Neonatal outcomes in subgroups of women with preterm prelabor rupture of membranes before 34 weeks

Objective: To evaluate the influence of microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) on short-term neonatal outcome in women with preterm prelabor rupture of membranes before 34 weeks of gestation.

Methods: A prospective observational cohort study including 122 pregnant women with PPROM between 24+0 and 34+0. MIAC was defined as a positive PCR result for Ureaplasma species, Mycoplasma hominis and Chlamydia trachomatis and/or positive PCR result for the 16S rRNA gene in the amniotic fluid. HCA was defined according to the Salafia classification. Maternal and short-term neonatal outcomes were evaluated according to the presence or absence of MIAC and/or HCA.

Results: The presence of both MIAC and HCA was observed in 36% (45/122) of women, HCA alone in 34% (41/122) and MIAC in 5% (6/122). A significantly higher incidence of early onset sepsis was observed in newborns born from women with both MIAC and HCA [33% (15/45)] compared with women with HCA alone [12% (5/41)] or MIAC alone [0% (0/6)] or women without MIAC or HCA detected [0% (0/30); p?=?0.001].

Conclusions: The presence of both MIAC and HCA increases the risk of early onset sepsis in pregnancies complicated by preterm prelabor rupture of membranes before 34 weeks of gestation.     

A systematic review of intentional delivery in women with preterm prelabor rupture of membranes

Objective.?To evaluate the effect of intentional delivery versus expectant management in women with preterm prelabor rupture of membranes (PPROM).

Methods.?We searched electronic databases and trials registries, contacted experts, and checked reference lists of relevant studies. Studies were included if they were randomized controlled trials comparing intentional delivery versus expectant management after PPROM, the gestational age of participants was between 30 and 36 weeks, and the study reported one of several pre-determined outcomes.

Results.?Four studies were included in the meta-analysis. No difference was found between intentional delivery and expectant management in neonatal intensive care unit (NICU) length of stay (LOS) (weighted mean difference (WMD) ?0.81 day, 95% confidence interval (CI) ?1.66, 0.04), respiratory distress syndrome (risk difference (RD) ?0.01, 95% CI ?0.07, 0.06), and confirmed neonatal sepsis (RD ?0.01, 95% CI ?0.05, 0.04). One study found a significantly lower incidence of suspected neonatal sepsis among the intentional delivery group (RD ?0.31, 95% CI ?0.50, ?0.12; number needed to treat (NNT) 3, 95% CI 2, 8). Maternal LOS was significantly shorter for the intentional delivery group (WMD ?1.39 day, 95% CI ?2.03, ?0.75). There was a significant difference in the incidence of clinical chorioamnionitis favoring intentional delivery (RD ?0.16, 95% CI ?0.23, ?0.10; NNT 6, 95% CI 5, 11). There was no significant difference in the incidence of other maternal outcomes, including cesarean section (RD 0.05, 95% CI ?0.01, 0.11).

Conclusions.?Intentional delivery may be favorable to expectant management for some maternal outcomes (chorioamnionitis and LOS). There is insufficient evidence to suggest that either strategy is beneficial or harmful for the baby. Large multicenter trials with primary neonatal outcomes are required to assess whether intentional delivery is associated with less neonatal morbidity.     

Twin versus singleton pregnancies complicated by preterm premature rupture of membranes

Objective: To compare latency period, infectious morbidity, neonatal morbidity and neonatal mortality in twin versus singleton pregnancies complicated by preterm premature rupture of membranes (PPROM) remote from term. Methods: A retrospective, matched cohort study comparing 41 twin and 82 singleton pregnancies complicated by PPROM between 24-0/7 and 31-6/7 weeks’ gestation. The data were obtained by reviewing maternal and neonatal charts. Results: The median latency periods were 3.6 days (interquartile range 1.5–13.9 days) for twins and 6.2 days (interquartile range 2.9–11.8 days) for singletons (p?=?0.86). Twins were less likely to be complicated by clinical chorioamnionitis when compared with singletons (4/41 [9.8%] vs. 19/82 [23.2%], relative risk [RR] 0.42, 95% confidence interval [CI] 0.18–0.96). Histological evidence of chorioamnionitis was also lower in twins compared with singletons (14/39 [35.9%] vs. 46/68 [67.7%], RR 0.56, 95% CI, 0.34–0.92). These differences persisted after adjusting for race, insurance status, latency period and route of delivery. Neonatal morbidity and mortality rates were similar between the two groups. Conclusions: There was not a statistically significant difference in the latency periods for twin and singleton pregnancies complicated by PPROM. Clinical chorioamnionitis and histological evidence of infection were significantly less common in twins compared with singletons.     

Optimal time for delivery with preterm premature rupture of membranes from 32 to 36 6/7 weeks

Objective.?To evaluate the optimal time for delivery in singleton pregnancies with preterm premature rupture of membranes (PPROM) when delivered between 32 and 36 6/7 weeks gestational age (GA).

Study design.?We performed a retrospective cohort study of all singleton pregnancies with PPROM who delivered between 32 and 36 6/7 weeks gestation at our institution. We matched the delivery and NICU datasets to determine composite morbidity (COMP MORB) and NICU length of stay (LOS) stratified by weeks of gestation. COMP MORB was defined as one or more of: bronchopulmonary dysplasia, respiratory distress syndrome, necrotizing entercolitis, intraventricular hemorrhage, dissiminated intravascular coagulation, and culture proven sepsis. We used χ² and student ‘t’ test as appropriate and a receiver operating characteristc curve (ROC).

Results.?There were 195 newborns with PPROM with a range of 30 babies at 36 weeks to a high of 53 at 34 weeks. The mean (±SD) NICU LOS was 22.5 (±9.9) days at 32 weeks, 17.8 (±10.0) days at 33 weeks, 14.8 (±11.0) days at 34 weeks, 4.5 (±4.7) days at 35 weeks, and 1.5 (±4.4) days at 36 weeks (p?<0.0001). There was no difference in duration of ROM by GA with a range of 6.8 to 1.9 by week (p?=?NS). The ROC curve had a cut point for COMP MORB at 34.1 weeks GA (sens?=?95%, FPR 48.6%, area under curve 0.782, p?=?0.0002).

Conclusion.?Our study suggests that delivery of PPROM pregnancies at 34.1 weeks GA avoids 95% of composite morbidity, and delivery after 35 weeks GA will decrease the NICU LOS.     

Amniotic fluid cathepsin-G in pregnancies complicated by the preterm prelabor rupture of membranes

Objective: The aim of this study was to evaluate the amniotic fluid cathepsin-G concentrations in women with preterm prelabor rupture of membranes (PPROM) based on the presence of the microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation (IAI).

Methods: A total of 154 women with singleton pregnancies complicated by PPROM were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis. Amniotic fluid cathepsin-G concentrations were assessed by ELISA. MIAC was determined using a non-cultivation approach. IAI was defined as an amniotic fluid bedside interleukin-6 concentration?≥?745?pg/mL.

Results: Women with MIAC had higher amniotic fluid cathepsin-G concentrations than women without MIAC (with MIAC: median 82.7?ng/mL, versus without MIAC: median 64.7?ng/mL; p?=?0.0003). Women with IAI had higher amniotic fluid cathepsin-G concentrations than women without this complication (with IAI: median 103.0?ng/mL, versus without IAI: median 66.2?ng/mL; p?p?Conclusions: The presence of either microbial-associated or sterile IAI was associated with increased amniotic fluid cathepsin-G concentrations in pregnancies complicated by PPROM. Amniotic fluid cathepsin-G appears to be a potential marker of IAI.     

Optimum mode of delivery in gestations complicated by preterm premature rupture of the membranes

Objectives: To provide evidence about the preferable mode of delivery, vaginal (VD) or caesarean section (CS), in PPROM. Methods: A retrospective study of 190 cases. Survival analysis was used to identify statistically significant differences in mortality rates. Results: A total of 126 pregnancies were included in our study. Mean gestational age of rupture was 28⁺⁰ weeks (min?=?15, max?=?36⁺⁴, sd?=?5.796). Mean birth age was 30⁺⁰ weeks (min?=?15, max?=?37⁺², sd?=?5.353). CS was performed in 55 cases (43.7%), VD in 71 cases (56.3%). Data analysis showed that, regardless of presentation, there was a statistically significant benefit on survival in favor of the CS in births below 30 gestational weeks (n?=?39, nCS?=?18, nND?=?21, χ²?=?7.946, p?=?0.005). Hazard ratio estimation set the critical gestational age at 28 weeks. For vaginal deliveries, breech presentation was associated with inferior survival outcome compared to vertex (nTotal?=?71; nVertex?=?63, nBreech?=?8, χ²?=?13.012, p?<?0.001.Also in breech presentation, VD survival outcome was inferior to CS (nTotal?=?9; nVD?=?6, nCS?=?3, χ²?=?5.145, p?<?0.05). Conclusions: According to our results, in cases of PPROM, CS was beneficial below 28 weeks and in breech presentation below 30 weeks.     

Periodontal disease and intra-amniotic complications in women with preterm prelabor rupture of membranes

Objective: Periodontal disease is frequently suggested as a possible causal factor for preterm delivery. The link between periodontal disease and preterm delivery is a possible translocation of periopathogenic bacteria to the placenta and amniotic fluid as well as a systemic response to this chronic inflammatory disease. However, there is a lack of information on whether there is an association between clinical periodontal status in women with preterm prelabor rupture of membranes (PPROM) and the presence of microbial invasion of the amniotic cavity (MIAC) and intra-amniotic inflammation (IAI). Therefore, the main aim of this study was to evaluate the incidence and severity of periodontal disease in women with PPROM. The secondary aim was to characterize an association between periodontal status and the presence of intra-amniotic PPROM complications (MIAC and/or IAI).

Materials and methods: Seventy-eight women with PPROM at gestational ages between 24?+?0 and 36?+?6 weeks were included in this study. The samples of amniotic fluid were obtained at admission via transabdominal amniocentesis, and amniotic fluid interleukin (IL)-6 concentrations were determined using a point-of-care test. All women had a full-mouth recording to determine the periodontal and oral hygiene status. Probing pocket depth and clinical attachment loss were measured at four sites on each fully erupted tooth.

Results: In total, 45% (35/78) of women with PPROM had periodontal disease. Mild, moderate, and severe periodontal disease was present in 19% (15/78), 19% (15/78), and 6% (5/78) of women, respectively. The presence of MIAC and IAI was found in 28% (22/78) and 26% (20/78) of women, respectively. Periopathogenic bacteria (2?×?Streptococcus intermedius and 1?×?Fusobacterium nucleatum) was found in the amniotic fluid of 4% (3/78) of women. There were no differences in periodontal status between women with MIAC and/or IAI and women without these intra-amniotic complications.

Conclusions: The presence of MIAC and IAI was not related to the periodontal status of women with PPROM.     

Maternal obesity is associated with chorioamnionitis and earlier indicated preterm delivery among expectantly managed women with preterm premature rupture of membranes

Objective: To determine the association between maternal obesity and delivery due to chorioamnionitis prior to labor onset, among expectantly managed women with preterm premature rupture of membranes (pPROM).

Methods: This was a secondary analysis of a multicenter randomized trial of magnesium sulfate versus placebo to prevent cerebral palsy or death among offspring of women with anticipated delivery at 24–31-week gestation. After univariable analysis, Cox proportional hazard evaluated the association between maternal obesity and chorioamnionitis, while Laplace regression investigated how obesity affects the gestational age at delivery of the first 20% of women developing the outcome of interest.

Results: A total of 164 of the 1942 women with pPROM developed chorioamnionitis prior to labor onset. Obese women had a 60% increased hazard of developing such complication (adjusted HR 1.6, 95%CI 1.1–2.1, p?=?.008), prompting delivery 1.5 weeks earlier, as the 20th survival percentile was 27.2-week gestation (95%CI 26–28.6) among obese as opposed to 28.8 weeks (95%CI 27.4–30.1) (p?=?.002) among nonobese women.

Conclusions: Maternal obesity is a risk factor for chorioamnionitis prior to labor onset. Future studies will determine if obesity is important enough to change the management of latency after pPROM according to maternal BMI.     

The association between histological chorioamnionitis,funisitis and neonatal outcome in women with preterm prelabor rupture of membranes

Abstract

Objective: To determine the impact of histological chorioamnionitis (HCA) and funisitis on neonatal outcome in preterm prelabor rupture of membranes (PPROM) pregnancies.

Methods: Women with PPROM between 24?+?0 to 36?+?6 weeks of gestation, admitted to the Department of Obstetrics and Gynecology at the University Hospital Hradec Kralove in the Czech Republic, between July 2008 and October 2010, were enrolled in the study (n?=?231).

Results: The incidence of early-onset sepsis (EOS) differed significantly in neonates born to women with and without HCA, after adjustment for gestational age (11% versus 1%, p?=?0.011). The incidence of EOS in neonates was also significantly different, after adjustment for gestational age, in cases with and without funisitis (18% versus 4%, p?=?0.002). The same was also found for retinopathy of prematurity (ROP) cases with and without funisitis (23% versus 4%, p?=?0.014), after adjustment for gestational age.

Conclusions: HCA and funisitis increase the risk of adverse perinatal outcome in PPROM pregnancies.     

Risk factors for cerebral palsy in PPROM and preterm delivery with intact membranes*

Objective: Gestational age (GA) at delivery and spontaneous prematurity are independent risk factors for cerebral palsy (CP). The aim of this study is to investigate perinatal risk factors for CP in spontaneous preterm delivery.

Methods: A retrospective cohort study of all single pregnancies complicated by spontaneous preterm labor (PTL) or PPROM with delivery at <34 weeks from January 2006 to December 2012 was performed. We compared demographic, obstetric, neonatal, and placental histology variables in cases of spontaneous preterm birth in reference to the development of CP. Statistical analysis included chi-square, one-way ANOVA and logistic regression analysis. p?<?0.05 was considered significant.

Results: Two hundred sixty-one women were included for this study. Of 249 survivors, 5 babies died during the first year of life, 52 did not fulfill the inclusion criteria for neurologic follow-up, and 24 were lost to follow up. Thus 168 infants in the study cohort underwent neurologic follow-up. We observed 26 cases of CP. Factors related to CP were lower GA at PROM (p?=?0.007) and longer latency from PPROM to delivery (p?=?0.002) in the PPROM group, lower GA at delivery (p?<?0.001) and presence of funisitis (p?<0.001) in the PTL group.

Conclusions: GA at membrane rupture in PPROM and GA at delivery in PTL are significantly associated with CP. A process leading to neurological damage may be initiated at the moment of membranes rupture in cases of PPROM and at the time of PTL in the group with intact membranes.     

Neonatal outcomes in the setting of preterm premature rupture of membranes complicated by chorioamnionitis

Objective.?To examine the outcomes of neonates born to women with chorioamnionitis in the setting of preterm premature rupture of membranes (PPROM).

Methods.?A retrospective cohort study was conducted of deliveries with diagnosis of PPROM between 24 and 34 weeks of gestation at an academic medical center. Patients who delivered with the diagnosis of clinical chorioamnionitis were compared with patients who delivered without this diagnosis. Neonatal outcomes including Apgar scores, intracranial hemorrhage (ICH), sepsis, pneumonia, respiratory distress syndrome (RDS), and necrotizing enterocolitis (NEC) were assessed. Dichotomous outcomes were compared using chi-square test. Multivariable regression analyses were performed to control for potential confounding variables.

Results.?Of the 1153 patients diagnosed with PPROM, 29.0% were diagnosed with chorioamnionitis prior to delivery. Neonates born to mothers with a diagnosis of chorioamnionitis in the setting of PPROM had higher incidences (34.8%) of low 5-min Apgar scores, RDS, NEC, ICH, and pneumonia compared with 22.9% in neonates born to mothers without chorioamnionitis (p?<?0.001).

Conclusions.?Patients who develop chorioamnionitis in the setting of PPROM are at higher risk for adverse neonatal outcomes compared with patients without chorioamnionitis in the setting of PPROM.     

Perinatal outcomes in pregnancies with oligohydramnios after preterm premature rupture of membranes

Objective: Our purpose was to determine whether singleton pregnancies complicated by preterm premature rupture of membranes (PPROM) and oligohydramnios are at an increased risk of having maternal and neonatal morbidity.

Methods: We performed a retrospective analysis of 389 women with PPROM between 24 and 34 weeks of gestation in a single tertiary center during 2008–2014. Patients were divided into two groups on the basis of amniotic fluid index (AFI)?n?=?188) or AFI?≥?5?cm (n?=?201). Perinatal outcomes were compared according to amniotic fluid volume. The Student's t-test and Mann–Whitney U test were used to compare variables with normal and abnormal distribution, respectively. Categorical variables were examined by the chi-square test.

Results: Patients with an AFI?p?p?=?0.029) and emergency cesarean delivery (p?=?0.043) and a lower neonatal Apgar score at first minute (p?=?0.004).

Conclusion: Initial oligohydramnios after PPROM is associated with shorter latency to delivery, higher rate of clinical chorioamnionitis, higher rate of emergency cesarean delivery, and lower 1-min Apgar score.     

Amniotic fluid fetal hemoglobin in normal pregnancies and pregnancies complicated with preterm labor or prelabor rupture of membranes

Objective. Hemoglobin and its catabolic products have been associated with amniotic fluid (AF) discoloration and intra-amniotic infection/inflammation (IAI). However, the origin of AF hemoglobin (maternal or fetal) has not been determined. The aims of this study were to determine if fetal hemoglobin can be detected in AF obtained from normal pregnancies, and whether there is an association between AF fetal hemoglobin concentrations and gestational age, spontaneous labor (term and preterm), preterm prelabor rupture of membranes (PPROM) and IAI.

Study design. This cross-sectional study included pregnant women in the following groups: (1) mid-trimester (n = 60); (2) term not in labor (n = 21); (3) term in labor (n = 47); (4) spontaneous preterm labor with intact membranes (PTL) without IAI who delivered at term (n = 89); (5) PTL without IAI who delivered preterm (n = 74); (6) PTL with IAI (n = 78); (7) PPROM with (n = 48) and (8) without IAI (n = 48). AF fetal hemoglobin concentrations were determined by ELISA. Non-parametric statistics were used for analyses.

Results. (1) Fetal hemoglobin was detected in 80.4% of all AF samples; (2) women at term not in labor had a higher median AF fetal hemoglobin concentration than those at mid-trimester (p = 0.008); (3) labor at term was not associated with a significant difference in the median AF fetal hemoglobin concentration; (4) the median AF fetal hemoglobin concentration was not significantly different among the three PTL groups or between the PPROM groups; (5) women with PTL and IAI had a lower AF fetal hemoglobin percentage of the total hemoglobin than those without IAI who delivered preterm (p = 0.03) or at term (p < 0.001); (6) The median AF fetal hemoglobin concentration was higher in pregnancies complicated with PTL or PPROM than in women at term (p < 0.001 for all comparison).

Conclusions. (1) The concentration of immunoreactive AF fetal hemoglobin increases with gestational age; (2) the median AF fetal hemoglobin concentration is higher in pregnancies complicated with PTL or PPROM than in term pregnancies; (3) among women with PTL or PPROM, the AF fetal hemoglobin concentrations were not associated with IAI; (4) however, women with PTL and IAI had a lower percentage of AF fetal hemoglobin of the total hemoglobin than those without IAI, suggesting different mechanisms of disease.     

The fetal inflammatory response in subgroups of women with preterm prelabor rupture of the membranes

Abstract

Objective: To evaluate the influence of microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) on the intensity of the fetal inflammatory response and the occurrence of fetal inflammatory response syndrome (FIRS) in preterm prelabor rupture of membranes (PPROM).

Methods: One hundred and forty-nine women with singleton pregnancies complicated by PPROM between the gestational ages 24?+?0 and 36?+?6 weeks were included in the study. Blood samples were obtained by venipuncture from the umbilical cord after the delivery of the newborn. The umbilical cord blood interleukin (IL)-6 levels were evaluated using ELISA kits. The fetal inflammatory response was determined by IL-6 levels, and FIRS was defined as an umbilical cord blood IL-6 >11?pg/mL.

Result: IL-6 levels and the occurrence of FIRS were higher in women complicated with both MIAC and HCA (median IL-6 35.5?pg/mL, FIRS in 68%) than in women with HCA alone (median IL-6 5.8?pg/mL, FIRS in 36%), MIAC alone (median IL-6 2.8?pg/mL, FIRS in 17%) or women without MIAC or HCA (median IL-6 4.3?pg/mL, FIRS in 29%). There were no differences in IL-6 levels or rates of FIRS among women with MIAC alone or HCA alone and women without both MIAC and HCA.

Conclusion: A higher fetal inflammatory response mediated by umbilical cord blood IL-6 was identified when both MIAC and HCA were detected in pregnancies complicated by PPROM.     

Factors associated with latency period in preterm prelabor rupture of membranes

Objective: To determine the factors associated with prolonged latency periods in preterm prelabor rupture of membrane (PPROM).

Methods: This retrospective study analyzed data from singleton pregnant women with gestational age between 28 and 34 weeks suffering from PROM. Multivariate regression analysis was used to evaluate the association between the factors and latency period?≥?2 and?≥?7 days.

Results: A total of 231 cases of PPROM were included. Prolong latency period?≥2 and 7 days were achieved in 141 (61%) and 54 (23.4%) cases. Higher gestational age at PPROM and cervical dilatation?>2?cm were associated with a shorter latency period <2 days. Multiparity and presence of uterine contraction at admission were associated with a shorter latency period <7 days. Prophylactic antibiotics [odds ratio (ORs) 6.69, 95% confidence interval (CI) 3.0–14.89], and tocolysis (ORs 2.74, 95%CI 1.25–6.02) were factors associated with latency period?≥?2 days. Only prophylactic antibiotics (ORs 7.7, 95%CI 2.54–23.34) was a factor associated with latency period?≥7 days.

Conclusions: Prophylactic antibiotics and tocolysis are two major factors associated with latency period?≥2 days in PPROM, where prophylactic antibiotics is the main factor associated with latency period?≥7 days in PPROM.     

Amniotic fluid soluble Toll-like receptor 4 in pregnancies complicated by preterm prelabor rupture of the membranes

Objective: To determine amniotic fluid soluble Toll-like receptor 4 (sTLR4) levels in women with preterm prelabor rupture of the membranes according to the presence of microbial invasion of the amniotic cavity and histological chorioamnionitis and its relation to neonatal outcome. Methods: One hundred two women with singleton pregnancies with a gestational age between 24?+?0 and 36?+?6 weeks were included in a prospective cohort study. Amniocenteses were performed, and the concentrations of sTLR4 in the amniotic fluid were determined using sandwich enzyme-linked immunosorbent assay technique. Results: Women with the presence of microbial invasion of the amniotic cavity had higher sTLR4 levels [median 54.2?ng/mL, interquartile range (IQR) 10.15–289.9] than those without this condition (median 18.1?ng/mL, IQR 8.1–29.9; p?=?0.001). Women with the presence of histological chorioamnionitis had a higher sTLR4 level (median 28.0?ng/mL, IQR 11.15–178.1) compared with women without histological chorioamnionitis (median 13.0?ng/mL, IQR 7.8–28.7; p?=?0.003). A mixed linear model was used to adjust for confounders. The difference was found only between women with and without microbial invasion of the amniotic cavity in this model. Conclusions: Microbial invasion of the amniotic cavity was associated with higher amniotic fluid sTLR4 levels independent of confounders.     

Microbial invasion and histological chorioamnionitis upregulate neutrophil-gelatinase associated lipocalin in preterm prelabor rupture of membranes

Our recent exploratory proteomic study suggested increased levels of neutrophil-gelatinase associated lipocalin (P80188, NGAL_HUMAN) due to microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) in women with preterm prelabor rupture of the membranes. In this study, we verified the proteomics findings by assessing the amniotic fluid NGAL by ELISA in the original exploratory cohort. The NGAL level was significantly higher in women positive for both MIAC and HCA compared to women with both conditions ruled out (median 75.1?ng/ml versus 27.9?ng/ml; p?<?0.0001). For independent validation and to assess NGALs potential to stratify women positive for both MIAC and HCA from women in whom at least one of these conditions was absent, we subsequently designed a retrospective replication cohort. Significantly higher NGAL levels were found in women positive for both MIAC and HCA (median 65.9?ng/ml versus 34.2?ng/ml; p?=?0.0061). Significantly higher levels of NGAL were confirmed only in strata below 32 weeks of gestation. Based on the observed likelihood ratio, the best predictive cutoff level (47.1?ng/ml) was evaluated in both cohorts. Data from the verification cohort implied that NGAL is a valuable clinical marker for revealing MIAC leading to HCA; however, this potential was not replicated in the replication cohort.     

Outcome of pregnancies with preterm prelabor rupture of membranes before 27 weeks’ gestation: a retrospective cohort study

Objective

Preterm prelabor rupture of membranes (PPROM) before 27 weeks’ gestation is associated with severe perinatal complications, but quantitative estimates are lacking. The aim of this study was to report and predict outcomes of pregnancies complicated by early PPROM and to study antepartum risk factors that might predict perinatal death in future patients.

Study design

We performed a retrospective cohort study of women with PPROM between 13⁺⁰ weeks and 27⁺⁰ weeks’ gestation between 1994 and 2009 in three perinatal centers.

Main outcome measures

Perinatal mortality, composite neonatal morbidity and premature delivery. A model to predict these outcomes was developed from antepartum variables.

Results

We identified 314 women with PPROM before 27 weeks, including 28 multiple pregnancies. Six pregnancies (2%) were terminated before 24 weeks’ gestation, and three were lost to follow up, leaving 305 pregnancies for analysis. Overall, there were 166 perinatal deaths (49%). The perinatal mortality rate decreased with increasing gestational age at PPROM (from 70% in the group PPROM 13–20 weeks to 27% in the group PPROM 24–27 weeks). Of the 170 surviving neonates, 70 suffered from serious morbidity (41%). Early gestational age at PPROM, long interval between PPROM and birth and positive vaginal culture (any bacteria) were associated with perinatal mortality.

Conclusion

Perinatal mortality in PPROM before 27 weeks occurred in half of the cases and among those who survive approximately 40% suffered serious morbidity. Antenatal parameters can be helpful to predict perinatal mortality.