European Journal of Obstetrics & Gynecology

and Reproductive Biology

Volume 236, May 2019, Pages 1-6

Review article

Preterm premature rupture of the membranes:

Guidelines for clinical practice from the French
College of Gynaecologists and Obstetricians (CNGOF)
Thomas Schmitz a b c , Loïc Sentilhes d, Elsa Lorthe e c, Denis Gallot g f, Hugo Madar d, Muriel Doret-Dion h,
Gaël Beucher i, Caroline Charlier k l j, Charles Cazanave n m, Pierre Delorme k o c, Charles Garabédian q p, Elie Azria k r c,
Véronique Tessier s o, Marie-Victoire Sénat u t, Gilles Kayem c v w

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Abstract

In France, the frequency of premature rupture of the membranes (PROM) is 2%–3% before 37 weeks'
gestation (level of evidence [LE] 2) and less than 1% before 34 weeks (LE2). Preterm delivery and
intrauterine infection are the major complications of preterm PROM (PPROM) (LE2). Prolongation of the
latency period is beneficial (LE2). Compared with other causes of preterm delivery, PPROM is associated
with a clear excess risk of neonatal morbidity and mortality only in cases of intrauterine infection, which is
linked to higher rates of in utero fetal death (LE3), early neonatal infection (LE2), and necrotizing
enterocolitis (LE2).

The diagnosis of PPROM is principally clinical (professional consensus). Tests to detect IGFBP-1 or PAMG-1
are recommended in cases of uncertainty (professional consensus).

Hospitalization is recommended for women diagnosed with PPROM (professional consensus). Adequate
evidence does not exist to support recommendations for or against initial tocolysis (Grade C). If tocolysis is
prescribed, it should not continue longer than 48 h (Grade C). The administration of antenatal
corticosteroids is recommended for fetuses with a gestational age less than 34 weeks (Grade A) and
magnesium sulfate if delivery is imminent before 32 weeks (Grade A). The prescription of antibiotic
prophylaxis at admission is recommended (Grade A) to reduce neonatal and maternal morbidity (LE1).
Amoxicillin, third-generation cephalosporins, and erythromycin (professional consensus) can each be used
individually or eythromycin and amoxicillin can be combined (professional consensus) for a period of 7 days
(Grade C). Nonetheless, it is acceptable to stop antibiotic prophylaxis when the initial vaginal sample is
negative (professional consensus). The following are not recommended for antibiotic prophylaxis:
amoxicillin-clavulanic acid (professional consensus), aminoglycosides, glycopeptides, first- or second-
generation cephalosporins, clindamycin, or metronidazole (professional consensus).

Women who are clinically stable after at least 48 h of hospital monitoring can be managed at home
(professional consensus).

Monitoring should include checking for clinical and laboratory factors suggestive of intrauterine infection
(professional consensus). No guidelines can be issued about the frequency of this monitoring (professional
consensus). Adequate evidence does not exist to support a recommendation for or against the routine
initiation of antibiotic therapy when the monitoring of an asymptomatic woman produces a single isolated
positive result (e.g., elevated CRP, or hyperleukocytosis, or a positive vaginal sample) (professional
consensus).

In cases of intrauterine infection, the immediate intravenous administration (Grade B) of antibiotic therapy
combining a beta-lactam with an aminoglycoside (Grade B) and early delivery of the child are both
recommended (Grade A). Cesarean delivery of women with intrauterine infections is reserved for the
standard obstetric indications (professional consensus).

Expectant management is recommended for uncomplicated PROM before 37 weeks (Grade A), even when a
sample is positive for Streptococcus B, as long as antibiotic prophylaxis begins at admission (professional
consensus). Oxytocin and prostaglandins are two possible options for the induction of labor in women with
PPROM (professional consensus).

Introduction

The sponsor (the French College of Gynecologists and Obstetricians (CNGOF)) appointed a steering
committee (Appendix A) to define the exact questions to be put to the experts, to choose them, follow their
work and draft the synthesis of recommendations resulting from their work [1]. The experts analyzed the
scientific literature on the subject to answer the questions raised. A literature review identified the relevant
articles through mid-2018 by searching the MEDLINE database and the Cochrane Library. The search was
restricted to articles published in English and French. Priority was given to articles reporting results of
original research, although review articles and commentaries were also consulted. Guidelines published by
organizations or institutions such as the American College of Obstetricians and Gynecologists (ACOG), the
Royal College of Obstetricians and Gynaecologists (RCOG), the Canadian Society of Gynecology and
Obstetrics (SOGC), the National Institute for Health and Clinical Excellence (NICE) as well as previous
guidelines published by the CNGOF were reviewed, and additional studies were located by reviewing
bibliographies of identified articles. For each question, each overview of validated scientific data was
assigned a level of evidence based on the quality of its data, in accordance with the framework defined by
the HAS (French Health Authority), summarized below. Details on the systematic review process are
provided in each article [[2], [3], [4], [5], [6], [7], [8]] dealing with the questions raised in the Content
section.

LE1: very powerful randomized comparative trials, meta-analysis of randomized comparative trials;

LE2: not very powerful randomized trial, well-run non-randomized comparative studies, cohort studies;
LE3: case-control studies;

LE4: non-randomized comparative studies with large biases, retrospective studies, cross-sectional studies,
and case series.

A synthesis of recommendations was drafted by the organizing committee based on the replies given by the
expert authors. Each recommendation for practice was allocated a grade, defined by the HAS as follows:

Grade A: Recommendations are based on good and consistent scientific evidence

Grade B: Recommendations are based on limited or inconsistent scientific evidence

Grade C: Recommendations are based primarily on consensus and expert opinion

Professional consensus: In the absence of any conclusive scientific evidence, some practices have
nevertheless been recommended on the basis of agreement between the members of the working group
(professional consensus).

All texts were reviewed by persons not involved in the work, i.e., practitioners in the various specialties
(Appendix) concerned and working in different situations (public, private, university or non-university
establishments). Once the review was completed, changes were made, if appropriate, considering the
assessment of the quality of the evidence.

The original long texts in French are cited [[2], [3], [4], [5], [6], [7], [8]], but their individual references are
not included here in view of the enormous space they would occupy in this article intended to summarize
the guidelines.

Section snippets

Epidemiology, risk factors, and the child's prognosis

According to the 2016 French national perinatal survey, premature rupture of the membranes (PROM)
before 37 weeks occurs in 2–3% of pregnancies, and PROM before 34 weeks in less than 1% (LE2). Its
frequency increases as the pregnancy advances (LE2) and is higher in multiple than in singleton pregnancies
(LE2). Most women give birth in the week that follows the rupture, and the duration of latency (defined as
the interval between PROM and the birth) diminishes as gestational age at PROM rises…

Diagnosis

PROM is noticed most often by the discharge of amniotic fluid, easily recognizable. In these cases a
laboratory diagnostic test is not required (professional consensus).

Ultrasound assessment of the quantity of amniotic fluid cannot either confirm or rule out the diagnosis of
PROM (LE4). In uncertain clinical situations, an immunochromatographic test to detect Insulin-like Growth
Factor-Binding Protein-1 (IGFBP-1) or Placenta Alpha 1-Microglobulin (PAMG-1) is recommended to
diagnose PROM,…
Therapeutic management (excluding antibiotic therapy)

The woman should be hospitalized at diagnosis of preterm PROM if the fetus has reached viability
(professional consensus). Clinical examination aims to look for signs of intrauterine infection: fever, fetal
tachycardia, uterine contractions, or purulent vaginal discharge (professional consensus). If a cervical
evaluation seems necessary, an examination by speculum or a digital or ultrasound cervical examination
can be performed (professional consensus). Cervical assessments should be limited,…

Choices and duration of antibiotic prophylaxis

Antibiotic prophylaxis should be prescribed at admission for preterm PROM (Grade A), because it is
associated with a reduction in neonatal morbidity and maternal (LE1). Streptococcus agalactiae (group-B
streptococci) and Escherichia coli are the principal infectious agents involved in early neonatal bacterial
infection (LE3) and should be the target of the antibiotic prophylaxis (professional consensus).

Theoretical arguments indicate that amoxicillin (parenteral or oral) or third-generation…

Intrauterine infection: diagnosis and treatment

Intrauterine infection can be clinically diagnosed when all of the following criteria are met (professional
consensus):

Fever, defined by a maternal temperature equal to or greater than 38 °C, confirmed after an interval of 30
min, with no nongynecologic infectious cause identified, associated with at least two of the following
criteria:
- persistent fetal tachycardia > 160 bpm,…

- uterine pain or painful uterine contractions or spontaneous labor,…

- purulent amniotic fluid.…

Maternal plasma CRP and…

Mode of delivery in the absence of complications

Because a long latency period is not associated with an increased risk of neonatal complications before 34
weeks (LE3), it is recommended that labor not be induced for uncomplicated PROM (Grade C).

After 34 weeks of gestation, regardless of the gestational age at which PROM occurred, expectant
management is associated with a higher frequency of intrauterine infection (LE2) but not of neonatal sepsis
(LE1). An interventionist attitude is associated with higher rates of respiratory distress (LE2)…

PROM before fetal viability

Previable PROM, that is, PROM before fetal viability, is rare, with a frequency ranging from 0.3% to 1% (LE4).
After previable PROM, 50% to 60% of women nonetheless retain a satisfactory quantity of amniotic fluid
(LE3), 23% to 53% give birth in the week after PROM, and slightly more than 35% of the women have not
given birth 2 weeks after PROM (LE3). Oligohydramnios during the initial ultrasound is associated with a
higher risk of a short latency period (LE4).

The frequency of medical…

Recommended articles

References (8)

E. Lorthe
Epidemiology, risk factors and child prognosis: CNGOF preterm premature rupture of
membranes guidelines
Gynecol Obstet Fertil Senol (2018)

D. Gallot
Diagnosis of rupture of fetal membranes: CNGOF preterm premature rupture of membranes
guidelines
Gynecol Obstet Fertil Senol (2018)

H. Madar
Management of preterm premature rupture of membranes (except for antibiotherapy): CNGOF
preterm premature rupture of membranes guidelines
Gynecol Obstet Fertil Senol (2018)

M. Doret-Dion et al.
Antibiotic prophylaxis in preterm premature rupture of membranes: CNGOF preterm premature
rupture of membranes guidelines
Gynecol Obstet Fertil Senol (2018)

There are more references available in the full text version of this article.

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