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Obstetrical complications, often referred to as the "great obstetrical syndromes," are among the most common global causes of mortality and morbidity in young women and their infants. However, treatments for these syndromes are underdeveloped compared with other fields of medicine and are urgently needed. This current paucity of treatments for obstetrical complications is a reflection of the challenges of drug development in pregnancy. The appetite of pharmaceutical companies to invest in research for obstetrical syndromes is generally reduced by concerns for maternal, fetal, and infant safety, poor definition, and high-risk regulatory paths toward product approval. Notably, drug candidates require large investments for development with an unguaranteed return on investment. Furthermore, the discovery of promising drug candidates is hampered by a poor understanding of the pathophysiology of obstetrical syndromes and their uniqueness to human pregnancies. This limits translational extrapolation and de-risking strategies in preclinical studies, as available for other medical areas, compounded with limited fetal safety monitoring to capture early prenatal adverse reactions. In addition, the ethical review committees are reluctant to approve the inclusion of pregnant women in trials, and in the absence of regulatory guidance in obstetrics, clinical development programs are subject to unpredictable regulatory paths. To develop effective and safe drugs for pregnancy complications, substantial commitment, and investment in research for innovative therapies are needed in parallel with the creation of an enabling ethical, legislative, and guidance framework. Solutions are proposed to enable stakeholders to work with a common set of expectations to facilitate progress in this medical discipline. Addressing this significant unmet need to advance maternal and possibly perinatal health requires the involvement of all stakeholders and specifically patients, couples, and clinicians facing pregnancy complications in the dearth of appropriate therapies. This paper focused on the key pharmaceutical research and development challenges to achieve effective and safe treatments for obstetrical syndromes. [ABSTRACT FROM AUTHOR]

Despite current recommendations against its use, activity restriction remains a common intervention used to prevent preterm birth in multiple clinical settings. Hypertensive disorders of pregnancy, preterm premature rupture of membranes, multiple gestations, vaginal bleeding, short cervical length, placenta previa, and fetal growth restriction are also common reasons for antepartum hospital admission and frequently lead to a recommendation for activity restriction. However, numerous reports have shown that activity restriction does not prevent adverse obstetrical outcomes but does confer significant physical and psychosocial risks. This consult reviews the current literature on activity restriction and examines the evidence regarding its use in obstetrical management. The recommendations by the Society for Maternal-Fetal Medicine are as follows: (1) we recommend against the routine use of any type of activity restriction in pregnant women at risk of preterm birth based on preterm labor symptoms, arrested preterm labor, or shortened cervix (GRADE 1B); (2) we recommend against the use of routine inpatient hospitalization and activity restriction for the prevention of preterm birth in women with multiple gestations (GRADE 1A); and (3) given the lack of data definitively demonstrating that activity restriction improves perinatal outcome in pregnancies complicated by fetal growth restriction, preterm premature rupture of membranes, or hypertensive diseases of pregnancy, coupled with evidence of adverse effects of activity restriction, we suggest that activity restriction not be prescribed for the treatment of pregnancies complicated by fetal growth restriction, preterm premature rupture of membranes, or hypertensive disease (GRADE 2B). [ABSTRACT FROM AUTHOR]

The term placental bed was coined to describe the maternal-fetal interface (ie, the area in which the placenta attaches itself to the uterus). Appropriate vascularization of this area is of vital importance for the development of the fetus; this is why systematic investigations of this area have now been carried out. Initially, the challenge was the identification and classification of the various successive branching of uterine arteries in this area. These vessels have a unique importance because failure of their physiological transformation is considered to be the anatomical basis for reduced perfusion to the intervillous space in women with preeclampsia, fetal growth restriction, preterm labor, preterm premature rupture of membranes, abruptio placentae, and fetal death. To investigate in depth the pathophysiology of the placental bed, some 60 years ago, a large number of placental bed biopsies, as well as of cesarean hysterectomy specimens with placenta in situ, from both early and late normotensive and hypertensive pregnancies, were carefully dissected and analyzed. Thanks to the presence of a series of specific physiological changes, characterized by the invasion and substitution of the arterial intima by trophoblast, this material allowed the identification in the placental bed of normal pregnancies of the main vessels, the uteroplacental arteries. It was then discovered that preeclampsia is associated with defective or absent transformation of the myometrial segment of the uteroplacental arteries. In addition, in severe hypertensive disease, atherosclerotic lesions were also found in the defective myometrial segment. Finally, in the basal decidua, a unique vascular lesion, coined acute atherosis, was also identified This disorder of deep placentation, coined defective deep placentation, has been associated with the great obstetrical syndromes, grouping together preeclampsia, intrauterine growth restriction, preterm labor, preterm premature rupture of membranes, late spontaneous abortion, and abruptio placentae. More recently, simplified techniques of tissue sampling have been also introduced: decidual suction allows to obtain a large number of decidual arteries, although their origin in the placental bed cannot be determined. Biopsies parallel to the surface of the basal plate have been more interesting, making possible to identify the vessels' region (central, paracentral, or peripheral) of origin in the placental bed and providing decidual material for immunohistochemical studies. Finally, histochemical and electron microscopy investigations have now clarified the pathology and pathogenetic mechanisms underlying the impairment of the physiological vascular changes. [ABSTRACT FROM AUTHOR]

Background: Preterm birth is the leading cause of infant morbidity and mortality worldwide. Elevated levels of oxidative stress have been associated with an increased risk of delivering before term. However, most studies testing this hypothesis have been conducted in racially and demographically homogenous study populations, which do not reflect the diversity within the United States.Objective: We leveraged 4 cohorts participating in the Environmental Influences on Child Health Outcomes Program to conduct the largest study to date examining biomarkers of oxidative stress and preterm birth (N=1916). Furthermore, we hypothesized that elevated oxidative stress would be associated with higher odds of preterm birth, particularly preterm birth of spontaneous origin.Study Design: This study was a pooled analysis and meta-analysis of 4 birth cohorts spanning multiple geographic regions in the mainland United States and Puerto Rico (208 preterm births and 1708 full-term births). Of note, 8-iso-prostaglandin-F2α, 2,3-dinor-5,6-dihydro-8-iso-prostaglandin-F2α (F2-IsoP-M; the major 8-iso-prostaglandin-F2α metabolite), and prostaglandin-F2α were measured in urine samples obtained during the second and third trimesters of pregnancy. Logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals for the associations between averaged biomarker concentrations for each participant and all preterm births, spontaneous preterm births, nonspontaneous preterm births (births of medically indicated or unknown origin), and categories of preterm birth (early, moderate, and late). Individual oxidative stress biomarkers were examined in separate models.Results: Approximately 11% of our analytical sample was born before term. Relative to full-term births, an interquartile range increase in averaged concentrations of F2-IsoP-M was associated with higher odds of all preterm births (odds ratio, 1.29; 95% confidence interval, 1.11-1.51), with a stronger association observed for spontaneous preterm birth (odds ratio, 1.47; 95% confidence interval, 1.16-1.90). An interquartile range increase in averaged concentrations of 8-iso-prostaglandin-F2α was similarly associated with higher odds of all preterm births (odds ratio, 1.19; 95% confidence interval, 0.94-1.50). The results from our meta-analysis were similar to those from the pooled combined cohort analysis.Conclusion: Here, oxidative stress, as measured by 8-iso-prostaglandin-F2α, F2-IsoP-M, and prostaglandin-F2α in urine, was associated with increased odds of preterm birth, particularly preterm birth of spontaneous origin and delivery before 34 completed weeks of gestation. [ABSTRACT FROM AUTHOR]

Objective: Given that many studies report on a limited spectrum of adverse events of transvaginal cervical cerclage for preventing preterm birth, but are not powered to draw conclusions about its safety, the objective of this study was to conduct a systematic review with pooled risk analyses of perioperative complications and compare characteristics on the basis of indication for cerclage in singleton pregnancies.Data Sources: Ovid MEDLINE, Ovid Embase, Web of Science, the Cochrane Central Register of Controlled Trials (CENTRAL), and the prospective trial registers ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched from inception to April 2020.Study Eligibility Criteria: All randomized controlled trials and both retrospective and prospective observational cohort studies reporting about complications in history-indicated cerclage, ultrasound-indicated cerclage, or physical examination-indicated cerclage were eligible. Studies were included if they contained original data on the occurrence of adverse events during surgery or within 24 hours after surgery.Methods: The Cochrane risk of bias tool for randomized controlled trials and the Newcastle-Ottawa scale for cohort and case-control studies were used for the critical appraisal. The pooled risk assessment was conducted using meta and metafor packages in R (studio), version 4.0.3.Results: The search yielded 2328 potential studies; 3 randomized controlled trials, 3 prospective, and 38 retrospective cohort studies were included in the final analysis. Of the 4511 women with singleton gestations, 1561 (34.6%) underwent history-indicated cerclage, 1348 (29.9%) underwent ultrasound-indicated cerclage, and 1549 (33.3%) underwent physical examination-indicated cerclage. Most perioperative complications occurred in physical examination-indicated cerclage, especially hemorrhage (2.3%; 95% confidence interval, 0.0-7.6) and preterm premature rupture of membranes (2.5%; 95% confidence interval, 0.91-4.5). The fewest complications occurred in history-indicated cerclage, varying from 0.0% of preterm premature rupture of membranes (95% confidence interval, 0.0-1.7) to 0.9% of hemorrhage (95% confidence interval, 0.0-7.9). In ultrasound-indicated cerclage, the most common complication was hemorrhage (1.4%; 95% confidence interval, 0.0-4.1), followed by lacerations (0.6%; 95% confidence interval, 0.0-3.1) and preterm premature rupture of membranes (0.3%; 95% confidence interval, 0.0-0.8).Conclusion: The highest risk of perioperative complications was observed in physical examination-indicated cerclage in comparison with ultrasound- and history-indicated cerclage. However, the occurrence of complications is poorly documented in the published literature, as is the timing of the complications (ie, perioperative or later in pregnancy). There is an urgent need for uniform complication reporting policy in both cohort studies and randomized controlled trials on cerclage. [ABSTRACT FROM AUTHOR]

Background: In patients with preterm premature rupture of membranes, intrauterine inflammation and/or infection is frequently present, can lead to fetal inflammatory response syndrome, and is associated with adverse neonatal outcome. Clinical decision making requires balancing the potential benefits of pregnancy prolongation against the risk of intrauterine infection. Diagnostic tests in maternal serum are of moderate prediction value and amniocentesis is an invasive procedure. Therefore, markers obtained noninvasively would be helpful in patients with expectant management.Objectives: To determine the predictive values of amniotic fluid interleukin-6 and tumor necrosis factor-α in vaginal secretions for fetal inflammatory response syndrome and/or histologic funisitis and for adverse neonatal outcome in patients with preterm premature rupture of membranes.Study Design: In this prospective multicenter case-control study, vaginal secretions were sampled daily with a noninvasive method from 99 women with preterm premature rupture of membranes and expectant management. Amniotic fluid interleukin-6 and tumor necrosis factor-α were measured by 2 different immunoassays (an automated chemiluminescent enzyme immunoassay and a lateral flow immunoassay). After delivery, patients were divided into a control or a fetal inflammatory response syndrome group according to neonatal interleukin-6 in cord plasma and/or the presence of funisitis. Univariate and multivariate regression analyses were performed and prediction models were developed by calculating receiver operating characteristic curves.Results: Gestational age at delivery was lower and latency period was longer in the fetal inflammatory response syndrome group compared to the control group. The strongest risk factor for composite adverse neonatal outcome was fetal inflammatory response syndrome (odds ratio, 2.48; confidence interval, 1.40-4.38). The median concentrations of amniotic fluid interleukin-6 and tumor necrosis factor-α in vaginal secretions were significantly higher in the fetal inflammatory response group compared to the control group in both immunoassays (P < .001). The area under the curve of the clinical reference model (including common clinical parameters) was 0.66. Adding interleukin-6 and tumor necrosis factor-α into the model improved the area under the curve to 0.92 (in both assays, interleukin-6 IMMULITE and QuickLine); 0.87 (tumor necrosis factor-α IMMULITE) and 0.94 (tumor necrosis factor-α QuickLine), respectively.Conclusion: The strongest risk factor for worse neonatal outcome (composite neonatal outcome) was fetal inflammatory response syndrome. Amniotic fluid interleukin-6 and tumor necrosis factor-α seem to be good predictors for fetal inflammatory response syndrome and for histologic funisitis and may improve the clinical management of patients with preterm premature rupture of membranes. The noninvasive technique of sampling amniotic fluid from vaginal secretions facilitates daily measurements and bedside assessment of cytokines and is in this respect preferable to invasive amniocentesis. [ABSTRACT FROM AUTHOR]

Preterm premature rupture of the membranes near the limit of fetal viability is an uncommon complication of pregnancy, affecting approximately 4 in 1000 gravidas. However, maternal, fetal, and neonatal complications resulting from this condition are significant and include chorioamnionitis, pulmonary hypoplasia, restriction deformities, fetal loss, and complications of extreme prematurity among surviving infants. In this article, we review the literature regarding pregnancy outcomes after preterm premature rupture of the membranes near the limit of viability, and the data on traditional and nontraditional interventions to improve outcomes. An approach to patients who present with preterm premature rupture of the membranes near the limit of viability will be proposed. [Copyright &y& Elsevier]

Over the last decade, it has become increasingly apparent that the cause of preterm birth is multifactorial, involving both genetic and environmental factors. With the development of new technologies capable of probing the genome, exciting possibilities now present themselves to gain new insight into the mechanisms leading to preterm birth. This review aims to develop research guidelines for the conduct of genetic epidemiology studies of preterm birth with the expectation that this will ultimately facilitate the comparison of data sets between study cohorts, both nationally and internationally. Specifically, the 4 areas addressed in this review includes: (1) phenotypic criteria, (2) study design, (3) considerations in the selection of control populations, and (4) candidate gene selection. This article is the product of discussions initiated by the authors at the 3rd International Workshop on Biomarkers and Preterm Birth held at the University of California, Los Angeles, Los Angeles, CA, in March 2005. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to identify risk factors for second trimester premature preterm rupture of membranes or advanced cervical dilation in a high-risk population. Study design: A retrospective case control study was performed that compared women with premature preterm rupture of membranes or advanced cervical dilation to term control subjects. The cases included all singleton pregnancies between 14 and 24 weeks of gestation with premature preterm rupture of membranes or advanced cervical dilation between 1996 and 2000. The next 2 term deliveries were chosen as control subjects. The variables compared between cases and control subjects included pregnancy history, infectious and medical histories, cervical/uterine procedures, and habits. This study had institutional review board approval. Results: There were 102 women with premature preterm rupture of membranes, 56 women with advanced cervical dilation, and 316 control subjects. The mean gestational ages for premature preterm rupture of membranes or advanced cervical dilation were 20 ± 2.6 and 19.9 ± 2.6 weeks. Tobacco use, history of or current cervical incompetence, previous second trimester delivery, previous termination at <20 weeks of gestation, and previous premature preterm rupture of membranes were associated significantly with premature preterm rupture of membranes or advanced cervical dilation compared with term control subjects. When controlled for parity, age, marital status, and race, these variables remained significant. Bacterial vaginosis in current pregnancy was associated significantly with only advanced cervical dilation but not premature preterm rupture of membranes compared with control subjects. A history of Chlamydia was most common in the term control subjects (19.6%). Conclusion: In a high-risk population of inner city women, only pregnancy history and tobacco use distinguished women with second trimester premature preterm rupture of membranes or advanced cervical dilation from term control subjects. No infectious risk factors distinguished control women from women with premature preterm rupture of membranes. The only modifiable risk identified was tobacco use. [ABSTRACT FROM AUTHOR]

Objective: We investigated differences between singleton and twin gestations in immune mediators in midtrimester amniotic fluid. Study design: Amniotic fluid from 252 singleton and 46 twin gestations were tested by enzyme-linked immunosorbent assay for interleukin-1β, interleukin-1 receptor antagonist, interleukin-4, tumor necrosis factor-α, nitric oxide, Clara cell protein 16, leptin, and the 70-kDa heat shock protein. A subset of amniotic fluid was also tested for leukemia inhibitory factor, angiogenin, and migration inhibitory factor-related protein 8 and migration inhibitory factor-related protein 14. Data were analyzed by the Mann-Whitney U test and Spearman rank correlation. Results: Median concentrations of interleukin-1β, tumor necrosis factor-α, interleukin-4, Clara cell protein 16, leptin, and angiogenin were increased in amniotic fluid from twins; median levels of the 70-kDa heat shock protein, leukemia inhibitory factor, migration inhibitory factor-related protein 8, and migration inhibitory factor-related protein 14 were highest in amniotic fluid from singletons (P<.001). Conclusion: Elevated levels of immune activators may contribute to the increased rate of preterm premature rupture of membranes and spontaneous preterm birth in twin populations. [ABSTRACT FROM AUTHOR]

Objective: Amniotic access for fetal diagnosis and therapy can lead to membrane leaks, separation, and preterm premature rupture of membranes. Morbidity limits the beneficial effects of fetal intervention. We propose to examine a novel preventive "presealant" membrane puncture technique and evaluate it in vitro. Study design: Fetal membranes from normal term deliveries were fastened to a pressure controlled pump and punctured after presealant placement. Distinct bioadhesixes were then compared for sealing efficacy by the measurement of leak pressures. Membranes were also evaluated for changes in tensile rupture strength after treatment. Results: Preemptive sealing by 2 of the presealants achieved significantly higher leak pressures compared with control membranes (85 and 78, respectively, vs 27 cm of water; P < .05). One of the presealants worked effectively in a membrane-sealant-membrane interface (62 vs 30 cm of water; P < .05). All treated membranes, however, demonstrated diminished tensile rupture forces compared with control membranes (124 vs 170 g/cm²; P > .05). Conclusion: The application of a presealant is effective for the prevention of iatrogenic rupture in an in vitro model and may be beneficial for clinical application. Further studies with different bioadhesives are needed, given the limitations of the glues that are described in this study. [ABSTRACT FROM AUTHOR]

Objective: Fetal inflammatory response has been previously shown to be involved in the pathogenesis of preterm premature rupture of membranes. We investigated the association between polymorphisms at position -670 in the Fas gene and position -124 in the Fas ligand gene demonstrated in neonatal oral mucosa cells and preterm premature rupture of membranes. Study design: Thirty-six singleton pregnancies were studied. Eighteen pregnancies were complicated by preterm premature rupture of membranes, and 18 were delivered at term without preterm premature rupture of membranes. Buccal swabs were obtained from each neonate, and extracted deoxyribonucleic acid was analyzed by polymerase chain reaction based restriction fragment length polymorphism for an adenine (A) to guanine (G) substitution at position -670 in the Fas promoter gene and at position -124 in the Fas ligand gene. χ² and Fisher's exact tests were used for statistical analysis. Results: There was no difference with respect to race, maternal age, and parity between the 2 groups. Frequencies of Fas -670 AG, -AA, and -GG genotypes in preterm premature rupture of membranes group were significantly different from those in the control group (P = .004). The frequency of the heterozygous AG genotype was significantly higher in preterm premature rupture of membranes group as compared with controls (83.3% versus 33.3%, P = .003). Fas -670 AA genotype was not observed among patients with preterm premature rupture of membranes. Similarly, the difference of frequencies of the Fas ligand -124 AG, -AA, and -GG genotypes among preterm premature rupture of membranes group and controls was observed but did not reach statistical significance. Neither of the groups demonstrated homozygous GG genotype at position -124 of the Fas ligand gene. Conclusion: Our data indicate an association between preterm premature rupture of membranes and increased prevalence of neonatal AG genotype at -670 Fas promoter gene. Genetically predetermined regulation of the Fas/Fas ligand system appears to play an important role in the pathogenesis of the preterm premature rupture of membranes. [ABSTRACT FROM AUTHOR]

Objective: We examined trends in twin preterm birth <37 weeks following ruptured membranes (ROM), medically indicated preterm birth, and preterm birth following spontaneous onset of labor (PTL). We further examined whether these changes in preterm birth subtypes were associated with trends in twin perinatal mortality. Study design: We carried out a retrospective cohort study of 1,172,405 twin live births and stillbirths delivered in the US between 1989 and 2000. Trends in preterm birth subtypes, and perinatal mortality (stillbirths at ⩾22 weeks plus neonatal deaths within 28 days), were examined through ecologic logistic regression models after adjusting for confounders. Results: Preterm birth among white twins increased from 46.6% between 1989 and 1990 to 56.7% from 1999 to 2000, and from 56.1% to 61.0% among black twins over the same period. Medically indicated preterm birth increased by 50% (95% CI 49-52) among whites, and by 33% (95% CI 29-36) among blacks. PTL increased by 24% among whites, but remained virtually unchanged among blacks between the 2 periods. Preterm birth following ROM also remained unchanged between the 2 periods among whites, but declined by 7% among blacks. Perinatal mortality among twin births declined by 41% (95% CI 38-44) among whites, and by 37% (95% CI 32-42) among blacks between 1989 and 1990 and 1999 and 2000. This mortality decline was most closely associated with the increase in medically indicated preterm birth among whites, and with the decrease in preterm birth following ROM among blacks. Conclusion: Temporal trends in twin preterm birth varied substantially based on underlying subtypes and race. The increase in medically indicated twin preterm birth is associated with a large reduction in perinatal mortality. [ABSTRACT FROM AUTHOR]

Objective: Gestational age at delivery and spontaneous prematurity are independent risk factors for white matter damage (WMD). However, among infants delivered spontaneously after preterm premature rupture of membranes (PPROM), latency of PPROM has been inconsistently correlated with risk of WMD. We have explored whether gestational age at membrane rupture is independently associated with WMD. Study design: Using a cohort of 196 liveborn singleton nonanomalous neonates born at 24.0 to 33.6 weeks from January 1993 to December 2002 after pPROM and who survived 7 days, we compared the characteristics of those who developed WMD (n = 15) with those who did not (n = 181) using Fisher exact test, Student t test, and logistic regression analysis, with a 2-tailed P < .05 or odds ratio (OR) with 95% CI not inclusive of the unity considered significant. Results: Stepwise logistic regression analysis demonstrated that gestational age at PPROM (P < .001, OR 0.79) was significantly associated with WMD. The association was independent of corticosteroid administration (P = .016), latency interval (P = .69), gestational age at delivery (P = .99), and birth weight (P = .62). Conclusion: Among premature infants born at <34 weeks after pPROM, gestational age at diagnosis is independently associated with WMD. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to compare perinatal outcomes among women with conservatively treated preterm premature rupture of membranes at 24 to 32 weeks of gestation in the presence or absence of vaginal bleeding. Study design: This is a secondary analysis of 581 women with and without vaginal bleeding within 1 week of admission with preterm premature rupture of membranes at 24 to 32 weeks of gestation who were enrolled in a multicenter trial of antibiotic therapy during conservative treatment. The main outcome was latency to delivery. Other outcome variables included clinical abruptio placentae, amnionitis, perinatal death, severe intraventricular hemorrhage, and respiratory distress syndrome. Results: Outcome data were available for 581 patients (n = 50 with bleeding). Latency to delivery was not affected by the presence or absence of bleeding. In general, a history of bleeding was associated with higher frequencies of subsequently diagnosed abruptio placentae (12% vs 3.5%; P = .01), perinatal death (16% vs 4.9%; P = .006), intraventricular hemorrhage (14.3 % vs 5.9%; P = .03), and respiratory distress syndrome (69.4% vs 40.4%; P < .0001), when compared with those women with nonbleeding events. Women with bleeding were less likely to be black (42% vs 60%; P = .002) and had a lower mean gestational age at preterm premature rupture of membranes (27.6 vs 28.5 weeks; P = .02) when compared with white, Hispanic, and other. After an adjustment of data was made for potentially confounding factors, women with recent bleeding were more likely to be diagnosed with abruptio placentae at delivery (odds ratio, 2.8; 95% CI, 1.03–7.8; P = .04), and their infants were more likely to have respiratory distress syndrome (odds ratio, 3.1; 95% CI, 1.5–6.6; P = .004). Conclusion: Vaginal bleeding before preterm premature rupture of membranes is associated with increased rates of neonatal respiratory distress syndrome and abruptio placentae, but not with reduced latency to delivery. [ABSTRACT FROM AUTHOR]

Objective: To compare morbidities of neonates born to women who developed chorioamnionitis after premature preterm rupture of membranes versus those who did not. Study design: We reviewed outcomes in singleton pregnancies with confirmed premature preterm rupture of membranes at 24 weeks or beyond that resulted in delivery less than 37 weeks. Management of premature preterm rupture of membranes included the use of antibiotics, betamethasone if less than 32 weeks, and expectant management with induction at 34 weeks or greater. Composite neonatal major and minor morbidity rates were compared between pregnancies complicated by chorioamnionitis and those that were not. Results: From August 1998 to August 2000, 430 cases of premature preterm rupture of membranes were identified among 6003 deliveries (7.2%). Thirteen percent of women (56/430) with premature preterm rupture of membranes developed chorioamnionitis. The incidence of chorioamnionitis increased significantly with decreasing gestational age. The composite neonatal major morbidity rate was significantly higher in neonates whose mothers developed chorioamnionitis (55%) versus those who did not (18%, P < .0001). In a multiple logistic regression model, chorioamnionitis (P < .0001), infant gender (P = .007), latency (P = .03), and gestational age at delivery (P < .0001) were significantly associated with composite neonatal morbidity. Conclusion: Neonatal morbidities are significantly higher among pregnancies with premature preterm rupture of membranes complicated by chorioamnionitis when compared with pregnancies that were not. [ABSTRACT FROM AUTHOR]

Objective: The relationship between a polymorphism at position -670 in the Fas gene (TNFRSF6) and preterm premature rupture of membranes (PPROM) in multifetal pregnancies was examined. Methods: Buccal swabs from 119 mother-infant sets were analyzed for an adenine (A) to guanine (G) substitution at position -670 in the TNFRSF6 promoter. Pregnancy outcome data were subsequently obtained. Analysis was by Fisher exact test. Results: Maternal allele G homozygosity (TNFRSF6*G) was observed in 42.4% of 33 PPROM pregnancies as opposed to 19.5% of 77 with no spontaneous preterm birth (P = .01). Similarly, TNFRSF6*G homozygosity was present in 37.5% of 32 first-born neonates from PPROM pregnancies as opposed to 18.7% of 75 uncomplicated pregnancies (P = .04). PPROM occurred in 8 of 14 (57.1%) pregnancies in which mother and all neonates were TNFRSF6*G homozy-gotes as opposed to 25 of 105 (23.8%) cases in which uniform TNFRSF6*G homozygosity was not observed (P = .02). Conclusions: A genetic variant in the Fas gene is associated with an increased rate of PPROM in multifetal pregnancies. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to characterize variations in the management for women with preterm premature rupture of membranes (PPROM) among maternal-fetal medicine (MFM) specialists in the context of current recommendations for clinical practice and evidenced-based practice. Study design: We performed a Web-based survey of 1375 MFM providers. Participants were queried on practice characteristics and management issues including use of tocolytics, antibiotics, steroids, and timing of delivery. Results: A total of 508 providers (37%), representing all 50 states and 13 countries, responded to the survey. Only 30% reported a formal departmental protocol for managing women with PPROM. Consistent use of steroids (99.4%) and antibiotics (99.6%) were reported. Administration of steroids was confined to ≤32 weeks by 37%, and ≤34 weeks by 51% of practitioners. Repeated dosing of steroids was uncommon (16%). The antibiotics use and rationale for use varied among respondents. Tocolytics were used by 73% of respondents with magnesium sulfate the main agent used (98%). Use of tocolytics was generally used for 48 hours or less to attain steroid benefit (88%). Amniocentesis was used by 66% of practitioners in the acute evaluation of PPROM. Fetal lung maturity testing was reported by 78% with variability noted with respect to the test used. Outpatient management of women with PPROM after viability was noted by 43% of respondents. Gestational age at which expectant management is abandoned in women with PPROM varied significantly between respondents: ≥34 weeks by 56%, ≥35 weeks by 26%, ≥36 weeks by 12%, and ≥37 weeks by 4.0%. Conclusion: Although many management practices for women with PPROM are consistent with currently available evidence and practice recommendations, substantial variations still exist among MFM providers. [ABSTRACT FROM AUTHOR]

Objective: The association between the detection of Mycoplasma hominis or Ureaplasma urealyticum in midtrimester amniotic fluid and amniotic fluid cytokine concentrations and subsequent pregnancy outcome were examined. Study design: Amniocentesis was performed between 15 and 19 weeks of gestation in 179 asymptomatic women. Aliquots were assayed for M hominis and U urealyticum by polymerase chain reaction coupled to enzyme-linked immunosorbent assay. Intra-amniotic levels of interleukin-1β, interleukin-1 receptor antagonist, interleukin-4, interleukin-6, and tumor necrosis factor-α were determined by enzyme-linked immunosorbent assay. Pregnancy outcomes were obtained after the completion of all testing. Results: U urealyticum was detected in 22 of 172 amniotic fluids (12.8%); M hominis was present in 11 of 179 amniotic fluids (6.1%). There was no relationship between U urealyticum detection and the concentration of any cytokine. Detection of M hominis was associated with elevated intraamniotic concentrations of interleukin-4 (P = .01). Preterm premature rupture of membranes that was followed by preterm birth occurred in 5 women (2.8%); 5 women (2.8%) had a spontaneous preterm birth with intact membranes. All 5 of the women with preterm premature rupture of membranes (100%) tested positive for either U urealyticum or M hominis, as opposed to none of the women with spontaneous preterm birth and to 27 of 161 women (16.8%) with a term birth (P = .0002). Conclusion: The detection of M hominis or U urealyticum in midtrimester amniotic fluid by polymerase chain reaction-enzyme-linked immunosorbent assay may be a risk factor for subsequent preterm premature rupture of membranes. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine the relationship between preterm premature rupture of membranes, tumor necrosis factor-α, and heat shock protein-70 gene polymorphisms in multifetal gestations. Study design: Buccal swabs from 101 mother-neonate pairs of multifetal pregnancies were tested for single nucleotide polymorphisms at position -308 of the tumor necrosis factor-α gene and +1267 of the heat shock protein-70 gene. Pregnancy outcome data were obtained subsequently. Results: Tumor necrosis factor-α allele 2 carriage by the first-born occurred in 10 of 27 pregnancies (37.0%) that resulted in preterm premature rupture of membranes compared with 6 of 67 pregnancies (9.0%) without preterm premature rupture of membranes (P = .002). The allele frequency of tumor necrosis factor-α allele 2 and heat shock protein-70 allele 2 in the first born was higher in pregnancies that were complicated by preterm premature rupture of membranes (18.5% vs 4.5%; P = .003; and 57.7% vs 41.3%; P = .04, respectively). There was no relationship between tumor necrosis factor-α allele 2 or heat shock protein-70 allele 2 carriage by the second fetus or mother and preterm premature rupture of membranes. Conclusion: Tumor necrosis factor-α allele 2 and/or heat shock protein-70 allele 2 carriage by the first-born fetus is associated with preterm premature rupture of membranes in multifetal pregnancies. [ABSTRACT FROM AUTHOR]

Objective: The Toll-like receptor-2 and -4 recognize microbial products that are associated with gram-positive and gram-negative bacteria, respectively. This study examined Toll-like receptor-2 and -4 expression in fetal membranes in response to labor at term and histologic chorioamnionitis. Study design: Immunohistochemistry and real-time quantitative reverse transcriptasepolymerase chain reaction were used to examine the chorioamnion from patients with (1) preterm labor and intact membranes, (2) preterm premature rupture of membranes who were delivered ≤34 weeks of gestation, and (3) women at term with or without labor. All groups were stratified on the basis of the presence of histologic chorioamnionitis. Results: Toll-like receptor-2 expression was significantly higher in patients with chorioamnionitis than in patients without this condition (all P < .05). The Toll-like receptor-2 and -4 messenger RNA amounts were significantly higher in membranes from women at term with spontaneous labor than women who were not in labor (P = .001 and .002, respectively). Toll-like receptor-2 expression was polarized to the basal surface of amniotic epithelial cells in patients without chorioamnionitis, but this distribution was lost in the presence of inflammation. Conclusion: Spontaneous labor at term and preterm delivery with histologic chorioamnionitis, regardless of the membrane status (intact or ruptured), are associated with an increased expression of Toll-like receptor-2 and -4 in the chorioamniotic membranes. These observations have implications for understanding the biologic nature of innate immunity. [ABSTRACT FROM AUTHOR]

Objective: This study was conducted to determine the frequency and clinical significance of intraamniotic inflammation in patients with preterm premature rupture of the membranes. Study design: Amniotic fluid was retrieved from 219 patients with preterm premature rupture of the membranes; the fluid was cultured for aerobic and anaerobic bacteria and mycoplasmas and assayed for neutrophil collagenase, which is also known as matrix metalloproteinase-8. Matrix metalloproteinase-8 was used because previous studies indicated that this was a sensitive and specific index of inflammation and that is correlated with the amniotic fluid white blood cell count. Intra-amniotic inflammation was defined as an elevated amniotic fluid matrix metalloproteinase-8 concentration (> 23 ng/mL). Nonparametric and survival techniques were used for statistical analysis. Results: The overall rate of intra-amniotic inflammation was 42% (93/219 samples); proven intraamniotic infection was detected only in 23% (50/219 samples). Intra-amniotic inflammation with a negative amniotic fluid culture for micro-organisms was found in 23% (51/219 samples) and was as common as proven intra-amniotic infection. Pregnancy outcome was worse in patients with intraamniotic inflammation and a negative culture than in those patients with a negative culture and without inflammation. There were no differences in the interval-to-delivery or rate of complications between patients with intra-amniotic inflammation and a negative culture and patients with proven amniotic fluid infection. Conclusion: We conclude that intra-amniotic inflammation, regardless of culture result, is present in 42% of patients with preterm premature rupture of the membranes and that it is a risk factor for impending preterm delivery and adverse outcome. We propose that intra-amniotic inflammation, rather than infection, be used to classify and treat patients with preterm premature rupture of the membranes. [ABSTRACT FROM AUTHOR]

Objective: This study was performed to determine whether a qualitative human chorionicgonadotropin (hCG) test using cervicovaginal washings obtained from pregnant women is a useful predictor of recent preterm premature rupture of the membranes (PPROM). Study design: A prospective observational analysis of qualitative hCG testing on cervicovaginal washings in patients with either known PPROM or with intact membranes was performed. Patients with singleton gestations between 24 and 34 completed weeks were included. PPROM patients had documented comfirmatory tests, including visualized pooling of amniotic fluid in the vaginal vault that was nitrazine-positive and demonstrated ferning. Those with vaginal bleeding or an anomalous fetus were excluded. Before collection, all patients were screened for bacterial vaginosis and trichomoniasis. Washings were then collected from the posterior vaginal fornix with the use of a 5-mL sterile saline irrigation and aspiration technique. Samples were then agitated manually and applied to the Quickvue Onestep qualitative pregnancy test (Quidell, San Diego, Calif) with a threshold of 25 mIU/mL. Data were analyzed with the t test, X2, and Fischer exact tests. Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values were calculated. When applicable, all 2-tailed P < .05 were considered significant. Results: Fifty-two patients were enrolled in the study with 24 in the PPROM group and 28 in the control group. The 2 groups were similar with respect to demographic characteristics and wet preparation results. The mean gestation age was 31.4 ± 2.4 (X ± SD) and 30.8 ± 2.7 weeks in the PPROM and control groups, respectively. The hCG test was positive in 19 (79%) of the PPROM patients and in 1 (3.6%) of the controls (sensitivity 79%, specificity 96%, PPV 95%, NPV 84%). Conclusion: Qualitative hCG testing of cervicovaginal washings appears to be an useful predictor of PPROM. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine whether patients with first-trimester threatened abortion are at increased risk for poor pregnancy outcome. The study comprised 16,506 patients: 14,160 patients without bleeding, 2094 patients with light bleeding, and 252 patients with heavy bleeding. Patients with vaginal bleeding, light or heavy, were more likely to experience a spontaneous loss before 24 weeks of gestation (odds ratio, 2.5 and 4.2, respectively) and cesarean delivery (odds ratio, 1.1 and 1.4. respectively). Light bleeding subjects were more likely to have preeclampsia (odds ratio, 1.5), preterm delivery (odds ratio, 1.3), and placental abruption (odds ratio, 1.6). Heavy vaginal bleeding subjects were more likely to have intrauterine growth restriction (odds ratio. 2.6), preterm delivery (odds ratio, 3.0), preterm premature rupture of membranes (odds ratio, 3.2), and placental abruption (odds ratio, 3.6). First-trimester vaginal bleeding is an independent risk factor for adverse obstetric outcome that is directly proportional to the amount of bleeding. [ABSTRACT FROM AUTHOR]

Background: As compared with singleton gestations, twin pregnancies are associated with a significantly higher risk of preterm birth and maternal complications as well as fetal and neonatal morbidity and mortality. Multifetal pregnancy reduction is a technique developed in the 1980s to reduce the fetal number in higher-order multiple pregnancies to reduce the risk of adverse pregnancy outcomes, most importantly preterm birth.Objective: The objective of the study was to compare pregnancy outcomes and loss rates in elective twin pregnancy reduction to ongoing twin gestations in a large contemporary cohort.Study Design: This was a retrospective review of dichorionic diamniotic twin gestations that underwent first-trimester ultrasound at our institution from January 2008 to September 2016. Planned elective 2-to-1 multifetal pregnancy reductions at less than 15 weeks' gestation were compared with ongoing dichorionic diamniotic twin gestations. Data were collected via chart review. Demographics between 2-to-1 reduced singletons and ongoing twins were assessed using a Student t test or a Wilcoxon rank-sum test, as appropriate, for continuous variables and χ2 or Fisher exact tests, as appropriate, for categorical variables. Univariable and multivariable logistic regressions were used to compare pregnancy outcomes between ongoing twins and reduced singletons adjusting for maternal age, body mass index, race, in vitro fertilization, use of chorionic villus sampling, prior term birth, and prior preterm birth.Results: Of 1070 dichorionic diamniotic twin pregnancies identified, completed follow-up data were available and analyzed for 855 patients (79.9%). Among those, 250 (29.2%) were 2-to-1 singletons and 605 (70.8%) were ongoing twins. Reduced singleton patients were slightly older, more likely white, and had lower body mass index. They were also more likely to have undergone in vitro fertilization (63.6% vs 48.8%), had chorionic villus sampling (92% vs 37.5%), and had prior term births (54% vs 35.7%). Compared with 2-to-1 singletons, the adjusted odds of having preterm delivery at 37 weeks for ongoing twins were 5.62 times (95% confidence interval, 3.67-8.61; P < .001) and 2.22 times (95% confidence interval, 1.20-4.11; P < .001) at 34 weeks. While intrauterine growth restriction, placental abruption, and gestational diabetes were not significant, ongoing twins were more likely to have a cesarean delivery (odds ratio, 5.53, 95% confidence interval, 3.60-8.49; P < .001) and preeclampsia (odds ratio, 3.33, 95% confidence interval, 1.60-6.96; P < .001) after adjusting for maternal characteristics. There were also significant differences between groups for preterm premature rupture of membranes and low birthweight at less than the fifth and 10th percentiles. Total pregnancy loss (at 24 and 20 weeks) was similar between singleton and ongoing twins (4% vs 2.5%, P = .23, and 3.6% vs 1.7%, P = .09 for respective weeks). There were no significant differences in the rate of unintended pregnancy loss (2.4% vs 2.3%; P = .94) and the rate of intrauterine fetal death greater than 24 weeks (1.2% vs 0.7%; P = .43) in reduced singleton versus ongoing twin group, respectively.Conclusion: In our study, patients who elected to reduce to a singleton pregnancy had a higher gestational age of delivery and lower rates of preterm birth and pregnancy complications without an increased risk of pregnancy loss. [ABSTRACT FROM AUTHOR]

The term placental bed was coined to describe the maternal-fetal interface (ie, the area in which the placenta attaches itself to the uterus). Appropriate vascularization of this area is of vital importance for the development of the fetus; this is why systematic investigations of this area have now been carried out. Initially, the challenge was the identification and classification of the various successive branching of uterine arteries in this area. These vessels have a unique importance because failure of their physiological transformation is considered to be the anatomical basis for reduced perfusion to the intervillous space in women with preeclampsia, fetal growth restriction, preterm labor, preterm premature rupture of membranes, abruptio placentae, and fetal death. To investigate in depth the pathophysiology of the placental bed, some 60 years ago, a large number of placental bed biopsies, as well as of cesarean hysterectomy specimens with placenta in situ, from both early and late normotensive and hypertensive pregnancies, were carefully dissected and analyzed. Thanks to the presence of a series of specific physiological changes, characterized by the invasion and substitution of the arterial intima by trophoblast, this material allowed the identification in the placental bed of normal pregnancies of the main vessels, the uteroplacental arteries. It was then discovered that preeclampsia is associated with defective or absent transformation of the myometrial segment of the uteroplacental arteries. In addition, in severe hypertensive disease, atherosclerotic lesions were also found in the defective myometrial segment. Finally, in the basal decidua, a unique vascular lesion, coined acute atherosis, was also identified This disorder of deep placentation, coined defective deep placentation, has been associated with the great obstetrical syndromes, grouping together preeclampsia, intrauterine growth restriction, preterm labor, preterm premature rupture of membranes, late spontaneous abortion, and abruptio placentae. More recently, simplified techniques of tissue sampling have been also introduced: decidual suction allows to obtain a large number of decidual arteries, although their origin in the placental bed cannot be determined. Biopsies parallel to the surface of the basal plate have been more interesting, making possible to identify the vessels' region (central, paracentral, or peripheral) of origin in the placental bed and providing decidual material for immunohistochemical studies. Finally, histochemical and electron microscopy investigations have now clarified the pathology and pathogenetic mechanisms underlying the impairment of the physiological vascular changes. [ABSTRACT FROM AUTHOR]

Background: Streptococcus agalactiae (GBS) is a common pathogen known to cause neonatal and maternal infectious morbidity. Streptococcus pseudoporcinus (S pseudoporcinus) is a separate, recently identified β-hemolytic gram-positive coccus that can cause false-positive results on standard GBS agglutination testing assays.Objective: To determine the prevalence and clinical implications of Streptococcus pseudoporcinus colonization in pregnancy.Materials and Methods: This is a 2-year retrospective cohort study comparing pregnant women colonized with GBS to those colonized with S. pseudoporcinus. A proteomics method of identification, namely, matrix-assisted laser desorption ionization time-of-flight mass spectrometry, was used to distinguish between S. pseudoporcinus and GBS colonization. Antibiotic susceptibility testing was carried out on all specimens. Maternal and neonatal chart reviews were conducted to identify predictors of S. pseudoporcinus colonization and to compare maternal and neonatal outcomes.Results: S. pseudoporcinus colonization occurred in 1.6% of all pregnancies. A total of 2.5% of all GBS-positive results by agglutination assay were false positive, instead reflecting S. pseudoporcinus colonization. Clindamycin resistance among S. pseudoporcinus isolates is uncommon. S. pseudoporcinus colonization in pregnancy is independently associated with African American race, tobacco use, and body mass index ≥35. Preterm premature rupture of membranes or spontaneous preterm birth was more common in patients colonized with S. pseudoporcinus.Conclusion: Although the prevalence of S. pseudoporcinus colonization is low, it primarily occurs in African American women and is associated with preterm premature rupture of membranes or spontaneous preterm birth when compared to individuals colonized with GBS. [ABSTRACT FROM AUTHOR]

Background: Most clinical guidelines state that with early preterm premature rupture of membranes, obstetric and pediatric teams must share a realistic and individualized appraisal of neonatal outcomes with parents and consider their wishes for all decisions. However, we currently lack reliable and relevant data, according to gestational age at rupture of membranes, to adequately counsel parents during pregnancy and to reflect on our policies of care at these extreme gestational ages.Objective: We sought to describe both perinatal and 2-year outcomes of preterm infants born after preterm premature rupture of membranes at 22-25 weeks' gestation.Study Design: EPIPAGE-2 is a French national prospective population-based cohort of preterm infants born in 546 maternity units in 2011. Inclusion criteria in this analysis were women diagnosed with preterm premature rupture of membranes at 22-25 weeks' gestation and singleton or twin gestations with fetus(es) alive at rupture of membranes. Latency duration, antenatal management, and outcomes (survival at discharge, survival at discharge without severe morbidity, and survival at 2 years' corrected age without cerebral palsy) were described and compared by gestational age at preterm premature rupture of membranes.Results: Among the 1435 women with a diagnosis of preterm premature rupture of membranes, 379 were at 22-25 weeks' gestation, with 427 fetuses (331 singletons and 96 twins). Median gestational age at preterm premature rupture of membranes and at birth were 24 (interquartile range 23-25) and 25 (24-27) weeks, respectively. For each gestational age at preterm premature rupture of membranes, nearly half of the fetuses were born within the week after the rupture of membranes. Among the 427 fetuses, 51.7% were survivors at discharge (14.1%, 39.5%, 66.8%, and 75.8% with preterm premature rupture of membranes at 22, 23, 24, and 25 weeks, respectively), 38.8% were survivors at discharge without severe morbidity, and 46.4% were survivors at 2 years without cerebral palsy, with wide variations by gestational age at preterm premature rupture of membranes. Survival at 2 years without cerebral palsy was low with preterm premature rupture of membranes at 22 and 23 weeks but reached approximately 60% and 70% with preterm premature rupture of membranes at 24 and 25 weeks.Conclusion: Preterm premature rupture of membranes at 22-25 weeks is associated with high incidence of mortality and morbidity, with wide variations by gestational age at preterm premature rupture of membranes. However, a nonnegligible proportion of children survive without severe morbidity both at discharge and at 2 years' corrected age. [ABSTRACT FROM AUTHOR]

Background: There are conflicting results regarding tocolysis in cases of preterm premature rupture of membranes. Delaying delivery may reduce neonatal morbidity because of prematurity and allow for prenatal corticosteroids and, if necessary, in utero transfer. However, that may increase the risks of maternofetal infection and its adverse consequences.Objective: The objective of the study was to investigate whether tocolytic therapy in cases of preterm premature rupture of membranes is associated with improved neonatal or obstetric outcomes.Study Design: Etude Epidémiologique sur les Petits Ages Gestationnels 2 is a French national prospective, population-based cohort study of preterm births that occurred in 546 maternity units in 2011. Inclusion criteria in this analysis were women with preterm premature rupture of membranes at 24-32 weeks' gestation and singleton gestations. Outcomes were survival to discharge without severe morbidity, latency prolonged by ≥48 hours and histological chorioamnionitis. Uterine contractions at admission, individual and obstetric characteristics, and neonatal outcomes were compared by tocolytic treatment or not. Propensity scores and inverse probability of treatment weighting for each woman were used to minimize indication bias in estimating the association of tocolytic therapy with outcomes.Results: The study population consisted of 803 women; 596 (73.4%) received tocolysis. Women with and without tocolysis did not differ in neonatal survival without severe morbidity (86.7% vs 83.9%, P = .39), latency prolonged by ≥48 hours (75.1% vs 77.4%, P = .59), or histological chorioamnionitis (50.0% vs 47.6%, P = .73). After applying propensity scores and assigning inverse probability of treatment weighting, tocolysis was not associated with improved survival without severe morbidity as compared with no tocolysis (odds ratio, 1.01 [95% confidence interval, 0.94-1.09], latency prolonged by ≥48 hours (1.03 [95% confidence interval, 0.95-1.11]), or histological chorioamnionitis (1.03 [95% confidence interval, 0.92-1.17]). There was no association between the initial tocolytic drug used (oxytocin receptor antagonists or calcium-channel blockers vs no tocolysis) and the 3 outcomes. Sensitivity analyses of women with preterm premature rupture of membranes at 26-31 weeks' gestation, women who delivered at least 12 hours after rupture of membranes, women with direct admission after the rupture of membranes and the presence or absence of contractions gave similar results.Conclusion: Tocolysis in cases of preterm premature rupture of membranes is not associated with improved obstetric or neonatal outcomes; its clinical benefit remains unproven. [ABSTRACT FROM AUTHOR]

Background: Since the results of the Management of Myelomeningocele Study were published, maternal-fetal surgery for the in utero treatment of spina bifida has become accepted as a standard of care alternative. Despite promise with fetal management of myelomeningocele repair, there are significant complications to consider. Chorioamniotic membrane separation and preterm premature rupture of membranes are known complications of invasive fetal procedures. Despite their relative frequency associated with fetal procedures, few data exist regarding risk factors that may be attributed to their occurrence or the natural history of pregnancies that are affected with chorionic membrane separation or preterm premature rupture of membranes related to the procedure.Objective: The objective of this study was to review chorioamniotic membrane separation and preterm premature rupture of membranes in a cohort of patients undergoing fetal management of myelomeningocele repair including identification of risk factors and outcomes.Study Design: This was a retrospective review of patients undergoing fetal management of myelomeningocele repair and subsequent delivery from January 2011 through December 2013 at 1 institution. Patients were identified through the institutional fetal management of myelomeningocele repair database and chart review was performed. Perioperative factors and outcomes among patients with chorioamniotic membrane separation and preterm premature rupture of membranes were compared to those without. Risk factors associated with the development of chorioamniotic membrane separation and preterm premature rupture of membranes were determined.Results: A total of 88 patients underwent fetal management of myelomeningocele repair and subsequently delivered during the study period. In all, 21 patients (23.9%) were diagnosed with chorioamniotic membrane separation by ultrasound and preterm premature rupture of membranes occurred in 27 (30.7%). Among the chorioamniotic membrane separation patients, 10 (47.6%) were diagnosed with global chorioamniotic membrane separation and 11 (52.4%) with local chorioamniotic membrane separation. Earlier gestational age at the time of fetal surgery was a significant risk factor for the development of chorioamniotic membrane separation (P = .01) and preterm premature rupture of membranes (P < 0.0001). Chorioamniotic membrane separation was significantly associated with preterm premature rupture of membranes (59.1% vs 21.2%, P = .008) and earlier gestational age at delivery (32.1 ± 4.2 vs 34.4 ± 3.5 weeks, P = .01). The average number of days from chorioamniotic membrane separation to preterm premature rupture of membranes was 11.0 ± 10.1 and from chorioamniotic membrane separation to delivery was 31.0 ± 22.5. The mean time interval between fetal management of myelomeningocele repair and preterm premature rupture of membranes was 47.9 days. Mean latency period from preterm premature rupture of membranes to delivery was 25 days. Gestational age at delivery was significantly lower in patients with preterm premature rupture of membranes (31.6 ± 3.4 vs 34.9 ± 3.5 weeks, P = .0001). Using logistic regression analysis, nulliparity, gestational age at fetal management of myelomeningocele repair, and membrane separation remained significant risk factors for preterm premature rupture of membranes.Conclusion: Chorioamniotic membrane separation after fetal management of myelomeningocele repair is a significant risk factor for subsequent development of preterm premature rupture of membranes and preterm delivery. Fetal management of myelomeningocele repair <23 weeks is associated with higher rates of preterm premature rupture of membranes and chorioamniotic membrane separation. Therefore fetal management of myelomeningocele repair should be deferred until ≥23 weeks to mitigate these complications. Nulliparity also appears to increase the risk for preterm premature rupture of membranes. [ABSTRACT FROM AUTHOR]

After hospitalization subsequent to preterm premature rupture of membranes at 29 weeks, our patient was scheduled for induction of labor at 34 weeks. When the fetus was found to be breech with oligohydramnios, amnioinfusion was performed to facilitate external cephalic version, and this successful procedure enabled the patient to deliver vaginally. [ABSTRACT FROM AUTHOR]

Objective We sought to determine whether transvaginal cervical length (TVCL), amniotic fluid index (AFI), or a combination of both can predict delivery latency within 7 days in women presenting with preterm premature rupture of membranes (PPROM). Study Design This was a prospective observational study of TVCL measurements in 106 singleton pregnancies with PPROM between 23-33 weeks. Delivery latency was defined as the period (in days) from the initial TVCL after PPROM to delivery of the infant, with our primary outcome being delivery within 7 days of TVCL. The independent predictability of significant characteristics for delivery within 7 days was determined using multiple logistic regression. Sensitivity, specificity, and predictive values were used to examine whether the presence of a short TVCL, AFI, or a combination of both affected the risk of delivery within 7 days. Results Delivery within 7 days occurred in 51/106 (48%) of pregnancies. Median duration (interquartile range) from PPROM to delivery and TVCL to delivery was 8 days (4.0–16.0) and 8 days (3.0–15.0), respectively. Using multiple regression TVCL as a continuous variable (odds ratio, 0.65; 95% confidence interval, 0.44–0.97; P < .05), AFI ≤5 cm (odds ratio, 4.69; 95% confidence interval, 1.58–13.93; P < .01) were determined to be independent predictors of delivery within 7 days. In all, 42 women (40%) had a TVCL ≤2 cm, while 62 (59%) had AFI ≤5 cm. A total of 26 women (25%) had a combination of both TVCL ≤2 cm and AFI ≤5 cm, while 28 women (27%) had neither characteristic. The predictive value of delivery within 7 days for a TVCL ≤2 cm was 62%, and for an AFI ≤5 cm was 58%. Having a combination of low TVCL and low AFI did not increase the predictive value of delivery within 7 days (58%). In contrast, only 3 of 27 women (11%) with neither characteristic delivered within 7 days. The predictive value of delivery >7 days for TVCL >2 cm alone was 61%. This predictive value changed when analyzed in conjunction with an AFI ≤5 cm and >5 cm at 42% and 89%, respectively. Conclusion A shorter TVCL and an AFI ≤5 cm independently predict delivery within 7 days in women presenting with PPROM. The combination of an AFI >5 cm and TVCL >2 cm greatly improved the potential to remain undelivered at 7 days following cervical length assessment. These findings may be helpful for counseling and optimizing maternal and neonatal care in women with PPROM. [ABSTRACT FROM AUTHOR]

Objective The objective of the study was to determine the obstetric and neonatal outcomes of expectantly managed multifetal pregnancies complicated by early preterm premature rupture of membranes (PPROM) prior to 26 weeks. Study Design This was a retrospective cohort of all multifetal pregnancies complicated by documented PPROM occurring before 26 0/7 weeks and managed expectantly by a single maternal-fetal medicine practice between July 4, 2002, and Sept. 1, 2013. Neonatal and maternal outcomes were assessed and comparisons made between the fetus with ruptured membranes and the first fetus to deliver with intact membranes. Results Twenty-three pregnancies (46 fetuses) were analyzed with a median gestational age at PPROM of 22.9 weeks; 74% experienced PPROM at less than 24 weeks’ gestation. A median latency of 11 days was achieved with expectant management. Of the 46 neonates, 20 (43%) survived to hospital discharge. Of these, 12 (60%) experienced severe neonatal morbidity defined as defined as grade III or IV intraventricular hemorrhage, bronchopulmonary dysplasia, pulmonary hypoplasia, necrotizing enterocolitis requiring surgical intervention, and/or grade 3 or 4 retinopathy of prematurity. Eight neonates survived to hospital discharge without severe neonatal morbidity. The multiple with ruptured membranes was more likely to experience intrauterine demise but otherwise had similar outcomes as the multiple with intact membranes. Maternal morbidity was considerable, with 7 of 23 pregnancies (30%) complicated by clinical chorioamnionitis, 12 of 23 (52%) delivering by cesarean, of which 3 of 12 (25%) were classical cesarean deliveries. Conclusion Overall, neonatal survival to hospital discharge was 43%, but only 17% survived without significant neonatal morbidity. These data provide a basis for counseling and management of women with multifetal gestation complicated by very early PPROM. [ABSTRACT FROM AUTHOR]

Objective The decision of whether to retain or remove a previously placed cervical cerclage in women who subsequently rupture fetal membranes in a premature gestation is controversial and all studies to date are retrospective. We performed a multicenter randomized controlled trial of removal vs retention of cerclage in these patients to determine whether leaving the cerclage in place prolonged gestation and/or increased the risk of maternal or fetal infection. Study Design A prospective randomized multicenter trial of 27 hospitals was performed. Patients included were those with cerclage placement at ≤23 weeks 6 days in singleton or twin pregnancies, with subsequent spontaneous rupture of membranes between 22 weeks 0 days and 32 weeks 6 days. Patients were randomized to retention or removal of cerclage. Patients were then expectantly managed and delivered only for evidence of labor, chorioamnionitis, fetal distress, or other medical or obstetrical indications. Management after 34 weeks was at the clinician's discretion. Results The initial sample size calculation determined that a total of 142 patients should be included but after a second interim analysis, futility calculations determined that the conditional power for showing statistical significance after randomizing 142 patients for the primary outcome of prolonging pregnancy was 22.8%. Thus the study was terminated after a total of 56 subjects were randomized with complete data available for analysis, 32 to removal and 24 to retention of cerclage. There was no statistical significance in primary outcome of prolonging pregnancy by 1 week comparing the 2 groups (removal 18/32, 56.3%; retention 11/24, 45.8%) P = .59; or chorioamnionitis (removal 8/32, 25.0%; retention 10/24, 41.7%) P = .25, respectively. There was no statistical difference in composite neonatal outcomes (removal 16/33, 50%; retention 17/30, 56%), fetal/neonatal death (removal 4/33, 12%; retention 5/30, 16%); or gestational age at delivery (removal mean 200 days; retention mean 198 days). Conclusion Statistically significant differences were not seen in prolongation of latency, infection, or composite neonatal outcomes. However, there was a numerical trend in the direction of less infectious morbidity, with immediate removal of cerclage. These findings may not have met statistical significance if the original sample size of 142 was obtained, however they provide valuable data suggesting that there may be no advantage to retaining a cerclage after preterm premature rupture of membranes and a possibility of increased infection with cerclage retention. [ABSTRACT FROM AUTHOR]

Objective Data regarding long-term outcomes of neonates reaching viability following early preterm premature rupture of membranes (PPROM; <25.0 weeks at rupture) are limited. We hypothesized that babies delivered after early PPROM would have increased rates of major childhood morbidity compared with those with later PPROM (≥25.0 weeks at rupture). Study Design This was a secondary analysis of a multicenter randomized controlled trial of magnesium sulfate vs placebo for cerebral palsy prevention. Women with singletons and PPROM of 15-32 weeks were included. All women delivered at 24.0 weeks or longer. Those with PPROM less than 25.0 weeks (cases) were compared with women with PPROM at 25.0-31.9 weeks (controls). Composite severe neonatal morbidity (sepsis, severe intraventricular hemorrhage, periventricular leukomalacia, severe necrotizing enterocolitis, bronchopulmonary dysplasia, and/or death) and composite severe childhood morbidity at age 2 years (moderate or severe cerebral palsy and/or Bayley II Infant and Toddler Development scores greater than 2 SD below the mean) were compared. Results A total of 1531 women (275 early PPROM cases) were included. Demographics were similar between the groups. Cases delivered earlier (26.6 vs 30.1 weeks, P < .001) and had a longer rupture-to-delivery interval (20.0 vs 10.4 days, P < .001). Case neonates had high rates of severe composite neonatal morbidity (75.6% vs 21.8%, P < .001). Children with early PPROM had higher composite severe childhood morbidity (51.6% vs 22.5%, P < .001). Early PPROM remained associated with composite severe childhood morbidity in multivariable models, even when controlling for delivery gestational age and other confounders. Conclusion Early PPROM is associated with high rates of neonatal morbidity. Early childhood outcomes at age 2 years remain poor compared with those delivered after later PPROM. [ABSTRACT FROM AUTHOR]

Objective: Relaxin H2 (RLN2) is a systemic hormone (sRLN) that is produced by the corpus luteum, whereas decidual RLN (dRLN) acts only locally. Elevated sRLN is associated with spontaneous preterm birth (sPTB) and elevated dRLN with preterm premature rupture of membranes (PPROM). Associations were sought between single nucleotide polymorphisms (SNPs) in the RLN2 promoter with levels of dRLN and sRLN in Filipino patients with sPTB, PPROM, or normal term delivery. Study Design: Stringent selection of women with sPTB (n = 20) or PPROM (n = 20) and term control subjects (n = 20) was made from >8000 samples from Filipino patients who delivered at 34-36 weeks' gestation. Twelve SNPs were genotyped on maternal blood, with 9 excluded based on the high linkage disequilibrium or being the same as in the control population. Quantitative immunocytochemistry on parietal decidual tissue was performed (n = 60); sRLN was measured by enzyme-linked immunosorbent assay in a subset of patients (n = 21). Results: SNP rs4742076 was associated significantly with PPROM (P < .001) and increased expression of dRLN (P < .001). The genotype TT had increased dRLN in PPROM (P < .05). SNP rs3758239 was associated significantly with both PPROM and sPTB (P < .01), and genotype AA had increased dRLN expression (P < .05). The sRLN showed a trend of higher levels in PPROM and sPTB, but was not significant. Conclusion: SNP rs4742076 in the RLN2 promoter was associated with increased dRLN expression and PPROM; SNP rs3758239 was associated with both PPROM and sPTB in these Filipino patients. Specific homozygous genotypes were identified for both SNPs and were shown to be associated with increased dRLN tissue expression. [Copyright &y& Elsevier]

Objective: The purpose of this study was to determine the perinatal impact of the 2007 American College of Obstetricians and Gynecologists Practice Bulletin on preterm premature membrane rupture. Study Design: Perinatal outcomes were compared in women who had experienced preterm membrane rupture in the 3 years before the 2007 Practice Bulletin to similar women who experienced preterm premature rupture of membranes in the 3 years after the issue and implementation of the guideline. Results: After adjustment for gestational age at membrane rupture and steroids, composite severe morbidity (death, respiratory distress syndrome, assisted ventilation for ≥6 hours, sepsis, pneumonia, grade 3 or 4 intraventricular hemorrhage, or necrotizing enterocolitis) was similar by group. Infants in the “after” group experienced less pneumonia and sepsis, similar respiratory morbidity, but more labor inductions and postpartum hemorrhage. Conclusion: The new guideline significantly decreases severe neonatal infections but is associated with more frequent labor induction and postpartum hemorrhage. [ABSTRACT FROM AUTHOR]

Objective: We sought to compare rates of recurrent spontaneous preterm birth (SPTB) in women receiving 17-α-hydroxyprogesterone caproate (17P) with prior SPTB due to preterm labor (PTL) vs preterm premature rupture of membranes (PPROM). Study Design: Women with singleton gestation having 1 prior SPTB enrolled at 16-24.9 weeks'' gestation for weekly outpatient 17P administration were identified from a database. Rates of recurrent SPTB were compared between those with prior SPTB due to PTL or PPROM overall and by gestational age at prior SPTB. Results: Records from 2123 women were analyzed. The prior PTL group vs the prior PPROM group experienced higher rates of recurrent SPTB at <37 weeks (29.7% vs 22.9%, P = .004), <35 weeks (14.0% vs 9.1%, P = .004), and <32 weeks (5.9% vs 3.3%, P = .024), respectively. Conclusion: Reason and gestational age of prior SPTB influence the likelihood of recurrent SPTB in women receiving 17P prophylaxis. [Copyright &y& Elsevier]

Objective: We sought to determine if 17-alpha-hydroxyprogesterone (17P) extends gestation vs placebo in women with preterm premature rupture of the membranes (PPROM). Study Design: Women with vertex presentations with PPROM, 20-30 weeks'' gestation, were randomized to receive weekly 17P or placebo in an attempt to prolong the pregnancy. A total of 69 patients (17P, n = 33; placebo, n = 36) were randomized into this study. Results: Initial cervical dilatation, gestational age at enrollment, and interval to delivery were not different between the 2 groups (P = .914, .424, and .146, respectively). Time of randomization to delivery (P = .250), mode of delivery (relative risk, 1.16; 95% confidence interval, 0.66–2.06), and the neonatal outcome statistics of morbidity (P = .820) and mortality (relative risk, 1.28; 95% confidence interval, 0.59–2.75) were similar between the 2 groups. Conclusion: In patients with PPROM, 17P did not extend gestation vs placebo and cannot be recommended for treatment in such women. [Copyright &y& Elsevier]

Objective: We sought to compare neonatal outcome in cases of uncomplicated preterm premature rupture of membranes (PPROM) (ie, no evidence of clinical chorioamnionitis, placental abruption, or fetal distress) with that of spontaneous preterm deliveries (PTDs) and to determine the effect of the latency period. Study Design: The study group included women with PPROM at gestational age 280/7-336/7 weeks (n = 488). Neonatal outcome was compared with a matched control group of women with spontaneous PTD (n = 1464). Results: Neonates in the uncomplicated PPROM group were at increased risk for composite adverse outcome (53.7% vs 42.0%; P < .001), mortality (1.6% vs 0.0%; P < .001), respiratory morbidity (32.8% vs 26.4%; P = .006), necrotizing enterocolitis, jaundice, hypoglycemia, hypothermia, and polycythemia. Neonatal adverse outcome was more likely in cases of latency period >7 days, oligohydramnios, male fetus, and nulliparity. Conclusion: Consultation regarding prematurity-related morbidity in infants exposed to uncomplicated PPROM cannot be extrapolated from PTDs and should be stratified by the duration of the latency period and the other risk factors identified in the current study. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to investigate whether precipitated egg white could be used as a sealant for iatrogenic injury to fetal membranes. Study Design: Membranes were collected, washed, and affixed to the bottom of glass cylinders filled with second-trimester amniotic fluid. An iatrogenic defect with an 8-gauge needle was created in the test column, and precipitated egg white was added. Fluid levels in test and control columns were compared over a 14 day period. The amount of fluid added to columns was compared using the Wilcoxon rank sum test; P < .05 was considered significant. Results: Test columns (20/21) maintained seal integrity for 14 days and required less amniotic fluid to be added as compared with controls: median: 55.1 mL (range, 20–137 mL) vs 61.6 mL (range, 22–159 mL), respectively (P < .01). Conclusion: Precipitated egg white has the potential to seal iatrogenic membrane defects for up to 14 days'' duration. [Copyright &y& Elsevier]

Objective: Preterm premature rupture of membranes (PPROM) is the leading identifiable cause of prematurity. We hypothesized that, when controlled for delivery gestational age, potential prolonged exposure to inflammation/infection could be harmful to the developing fetus. Study Design: We studied a retrospective cohort of pregnancies with PPROM at 22.0–33.9 weeks'' gestation. The primary outcome was perinatal survival without major morbidity (grade III/IV intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia). Regression models assessed predictors of perinatal morbidity. Results: Three hundred six women were included. PPROM occurred at a median of 29.4 weeks'' gestation (interquartile range [IQR], 24.7–32.1 weeks'' gestation). Median latency was 8 days (IQR, 3–15 days). Median delivery age was 31.4 weeks'' gestation (IQR, 27.4–33.3 weeks'' gestation). Two hundred seventy-seven infants (91%) survived; 233 infants (84% of survivors, 76% of all babies) did not have major morbidities. Gestational age (odds ratio, 0.60; 95% confidence interval, 0.53–0.68) and congenital sepsis (odds ratio, 13.2; 95% confidence interval, 3.9–44.5), but not latency, predicted perinatal morbidity in multivariate models. Conclusion: Latency does not appear to worsen outcomes in pregnancies that are complicated by PPROM. [Copyright &y& Elsevier]

Objective: The objective of the study was to estimate practice patterns regarding bed rest in women with preterm premature rupture of membranes (PPROM) and arrested preterm labor. Study Design: This was a mail-based survey of all Society for Maternal-Fetal Medicine members in the United States asking whether they would recommend bed rest in the setting of arrested preterm labor or PPROM at 26 weeks. Bed rest was defined as no more than 1-2 hours per day out of bed, with permitted activities including bathroom use, bathing, and brief ambulation inside the home/hospital. Results: Seventy-one percent and 87% would recommend bed rest for women with cervical dilation and arrested preterm labor and women with PPROM, respectively, even though the majority believed bed rest was associated with minimal or no benefit. Female sex, nonacademic practice, and practice location in the South or West were independently associated with the recommendation for bed rest. Conclusion: Despite the belief that bed rest is associated with minimal or no benefit, most maternal-fetal medicine specialists recommend bed rest for arrested preterm labor and PPROM. Randomized, prospective trials are needed to evaluate the efficacy of bed rest in these settings. [Copyright &y& Elsevier]

Objective: The purpose of this study was to test the hypothesis that race is associated with the risk of preterm birth due to preterm premature rupture of membranes (PPROM) and its recurrence. Study Design: We conducted a population-based cohort study using the Missouri Department of Health''s maternally linked birth certificate database (1989-1997) to assess racial effects on the occurrence and recurrence of PPROM, while adjusting for socioeconomic and maternal medical risk factors (n = 644,462). Results: Black mothers were more likely to have PPROM compared to white mothers (aOR, 2.3; 95% CI, 2.0-2.5). The magnitude of risk of PPROM for black mothers compared to white mothers was greatest at < 28 weeks of gestation (aOR 2.8, 95% CI, 2.5-3.2). Black mothers were at significantly higher risk of recurrent PPROM compared to white mothers (aOR 6.4, 95% CI, 3.7-11.0). Conclusion: There is an overrepresentation in the occurrence and recurrence of PPROM in black mothers that persists after adjusting for known risk factors. [Copyright &y& Elsevier]

Objective: The purpose of this study was to compare the efficacy and outcomes of 2 different antibiotic regimens that are used to prolong latency in preterm premature rupture of membranes. The primary objective was to determine whether the use of ampicillin-sulbactam/amoxicillin + clavulanate was associated with an increased risk of necrotizing enterocolitis. Study Design: A retrospective review of pregnancies that were complicated by preterm premature rupture of membranes from 1999-2006 at 2 institutions was performed. Outcomes were compared between subjects who received parenteral ampicillin-sulbactam followed by oral amoxicillin + clavulanate (protocol A) and subjects who received parenteral cefazolin and erythromycin followed by oral cephalexin and erythromycin (protocol B). Results: There were 147 women who were evaluated; 88 women received protocol A, and 59 women received protocol B. There were no differences in latency period, gestational age at delivery, or route of delivery. The incidence of necrotizing enterocolitis was 8.0% and 10.2% for protocol A and protocol B, respectively (P = .64). Conclusion: Ampicillin-sulbactam/amoxicillin + clavulanate was not associated with an increase in neonatal necrotizing enterocolitis. Erythromycin in combination with cefazolin and cephalexin is an effective latency antibiotic regimen. [Copyright &y& Elsevier]

Objective: To examine whether the MMP-8 PTD Check (SK Pharma Co, Ltd, Kyunggi-do, Korea), a rapid bedside test that can be performed in 15 minutes, is of value in the identification of intraamniotic infection and/or inflammation and in the assessment of the likelihood of adverse pregnancy outcome in patients with preterm premature rupture of membranes (PPROM). Study Design: Amniotic fluid was retrieved by transabdominal amniocentesis in 141 women with PPROM (<35 weeks’ gestation). Fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas; the remaining amniotic fluid was stored. The stored amniotic fluid was analyzed for interleukin-6 and MMP-8 PTD Check test. Intraamniotic infection/inflammation was defined as a positive amniotic fluid culture and/or elevated amniotic fluid interleukin-6 concentration (>2.6 ng/mL). Nonparametric and survival analysis were used. Results: The prevalence of intraamniotic infection/inflammation was 43% (60/141 women) and that of proven amniotic fluid infection was 18% (25/141 women). Patients with a positive MMP-8 PTD Check test result had a significantly higher rate of intraamniotic infection/inflammation (77% [54/70 women] vs 9% [6/71 women]; P < .001); proven amniotic fluid infection (33% [23/70 women] vs 3% [2/71 women]; P < .001), and adverse outcome than those with a negative MMP-8 PTD Check test result. Adverse outcome included shorter interval to delivery and higher rate of preterm delivery, histologic chorioamnionitis, funisitis, low Apgar scores, and significant neonatal morbidity. A positive MMP-8 PTD Check test result had a sensitivity of 90%, a specificity of 80%, a positive predictive value of 77%, and a negative predictive value of 92% in the identification of intraamniotic infection/inflammation, and was an independent predictor of interval to delivery (hazards ratio, 3.7; 95% CI, 2.4-5.9) and significant neonatal morbidity (odds ratio, 3.1; 95% CI, 1.2-7.9). Conclusion: The MMP-8 PTD Check test is a rapid, simple, and sensitive bedside test to detect intraamniotic infection/inflammation and to predict adverse outcome that includes short latency, chorioamnionitis, and significant neonatal morbidity in patients with PPROM. The results of this study bring the rapid detection of intraamniotic infection/inflammation to the bedside in clinical obstetrics. [Copyright &y& Elsevier]

Objective: Preterm premature rupture of membranes (PPROM) continues to be a major cause of preterm births. The objective of this study was to compare the morbidity of patients with PPROM nonvertex presentations with patients with PPROM with vertex presentations. Study Design: A retrospective analysis of data from 74 patients with PPROM with nonvertex presentations (study group) and 74 patients with PPROM with vertex presentations (control group) comprised the 2 study groups. All patients that met the study admission criteria were treated in a similar manner at 1 of 3 level-III hospitals. The gestational ages at delivery of all patients were between 23-34 weeks, and the gestational ages between case and control patients were matched for gestational age. Results: A statistically significant (P = .03) higher incidence of a prolapsed umbilical cord was found in the study group (n = 8; 10.8%) relative to the control group (n = 1; 1.4%). More infants in the study group had low 5-minute Apgar scores (<5) and/or low cord pH (<7.20; n = 25 [33.8%]) than in the control group (n = 12 [16.2%]; P = .02). Five infants with breech presentations underwent a precipitous unplanned vaginal delivery. Significant morbidity was not detected in these 5 infants. Conclusion: After transfer to an antenatal ward, patients with PPROM with nonvertex presentations appear to have a significantly higher risk for prolapsed umbilical cords, lower Apgar scores, and/or lower umbilical cord blood pH values, when compared with their vertex counterparts. Additionally, there appears to be substantial risk of an unintended, vaginal breech delivery. [Copyright &y& Elsevier]

Objective: To determine whether the adjunctive administration of aminophylline and magnesium sulfate to mothers at risk for preterm birth can reduce the rate of intraventricular hemorrhage in neonates born at less than 30 weeks of gestation. Study design: A prospective study was conducted to determine whether the rate of intraventricular hemorrhage was different in patients at risk for preterm delivery treated with ritodrine, magnesium sulfate, aminophylline, and corticosteroids (group A) versus patients treated with ritodrine and corticosteroids (group B). During the study period (January 1996 to December 2001), 125 patients enrolled in the study. Treatment was assigned by alternative allocation, and the study was designed to compare the rate of intraventricular hemorrhage in neonates born before the 30th week of gestation (primary outcome), 78 newborns in group A and 68 in group B. The proportion of neonates with intraventricular hemorrhage was calculated, and data were analyzed with Student t test, χ2, and logistic regression analysis. Results: The frequency of severe respiratory distress syndrome needing surfactant replacement and high-pressure positive ventilation, patent ductus arteriosus, and retinopathy of prematurity was not different between the 2 groups. However, the rate of intraventricular hemorrhage was lower in neonates born before 30 weeks whose mothers received adjunctive aminophylline and magnesium sulphate (group A) than in the group that did not receive these 2 agents (group B). The overall frequency of intraventricular hemorrhage was 5.1% (4/78) versus 20.6% (14/68) (P <.001), and the frequency of intraventricular hemorrhage grade 3–4 was 1.3% (1/78) versus 10.3 % (7/68; P < .001), respectively. [ABSTRACT FROM AUTHOR]