Search

Background: Preterm premature rupture of membranes (PPROM) contributes to over one-third of preterm births, and PPROM infants are more susceptible to infections. However, the risk factors remain poorly understood. We here aim to investigate the association of duration of premature rupture of membranes (PROM) and environmental microbiota with the gut microbiota and infection in PPROM infants. Methods: Forty-six premature infants were recruited from two hospitals, and infant fecal and environmental samples were collected. 16 s rRNA sequencing was performed to analyze the fecal and environmental microbiome. Human inflammatory cytokines in cord vein plasma were measured. Results: The gut microbiota composition of PPROM infants was different from that of non-PPROM infants, and the microbiome phenotypes were predicted to be associated with a higher risk of infection, further evidenced by the significantly increased levels of IL-6 and IL-8 in cord vein plasma of PPROM infants. The diversity of the gut microbiota in PPROM infants increased significantly as the duration of PROM excessed 12 h, and Pseudomonas contributed significantly to the dynamic changes. The Pseudomonas species in the gut of PPROM infants were highly homologous to those detected in the ward environment, suggesting that prolonged PROM is associated with horizontal transmission of environmental pathogens, leading to a higher risk of infection. Conclusions: This study highlights that the duration of PROM is associated with the accumulation of environmental pathogens in the gut of PPROM infants, which is a risk factor for nosocomial infections. Improving environmental hygiene could be effective in optimizing the clinical care of PPROM infants.

Objective: To compare obstetrical and neonatal outcomes in patients with p-PROM (preterm premature rupture of membranes) at less than 30 weeks of gestational age before and after the application of protocols developed on the basis of international guidelines and to identify local barriers and strategies for their implementation. Study design: Single and twin pregnancies with p-PROM

Objective: The prognosis of preterm premature rupture of membranes (PPROM) combined with chorioamnionitis is often unsatisfactory for both mother and newborn. Although tragic outcomes can be avoided if treated early, no effective prediction method for decision-making is available currently. This study aimed to establish an effective method with maternal inflammation indexes to predict preterm premature rupture of membranes with concomitant chorioamnionitis. Materials and methods: This retrospective study examined the data of 206 singleton PPROM cases and 60 normal full-term cases. The PPROM cases included 93 cases of PPROM with chorioamnionitis and 113 cases of PPROM without chorioamnionitis based on clinical manifestations, laboratory examinations, and histopathological diagnosis. Normal full-term cases were included as the control group. Peripheral blood levels of selected inflammatory indicators were observed 12 h after fetal membrane rupture. Associations between selected inflammatory indicators and chorioamnionitis diagnosis were analyzed. Results: Selected factors except for procalcitonin predicted chorioamnionitis in PPROM patients. Combined results of C-reactive protein and white blood cell (WBC) count showed best predictive ability with area under curve, sensitivity, and specificity of 0.702, 60.22%, and 76.11%, respectively. Furthermore including Interleukine-6 and neutrophil count provided similar predictive results. Conclusions: The best predictive factor combinations for PPROM-CAM were C-reactive protein and white blood cell count. Results of this study provide a useful clinical reference for PPROM-CAM and may improve maternal and infant prognostic outcomes.

Objective: Prematurity is the most important prognostic factor for infants born following preterm premature rupture of membranes (PPROM). Therefore, when PPROM occurs between 22 and 33 weeks of gestation, prolonging pregnancy is recommended. Determination of management strategies requires screening for the presence of intra-amniotic infection or inflammation at the time of PPROM diagnosis. If intra-amniotic infection/inflammation is not detected, it is important to monitor the patient to diagnose any new infection/inflammation. We examined the period from PPROM to secondary intra-amniotic infection/inflammation and associated factors. Materials and methods: This retrospective study was conducted at a single facility. We examined 26 patients who experienced PPROM between 26 and 33 weeks of gestation and were negative for intra-amniotic infection/inflammation at the time of diagnosis and underwent serial amniocentesis. Antibiotic therapy comprising ampicillin, amoxicillin, and clarithromycin for 7 days was started after the first amniocentesis. The period from PPROM to secondary intra-amniotic infection/inflammation was analyzed using a Kaplan–Meier survival curve. The onset of intra-amniotic infection/inflammation was considered as the time at which amniotic fluid bacterial culture results became positive, the time when amniotic fluid Interleukin (IL)-6 increased beyond 2.6 ng/mL, or the day of delivery if histological chorioamnionitis was observed in the delivered placenta. Patients were treated as censored if no intra-amniotic infection/inflammation could be confirmed in the amniotic fluid and delivered placenta. Results: The median time from PPROM to secondary intra-amniotic infection/inflammation was 18 days. Six patients developed intra-amniotic infection/inflammation, while 13 patients without intra-amniotic infections/inflammation delivered fewer than 7 days after PPROM. No confounding factors at the time of PPROM diagnosis were associated with the time from PPROM until secondary intra-amniotic infection/inflammation. Conclusions: The time between PPROM and onset of secondary intra-amniotic infection/inflammation appears prolonged. Treatments other than antimicrobial agents may need to be added to prolong pregnancy.

BACKGROUND: Preterm premature rupture of membranes accounts for approximately one-quarter of all preterm deliveries and occurs in 2% to 3% of all pregnancies. With subclinical infection being a suspected cause of preterm premature rupture of membranes, the administration of prophylactic antibiotics is an accepted standard of care to extend the latency period. Historically, erythromycin was used in the antibiotic regimen recommended for women with preterm premature rupture of membranes during expectant management; however, azithromycin has recently been shown to be a suitable alternative. OBJECTIVE: This study aimed to evaluate whether extended azithromycin administration affects the latency time in preterm premature rupture of membranes. STUDY DESIGN: This was a retrospective multi-institutional cohort study in Washington, District of Columbia, of patients admitted from January 2012 to December 2019 with preterm premature rupture of membranes of singleton pregnancies between 23 0/7 and 33 6/7 weeks of gestation. Patients were excluded if they had multiple pregnancies, had an allergy to penicillin or macrolides, were in labor, had suspected placental abruptions, had overt chorioamnionitis, or had nonreassuring fetal status on presentation indicating the need for prompt delivery. Patients that received limited azithromycin administration (3 days (2.6 days [interquartile range, 2.2–3.1] for limited azithromycin administration vs 5.8 days [interquartile range, 4.8–6.9] for extended azithromycin administration; P

Objective: To investigate the incidence of umbilical cord prolapse (UCP) and its influence on infant prognosis in pregnant women with preterm premature rupture of membranes (PPROM). Materials and methods: We conducted a retrospective cohort study in a single tertiary perinatal center between 2009 and 2017. Singleton pregnancies with PPROM that occurred between 22 and 33 weeks of gestation were included. Infantile composite adverse outcome consisted of death, severe intraventricular hemorrhage, cystic periventricular leukomalacia, necrotizing enterocolitis, and sepsis before discharge. Infantile outcomes were compared between pregnancies that were complicated by UCP and those that were not. Results: Out of 208 singleton pregnancies included in the analysis, UCP occurred in 12 (5.8%) cases. The gestational age of pregnancies with UCP was significantly lesser than that of those without UCP. The incidence of infantile composite adverse outcome in patients with UCP was 16.7%, and this was not significantly higher than the incidence in patients without UCP (6.6%, P = 0.21). UCP was not shown to be associated with infantile composite adverse outcome in a multivariate regression model. Gestational age

Background: The reason for increased serum creatinine levels in preterm infants often remains unclear. We aimed to determine whether postnatal serum creatinine in preterm infants correlates with intake of amniotic fluid, represented by the amount of amniotic fluid after preterm premature rupture of membranes (PPROM). Methods: 74 preterm infants with PPROM > 48 h duration were retrospectively studied. Postnatal creatinine concentration was determined at day 2–5, 10–17 and 26–33 of life and compared between infants with normal intrauterine amniotic volumes, oligohydramnios and anhydramnios. Results: Mean gestational age of included patients was 29.7 weeks (range: 24.0–36.1 weeks) and mean birth weight was 1452 g (range: 560–2940 g). Serum creatinine concentration was similar at day 2–5 and day 10–17 of life between the three groups. We observed a significant decrease in creatinine concentration from day 2–5 to day 26–33 in infants with normal amniotic fluid volume and oligohydramnios (p = 0.0001 and p = 0.0071, respectively), but not in anhydramnios. On day 26–33 of life, infants with anhydramnios showed significantly higher creatinine levels compared to infants with normal amniotic fluid volume and oligohydramnios (p = 0.0211). Conclusion: Postnatal serum creatinine of preterm infants at day 26–33 of life is elevated in infants with PPROM-induced anhydramnios, but not in oligohydramnios.

Background: Diabetes mellitus is a leading cause of nephropathy and end-stage renal disease. However, diabetic nephropathy during pregnancy in patients with normal glomerular filtration rate and subsequent progression to end-stage renal disease has not been well studied. Cases: This report presents two patients with poorly controlled type 1 diabetes mellitus who had diabetic nephropathy with preserved estimated glomerular filtration rate (Case 1: 117 mL/min/1.73m2; Case 2: 79 mL/min/1.73m2) and shared a similar clinical course, with glomerular filtration rates decreasing by approximately one-half during pregnancy and progression to end-stage renal disease within the first year postpartum. Both women had a long history of type 1 diabetes: 18 years and 24 years for case 1 and case 2 respectively. The first patient's course of pregnancy was complicated by difficult-to-control blood glucose and hypertension with subsequent preeclampsia. The second patient's course of pregnancy was complicated by difficult-to-control blood sugars and preterm labor resulting in classical cesarean delivery at 24 weeks. Both patients had renal biopsies shortly after delivery as their renal function continued to worsen postpartum. Both kidney biopsies demonstrated advanced diabetic nephropathy changes and ultimately required chronic renal replacement therapy within 7–9 months postpartum. Conclusion: Comprehensive family planning discussions with women who have diabetic nephropathy should include the risks of renal disease progression, even in those patients with preserved renal function at the time of conception.

Objective: Symmetrical peripheral gangrene (SPG) is an uncommon but important clinical syndrome. We present a case of acute chorioamnionitis complicated with SPG. Case report: A 33-year-old female (gravida 5, para 2) was admitted with preterm premature rupture of membranes (PPROM) at 20 weeks and four days of gestation. She received cervical cerclage four days ago. Seven days after the diagnosis of PPROM, she developed fever, tachypnea and tachycardia. Termination of pregnancy was decided for clinical diagnosis of sepsis. After the abortus was born, gangrene change on the nose was noticed. Afterwards, this patient developed acrocyanosis of extremities. SPG developed following sepsis with intravascular disseminated coagulation (DIC). After intensive care, the patient underwent hyperbaric oxygen therapy and fasciectomy of the left forearm. Conclusion: We suggest awareness of SPG associated with acute chorioamnionitis. Early recognition of SPG, multidisciplinary care, and treatment of its underlying conditions are the mainstays of management.

Background: Brain injury and poor neurodevelopment have been consistently reported in infants and adults born before term. These changes occur, at least in part, prenatally and are associated with intra-amniotic inflammation. The pattern of brain changes has been partially documented by magnetic resonance imaging but not by neurosonography along with amniotic fluid brain injury biomarkers., Objective: This study aimed to evaluate the prenatal features of brain remodeling and injury in fetuses from patients with preterm labor with intact membranes or preterm premature rupture of membranes and to investigate the potential influence of intra-amniotic inflammation as a risk mediator., Study Design: In this prospective cohort study, fetal brain remodeling and injury were evaluated using neurosonography and amniocentesis in singleton pregnant patients with preterm labor with intact membranes or preterm premature rupture of membranes between 24.0 and 34.0 weeks of gestation, with (n=41) and without (n=54) intra-amniotic inflammation. The controls for neurosonography were outpatient pregnant patients without preterm labor or preterm premature rupture of membranes matched 2:1 by gestational age at ultrasound. Amniotic fluid controls were patients with an amniocentesis performed for indications other than preterm labor or preterm premature rupture of membranes without brain or genetic defects whose amniotic fluid was collected in our biobank for research purposes matched by gestational age at amniocentesis. The group with intra-amniotic inflammation included those with intra-amniotic infection (microbial invasion of the amniotic cavity and intra-amniotic inflammation) and those with sterile inflammation. Microbial invasion of the amniotic cavity was defined as a positive amniotic fluid culture and/or positive 16S ribosomal RNA gene. Inflammation was defined by amniotic fluid interleukin 6 concentrations of >13.4 ng/mL in preterm labor and >1.43 ng/mL in preterm premature rupture of membranes. Neurosonography included the evaluation of brain structure biometric parameters and cortical development. Neuron-specific enolase, protein S100B, and glial fibrillary acidic protein were selected as amniotic fluid brain injury biomarkers. Data were adjusted for cephalic biometrics, fetal growth percentile, fetal sex, noncephalic presentation, and preterm premature rupture of membranes at admission., Results: Fetuses from mothers with preterm labor with intact membranes or preterm premature rupture of membranes showed signs of brain remodeling and injury. First, they had a smaller cerebellum. Thus, in the intra-amniotic inflammation, non-intra-amniotic inflammation, and control groups, the transcerebellar diameter measurements were 32.7 mm (interquartile range, 29.8-37.6), 35.3 mm (interquartile range, 31.2-39.6), and 35.0 mm (interquartile range, 31.3-38.3), respectively (P=.019), and the vermian height measurements were 16.9 mm (interquartile range, 15.5-19.6), 17.2 mm (interquartile range, 16.0-18.9), and 17.1 mm (interquartile range, 15.7-19.0), respectively (P=.041). Second, they presented a lower corpus callosum area (0.72 mm 2 [interquartile range, 0.59-0.81], 0.71 mm 2 [interquartile range, 0.63-0.82], and 0.78 mm 2 [interquartile range, 0.71-0.91], respectively; P=.006). Third, they showed delayed cortical maturation (the Sylvian fissure depth-to-biparietal diameter ratios were 0.14 [interquartile range, 0.12-0.16], 0.14 [interquartile range, 0.13-0.16], and 0.16 [interquartile range, 0.15-0.17], respectively [P<.001], and the right parieto-occipital sulci depth ratios were 0.09 [interquartile range, 0.07-0.12], 0.11 [interquartile range, 0.09-0.14], and 0.11 [interquartile range, 0.09-0.14], respectively [P=.012]). Finally, regarding amniotic fluid brain injury biomarkers, fetuses from mothers with preterm labor with intact membranes or preterm premature rupture of membranes had higher concentrations of neuron-specific enolase (11,804.6 pg/mL [interquartile range, 6213.4-21,098.8], 8397.7 pg/mL [interquartile range, 3682.1-17,398.3], and 2393.7 pg/mL [interquartile range, 1717.1-3209.3], respectively; P<.001), protein S100B (2030.6 pg/mL [interquartile range, 993.0-4883.5], 1070.3 pg/mL [interquartile range, 365.1-1463.2], and 74.8 pg/mL [interquartile range, 44.7-93.7], respectively; P<.001), and glial fibrillary acidic protein (1.01 ng/mL [interquartile range, 0.54-3.88], 0.965 ng/mL [interquartile range, 0.59-2.07], and 0.24 mg/mL [interquartile range, 0.20-0.28], respectively; P=.002)., Conclusion: Fetuses with preterm labor with intact membranes or preterm premature rupture of membranes had prenatal signs of brain remodeling and injury at the time of clinical presentation. These changes were more pronounced in fetuses with intra-amniotic inflammation., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Prediction of delivery latency complicated with preterm premature rupture of membrane (PPROM) is crucial for reducing maternal and neonatal complications. Therefore, we investigated the correlations between latency period and cut-off values of ultrasonographic parameters, ultimately predicting delivery latency. Materials and methods: The retrospective study was performed on 121 PPROM patients enrolled between March 2010 and July 2015. Parameters including amniotic fluid index (AFI), single deepest pocket (SDP) and transvaginal cervical length (TVCL) were measured in 99 singleton pregnancies with PPROM. Latency was defined as the period from sonographic measurements to delivery day. The parameters were analyzed independently by Wilcoxon rank sum test and Fisher's exact test. Cut-off values were determined using a receiver operating characteristic (ROC) curve. Results: In delivery latency within 3 days, AFI and SDP were decreased with significantly shorter TVCL. AFI and SDP had the highest sensitivity (82.2%) and SDP combined with TVCL showed the highest specificity (75.9%) in area under curve (AUC) value. The predicted median latency period was less than 2 days within the cutoff value of parameter (AFI ≤ 7.72, SDP ≤ 3.2 and TVCL ≤ 1.69). Conclusion: AFI and SDP combined with TVCL could be useful predictive parameters of the latency interval from PPROM to delivery.

Objective: To investigate the changes in Doppler indices of the fetal ductus venosus (DV) and umbilical artery (UMA) after amnioinfusion in pregnant women with preterm premature rupture of membranes (pPROM). Pregnancies with pPROM and severe oligohydramnios cause sequelae in newborns and mothers. Materials and Methods: This cross-sectional study included a group of 25 patients with pPROM before 26 weeks' gestation. Color Doppler imaging was used to measure the impedance index and quantitative blood flow in the DV and systolic/diastolic ratio (S/D) of the UMA before and 30 minutes after the end of amnioinfusion. The following velocity parameters were measured: (1) DV peak systolic velocity; (2) DV time-averaged velocity; (3) DV maximum forward velocity during atrial contraction; (4) DV S/D; (5) DV pulsatility index (PI); (6) DV Pourcelot's resistance index (RI); (7) fetal heart rate; and (8) UMA S/D. Results: Twenty-one of the 25 patients underwent a total of 27 amnioinfusions. The mean PI and RI of the DV, and S/D of the DV and UMA decreased significantly after amnioinfusion (PI, 0.75 ± 0.24 vs. 0.60 ± 0.18, p = 0.009; RI, 0.60 ± 0.15 vs. 0.50 ± 0.13; DV S/D, 3.07 ± 1.81 vs. 2.13 ± 0.66, p = 0.008; UMA S/D, 3.58 ± 0.87 vs. 2.88 ± 0.62, p = 0.001). Conclusion: Amnioinfusion increases the space for the fetuses and reduces the impedance of the fetoplacental circulation. Improvements in DV and UMA flow may benefit fetuses suffering severe oligohydramnios in mid-pregnancy.

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., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

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-F 2α , 2,3-dinor-5,6-dihydro-8-iso-prostaglandin-F 2α (F 2 -IsoP-M; the major 8-iso-prostaglandin-F 2α metabolite), and prostaglandin-F 2α 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 F 2 -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-F 2α 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-F 2α , F 2 -IsoP-M, and prostaglandin-F 2α in urine, was associated with increased odds of preterm birth, particularly preterm birth of spontaneous origin and delivery before 34 completed weeks of gestation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To assess the relationship between the first-trimester maternal serum pregnancy-associated plasma protein-A (PAPP-A) levels and pregnancies complicated by preterm delivery. Materials and Methods: The correlation between PAPP-A levels and gestational age at delivery was analyzed by linear regression. The probabilities of low PAPP-A multiples of the median (MoM) levels between preterm delivery and control population were analyzed by logit model. Results: A positive correlation was noted between the first-trimester PAPP-A MoM levels and gestational age at delivery between 34–38 weeks (p < 0.001). Lower PAPP-A MoM level had a significantly higher likelihood of preterm delivery (p < 0.05). When preterm premature rupture of membranes (PPROM) and preterm labor (PTL) were analyzed separately, there was an increasing likelihood of PPROM with decreasing PAPP-A MoM levels (p < 0.05), but not for PTL with intact membranes. Conclusion: Low maternal serum PAPP-A levels during the first trimester may reflect a trophoblast invasion defect in the maternal-fetal interface, resulting in subsequent preterm delivery, particularly in those of PPROM.

Objective: To evaluate the efficacy and safety of aggressive management of oligohydramnios. Methods: Forty women with oligohydramnios (< 30 complete weeks), either because of preterm premature rupture of membranes or with intact membranes, were prospectively enrolled in this study. Eleven women were assigned to the treatment group and 29 to the control group. Transabdominal amnioinfusion was performed with warm Ringer's lactate or normal saline in all 11 patients in the treatment group. In addition, cerclage was performed in patients with ruptured amniotic membranes. Amniopatch was used to salvage a patient with immediate amniorrhea (< 6 hours) after the above procedures. Results: Nine of the 11 patients prolonged their pregnancy for at least 3 weeks (81.8%), while all 29 patients in the control group delivered their babies within 3 weeks of diagnosis of oligohydramnios (p < 0.05). Signs of maternal infection were noted in two patients in the treatment group (18.2%). The newborns of eight patients in the treatment group survived beyond 1 month (72.7%), whereas this occurred in only six control patients (20.7%; p < 0.05). Conclusion: Aggressive management seemed to provide prolongation of pregnancy compared with no treatment. Amniopatch salvaged the immediate amniorrhea in our patient.

Objective: The prognosis of preterm premature rupture of membranes (PPROM) combined with chorioamnionitis is often unsatisfactory for both mother and newborn. Although tragic outcomes can be avoided if treated early, no effective prediction method for decision-making is available currently. This study aimed to establish an effective method with maternal inflammation indexes to predict preterm premature rupture of membranes with concomitant chorioamnionitis., Materials and Methods: This retrospective study examined the data of 206 singleton PPROM cases and 60 normal full-term cases. The PPROM cases included 93 cases of PPROM with chorioamnionitis and 113 cases of PPROM without chorioamnionitis based on clinical manifestations, laboratory examinations, and histopathological diagnosis. Normal full-term cases were included as the control group. Peripheral blood levels of selected inflammatory indicators were observed 12 h after fetal membrane rupture. Associations between selected inflammatory indicators and chorioamnionitis diagnosis were analyzed., Results: Selected factors except for procalcitonin predicted chorioamnionitis in PPROM patients. Combined results of C-reactive protein and white blood cell (WBC) count showed best predictive ability with area under curve, sensitivity, and specificity of 0.702, 60.22%, and 76.11%, respectively. Furthermore including Interleukine-6 and neutrophil count provided similar predictive results., Conclusions: The best predictive factor combinations for PPROM-CAM were C-reactive protein and white blood cell count. Results of this study provide a useful clinical reference for PPROM-CAM and may improve maternal and infant prognostic outcomes., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

Recently, two randomized controlled, prospective trials, the Tracheal Occlusion to Accelerate Lung Growth (TOTAL) trials, reported the outcomes on fetal endoluminal tracheal occlusion (FETO) for isolated left congenital diaphragmatic hernia (CDH). FETO significantly improved outcomes for severe hypoplasia. The effect in moderate cases, where the balloon was inserted later in pregnancy, did not reach significance. In a pooled analysis investigating the effect of the heterogeneity of the treatment effect by the time point of occlusion and severity, the difference may be explained by a difference in the duration of occlusion. Nevertheless, FETO carries a significant risk of preterm birth. The primary objective of this review is to provide an overview of the rationale for fetal intervention in CDH and the results of the randomized trials. The secondary objective is to discuss the technical aspects of FETO. Finally, recent developments of potential alternative fetal approaches will be highlighted., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Maternal glucocorticoid exposure increases the risk of preterm delivery; however, the association between glucocorticoids and preterm premature rupture of membranes (pPROM)-a direct cause of preterm delivery-has rarely been investigated., Methods: To examine this association, we evaluated the clinical data of patients with systemic lupus erythematosus (SLE). Mechanism analysis was performed in both human amnion-derived mesenchymal cells (as a model for fetal membranes) and the amnion from SLE patients. We characterized the effects of glucocorticoids on the amnion in both models through comprehensive gene expression profiling and by electric cell-substrate impedance sensing in the mesenchymal cells., Results: The average glucocorticoid dose in cases with pPROM (13.3 mg/day, n = 10) was significantly higher than in those without pPROM (8.5 mg/day, n = 65; P < 0.01) among pregnant patients with well-controlled SLE (SLEDAI <4, n = 75); however, we did not observe a statistically significant difference in it between cases with or without chorioamnionitis. Glucocorticoid-treated human amnion mesenchymal cells showed decreased electric resistance between cells, indicating increased permeability. Differentially expressed genes upon glucocorticoid treatment were significantly enriched with cell adhesion-related genes. Among them, ITGA8 was strikingly induced in both the amnion mesenchymal cells and in amnion derived from patients with SLE., Discussion: We observed an association between glucocorticoids and pPROM with non-infectious etiology. Our findings indicate that glucocorticoids increase amnion permeability and modulate cell-adhesion related genes. ITGA8 represents a primary molecule that triggers pPROM through fibrotic remodeling and preventing resealing of the rupture site in fetal amnion., Competing Interests: Declaration of competing interest None., (Copyright © 2022. Published by Elsevier Ltd.)

Objective: Prematurity is the most important prognostic factor for infants born following preterm premature rupture of membranes (PPROM). Therefore, when PPROM occurs between 22 and 33 weeks of gestation, prolonging pregnancy is recommended. Determination of management strategies requires screening for the presence of intra-amniotic infection or inflammation at the time of PPROM diagnosis. If intra-amniotic infection/inflammation is not detected, it is important to monitor the patient to diagnose any new infection/inflammation. We examined the period from PPROM to secondary intra-amniotic infection/inflammation and associated factors., Materials and Methods: This retrospective study was conducted at a single facility. We examined 26 patients who experienced PPROM between 26 and 33 weeks of gestation and were negative for intra-amniotic infection/inflammation at the time of diagnosis and underwent serial amniocentesis. Antibiotic therapy comprising ampicillin, amoxicillin, and clarithromycin for 7 days was started after the first amniocentesis. The period from PPROM to secondary intra-amniotic infection/inflammation was analyzed using a Kaplan-Meier survival curve. The onset of intra-amniotic infection/inflammation was considered as the time at which amniotic fluid bacterial culture results became positive, the time when amniotic fluid Interleukin (IL)-6 increased beyond 2.6 ng/mL, or the day of delivery if histological chorioamnionitis was observed in the delivered placenta. Patients were treated as censored if no intra-amniotic infection/inflammation could be confirmed in the amniotic fluid and delivered placenta., Results: The median time from PPROM to secondary intra-amniotic infection/inflammation was 18 days. Six patients developed intra-amniotic infection/inflammation, while 13 patients without intra-amniotic infections/inflammation delivered fewer than 7 days after PPROM. No confounding factors at the time of PPROM diagnosis were associated with the time from PPROM until secondary intra-amniotic infection/inflammation., Conclusions: The time between PPROM and onset of secondary intra-amniotic infection/inflammation appears prolonged. Treatments other than antimicrobial agents may need to be added to prolong pregnancy., (Copyright © 2022. Published by Elsevier B.V.)

Objective: To investigate the incidence of umbilical cord prolapse (UCP) and its influence on infant prognosis in pregnant women with preterm premature rupture of membranes (PPROM)., Materials and Methods: We conducted a retrospective cohort study in a single tertiary perinatal center between 2009 and 2017. Singleton pregnancies with PPROM that occurred between 22 and 33 weeks of gestation were included. Infantile composite adverse outcome consisted of death, severe intraventricular hemorrhage, cystic periventricular leukomalacia, necrotizing enterocolitis, and sepsis before discharge. Infantile outcomes were compared between pregnancies that were complicated by UCP and those that were not., Results: Out of 208 singleton pregnancies included in the analysis, UCP occurred in 12 (5.8%) cases. The gestational age of pregnancies with UCP was significantly lesser than that of those without UCP. The incidence of infantile composite adverse outcome in patients with UCP was 16.7%, and this was not significantly higher than the incidence in patients without UCP (6.6%, P = 0.21). UCP was not shown to be associated with infantile composite adverse outcome in a multivariate regression model. Gestational age <25 weeks at delivery was significantly associated with infantile composite adverse outcome., Conclusions: The incidence of UCP was 5.8% among singleton pregnancies, with PPROM being managed expectantly between 22 and 33 weeks' gestation. Preterm UCP may not be associated with infantile adverse outcomes provided emergency cesarean delivery is available at all time., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

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., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: To investigate the role of thrombospondin motifs 9 (ADAMTS9) in preterm premature rupture of membranes (pPROM)., Materials and Methods: ADAMTS9 levels were measured in amnion cells from 24 patients of different groups (preterm vs. full-term birth, with vs. without PROM). ADAMTS9 was suppressed in human amnioblasts to investigate its effects on embryonic membrane cells and inflammation-induced cell damage. Pregnant mouse models were used to assess whether inflammation regulates ADAMTS9 by upregulating TNF-α and IL-6, contributing to the preterm birth occurrence., Key Findings: We found that ADAMTS9 protein and gene expression levels significantly differed among various groups (pPROM > full-term PROM > preterm non-PROM > full-term non-PROM). After ADAMTS9 suppression in human amnioblast WISH cells, TNF-α- and IL-6-induced apoptosis was decreased. In addition, TNF-α, IL-6, and ADAMTS9 protein and gene expression levels were increased in the embryos of mice treated with LPS compared with controls. In agreement, the rate of preterm birth was higher in the LPS group compared with controls., Significance: Taken together, these in vitro and in vivo findings suggest that TNF-α and IL-6 secreted by macrophages during inflammation regulate ADAMTS9 and induce pPROM., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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)., (Copyright © 2020. Published by Elsevier Inc.)

Background: The reason for increased serum creatinine levels in preterm infants often remains unclear. We aimed to determine whether postnatal serum creatinine in preterm infants correlates with intake of amniotic fluid, represented by the amount of amniotic fluid after preterm premature rupture of membranes (PPROM)., Methods: 74 preterm infants with PPROM > 48 h duration were retrospectively studied. Postnatal creatinine concentration was determined at day 2-5, 10-17 and 26-33 of life and compared between infants with normal intrauterine amniotic volumes, oligohydramnios and anhydramnios., Results: Mean gestational age of included patients was 29.7 weeks (range: 24.0-36.1 weeks) and mean birth weight was 1452 g (range: 560-2940 g). Serum creatinine concentration was similar at day 2-5 and day 10-17 of life between the three groups. We observed a significant decrease in creatinine concentration from day 2-5 to day 26-33 in infants with normal amniotic fluid volume and oligohydramnios (p = 0.0001 and p = 0.0071, respectively), but not in anhydramnios. On day 26-33 of life, infants with anhydramnios showed significantly higher creatinine levels compared to infants with normal amniotic fluid volume and oligohydramnios (p = 0.0211)., Conclusion: Postnatal serum creatinine of preterm infants at day 26-33 of life is elevated in infants with PPROM-induced anhydramnios, but not in oligohydramnios., (Copyright © 2020. Published by Elsevier B.V.)

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., (Copyright © 2019. Published by Elsevier Inc.)

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 χ 2 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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Prediction of delivery latency complicated with preterm premature rupture of membrane (PPROM) is crucial for reducing maternal and neonatal complications. Therefore, we investigated the correlations between latency period and cut-off values of ultrasonographic parameters, ultimately predicting delivery latency., Materials and Methods: The retrospective study was performed on 121 PPROM patients enrolled between March 2010 and July 2015. Parameters including amniotic fluid index (AFI), single deepest pocket (SDP) and transvaginal cervical length (TVCL) were measured in 99 singleton pregnancies with PPROM. Latency was defined as the period from sonographic measurements to delivery day. The parameters were analyzed independently by Wilcoxon rank sum test and Fisher's exact test. Cut-off values were determined using a receiver operating characteristic (ROC) curve., Results: In delivery latency within 3 days, AFI and SDP were decreased with significantly shorter TVCL. AFI and SDP had the highest sensitivity (82.2%) and SDP combined with TVCL showed the highest specificity (75.9%) in area under curve (AUC) value. The predicted median latency period was less than 2 days within the cutoff value of parameter (AFI ≤ 7.72, SDP ≤ 3.2 and TVCL ≤ 1.69)., Conclusion: AFI and SDP combined with TVCL could be useful predictive parameters of the latency interval from PPROM to delivery., (Copyright © 2018. Published by Elsevier B.V.)

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Diagnosis of chorioamnionitis (CA) is difficult because all clinical and biological signs are rarely concordant. According to recent literature, PCT could act as a specific marker of bacterial infection. Our main objective was to assess whether PCT could improve our management of patients with preterm premature rupture of membranes (pPROM), allowing earlier and more specific diagnosis for CA., Methods: Patients with pPROM from 24 and 34weeks of amenorrhea were included, from November 2013 to October 2014. PCT was collected twice a week, from pPROM until delivery. Obstetricians were blinded from PCT results, in order not to influence the management of the patients. PCT values were then compared to clinical and other biological diagnostic markers (CRP and white blood cells count [WBC])., Results: Thirty patients were included, with 11 cases of histological CA and 5 early-onset neonatal sepsis. With a cut-off value of 0.05ng/mL, the sensitivity of PCT to detect histological CA was 54%, the specificity was 79% and the positive and negative predictive value were respectively 60% and 75%. The positive likelihood ratio was 2.57 and the negative likelihood ratio was 0.58. Using PCT values, our medical decision of foetal extraction would have change in 5 cases (in a wrong way in 3 of them)., Conclusion: PCT in the diagnostic of CA is not useful in the management of patients., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Compare the maternal and neonatal outcomes in pregnancies complicated by preterm prelabour rupture of membranes (PPROM), which were managed either at home (HAD) or hospital (HC)., Materials and Methods: Retrospective study in two level III maternities during 2 years. Inclusion criteria in HAD were: singleton pregnancy, PPROM between 24 and 35 weeks of gestation, absence of chorioamnionitis, clinical stability at D7 of the rupture, cervical dilatation <3 cm, patient residing in the geographic area., Results: Thirty-two patients were included in the HAD group and 24 in the HC group. Our populations were similar in the 2 groups. The duration of latency was longer in the HAD group than in the HC group (27.5 d [20-37] versus 16.5 d [12.5 to 29.5]; P=0.026). Patients in the HAD group received fewer antibiotics with a similar rate of chorioamnionitis. No difference in terms of obstetrical and neonatal outcomes was observed. Number of days in neonatal resuscitation was lower in the HAD group than in the HC group (12.5 d [10-22] versus 43 d [20-52]; P=0.003)., Conclusion: HAD seems to be an alternative to continuous hospitalization for patients followed for PPROM between 24 and 35 weeks. A randomized study with a larger number of patients, including other data such as maternal satisfaction and cost analysis, would be interesting to confirm those preliminary results., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Introduction: We investigated the ability of cryopreserved human amniotic membrane (hAM) scaffold sealed with an underwater adhesive, bio-inspired by marine sandcastle worms to promote healing of iatrogenic fetal membrane defects in a pregnant swine model., Methods: Twelve Yucatan miniature pigs underwent laparotomy under general anesthesia at 70 days gestation (term = 114 days). The gestational sacs were assigned to uninstrumented (n = 24) and instrumented with 12 Fr trocar, which was further randomized into four different arms-no hAM patch, (n = 22), hAM patch secured with suture (n = 16), hAM patch with no suture (n = 14), and hAM patch secured with adhesive (n = 9). The animals were euthanized 20 days after the procedure. Gross and histological examination of the entry site was performed for fetal membrane healing., Results: There were no differences in fetal survival, amniotic fluid levels, or dye-leakage from the amniotic cavity between the groups. The fetal membranes spontaneously healed in instrumented sacs without hAM patches. In sacs with hAM patches secured with sutures, the patch was incorporated into the swine fetal membranes. In sacs with hAM patches without sutures, 100% of the patches were displaced from the defect site, whereas in sacs with hAM patches secured with adhesive 55% of the patches remained in place and showed complete healing (p = 0.04)., Discussion: In contrast to humans, swine fetal membranes heal spontaneously after an iatrogenic injury and thus not an adequate model. hAM patches became incorporated into the defect site by cellular ingrowth from the fetal membranes. The bioinspired adhesive adhered the hAM patches within the defect site., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Insulin-like growth factor binding protein-1 (IGFBP-1) constitutes a subgroup of the insulin-like growth factor binding protein systems, and its concentration in amniotic fluid is 100-1000 times higher than the concentration in other body fluids. The aim of this study was to evaluate the clinical application of a novel method immunomagnetic reduction (IMR) for quantitative measurement of IGFBP-1 concentrations in the cervicovaginal secretions to diagnose pregnant women with preterm premature rupture of membranes (PPROM)., Methods: We established a standard calibration curve of IMR intensity against IGFBP-1 concentration based on standard IGFBP-1 samples. We used the IMR assay to detect IGFBP-1 concentrations in the cervicovaginal secretions of pregnant women which were divided into two groups according to the presence or absence of PPROM., Results: The calibration curve extended from 0.1ng/mL to 10000ng/mL with an excellent correlation (R(2)=0.999). Twenty-two pregnant women between 22 and 34weeks of gestation were analyzed in this prospective study, of whom 10 were clinical evidence of PPROM, and 12 were intact membranes. Through the analysis of receiver-operating characteristic curve, the cut-off point for IMR to differentiate intact membranes from PPROM is 1.015%, which resulted in 90.0, 83.3, 81.8, and 90.9% for sensitivity, specificity, positive predictive value, and negative predictive value, respectively., Conclusions: It is evidenced that IMR assay can quantitatively analyze IGFBP-1 concentrations, and the results show the possibility to diagnose pregnant women with PPROM by IMR assay., (Copyright © 2014 Elsevier B.V. All rights reserved.)

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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

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., (Published by Elsevier Inc.)

Introduction: Nicotinamide adenine dinucleotide phosphate oxidases (NOX 1-5) are enzymes that generate cellular reactive oxygen species (ROS) besides mitochondria and might be important ROS sources associated with pregnancy complications, particularly preterm premature rupture of membranes (pPROM), that has been related to ROS., Objective: To characterize NOX enzymes expression in human fetal membranes., Methods: Differential expression and localization of NOX isoforms in human fetal membranes collected from women with uncomplicated pregnancies at term, preterm birth (PTB) or pPROM and in vitro in normal term membranes maintained in an organ explant system stimulated with water-soluble cigarette smoke extract (wsCSE) were documented by real time PCR and immunohistochemistry., Results: Fetal membranes from term deliveries, PTB and pPROM expressed NOX 2, 3 and 4 mRNAs whereas NOX 1 and 5 were not detected. NOX 2 expression was 2.3-fold higher in PTB than pPROM (p = 0.005) whereas NOX 3 was 2.2-fold higher in pPROM compared to PTB (p = 0.04). NOX 2 and 3 expressions at term mimicked pPROM and PTB, respectively. No difference in NOX 4 expression was observed among the studied groups. NOX 2, 3 and 4 were localized to both amniotic and chorionic cells. Expression of NOX 2, 3 and 4 were not significant in wsCSE-stimulated membranes compared to untreated controls., Discussion/conclusions: NOX enzymes are present in the fetal membranes and are differentially expressed in PTB and pPROM. Absence of any changes in NOXs expression after wsCSE stimulation suggests ROS generation in the membranes does not always correlate with NOX expression., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

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 © 2013 Mosby, Inc. All rights reserved.)