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Objective: To determine the management of patients with term prelabor rupture of membranes., Methods: Synthesis of the literature from the PubMed and Cochrane databases and the recommendations of French and foreign societies and colleges., Results: Term prelabor rupture of membranes is considered a physiological process until 12 h have passed since rupture (professional consensus). In cases of expectant management and with a low rate of antibiotic prophylaxis, home care may be associated with an increase in neonatal infections (LE3), compared with hospitalization, especially for women with group B streptococcus (GBS) colonization (LE3). Home care is therefore not recommended (grade C). In the absence of spontaneous labor within 12 h of rupture, antibiotic prophylaxis may reduce the risk of maternal intrauterine infection but not of neonatal infection (LE3). Its use after 12 h of rupture in term prelabor rupture of the membranes is therefore recommended (grade C). When antibiotic prophylaxis is indicated, intravenous beta-lactams are recommended (grade C). Induction of labor with oxytocin (LE1), prostaglandin E2 (LE1), or misoprostol (LE1) is associated with shorter rupture-to-delivery intervals than expectant management; immediate induction is not, however, associated with lower rates of neonatal infection (LE1), even among women with a positive GBS vaginal swab (LE2). Thus, expectant management can be offered without increasing the risk of neonatal infection (grade B). Induction of labor is not associated with either an increase or decrease in the cesarean rate (LE2), regardless of parity (LE2) or Bishop score at admission (LE3). Induction can thus be proposed without increasing the risk of cesarean delivery (grade B). No induction method (oxytocin, dinoprostone, misoprostol, or Foley catheter) has demonstrated superiority over any another method for reducing rates of intrauterine or neonatal infection or of cesarean delivery or for shortening the rupture-to-delivery intervals, regardless of parity or the Bishop score., Conclusion: Term prelabor rupture of membranes is a frequent event. A 12-hour interval without onset of spontaneous labor was chosen to differentiate a physiological condition from a potentially unsafe situation that justifies antibiotic prophylaxis. Expectant management or induction of labor can each be proposed, even in case of positive screening for group streptococcus. The decision should depend on the woman's wishes and maternity unit organization (professional consensus).

Objective: To determine the management of patients with term prelabor rupture of membranes., Methods: Synthesis of the literature from the PubMed and Cochrane databases and the recommendations of French and foreign societies and colleges., Results: Term prelabor rupture of membranes is considered a physiological process up to 12hours of rupture (Professional consensus). In case of expectant management and with a low rate of antibiotic prophylaxis, home care compared to hospitalization could be associated with an increase in neonatal infections (LE3), especially in case of group B streptococcus colonization (LE3). Home care is therefore not recommended (Grade C). In the absence of spontaneous labor within 12hours of rupture, antibiotic prophylaxis could reduce the risk of maternal intrauterine infection but not of neonatal infection (LE3). Its use after 12hours of rupture in term prelabor rupture of the membranes is therefore recommended (Grade C). When antibiotic prophylaxis is indicated, intravenous beta-lactams are recommended (Grade C). Induction of labor with oxytocin (LE1), prostaglandin E2 (LE1) or misoprostol (LE1), is associated with shorter rupture of membranes to delivery intervals when compared to expectant management. Compared with expectant management, immediate induction of labor is not associated with lower rates of neonatal infection (LE1), even among women with a positive streptococcus B vaginal swab (LE2). Thus, expectant management can be offered without increasing the risk of neonatal infection (Grade B). Induction of labor is not associated with an increase or decrease in the cesarean delivery rate (LE2), whatever parity (LE2) or Bishop score at admission (LE3). Induction can thus be proposed without increasing the risk of cesarean delivery (Grade B). No induction method (oxytocin, dinoprostone, misoprostol or Foley® catheter) has demonstrated superiority over another, whether to reduce rate of intrauterine or neonatal infection, rate of cesarean delivery or to shorten rupture of membranes to delivery intervals regardless of Bishop's score and parity., Conclusion: Term prelabor rupture of membranes is a frequent event. A 12-hour delay without onset of spontaneous labor was chosen to differentiate a physiological condition from a potentially unsafe situation justifying an antibiotic prophylaxis. Expectant management or induction of labor can both be proposed, even in case of positive screening for streptococcus B, depending on the patient's wishes and maternity units' organization (Professional consensus)., (Copyright © 2019. Published by Elsevier Masson SAS.)

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)., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Preterm premature rupture of membranes (PPROM) is associated with an increased risk of serious maternal, fetal, and neonatal morbidities. We compared neonatal outcomes of women with PPROM before 34 +0 weeks of gestation according to inpatient or outpatient management policy. 587 women with PPROM >48 hours, 246 (41.9%) in the group with an inpatient care policy (ICP) and 341 (58.1%) in the group with an outpatient care policy (OCP), were identified in France, from 2009 to 2012. Neonatal outcomes were compared between the two groups using logistic regression. A second analysis was performed to compare inpatient care and effective outpatient care (discharge from hospital) through propensity score matching. The outcome was a neonatal composite variable including one or more of the neonatal morbidity complications. The perinatal composite outcome was 14.6% with the ICP and 15.5% with the OCP (p = 0.76). After using the 1:1 ratio propensity score matching, effective outpatient care was not associated with a significantly higher risk of the perinatal composite outcome (OR 0.88, CI 0.35 to 2.25; p = 0.80) compared with inpatient care. Outpatient care is not associated with an increased rate of obstetric or neonatal complications and can be an alternative to hospital care for women with uncomplicated PPROM.

Objective: To determine management of women with preterm premature rupture of membranes (PPROM)., Methods: Bibliographic search from the Medline and Cochrane Library databases and review of international clinical practice guidelines., Results: In France, PPROM rate is 2 to 3% before 37 weeks of gestation (level of evidence [LE] 2) and less than 1% before 34 weeks of gestation (LE2). Prematurity and intra-uterine infection are the two major complications of PPROM (LE2). Compared to other causes of prematurity, PPROM is not associated with an increased risk of neonatal mortality and morbidity, except in case of intra-uterine infection, which is associated with an augmentation of early-onset neonatal sepsis (LE2) and of necrotizing enterocolitis (LE2). PPROM diagnosis is mainly clinical (professional consensus). In doubtful cases, detection of IGFBP-1 or PAMG-1 is recommended (professional consensus). Hospitalization of women with PPROM is recommended (professional consensus). There is no sufficient evidence to recommend or not recommend tocolysis (grade C). If a tocolysis should be prescribed, it should not last more than 48hours (grade C). Antenatal corticosteroids before 34 weeks of gestation (grade A) and magnesium sulfate before 32 weeks of gestation (grade A) are recommended. Antibiotic prophylaxis is recommended (grade A) because it is associated with a reduction of neonatal mortality and morbidity (LE1). Amoxicillin, 3rd generation cephalosporins, and erythromycin in monotherapy or the association erythromycin-amoxicillin can be used (professional consensus), for 7 days (grade C). However, in case of negative vaginal culture, early cessation of antibiotic prophylaxis might be acceptable (professional consensus). Co-amoxiclav, aminosides, glycopetides, first and second generation cephalosporins, clindamycin, and metronidazole are not recommended for antibiotic prophylaxis (professional consensus). Outpatient management of women with clinically stable PPROM after 48hours of hospitalization is a possible (professional consensus). During monitoring, it is recommended to identify the clinical and biological elements suggesting intra-uterine infection (professional consensus). However, it not possible to make recommendation regarding the frequency of this monitoring. In case of isolated elevated C-reactive protein, leukocytosis, or positive vaginal culture in an asymptomatic patient, it is not recommended to systematically prescribe antibiotics (professional consensus). In case of intra-uterine infection, it is recommended to immediately administer an antibiotic therapy associating beta-lactamine and aminoside (grade B), intravenously (grade B), and to deliver the baby (grade A). Cesarean delivery should be performed according to the usual obstetrical indications (professional consensus). Expectative management is recommended before 37 weeks of gestation in case of uncomplicated PPROM (grade A), even in case of positive vaginal culture for B Streptococcus, provided that an antibiotic prophylaxis has been prescribed (professional consensus). Oxytocin and prostaglandins are two possible options to induce labor in case of PPROM (professional consensus)., Conclusion: Expectative management is recommended before 37 weeks of gestation in case of uncomplicated PPROM (grade A)., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objective: Examine the predictive value for maternal-fetal infection of routine bedside tests detecting the proinflammatory cytokines, TNFα and IL-6, in the vaginal secretions of women with premature rupture of the membranes (PROM)., Study Design: This prospective two-center cohort study included all women hospitalized for PROM over a 2-year period. A bedside test assessed IL-6 and TNFα in vaginal secretions. Both centers routinely tested CRP and leukocytes, assaying both in maternal serum, and analyzed vaginal bacterial flora; all samples were repeated twice weekly until delivery., Results: The study included 689 women. In cases of preterm PROM (PPROM) before 37 weeks (n=184), a vaginal sample positive for one or more bacteria was the only marker associated with early neonatal infection (OR 5.6, 95%CI; 2.0-15.7). Its sensitivity was 82% (95%CI; 62-94) and its specificity 56% (95%CI; 47-65). All positive markers of infection were associated with the occurrence of chorioamnionitis. In cases of PROM from 37 weeks onward (n=505), only CRP >5mg/dL was associated with early neonatal infection (OR=8.3, 95%CI; 1.1-65.4) or clinical chorioamnionitis (OR=6.8, 95%CI; 1.5-30.0). The sensitivity of CRP >5mg/dL was 91% (95%CI; 59-100) and its specificity 45% (95%CI; 40-51) for predicting early neonatal infection, and 89% (95%CI; 65-99) and 46% (95%CI; 41-51), respectively, for predicting clinical chorioamnionitis., Conclusion: The association of vaginal cytokines with maternal-fetal infection is weak and thus prevents their use as a good predictor of maternal-fetal infection. CRP and vaginal samples may be useful for identifying a group of women at low risk of infection., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To assess the impact of extreme preterm premature rupture of membranes (PPROM) <25 weeks of gestation on preterm child outcome., Study Design: Retrospective study comparing the neonatal and 2-year outcomes of infants exposed to extremely PPROM <25 weeks with a non-exposed group of neonates in a tertiary care referral centre located in Paris, France, between 2003 and 2007. All women with singleton pregnancy and PPROM between 15(0/7) and 24(6/7) weeks of gestation were recruited. For each infant born alive, the next inborn neonate matched for gestational age and sex was selected as a control among neonates born alive after spontaneous preterm labour with intact membranes. The main outcome measures were neonatal outcome assessed by a combined criterion of adverse neonatal outcomes and the two-year neurodevelopmental outcome assessed by developmental Brunet-Lézine tests and neurological examinations., Results: In 78 cases of extremely PPROM, 22 live births occurred at a mean gestational age of 26(5/7) weeks. The percentage of neonates with adverse neonatal outcomes was significantly higher among PPROM than non-exposed cases (68.2 versus 27.3%). At 2 years of age, children from the PPROM group were more likely to have delayed acquisitions (64.3 versus 15.8%) and behavioural disorders (57.1 versus 15.8%). Mean Brunet-Lézine language score was significantly lower among those infants (78.9 versus 96.8)., Conclusion: PPROM <25 weeks is associated with increased neonatal mortality and morbidity and with increased risks of delayed acquisitions, behavioural disorders and lower language performance scores at 2 years in comparison with matched preterm neonates born after spontaneous preterm labour with intact membranes., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: To assess perinatal outcomes after expectant management in the case of preterm prelabour rupture of membranes (PPROM) before 25 weeks of gestation, according to the rate of termination of pregnancy (TOP)., Design: Retrospective comparative cohort study., Population: Singleton pregnancies complicated by PPROM between 15(0/7) and 24(6/7) weeks of gestation, from January 2003 to January 2007., Methods: Comparison of perinatal outcomes in two French tertiary care referral centres presumed to have different rates of TOP., Main Outcome Measure: Rates of TOP, survival and survival without major morbidity., Results: A total of 113 women experienced PPROM (49 in centre A and 64 in centre B). A lower proportion of patients opted for TOP in centre A (40.8%) than in centre B (56.3%). The baseline characteristics of patients and pregnancies, and gestational age at PPROM, were not different between the two centres. Mean gestational age at delivery (28.1 versus 25.4 weeks of gestation; P < 0.01), mean latency period (45.5 versus 16.1 days; P < 0.01), mean birthweight (1295 versus 929 g; P = 0.04) and survival (46.9 versus 20.3%; P < 0.01) were significantly higher in centre A than in centre B. The percentage of neonates alive without major morbidity was also higher in centre A than in centre B (42.9 versus 20.3%; P = 0.01)., Conclusions: Perinatal outcomes of pregnancies managed expectantly were not better in the centre where the TOP rate was higher. The perinatal risk of pregnancies complicated by pre-viable PPROM remains high., (© 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.)

Fetal membranes, amnion and chorion, line up the amniotic cavity and are essential for its integrity towards normal term of pregnancy. They consist of a pluristratified structure whose composition assures their cohesion and elasticity. They firstly function in retaining the fluctuant amniotic fluid in a half-rigid cavity. Their elastic limit depends on the organization of the extracellular matrix and firstly on the collagen type it contains. The compact layer of the amnion, responsible for the elastic limit, contains mainly type I collagen, organized in lattice; this allows elongation or spreading. Underneath, the spongy layer, principally of collagen III, is organized in a loose mesh, enriched in hydrated proteoglycans, which allows the absorption of the shocks and the sliding of the amnion on the chorion. The cascade of events leading to the membrane rupture displays: (i) membranes distension with elasticity loss, (ii) separation of the chorion from the amnion, (iii) chorion fracture, (iv) amnion distension which produces an hernia, (v) amnion rupture. The rupture mechanism was long thought to be a consequence of uterine contractions. However, the observation before labour of a zone of altered morphology, with biochemical variations (modifications of metalloprotease activity and of proteoglycans, apoptosis...) associated with focal physical weakness in the region overlying the cervix suggests programming of the rupture before parturition. A better understanding of the biochemical mechanisms of membranes rupture will provide new insights into how to anticipate and to intervene in the case of risk of premature rupture., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Background: Accurate prediction of infection, including maternal chorioamnionitis and early-onset neonatal infection, remains a critical challenge in cases of preterm rupture of membranes and may influence obstetrical management. The aim of our study was to investigate the predictive value for early-onset neonatal infection and maternal histological and clinical chorioamnionitis of maternal biological markers in routine use at or after 34 weeks of gestation in women with premature rupture of membranes., Methods: We conducted a two-center prospective study of all women admitted for premature rupture of membranes at or after 34 weeks of gestation. The association of C-reactive protein, white blood cell count, vaginal sample bacteriological results, and a prediction model at admission, for early-onset neonatal infection and maternal chorioamnionitis were analyzed by comparing areas under the receiver operating characteristic curves and specificity., Results: The study included 399 women. In all, 4.3% of the newborns had an early-onset neonatal infection and 5.3% of the women had clinical chorioamnionitis. Histological chorioamnionitis was detected on 10.8% of 297 placentas tested. White blood cell counts and C-reactive protein concentrations were significantly associated with early-onset neonatal infection and included in a prediction model. The area under the receiver operating characteristic curve of this model was 0.82 (95% CI [0.72, 0.92]) and of C-reactive protein, 0.80 (95% CI [0.68, 0.92]) (p = 1.0). Specificity was significantly higher for C-reactive protein than for the prediction model (48% and 43% respectively, p < 0.05). C-reactive protein was associated with clinical and histological chorioamnionitis, with areas under the receiver operating characteristic curve of 0.61 (95% CI [0.48, 0.74]) and 0.62 (95% CI [0.47, 0.74]), respectively., Conclusions: The concentration of C-reactive protein at admission for premature rupture of membranes is the most accurate infectious marker for prediction of early-onset neonatal infection in routine use with a sensitivity > 90%. A useful next step would be a randomized prospective study of management strategy comparing CRP at admission with active management to assess whether this more individualized care is a safe alternative strategy in women with premature rupture of membranes at or after 34 weeks.

Preterm premature rupture of the membranes is associated with a high risk of neonatal sepsis. An increase in the incidence of early-onset neonatal sepsis due to ampicillin-resistant Escherichia coli in premature infants has been observed in the past few years. Intrapartum prophylaxis with ampicillin has proven to be efficient for the prevention of early neonatal sepsis due to group B streptococci. To date, there is no strategy for the prevention of early neonatal sepsis due to ampicillin-resistant E. coli. Our aim was to investigate whether a standardized dosage regimen of intrapartum cefotaxime could provide concentrations in the cord blood greater than the cefotaxime MIC(90) for E. coli. Seven pregnant women hospitalized with preterm premature rupture of the membranes and colonized with ampicillin-resistant isolates of the family Enterobacteriaceae were included. Cefotaxime was given intravenously during delivery, as follows: 2 g at the onset of labor and then 1 g every 4 h until delivery. Blood specimens were collected from the mother 30 min after the first injection and just before the second injection, and at birth, blood specimens were simultaneously collected from the mother and the umbilical cord. The concentrations of cefotaxime in the cord blood ranged from 0.5 to 8.5 mg/liter. The MIC(90) of cefotaxime for E. coli strains (0.125 mg/liter) was achieved in all cases. This preliminary study supports the use of cefotaxime for intrapartum prophylaxis in women colonized with ampicillin-resistant isolates of Enterobacteriaceae. The effectiveness of this regimen for the prevention of neonatal sepsis needs to be evaluated with a larger population.