neonatal morbidity and mortality. Clinical diagnosis of
intra-amniotic infection, active labor, and non-reassuring
fetal status continue to be contraindications to expectant
management in this patient group. However, there are
adjunctive treatments that can increase latency and decrease
perinatal morbidities.

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Fig. Management of preterm premature rupture of membranes (PPROM). GBS: group B streptococcus; MFM: maternal-fetal
medicine. (Adapted from Mercer BM.)2
In a multicenter trial sponsored by the National Institute of
Child Health and Human Development MaternalFetal Medicine Units, patients who received broad-spectrum antibiotics
for 7 days had twice the latency period as those who received
placebo.18 Signicant decreases were also appreciated in intraamniotic infection, respiratory distress syndrome (RDS),
necrotizing enterocolitis, and bronchopulmonary dysplasia.
Antenatal corticosteroids given prior to 34 weeks have been
demonstrated to reduce the risk of RDS, intraventricular

hemorrhage, and perinatal death.19 A meta-analysis reviewing the use of antenatal corticosteroids in the patient with
early PPROM corroborated these ndings and added that no
signicant differences were noted in maternal or fetal
infection.20
Tocolysis in PPROM is a contentious subject, as the data is
insufcient to make a distinct recommendation either for or
against use. The concern for intra-amniotic infection keeps
many practitioners from using tocolytics in the management

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of patients with PPROM. The use of short-term tocolysis for


2448 h in order to administer antenatal corticosteroids may
be considered in the absence of clinical intra-amniotic infection.21 A Cochrane meta-analysis reports that the use of
tocolytics past this time frame has not been shown to
increase latency or improve neonatal outcomes, it in fact
reports an increase of chorioamnionitis in women with PROM
who receive tocolysis.13,15 However, this Cochrane points out
that many of the included studies did not routinely include
the contemporary practice of antenatal corticosteroids or
latency antibiotics.
Contemporary practice favors delivery after attaining 34
weeks gestation in the patient with PPROM as noted in a
recent survey of MaternalFetal Medicine specialists.22 There
are a subset of providers who prefer to consider delivery if
fetal pulmonary maturity is proven prior to reaching 34
weeks, typically via amniocentesis or vaginal pool sampling.2
Although this practice is not ubiquitous throughout obstetrics, some practitioners may include the amniocentesis
results in their decision to either expedite delivery or continue with expectant management based on fetal pulmonary
maturity.

Labor induction
The preferred method for labor induction in the patient with
PPROM remains controversial. The current available literature
addressing this subset of patients is sparse. Common current
practices are guided by studies that were aimed at determining the optimal timing of delivery.14,23 These trials did
demonstrate the benet of labor induction in late PPROM as
compared to expectant management, but optimal method of
induction was not a focus.
Contemporary labor induction practices with PPROM have
been guided by studies of term PROM as well as provider
experience. According to the American Congress of Obstetricians and Gynecologists, recent data in large randomized
trials suggest that for women with premature rupture of
membranes at term, labor should be induced at the time of
presentation, generally with oxytocin, to reduce the risk of
chorioamnionitis.24,25 While this study did suggest improved
outcomes with high-dose oxytocin use, its comparator was
low-dose oxytocin rather than a separate induction agent.25
This calls into question the possible use of alternative
methods for labor induction in not only term PROM, but in
PPROM as well.
The American Congress of Obstetricians and Gynecologists
also reports in the practice bulletin on labor induction that
intravaginal PGE2 appears to be safe and effective in the
setting of PROM.24,26 A 1977 study of 100 patients with term
PROM found that oral PGE2 was safe and effective and
conferred a shorter latency from PROM to delivery.27 Since
this trial, multiple studies have reported conicting data that
consistently support the use of prostaglandins as safe and
effective in the patient with PROM, but differ with regard to
prostaglandins superiority to oxytocin.2833 Butt et al.28 report
in their well-designed randomized controlled trial of 108
women with term PROM that although the time spent in
active labor as well as maternal and neonatal outcomes were

39 (2015) 495500

similar, oxytocin conveyed a shorter interval to delivery time


by greater than 3 h when compared to prostaglandin. Women
in both groups had a mean Bishop score of 6 at the start of
induction.28 A smaller Swedish study of 20 nulliparas found
that vaginal prostaglandin demonstrated superiority to intravenous oxytocin in both its ability to ripen the cervix within
5 h as well as to achieve vaginal delivery within 24 h.29 A large
prospective trial of 240 women from Turkey found oxytocin
infusion superior to intravaginal prostaglandin with regard to
both interval from induction to active labor and induction to
delivery.31 A recent meta-analysis specically reviewed the
use of misoprostol versus placebo or oxytocin in the patient
with term PROM. This analysis determined that labor outcomes using misoprostol were similar to oxytocin infusion
for delivery within 24 h of intervention and superior to oxytocin for delivery within 12 h.34 In addition, misoprostol was
not associated with an increase in tachysystole or poor
maternal or fetal outcomes.
Cervical ripeness is another factor that should be considered when preparing for labor induction, with a Bishop score
greater than 8 at the initiation of labor induction conferring a
similar probability of vaginal delivery to that of a woman with
spontaneous active labor.24 This premise guides many centers to initiate cervical ripening prior to labor induction for
those with a Bishop score r8. A recent large retrospective
cohort study reviewing intrapartum management of patients
with PROM described their typical practice of labor induction
with oxytocin infusion when the cervix is favorable and
cervical ripening with intravaginal prostaglandin in the setting of an unfavorable cervix.35 This study found that the
rates of cesarean delivery were similar among patients who
underwent labor induction following PROM at any gestational
age with vaginal delivery occurring in 82% of labor inductions.35 The use of both pharmacologic and mechanical
cervical ripening methods have been well documented in
the patient with intact membranes.36 Studies of osmotic
dilator use in labor induction suggest an increase in peripartum infection.37,38 This nding in conjunction with the
increased risk for ascending infection with a non-intact
amnion has deterred the use of these dilators in the setting
of PROM. This concern for ascending infection may impact
the use of mechanical dilators, including the Foley balloon for
cervical ripening in PPROM, though these risks remain theoretical. In fact, preliminary reports on the use of a balloon
catheter for labor induction with PROM suggests that its use
in cervical ripening and induction of labor may be safe,
efcacious, and well tolerated.15,39,40 Additionally, a study
showed that women with ruptured membranes and labor
induction initiated with a Foley catheter had a shorter
interval to delivery and a lower incidence of chorioamnionitis
as compared to women who initiated labor induction with
misoprostol.40 There are currently two multicenter trials in
the United States focusing on both standard Foley balloon as
well as a double balloon catheter in patients with PROM and
PPROM for mechanical cervical ripening. Both of these trials
use the mechanical dilators with oxytocin versus oxytocin
alone as the interventions with primary outcomes of induction to delivery time. Each study will also report infection
rates, as this is a potential concern with the introduction of a
foreign body into intrauterine cavity.41,42 These ongoing trials

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will hopefully provide additional guidance regarding the use


of mechanical dilators in PPROM.
As with each pregnancy, the management of the patient
with PPROM requires an individualized approach. From the
initial decision regarding expectant management versus
expedited delivery, there are many factors to consider.
Cervical favorability should play a role in the process of
selecting an agent for labor induction, as an unripe cervix
increases the risk of a cesarean delivery. Cervical ripening agents have also been shown to decrease the interval
from initiation of induction to delivery. Above all, when
deciding how to proceed with delivery and labor induction,
the overall health including short- and long-term outcomes for both the mother and neonate should be driving
force.

39 (2015) 495500

14.

15.

16.

17.

re fe r en ces

18.

1. Waters TP, Mercer B. Preterm PROM: prediction, prevention,


principles. Clin Obstet Gynecol. 2011;54(2):307312. http://dx.
doi.org/10.1097/GRF.0b013e318217d4d3.
2. Mercer BM. Preterm premature rupture of the membranes.
Obstet Gynecol. 2003;101(1):178193.
3. Hannah ME, Ohlsson A, Farine D, et al. Induction of labor
compared with expectant management for prelabor rupture
of the membranes at term. N Engl J Med. 1996;334(16):
10051010.
4. American College of Obstetrics and Gynecology. Premature
rupture of membranes: practice bulletin no. 139. Obstet
Gynecol. 2013;122(4):918930.
5. Spinillo A, Capuzzo E, Stronati M, Ometto A, Orcesi S, Fazzi E.
Effect of preterm premature rupture of membranes on neurodevelopmental outcome: follow up at two years of age. BJOG.
1995;102(11):882887.
6. Yoon BH, Romero R, Park JS, et al. Fetal exposure to an intraamniotic inammation and the development of cerebral
palsy at the age of three years. Obstet Gynecol. 2000;182(3):
675681.
7. Cousins LM, Smok DP, Lovett SM, Poeltler DM. AmniSure
placental alpha microglobulin-1 rapid immunoassay versus
standard diagnostic methods for detection of rupture of
membranes. Am J Perinatol. 2005;22(6):317320. http://dx.doi.
org/10.1055/s-2005-870896.
8. Lee SM, Lee J, Seong HS, et al. The clinical signicance
of a positive amnisure test in women with term labor with
intact membranes. J Matern Fetal Neonatal Med. 2009;22(4):
305310.
9. Mi Lee S, Romero R, Park JW, et al. The clinical signicance of
a positive amnisure test in women with preterm labor and
intact membranes. J Matern Fetal Neonatal Med. 2012;25(9):
16901698.
10. Moore R, Mansour J, Redline R, Mercer B, Moore J. The
physiology of fetal membrane rupture: insight gained from
the determination of physical properties. Placenta. 2006;27(11):
10371051.
11. Garite T, Freeman R. Chorioamnionitis in the preterm gestation. Obstet Gynecol. 1982;59(5):539545.
12. Mercer BM, Goldenberg RL, Moawad AH, et al. The preterm
prediction study: effect of gestational age and cause of
preterm birth on subsequent obstetric outcome. Obstet Gynecol. 1999;181(5):12161221.
13. Garite TJ, Keegan KA, Freeman RK, Nageotte MP. A randomized trial of ritodrine tocolysis versus expectant management

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

29.

30.

31.

499

in patients with premature rupture of membranes at 25 to 30


weeks of gestation. Obstet Gynecol. 1987;157(2):388393.
Naef RW, Albert JR, Ross EL, Weber BM, Martin RW, Morrison
JC. Premature rupture of membranes at 34 to 37 weeks
gestation: aggressive versus conservative management.
Obstet Gynecol. 1998;178(1):126130.
Mackeen AD, SeibelSeamon J, GrimesDennis J, Baxter JK,
Berghella V. Tocolytics for preterm premature rupture of
membranes. Cochrane Database Syst Rev. 2014;2:1100.
van der Ham David P, van der Heyden, Jantien L, Opmeer BC,
et al. Management of late-preterm premature rupture of
membranes: the PPROMEXIL-2 trial. Obstet Gynecol. 2012;207(4):
276.e1276.e10.
Buchanan SL, Crowther CA, Levett KM, Middleton P, Morris J.
Planned early birth versus expectant management for
women with preterm prelabour rupture of membranes prior
to 37 weeks gestation for improving pregnancy outcome.
Cochrane Database Syst Rev. 2010;3:187.
Mercer BM, Miodovnik M, Thurnau GR, et al. Antibiotic
therapy for reduction of infant morbidity after preterm
premature rupture of the membranes: a randomized controlled trial. J Am Med Assoc. 1997;278(12):989995.
Gilstrap LC, Christensen R, Clewell WH, et al. Effect of corticosteroids for fetal maturation on perinatal outcomes: NIH
consensus development panel on the effect of corticosteroids
for fetal maturation on perinatal outcomes. J Am Med Assoc.
1995;273(5):413418.
Harding JE, Pang J, Knight DB, Liggins GC. Do antenatal
corticosteroids help in the setting of preterm rupture of
membranes? Obstet Gynecol. 2001;184(2):131139.
Weiner CP, Renk K, Klugman M. The therapeutic efcacy and
cost-effectiveness of aggressive tocolysis for premature labor
associated with premature rupture of the membranes. Obstet
Gynecol. 1988;159(1):216222.
Ramsey PS, Nuthalapaty FS, Lu G, Ramin S, Nuthalapaty ES,
Ramin KD. Contemporary management of preterm premature rupture of membranes (PPROM): a survey of maternal
fetal medicine providers. Obstet Gynecol. 2004;191(4):14971502.
Mercer BM, Crocker LG, Boe NM, Sibai BM. Induction versus
expectant management in premature rupture of the membranes with mature amniotic uid at 32 to 36 weeks: a
randomized trial. Obstet Gynecol. 1993;169(4):775782.
American College of Obstetricians and Gynecologists. Induction of labor: practice bulletin no. 107. Obstet Gynecol. 2009;
114(2 (pt 1)):386397.
Merrill DC, Zlatnik FJ. Randomized, doublemasked comparison of oxytocin dosage in induction and augmentation of
labor. Obstet Gynecol. 1999;94(3):455463.
Ray DA, Garite TJ. Prostaglandin E2 for induction of labor in
patients with premature rupture of membranes at term.
Obstet Gynecol. 1992;166(3):836843.
HAUTH JC, CUNNINGHAM FG, WHALLEY PJ. Early labor
initiation with oral PGE2 after premature rupture of the
membranes at term. Obstet Gynecol. 1977;49(5):523526.
Butt KD, Bennett KA, Crane JM, Hutchens D, Young DC.
Randomized comparison of oral misoprostol and oxytocin
for labor induction in term prelabor membrane rupture.
Obstet Gynecol. 1999;94(6):994999.
Ekman-Ordeberg G, Uldbjerg N, Ulmsten U. Comparison of
intravenous oxytocin and vaginal prostaglandin E2 gel in
women with unripe cervixes and premature rupture of the
membranes. Obstet Gynecol. 1985;66(3):307310.
Ngai SW, To WK, Lao T, Ho PC. Cervical priming with oral
misoprostol in pre-labor rupture of membranes at term.
Obstet Gynecol. 1996;87(6):923926.
Kunt C, Kanat-Pektas M, Gungor ANC, et al. Randomized trial
of vaginal prostaglandin E2 versus oxytocin for labor

500

32.

33.

34.

35.

36.

SE

M I N A R S I N

E R I N A T O L O G Y

induction in term premature rupture of membranes. Taiwan J


Obstet Gynecol. 2010;49(1):5761.
Granstrom L, Ekman G, Ulmsten U. Cervical priming and labor
induction with vaginal application of 3 mg PGE2 in suppositories in term pregnant women with premature rupture of
amniotic membranes and unfavorable cervix. Acta Obstet
Gynecol Scand. 1987;66(5):429431.
Goeschen K. Premature rupture of membranes near term:
induction of labor with endocervical prostaglandin E2 gel or
intravenous oxytocin. Am J Perinatol. 1989;6(2):181184. http:
//dx.doi.org/10.1055/s-2007-999572.
Lin MG, Nuthalapaty FS, Carver AR, Case AS, Ramsey PS.
Misoprostol for labor induction in women with term premature rupture of membranes: a meta-analysis. Obstet Gynecol.
2005;106(3):593601.
Kunze M, Hart JE, Lynch AM, Gibbs RS. Intrapartum management of premature rupture of membranes: effect on cesarean
delivery rate. Obstet Gynecol. 2011;118(6):12471254. http://dx.
doi.org/10.1097/AOG.0b013e3182351b0c.
Boulvain M, Kelly A, Lohse C, Stan C, Irion O. Mechanical
methods for induction of labour. Cochrane Database Syst Rev.
2001(4):1272.

39 (2015) 495500

37. Krammer J, Williams MC, Sawai SK, OBrien WF. Preinduction cervical ripening: a randomized comparison of
two methods. Obstet Gynecol. 1995;85(4):614618.
38. Kazzi G, Bottoms S, Rosen M. Efcacy and safety of laminaria
digitata for preinduction ripening of the cervix. Obstet Gynecol.
1982;60(4):440443.
39. Wolff K, Swahn ML, Westgren M. Balloon catheter for induction of labor in nulliparous women with prelabor rupture of
the membranes at term. A preliminary report. Gynecol Obstet
Invest. 1998;46(1):14.
40. Mackeen AD, Walker L, Ruhstaller K, Schuster M, Sciscione A.
Foley catheter vs prostaglandin as ripening agent in pregnant
women with premature rupture of membranes. J Am Osteopath
Assoc. 2014;114(9):686692. http://dx.doi.org/10.7556/jaoa.2014.137.
41. ClinicalTrials.org. Evaluation of CRB in PROM patients. https://
www.clinicaltrials.gov/ct2/show/NCT02314728?term=labor+
induction+and+premature+rupture+of+membranes&rank=5.
2015 Accessed 26.04.15.
42. ClinicalTrials.org. FOLCROM trial: Foley catheter in rupture of
membranes. https://www.clinicaltrials.gov/ct2/show/
NCT01973036?term=labor+induction+and+premature+rupture+
of+membranes&rank=4. 2015. Accessed 26.04.15.

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