Factors and outcomes associated with longer latency in preterm premature rupture of membranes

Objective. To examine factors and outcomes associated with latency in preterm premature rupture of membranes (PPROM).

Methods. A retrospective cohort study was conducted of all deliveries with a diagnosis of PPROM at 24–34 weeks of gestation at an academic medical center for the period 1980–2001. Gestational age at PPROM was examined as the primary independent variable. Primary outcome was duration from rupture of membranes until delivery. The association with neonatal and maternal perinatal morbidity was examined with duration of latency. Dichotomous outcomes were compared using the Chi-square test. Multivariable regression analyses were performed to control for potential confounding variables.

Results. One thousand one hundred and sixty-eight patients were identified. Latency duration was inversely associated with gestational age at time of PPROM (p < 0.001). These findings persisted when potential confounders were controlled for in multivariable models. Neonatal sepsis and chorioamnionitis were not associated with increased duration of latency.

Conclusion. Earlier gestational age at time of PPROM is associated with longer latency duration, which, in turn, is not associated with increased neonatal sepsis or chorioamnionitis. These data can be used to counsel patients with PPROM about expected duration of latency and outcomes.     

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.     

Factors influencing survival in pre-viable preterm premature rupture of membranes

Objective: An observational study of a consecutive case series of pre-viable PPROM (16–24 gestational weeks) was performed between 2001 and 2007 in a single tertiary centre to identify factors that predict neonatal survival. Methods: Detailed obstetric, ultrasound and neonatal data were abstracted from clinical records. Univariate, multivariate and receiver operator curve (ROC) analyses were performed to identify predictors of neonatal survival to discharge. Results: A total of 143 cases of PPROM were identified. Survival to discharge was less with PPROM at 16–20 weeks than 20–24 weeks (17% versus 39%; p?=?0.042). GA at PPROM, latency, mode of delivery and electronic foetal monitoring (EFM) were all significant, independent, predictors of survival (p?<?0.05). Ultrasound assessed amniotic fluid index (AFI) was a poor predictor of survival (area under ROC?=?0.649, 95% CI?=?0.532–0.766). A multivariable predictive model, including GA at PPROM, latency, mode of delivery and EFM had an area under the ROC of 0.954 (95% CI?=?0.916–0.993, sensitivity 97%, specificity 89% and accuracy 92%). Conclusion: Pre-viable PPROM has a poor prognosis, though modern neonatal management techniques may improve survival in late pre-viable PPROM. The predictive model generated from this consecutive case series of this rare condition provides valuable data for counselling patients with this condition.     

Chorioamnionitis risk and neonatal outcome in preterm premature rupture of membranes

Objective The objective of this study was to compare the neonatal outcome in patients with preterm premature rupture of membranes with and without clinical chorioamnionitis.Study design This is a retrospective study that included 254 pregnant women with preterm rupture of membranes. The study group was divided according to the presence or absence of clinical chorioamnionitis defined as the presence of two or more of the following criteria: maternal temperature >38°C on two or more occasions 1 h apart, maternal tachycardia (120 beats/min), uterine tenderness, foul smelling amniotic fluid, maternal leukocytosis 20,000 mm^–3 with bands and positive C reactive protein. Also the study population was divided according to the use of tocolysis. Exclusion criteria included multiple pregnancy, fetal congenital anomalies, diabetes mellitus and severe preeclampsia. Amniotic fluid was collected from the cervix or from the transabdominal amniocentesis. Antibiotics and tocolysis were used according to the hospital protocols. Parametric and nonparametric statistics were used for comparisons.Results There were no significant differences in birth weight, Apgar scores at 1 and 5 min, rates of respiratory distress syndrome, intraventricular hemorrhage and necrotizing enterocolitis between patients with and without clinical chorioamnionitis or between women who received tocolysis and the ones that did not receive tocolysis. In cases of clinical chorioamnionitis and when tocolysis was used the neonates stayed longer in the neonatal intensive care unit (NICU).Conclusion Patients with preterm premature rupture of membranes and clinical chorioamnionitis have similar neonatal outcomes than the ones without clinical chorioamnionitis.     

The vaginal inflammatory milieu and the risk of early premature preterm rupture of membranes

OBJECTIVE: The purpose of this study was to determine the association of vaginal pH > or =5.0 and vaginal neutrophils >5 per oil field with preterm rupture of membranes (PPROM). STUDY DESIGN: This was a secondary analysis of the Vaginal Infections and Prematurity cohort, and was comprised of 12,734 evaluable women enrolled between 23 and 26 weeks' gestation. Women were tested for sexually transmitted infections and vaginal pH. Gram-stained smears were used for the detection of neutrophils. RESULTS: In this analysis, 5751 (41.3%) women had neutrophils >5 per oil field, and 2500 (18.0%) had pH > or =5.0. Both elevated pH and neutrophils were present in 1149 women (8.3%). The concomitant presence of both neutrophils and elevated pH was significantly associated with PPROM at 24 to 32 weeks. CONCLUSION: Elevated vaginal pH and neutrophils are most strongly associated with early third-trimester PPROM, reflecting the importance of infection and/or inflammation in the pathogenesis of this condition.     

Factors affecting the duration of the latency period in preterm premature rupture of membranes

Objective.?To investigate the natural course of preterm premature rupture of membranes (PPROM) at <34 + 0 weeks and to identify factors that affect the duration of the latency period.

Design.?A retrospective cohort study of all women diagnosed with PPROM prior to 34 + 0 weeks during 1998–2006. Latency period was defined as the time between onset of PPROM to either spontaneous delivery, labor induction at 34 + 0 weeks, or indicated delivery prior to 34 + 0 weeks because of suspected chorioamnionitis or nonreassuring fetal heart rate.

Results.?The overall rate of PPROM was 1.4% (905/66,775), of which 46% (417/905) occurred at <34 + 0 weeks. Overall, the latency period exceeded 48 h in about 73.4% of cases (306/471). Women with short latency periods (<48 h) were characterised by higher degree of cervical dilatation and higher gestational age at admission and were more likely to be nulliparous. The duration of the latency period ranged between 0 and 59 days and was inversely related to gestational age at admission (r = ?0.63, P < 0.001). Using Cox proportional hazards model, gestational age at admission (HR = 1.29, 95% CI = 1.22–1.37), oligohydroamnios (HR = 1.49, 95% CI = 1.18–1.87), cervical dilatation >1 cm (HR = 0.65, 95% CI = 0.52–0.83), fetal growth restriction (HR = 2.94, 95% CI = 1.24–6.94) and nulliparity (HR = 1.28, 95% CI = 1.12–1.63) were significantly associated with shorter duration of the latency period.

Conclusion.?In this study, we have identified several predictive factors for the duration of the latency period in cases of PPROM. This information may assist clinicians in risk stratification and in providing consultation for women presenting with PPROM prior to 34 weeks of gestation.     

Magnesium sulfate for cerebral palsy prevention

Magnesium sulfate (MgSO₄) has been shown to prevent cerebral palsy among children born to women at high risk of early preterm delivery. Three large, randomized placebo-controlled trials and a subsequent Cochrane Review suggest this intervention can decrease rates of cerebral palsy by 32% with a number needed to treat of 63 to prevent one case. Not only is MgSO₄ familiar to obstetricians, it also has an excellent safety profile. Simple protocols exist to help guide clinicians in using MgSO₄ for this indication. Evaluation of actual clinical practice shows that this use is both feasible and can be accomplished parsimoniously.     

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.     

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.     

Erythrocyte aggregation is increased in preterm premature rupture of the membranes

OBJECTIVE: To asses the degree of erythrocyte aggregation in the peripheral blood of women with preterm premature rupture of the membranes (PPROM). STUDY DESIGN: This was a prospective case control study. Twenty patients with preterm premature rupture of the membranes and matched controls were recruited at the Lis Maternity Hospital. A slide test and image analysis were used to quantitate the degree of erythrocyte aggregation. Hematological indices and markers of inflammation such as the erythrocyte sedimentation rate and C-reactive protein were also compared. RESULTS: The vacuum radius (VR) of the study group was significantly higher than in the control group at 14.8+/-1.6 microm versus 10.0+/-1.0 microm, respectively (P=0.03). Other hematological indices were not changed significantly between the groups. CONCLUSIONS: We found an increase in erythrocyte aggregation in the peripheral blood of patients with preterm premature rupture of the membranes. We used this sensitive marker of inflammation to further support the theory that PPROM is an inflammatory state.     

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.     

Maternal and neonatal outcomes based on the gestational age of midtrimester preterm premature rupture of membranes

Objectives.?Determine neonatal and maternal outcomes based on the gestational age (GA) that midtrimester preterm premature rupture of membranes (mtPPROM) occurs.

Study design.?A retrospective chart review was conducted on pregnancies with mtPPROM between 180/7 and 236/7 weeks gestation from January 2000 to December 2007. Antenatal complications, maternal morbidity, and neonatal survival and morbidity were analysed by the specific GA of mtPPROM. Statistical analysis was performed using Chi-square, Fisher's Exact, and Kruskal–Wallis tests.

Results.?A total of 105 patients met inclusion criteria. There was a trend for longer latency with earlier GA of mtPPROM (p?=?0.05). Neonatal survival to discharge was 26.6%, with an overall morbidity of 86%. Survival was significantly higher with mtPPROM at 22 0/7–23 6/7 weeks compared to 18 0/7–19 6/7 (p?=?0.01) and 20 0/7–21 6/7 weeks (p?=?0.01). There was no difference in neonatal morbidity based on the GA of mtPPROM.

Conclusions.?While neonatal survival improves at later GAs of mtPPROM, morbidity continues to be high.     

Duration of antibiotic therapy after preterm premature rupture of fetal membranes

OBJECTIVE: This study was undertaken to compare the efficacy of 3 days versus 7 days of ampicillin in prolonging gestation for at least 7 days in women with preterm premature rupture of membranes (PPROM). STUDY DESIGN: We performed a randomized clinical trial comparing 3 days of ampicillin with 7 days ampicillin in patients with PPROM. Our primary outcome was the prolongation of pregnancy for at least 7 days. Secondary outcomes included rates of chorioamnionitis, postpartum endometritis, and neonatal morbidity and mortality. RESULTS: Forty-eight patients were randomly selected. There was no statistically significant difference in the ability to achieve a 7-day latency (relative risk 0.83, 95% CI 0.51-1.38). In addition, there was no statistically significant difference in the rates of chorioamnionitis, endometritis, and our composite neonatal morbidity. CONCLUSION: In patients with PPROM, length of antibiotic therapy does not change the rate of a 7-day latency or affect the rate of chorioamnionitis, postpartum endometritis, or neonatal morbidity.     

Fetal tyhmus size as a predictor of histological chorioamnionitis in preterm premature rupture of membranes

Abstract

Objective: To predict histological chorioamnionitis (CA) in the cases of preterm premature rupture of membranes by using fetal thymus transverse and anteroposterior diameters and areal measurements.

Methods: Fifty healthy and 50 patients diagnosed with preterm premature rupture of membranes (PPROM) between 24 and 37 weeks of gestation were included in the study. Fetal thymus measurements were done and repeated on a weekly basis until delivery, Furthermore white blood cell, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were measured every other day until delivery, too. Following delivery, all patients’ placentas were sent to pathology.

Results: Histological CA was detected in 48% of the PPROM patients. There were no patients in either group with clinical CA. Thymus transverse diameter had 91% sensitivity, 81% specificity, 82% PPV, and 91% NPV in predicting histological CA in PPROM patients. No linear relationship was found between thymus anteroposterior diameter measurements and gestational age. Thymus area measurements have sensitivity of 75%, specificity of 81%, PPV of 78%, NPV of78% in determining CA in patients with PPROM.

Conclusion: Both thymus transverse diameter and area measurement are more significant than sedimentation and CRP values in predicting histological CA. Fetal thymus measurements can be used in early diagnosis of infections among high risk patients.     

Amniocentesis in the management of preterm premature rupture of the membranes: A retrospective cohort analysis

Objective. This retrospective analysis determined the utility of amniocentesis in the management of preterm premature rupture of the membranes (PPROM).

Study design. Consecutive patients with PPROM were managed with and without amniocentesis. Both groups received antibiotics and corticosteroids; tocolytics were withheld. Patients were induced if clinical or amniotic fluid (AF) proven chorioamnionitis occurred or gestational age goals were reached. Primary endpoints were individual and composite neonatal morbidity (CNM).

Results. One hundred forty-seven maternal patients were managed with amniocentesis (AC) and 146 were managed without amniocentesis (NAC). CNM was significantly reduced in the group managed with AC (OR 2.94, 95% CI 1.68–5.15, NAC vs. AC). NAC patients had similar rates of neonatal sepsis as well as CNM to those patients in the AC group with positive AF Gram stains and/or cultures.

Conclusions. Patients with PPROM who are managed with AC have significantly less CNM than NAC patients.     

The natural history of preterm premature rupture of membranes in twin pregnancies

Objective: To compare the characteristics of preterm premature rupture of membranes (PPROM) between twin and singleton pregnancies.

Methods: This was a retrospective study of all women with twin and singleton pregnancies admitted with PPROM between 24–34 weeks of gestation.

Results: Overall 698 women with PPROM were eligible for the study: 101 (14.5%) twins and 597 (85.5%) singletons. Twins presented with PPROM at a more advanced gestational age compared with singletons (29.1?±?2.7 vs. 28.5?±?2.8 weeks, p?=?0.03). The latency period was shorter in twins compared with singletons, especially for women presenting after 28 weeks of gestation (5.0?±?0.8 vs. 7.0?±?0.4 days, p?=?0.01). Women with twins were more likely to deliver within 48?h (OR:?2.7; 95%CI: 1.7–4.2) and were less likely to deliver within 2–7 days (OR: 0.5; 95%CI: 0.3–0.9) following PPROM. The rate of clinical chorioamnionitis or placental abruption following PPROM was lower in twins compared with singletons (15.8% vs. 26.0%, p?=?0.03).

Conclusions: PPROM in twin pregnancies tends to occur at a more advanced gestational age, is associated with a shorter latency period and is less likely to be complicated by chorioamnionitis or placental abruption compared with singletons. This information may be useful for counseling and management decisions in cases of PPROM in women with twins.     

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.     

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.     

Effect of terbutaline on latency period in preterm premature rupture of membranes

Aims: To assess whether terbutaline is able to prolong the latency period in women with preterm premature rupture of membranes (PPROM) and compare maternal and neonatal morbidity and mortality in the terbutaline and nontocolysis groups. Methods: This study retrospectively analyzed data from women with singleton pregnancies (gestational ages between 28 and 34 weeks) suffering from PPROM from January 1998 to December 2009. Results: A total of 163 cases of PPROM were analyzed; there were 61 cases (37.4%) in the terbutaline group and 102 cases (62.6%) in the nontocolysis group. The median latency period was comparable in the two groups (78 vs. 75 h, p = 0.44). The percentage of patients who did not deliver within 48 h was significantly higher in the terbutaline group compared with the nontocolysis group (78.7 vs. 62.7%, p = 0.03). There were no differences in maternal morbidity and mortality, and neonatal mortality between the two groups. Interestingly, neonatal infectious morbidity was significantly higher in the terbutaline group when compared with the nontocolysis group. Conclusions: Terbutaline cannot prolong the latency period in PPROM. There were no differences in maternal morbidity and mortality. However, neonatal infectious morbidity was higher in the terbutaline group.