BACKGROUND: Induction of labor (IOL) is recommended following prelabor rupture of membranes (PROM). The optimal method for IOL and need for cervical ripening in those with PROM and an unfavorable cervical examination is unclear.
OBJECTIVE: To determine if oxytocin or oral misoprostol results in a shorter time to delivery among nulliparous patients with an unfavorable cervical examination and PROM diagnosis and to evaluate patient satisfaction with both methods.
METHODS: This is a randomized clinical trial conducted at an urban tertiary care center from 2019 to 2023. Subjects were nulliparas ≥36 weeks with an unfavorable starting cervical exam (≤2 cm and Bishop <8). The primary outcome was time from IOL to delivery in hours compared between oxytocin vs oral misoprostol. Secondary outcomes included suspected intraamniotic infection, cesarean delivery, composite maternal and neonatal morbidity, and patient satisfaction (assessed by Birth Satisfaction Scale-Revised). Sub-group analyses for those with BMI ≥ 30 kg/m2 and cervical dilation ≥1 cm were performed. We required 148 subjects to have 80% power to detect a 2-hour difference in time to delivery. The study was stopped early by the data safety monitoring board due to feasibility concerns in recruiting desired sample size.
RESULTS: A total of 108 subjects were randomized: 56 oxytocin; 52 oral miso. The median gestational age at induction was 39.5 weeks; the mean starting cervical dilation was 1.1 cm. There was no statistical difference in time to delivery between groups overall: 14.9 hours oxytocin vs 18.1 hours oral misoprostol (P=.06). In sub-group analyses, there was a 5 hours shorter time to delivery with oxytocin for those with a BMI ≥ 30 kg/m2 (16.6 hours oxytocin vs 21.8 hours oral misoprostol, P .04) and 4.5 hours shorter time to delivery with oxytocin for those with cervix ≥1 cm (12.9 hours oxytocin vs 17.3 hours oral misoprostol, P .04). There were no differences in intraamniotic infection, cesarean delivery, maternal or neonatal morbidity between the groups. Patient satisfaction was higher for those receiving oxytocin compared to misoprostol (29.0 vs 26.3, P=.03).
CONCLUSIONS: Among nulliparas with PROM and an unfavorable cervix, there was no difference in overall time to delivery between oxytocin and oral misoprostol. This result should be interpreted with caution given early study discontinuation and inadequate power. However, a shorter time to delivery with oxytocin was noted in obese patients and those with cervical dilation of at least 1 cm. Furthermore, patient satisfaction was higher in the oxytocin group, and there was no increased risk of neonatal or maternal morbidity with oxytocin.

OBJECTIVE: To determine whether equivocal prelabor rupture of membranes (PROM) cases are associated with adverse outcomes.
METHODS: A retrospective study was conducted in a tertiary medical center between July 2012 and March 2022. The cohort comprised all women diagnosed with term PROM (≥37 gestational weeks), divided into two groups. (1) Certain PROM-suggestive history of a watery vaginal discharge confirmed by visualization of fluid leaking from the cervix or pooling in the vagina on speculum examination. (2) Uncertain PROM-suggestive history of a watery vaginal discharge not supported by speculum examination. All patients were hospitalized and gave birth spontaneously or following either expectant management for up to 24 h from PROM or induction. The primary outcome measure was cesarean delivery (CD) rate. Secondary outcome measures were adverse maternal/neonatal events.
RESULTS: Of the 2012 women included in the study, 1750 had certain PROM and 262 uncertain PROM. CD rate was 5.8% in the certain PROM group and 8.8% in the uncertain PROM group; the difference was not statistically significant (P = 0.074). There was a significant between-group difference in the rate of CD due to failed induction on univariate analysis (0.69% vs 2.67%, respectively, P = 0.007), but it was not maintained on multivariate logistic regression (odds ratio 0.37, 95% confidence interval: 0.12-1.17). Other maternal and neonatal outcomes were similar in the two groups.
CONCLUSIONS: Our findings indicate that following the same management guidelines for equivocal cases of ruptured membranes as for confirmed cases of term PROM did not compromise maternal or fetal outcomes.

Although there is growing awareness of the relationship between air pollution and preterm birth, limited data exist regarding the relationship with spontaneous preterm birth and severe neonatal outcomes.
This study aimed to examine the association between traffic-associated air pollution exposure in pregnancy and adverse perinatal outcomes including extremes of preterm birth, neonatal intensive care unit admissions, low birthweight, neonatal respiratory diagnosis, neonatal respiratory support, and neonatal sepsis evaluation.
This was a retrospective cohort study of singleton pregnancies of patients residing in a metropolitan area in the southern United States. Using monitors strategically located across the region, average nitrogen dioxide concentrations were obtained from the Environmental Protection Agency Air Quality System database. For patients living within 10 miles of a monitoring station, average exposure to nitrogen dioxide was estimated for individual patients\' pregnancy by trimester. Logistic regression models were used to assess the effect of pollutant exposure on gestational age at birth, indicated vs spontaneous delivery, and neonatal outcomes while adjusting for maternal age, self-reported race, parity, season of conception, diabetes mellitus, body mass index, registered Health Equity Index, and nitrogen dioxide monitor region. Adjusted odds ratios and 95% confidence intervals were calculated for an interquartile increase in average nitrogen dioxide exposure.
Between January 1, 2013 and December 31, 2021, 93,164 patients delivered a singleton infant. Of these, 62,189 had measured nitrogen dioxide exposure during the pregnancy from a nearby monitoring station. Higher average nitrogen dioxide exposure throughout pregnancy was significantly associated with preterm birth (adjusted odds ratio, 1.94; 95% confidence interval, 1.77-2.12) and an increase in neonatal intensive care unit admissions, low birthweight infants, neonatal respiratory diagnosis, neonatal respiratory support, and neonatal sepsis evaluation. This relationship persisted for nulliparous patients and spontaneous preterm birth, and had a greater association with earlier preterm birth.
In a metropolitan area, increased exposure to the air pollutant nitrogen dioxide in pregnancy was associated with spontaneous preterm birth and had a greater association with extremely preterm birth. A greater association with neonatal intensive care unit admissions, low-birthweight infants, neonatal respiratory diagnosis, neonatal respiratory support, and neonatal sepsis evaluation was found even in term infants.

BACKGROUND: The findings of the association of vaginal flora with preterm birth (PTB) or prelabor rupture of membranes (PROM) were conflicts. Moreover, vaginal flora was different by ethnicity and the evidence from China was limited.
METHODS: This study was a nested case control study, based on Yiwu birth cohort. We assessed vaginal microbiota in the second or third trimester, using 16S rDNA Amplicon Sequencing and explored the association between the diversity and composition of vaginal flora and PTB or PROM.
RESULTS: We finally included 144 pregnant women. In present study, the alpha diversity of TPROM (Term prelabor rupture of membranes) samples was lower than that of full term samples (Chao1 index: P < 0.05). When we further categorized PTB (Preterm birth) into SPB (PTB without PROM) and PPROM (Preterm prelabor rupture of membranes), there was no difference between SPB and full term. In addition, we found that the proportion of PCoA2 in TPROM group was different from that in full term group and preterm group. The difference between groups was significant according to anosim analysis (R = 0.059, P < 0.001). With LEfSe (Linear discriminant analysis Effect Size) analysis, we found that the abundance of Lactobacillus in the vaginal flora of pregnant women with preterm birth was the highest (P = 0.003).
CONCLUSIONS: In Chinese pregnant women, the alpha diversity in TPROM group was significantly lower than that in both PTB and full term group. However, there was no difference between PTB and full term. Lactobacillus was the most abundant in preterm birth group. More studies should be conducted to confirm our findings.

OBJECTIVE: Deep learning is applied in medicine mostly due to its state-of-the-art performance for diagnostic imaging. Supervisory authorities also require the model to be explainable, but most explain the model after development (post hoc) instead of incorporating explanation into the design (ante hoc). This study aimed to demonstrate a human-guided deep learning with ante-hoc explainability by convolutional network from non-image data to develop, validate, and deploy a prognostic prediction model for PROM and an estimator of time of delivery using a nationwide health insurance database.
METHODS: To guide modeling, we constructed and verified association diagrams respectively from literatures and electronic health records. Non-image data were transformed into meaningful images utilizing predictor-to-predictor similarities, harnessing the power of convolutional neural network mostly used for diagnostic imaging. The network architecture was also inferred from the similarities.
RESULTS: This resulted the best model for prelabor rupture of membranes (n=883, 376) with the area under curves 0.73 (95% CI 0.72 to 0.75) and 0.70 (95% CI 0.69 to 0.71) respectively by internal and external validations, and outperformed previous models found by systematic review. It was explainable by knowledge-based diagrams and model representation.
CONCLUSIONS: This allows prognostication with actionable insights for preventive medicine.

It is debated whether fetal endoscopic tracheal occlusion (FETO) is beneficial to fetuses with congenital diaphragmatic hernia (CDH) and whether FETO has different effects in moderate and severe CDH. We conducted a systematic review and meta-analysis including the latest evidence to assess the overall effects of FETO on clinical outcomes of CDH.
We searched PubMed, EMBASE, The Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database and Wanfang Database to retrieve eligible studies published before 8 September 2022. No language or study design restrictions were applied. Studies were included if CDH fetuses underwent FETO surgery and were compared with a cohort that underwent expectant management, with at least one outcome reported. The primary outcomes were mortality at 1, 6 and 12 months after birth, rates of pulmonary hypertension, use of extracorporeal membrane oxygenation (ECMO) and prematurity. Meta-analysis was conducted to obtain pooled odds ratios (ORs) and mean differences. The quality of included studies and pooled evidence was also assessed.
A total of 1187 CDH fetuses from 20 studies were included in the quantitative synthesis. FETO significantly reduced 1-month (OR, 0.56 (95% CI, 0.34-0.93); P = 0.02, number needed to treat (NNT) = 7.67) and 6-month (OR, 0.34 (95% CI, 0.18-0.65); P = 0.0009, NNT = 5.26) CDH mortality (moderate/low quality of evidence). Subgroup analysis suggested that the effects of FETO on the rates of pulmonary hypertension and ECMO usage were significant in severe CDH (low/moderate quality of evidence) but not in moderate CDH (low/very low quality of evidence). FETO was also associated with an increased risk of preterm prelabor rupture of membranes before 37 weeks\' gestation (OR, 4.94 (95% CI, 2.25-10.88); P < 0.0001, number needed to harm (NNH) = 3.13) and preterm birth before 37 weeks (OR, 5.24 (95% CI, 3.33-8.23); P < 0.00001, NNH = 2.79) (high/moderate quality of evidence). However, FETO was not associated with severe complications, such as preterm birth before 32 weeks, placental abruption or chorioamnionitis (very low/low quality of evidence).
FETO is associated with a reduction in mortality, rate of pulmonary hypertension and ECMO usage in severe CDH, while it reduces only the risk of mortality in moderate CDH. Although FETO increases the risk of late prematurity, it does not result in extreme prematurity. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

OBJECTIVE: To compare maternal and neonatal outcomes between oxytocin and vaginal misoprostol induction in women with term prelabor rupture of membranes (PROM) and unfavorable cervixes.
METHODS: In this retrospective study, 589 pregnant women with term singleton fetuses in cephalic presentation, reactive nonstress tests, PROM of 2-24 h duration, Bishop score <6, and no previous uterine surgery were reviewed and divided into oxytocin (n = 301) and misoprostol (n = 288) groups. The primary outcomes were the rate of vaginal delivery and delivery within 24 h.
RESULTS: After 24 h of induction, the misoprostol group showed a significantly higher proportion of vaginal delivery (64.6% vs. 49.5%, P < 0.001) and a lower cesarean section delivery rate (11.5% vs. 25.2%, P < 0.001) than the oxytocin group. More primiparas in the misoprostol group achieved vaginal delivery within 24 h than in the oxytocin group (60.5% vs. 45.4%, P = 0.001). Among primiparas, the misoprostol group had a significantly lower cesarean delivery rate (12.6% vs. 27.5%, P < 0.001).
CONCLUSIONS: Vaginal misoprostol induction in term PROM gravidas with unfavorable cervixes was associated with lower cesarean section and higher vaginal delivery rates within 24 h than oxytocin infusion. Vaginal misoprostol and oxytocin infusion had similar maternal and neonatal outcomes.

In 10% of term deliveries and 40% of preterm deliveries, the fetal membrane (FM) ruptures before labor. However, the ability to predict these cases of premature rupture of membranes (PROM) and preterm premature rupture of membranes (PPROM) is very limited. In this paper, our objective was to determine whether a prediction method based on T2 weighted magnetic resonance imaging (MRI) of the supra-cervical FM could predict PROM and PPROM.
This prospective cohort study enrolled 77 women between the 28th and 37th weeks of gestation. Two indicators of fetal membrane defects, including prolapsed depth >5 mm and signal abnormalities, are investigated for our prediction. Fisher\'s exact test was used to determine whether prolapsed depth >5 mm and/or signal abnormalities were associated with PROM and PPROM. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for prolapsed depth >5 mm, signal abnormalities, and the combination of prolapsed depth >5 mm and signal abnormalities.
Among 12 women with PROM (5 preterm and 7 term, prior to labor onset), 9 had membrane prolapse >5 mm and 5 had FM signal abnormalities. Among 65 women with rupture of membranes at term, 2 had membrane prolapse >5 mm and 1 had signal abnormalities. By Fisher\'s exact test both indicators, membrane prolapse >5 mm and signal abnormalities, were associated with PROM (P<0.001, P<0.001) and PPROM (P=0.001, P<0.001). Additionally, membrane prolapse >5 mm, signal abnormalities, and the combination of the two indicators all demonstrated high specificity for predicting PROM (96.9%, 98.5%, and 100%, respectively) and PPROM (90.3%, 97.2%, and 100%, respectively).
MRI can distinguish the supra-cervical fetal membrane in vivo and may be able to identify women at high risk of PPROM.

In the case of prelabor rupture of membranes at term, the risk for neonatal and maternal infectious morbidity increases progressively with time from prelabor rupture of membranes. Although most studies identified a benefit associated with early induction within the first 24 hours following term prelabor rupture of membranes, there is currently no precise data regarding how early should induction be scheduled.
This study aimed to identify the optimal timing of labor induction among women with term prelabor rupture of membranes by comparing the maternal and neonatal outcomes associated with labor induction with those of expectant management at any given 1-hour interval following prelabor rupture of membranes.
This was a secondary analysis of data from the TERMPROM trial, an international, multicenter, randomized clinical trial on immediate delivery vs expectant management of women with prelaor rupture of membranes at term (≥37+0/7 weeks\' gestation). We considered all participants as a single cohort of women with term prelabor rupture of membranes, irrespective of the original randomized study group allocation. For each given 1-hour time interval within the first 36 hours following prelabor rupture of membranes, we compared the outcomes of subjects for whom labor induction was initiated during this interval with those of subjects managed expectantly at the same time interval. The primary neonatal outcome was a composite of neonatal infection and admission to the neonatal intensive care unit. The primary maternal outcomes included maternal infection (clinical chorioamnionitis or postpartum fever) and cesarean delivery.
Of the 4742 subjects who met the study criteria, 2622 underwent labor induction, and 2120 experienced a spontaneous onset of labor. The rates of the neonatal composite outcome, neonatal admission to intensive care unit, and maternal infection increased progressively with time after prelabor rupture of membranes. The risk for these outcomes was lower among women who underwent induction when compared with those managed expectantly within the first 15 to 20 hours after prelabor rupture of membranes without affecting the risk for cesarean delivery. In addition, women who underwent labor induction within the first 30 to 36 hours had a shorter prelabor rupture of membranes to delivery time and a shorter total maternal hospital stay when compared with those managed expectantly at the same time interval. Among women managed expectantly, less than two-thirds (64%; 1365/2120) experienced a spontaneous onset of labor within the first 24 hours following prelabor rupture of membranes.
These findings suggest that immediate labor induction seems to be the optimal management strategy to minimize neonatal and maternal morbidity in the setting of prelabor rupture of membranes at term gestations. In cases for which immediate induction is not feasible, labor induction remains the preferred option over expectant management if performed within the first 15 to 20 hours after prelabor rupture of membranes.

Background: Prelabor rupture of membranes (PROM) is associated with maternal and neonatal infections. Although guidelines suggest prophylactic antibiotics for pregnant women with PROM, the optimal antibiotic regimen remains controversial. Synthesizing the data from different studies is challenging due to variations in reported outcomes. Objective: This study aimed to form the initial list of outcomes for the core outcome set (COS) that evaluates antibiotic use in PROM by identifying all existing outcomes and patients\' views. Methods: Relevant studies were identified by searching PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, and VIP databases. We also screened the references of the included studies as a supplementary search. We extracted basic information from the articles and the outcomes. Two reviewers independently selected the studies, extracted the data, extracted the outcomes, and grouped them into domains. Then, semi-structured interviews based on the potential factors collected by the systematic review were conducted at West China Second Hospital of Sichuan University. Pregnant women who met the diagnostic criteria for PROM were enrolled. Participants reported their concerns about the outcomes. Two researchers identified the pregnant women\'s concerns. Results: A total of 90 studies were enrolled in this systematic review. The median outcomes in the included studies was 7 (1-31), and 109 different unique outcomes were identified. Pre-term PROM (PPROM) had 97 outcomes, and term PROM (TPROM) had 70 outcomes. The classification and order of the core outcome domains of PPROM and TPROM were consistent. The physiological domain was the most common for PPROM and TPROM outcomes. Furthermore, 35.1 and 57.1% outcomes were only reported once in PPROM and TPROM studies, respectively. Thirty pregnant women participated in the semi-structured interviews; 10 outcomes were extracted after normalized, and the outcomes were reported in the systematic review. However, studies rarely reported pregnant women\'s concerns. Conclusion: There was considerable inconsistency in outcomes selection and reporting in studies about antibiotics in PROM. An initial core outcomes set for antibiotics in PROM was formed.