Buccal Versus Vaginal Misoprostol Combined with a Foley Catheter among Individuals with Obesity Undergoing Induction.

BACKGROUND: Combining pharmacologic agents with mechanical ripening achieves the shortest labor duration, yet there is no clear evidence on route of drug administration in obese individuals. The use of buccal misoprostol has shown greater patient acceptance but remains understudied. OBJECTIVE: Our objective was to evaluate the difference in time to delivery of buccal compared with vaginal misoprostol in combination with a Foley catheter (FC) for induction of labor (IOL) in the obese population. STUDY DESIGN: This was a secondary analysis of a randomized controlled trial comparing identical dosages (25 µg) of buccal and vaginal misoprostol in combination with a FC. The parent trial was an institutional review board-approved, randomized clinical trial conducted from June 2019 through January 2020. Labor management was standardized among participants. Women undergoing IOL at ≥37 weeks with a singleton gestation and cervical dilation ≤2 cm were included. Body mass index (BMI, kg/m2) was stratified. The primary outcome was time to delivery. RESULTS: A total of 215 participants were included. Demographic characteristics were similar between the three groups. Vaginal drug administration achieved a faster median time to delivery than the buccal route among patients with a body mass index greater than or equal to 30 kg/m2 (vaginal misoprostol-FC: 21.3 hours vs. buccal misoprostol-FC: 25.2 hours, p = 0.006). There was no difference in the cesarean delivery rate between the two groups. Furthermore, patients with a BMI greater than or equal to 30 kg/m2 receiving vaginal misoprostol delivered 1.2 times faster than women who received buccal misoprostol after censoring for cesarean delivery and adjusting for parity (hazard ratio: 1.2, 95% confidence interval: 1.1-1.7). There were no significant differences in maternal and neonatal outcomes. CONCLUSION: We found that vaginal misoprostol was superior to buccal misoprostol when combined with a FC among individuals with a BMI greater than or equal to 30 kg/m2. Vaginal misoprostol should be the preferred route of drug administration for term IOL in this population. KEY POINTS: · Vaginal misoprostol was superior to buccal route among patients with obesity.. · There was no difference in the cesarean delivery rate between the two groups.. · Vaginal misoprostol should be the preferred route of administration among patients with obesity..

Antibiotic treatment of bacterial vaginosis to prevent preterm delivery: Systematic review and individual participant data meta-analysis.

BACKGROUND: Bacterial vaginosis (BV) increases preterm delivery (PTD) risk, but treatment trials showed mixed results in preventing PTD. OBJECTIVES: Determine, using individual participant data (IPD), whether BV treatment during pregnancy reduced PTD or prolonged time-to-delivery. DATA SOURCES: Cochrane Systematic Review (2013), MEDLINE, EMBASE, journal searches, and searches (January 2013-September 2022) ("bacterial vaginosis AND pregnancy") of (i) clinicaltrials.gov; (ii) Cochrane Central Register of Controlled Trials; (iii) World Health Organization International Clinical Trials Registry Platform Portal; and (iv) Web of Science ("bacterial vaginosis"). STUDY SELECTION AND DATA EXTRACTION: Studies randomising asymptomatic pregnant individuals with BV to antibiotics or control, measuring delivery gestation. Extraction was from original data files. Bias risk was assessed using the Cochrane tool. Analysis used "one-step" logistic and Cox random effect models, adjusting gestation at randomisation and PTD history; heterogeneity by I2 . Subgroup analysis tested interactions with treatment. In sensitivity analyses, studies not providing IPD were incorporated by "multiple random-donor hot-deck" imputation, using IPD studies as donors. RESULTS: There were 121 references (96 studies) with 23 eligible trials (11,979 participants); 13 studies (6915 participants) provided IPD; 12 (6115) were incorporated. Results from 9 (4887 participants) not providing IPD were imputed. Odds ratios for PTD for metronidazole and clindamycin versus placebo were 1.00 (95% CI 0.84, 1.17), I2  = 62%, and 0.59 (95% CI 0.42, 0.82), I2  = 0 before; and 0.95 (95% CI 0.81, 1.11), I2  = 59%, and 0.90 (95% CI: 0.72, 1.12), I2  = 0, after imputation. Time-to-delivery did not differ from null with either treatment. Including imputed IPD, there was no evidence that either drug was more effective when administered earlier, or among those with a PTD history. CONCLUSIONS: Clindamycin, but not metronidazole, was beneficial in studies providing IPD, but after imputing data from missing IPD studies, treatment of BV during pregnancy did not reduce PTD, nor prolong pregnancy, in any subgroup or when started earlier in gestation.

The great obstetrical syndromes and the placenta.

Although historically pre-eclampsia, preterm birth, abruption, fetal growth restriction and stillbirth have been viewed as clinically distinct entities, a growing body of literature has demonstrated that the placenta and its development is the root cause of many cases of these conditions. This has led to the term 'the great obstetrical syndromes' being coined to reflect this common origin. Although these conditions mostly manifest in the second half of pregnancy, a failure to complete deep placentation (the transition from histiotrophic placentation to haemochorial placenta at 10-18 weeks of gestation via a second wave of extravillous trophoblast invasion), is understood to be key to the pathogenesis of the great obstetrical syndromes. While the reasons that the placenta fails to achieve deep placentation remain active areas of investigation, maternal inflammation and thrombosis have been clearly implicated. From a clinical standpoint these mechanisms provide a biological explanation of how low-dose aspirin, which affects the COX-1 receptor (thrombosis) and the COX-2 receptor (inflammation), prevents not just pre-eclampsia but all the components of the great obstetrical syndromes if initiated early in pregnancy. The optimal dose of low-dose aspirin that is maximally effective in pregnancy remains a question open for further research. Additionally, other candidate medications have been identified that may also prevent pre-eclampsia, and further study of them may offer therapeutic options beyond low-dose aspirin. Interestingly, three of the eight identified compounds (hydroxychloroquine, metformin and pravastatin) are known to decrease inflammation.

Aspirin delays the onset of hypertensive disorders of pregnancy among nulliparous pregnant women: A secondary analysis of the ASPIRIN trial.

OBJECTIVE: To assess the impact of low-dose aspirin (LDA) starting in early pregnancy on delaying preterm hypertensive disorders of pregnancy. DESIGN: Non-prespecified secondary analysis of a randomised masked trial of LDA. SETTING: The study was conducted among women in the Global Network for Women's and Children's Health's Maternal and Newborn Health Registry (MNHR) clusters, a prospective, population-based study in Kenya, Zambia, the Democratic Republic of the Congo (DRC), Pakistan, India (two sites-Belagavi and Nagpur) and Guatemala. POPULATION: Nulliparous singleton pregnancies between 6+0 weeks and 13+6 weeks in six low-middle income countries (Democratic Republic of Congo, Guatemala, India, Kenya, Pakistan, Zambia) enrolled in the ASPIRIN Trial. METHODS: We compared the incidence of HDP at delivery at three gestational age periods (<28, <34 and <37 weeks) between women who were randomised to aspirin or placebo. Women were included if they were randomised and had an outcome at or beyond 20 weeks (Modified Intent to Treat). MAIN OUTCOME MEASURES: Our primary outcome was pregnancies with HDP associated with preterm delivery (HDP@delivery) before <28, <34 and <37 weeks. Secondary outcomes included small for gestational age (SGA) <10th percentile, <5th percentile, and perinatal mortality. RESULTS: Among the 11 976 pregnancies, LDA did not significantly lower HDP@delivery <28 weeks (relative risk [RR] 0.18, 95% confidence interval [CI] 0.02-1.52); however, it did lower HDP@delivery <34 weeks (RR 0.37, 95% CI 0.17-0.81) and HDP@delivery <37 weeks (RR 0.66, 95% CI 0.49-0.90). The overall rate of HDP did not differ between the two groups (RR 1.08, 95% CI 0.94-1.25). Among those pregnancies who had HDP, SGA <10th percentile was reduced (RR 0.81, 95% CI 0.67-0.99), though SGA <5th percentile was not (RR 0.84, 95% CI 0.64-1.09). Similarly, perinatal mortality among pregnancies with HDP occurred less frequently (RR 0.55, 95% CI 0.33-0.92) in those receiving LDA. Pregnancies randomised to LDA delivered later with HDP compared with those receiving placebo (median gestational age 38.5 weeks vs. 37.9 weeks; p = 0.022). CONCLUSIONS: In this secondary analysis of a study of low-risk nulliparous singleton pregnancies, early administration of LDA resulted in lower rates of preterm HDP and delivery before 34 and 37 weeks but not in the overall rate of HDP. These results suggest that LDA works in part by delaying HDP.

Sleep-disordered Breathing in Pregnancy and after Delivery: Associations with Cardiometabolic Health.

Rationale: Knowledge gaps exist regarding health implications of sleep-disordered breathing (SDB) identified in pregnancy and/or after delivery. Objectives: To determine whether SDB in pregnancy and/or after delivery is associated with hypertension (HTN) and metabolic syndrome (MS). Methods: nuMoM2b-HHS (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be Heart Health Study) (N = 4,508) followed participants initially recruited during their first pregnancy. Participants returned for a visit 2-7 years after pregnancy. This study examined a subgroup who underwent SDB assessments during their first pregnancy (n = 1,964) and a repeat SDB assessment after delivery (n = 1,222). Two SDB definitions were considered: 1) apnea-hypopnea index (AHI) ⩾ 5 and 2) oxygen desaturation index (ODI) ⩾ 5. Associations between SDB and incident HTN and MS were evaluated with adjusted risk ratios (aRRs). Measurements and Main Results: The aRR for MS given an AHI ⩾ 5 during pregnancy was 1.44 (95% confidence interval [CI], 1.08-1.93), but no association with HTN was found. ODI ⩾ 5 in pregnancy was associated with both an increased risk for HTN (aRR, 2.02; 95% CI, 1.30-3.14) and MS (aRR, 1.53; 95% CI, 1.19-1.97). Participants with an AHI ⩾ 5 in pregnancy that persisted after delivery were at higher risk for both HTN (aRR, 3.77; 95% CI, 1.84-7.73) and MS (aRR, 2.46; 95% CI, 1.59-3.76). Similar associations were observed for persistent ODI ⩾ 5 after delivery. Conclusions: An AHI ⩾ 5 in pregnancy was associated with an increased risk of MS. An ODI ⩾ 5 in pregnancy was significantly associated with both HTN and MS. Participants with persistent elevations in AHI and ODI during pregnancy and at 2-7 years after delivery were at the highest risk for HTN and MS. Clinical trial registered with www.clinicaltrials.gov (NCT02231398).

A Machine Learning Algorithm using Clinical and Demographic Data for All-Cause Preterm Birth Prediction.

OBJECTIVE: Preterm birth remains the predominant cause of perinatal mortality throughout the United States and the world, with well-documented racial and socioeconomic disparities. To develop and validate a predictive algorithm for all-cause preterm birth using clinical, demographic, and laboratory data using machine learning. STUDY DESIGN: We performed a cohort study of pregnant individuals delivering at a single institution using prospectively collected information on clinical conditions, patient demographics, laboratory data, and health care utilization. Our primary outcome was all-cause preterm birth before 37 weeks. The dataset was randomly divided into a derivation cohort (70%) and a separate validation cohort (30%). Predictor variables were selected amongst 33 that had been previously identified in the literature (directed machine learning). In the derivation cohort, both statistical (logistic regression) and machine learning (XG-Boost) models were used to derive the best fit (C-Statistic) and then validated using the validation cohort. We measured model discrimination with the C-Statistic and assessed the model performance and calibration of the model to determine whether the model provided clinical decision-making benefits. RESULTS: The cohort includes a total of 12,440 deliveries among 12,071 individuals. Preterm birth occurred in 2,037 births (16.4%). The derivation cohort consisted of 8,708 (70%) and the validation cohort consisted of 3,732 (30%). XG-Boost was chosen due to the robustness of the model and the ability to deal with missing data and collinearity between predictor variables. The top five predictor variables identified as drivers of preterm birth, by feature importance metric, were multiple gestation, number of emergency department visits in the year prior to the index pregnancy, initial unknown body mass index, gravidity, and prior preterm delivery. Test performance characteristics were similar between the two populations (derivation cohort area under the curve [AUC] = 0.70 vs. validation cohort AUC = 0.63). CONCLUSION: Clinical, demographic, and laboratory information can be useful to predict all-cause preterm birth with moderate precision. KEY POINTS: · Machine learning can be used to create models to predict preterm birth.. · In our model, all-cause preterm birth can be predicted with moderate precision.. · Clinical, demographic, and laboratory information can be useful to predict all-cause preterm birth..

Combination Foley Catheter-Oxytocin versus Oxytocin Alone following Preterm Premature Rupture of Membranes.

OBJECTIVE: The benefit of mechanical ripening agents following preterm premature rupture of membranes (PPROM) has not been established. We sought to compare the time to delivery in women who received transcervical Foley catheter plus oxytocin infusion versus oxytocin infusion alone in patients with unfavorable cervices and PPROM. STUDY DESIGN: This is a retrospective cohort study of patients presenting with PPROM of a live, singleton gestation between 240/7 and 366/7 weeks' gestation from January 2005 to October 2018 at a single, tertiary care institution. Patients with an unfavorable cervical examination (≤2-cm dilation), no contraindication to labor and undergoing labor induction were analyzed. Time to delivery was analyzed using multivariable linear regression adjusting for cervical dilation at induction and nulliparity. Bivariate and multivariate analyses were used where appropriate. RESULTS: A total of 260 participants were included: 109 who received a Foley catheter and oxytocin (Foley/oxytocin) and 151 who had oxytocin alone. Demographic characteristics were similar between the two groups. Unadjusted time to delivery was significantly shorter in the oxytocin only group (Foley/oxytocin: 20.35 hours vs. oxytocin alone: 14.7 hours, p < 0.001). No differences in length of labor were detected after adjusting for cervical dilation at induction and nulliparity (p = 0.5). The unadjusted rate of cesarean delivery was higher in the combination Foley/oxytocin group (Foley/oxytocin: 16.5% vs. oxytocin alone: 7.3%, p = 0.03), but no differences were found in the adjusted analysis (p = 0.06). There were no differences in clinical chorioamnionitis rates between the two groups (Foley/oxytocin: 8.3% vs. oxytocin alone: 9.3%, p = 0.83). Furthermore, no significant differences were found in maternal and neonatal outcomes between the two groups. CONCLUSION: In patients with PROM, the use of a transcervical Foley catheter in addition to oxytocin is not associated with a shorter time to delivery compared with oxytocin alone. KEY POINTS: · Transcervical Foley catheter did not shorten length of labor in PPROM.. · Transcervical Foley catheter did not increase infection risk.. · Pitocin alone can be used in PPROM population..

Serum Cotinine and Adverse Cardiovascular Outcomes: A Cross-sectional Secondary Analysis of the nuMoM2b Heart Health Study.

OBJECTIVE: We aimed to (1) compare serum cotinine with self-report for ascertaining smoking status among reproductive-aged women; (2) estimate the relative odds of adverse cardiovascular (CV) outcomes among women by smoking status; (3) assess whether the association between adverse pregnancy outcomes (APOs) and CV outcomes varies by smoking status. STUDY DESIGN: We conducted a cross-sectional study of the nuMoM2b Heart Health Study. Women attended a study visit 2 to 7 years after their first pregnancy. The exposure was smoking status, determined by self-report and by serum cotinine. Outcomes included incident chronic hypertension (HTN), metabolic syndrome (MetS), and dyslipidemia. Multivariable logistic regression estimated odds ratios (ORs) for each outcome by smoking status. RESULTS: Of 4,392 women with serum cotinine measured, 3,610 were categorized as nonsmokers, 62 as secondhand smoke exposure, and 720 as smokers. Of 3,144 women who denied tobacco smoke exposure, serum cotinine was consistent with secondhand smoke exposure in 48 (1.5%) and current smoking in 131 (4.2%) After adjustment for APOs, smoking defined by serum cotinine was associated with MetS (adjusted OR [aOR] = 1.52, 95% confidence interval [CI]: 1.21, 1.91) and dyslipidemia (aOR = 1.28, 95% CI: 1.01, 1.62). When stratified by nicotine exposure, nonsmokers with an APO in their index pregnancy had higher odds of stage 1 (aOR = 1.64, 95% CI: 1.32, 2.03) and stage 2 HTN (aOR = 2.92, 95% CI: 2.17, 3.93), MetS (aOR = 1.76, 95% CI: 1.42, 2.18), and dyslipidemia (aOR = 1.55, 95% CI: 1.25, 1.91) relative to women with no APO. Results were similar when smoking exposure was defined by self-report. CONCLUSION: Whether determined by serum cotinine or self-report, smoking is associated with subsequent CV outcomes in reproductive-aged women. APOs are also independently associated with CV outcomes in women. KEY POINTS: · Cotinine was detected in 5.7% of reported nonsmokers.. · Smoking and APOs were independently associated with CV health.. · Smoking was associated with MetS and dyslipidemia..

PROMPT: Prospective Meta-analysis for Pessary Trials Study Protocol.

OBJECTIVE: Preterm birth, defined as birth before 37 weeks of gestation, is a leading cause of perinatal and infant mortality throughout the world. Preterm birth is also associated with long-term neurological disabilities and other significant health issues in children. A short cervix in the second trimester has been noted to be one of the strongest predictors of subsequent spontaneous preterm birth in both singleton and multiple pregnancies. Some studies have shown that cervical support in the form of an Arabin pessary lowers the risk of preterm birth in women with a singleton gestation and short cervical length; however, other studies have conflicting results. Our objective was to form an international collaborative of planned or ongoing randomized trials of pessary in singleton and twin gestations with a short cervix. STUDY DESIGN: In November 2014, an international group of investigators, who had initiated or were planning randomized trials of pessary for pregnant people with a short cervix and singleton or twin gestation to prevent preterm birth, formed a collaboration to plan a prospective individual patient data (IPD) meta-analysis of randomized trials (PROspective Meta-analysis of Pessary Trials [PROMPT]). The PROMPT investigators agreed on meta-analysis IPD hypotheses for singletons and twins, eligibility criteria, and a set of core baseline and outcome measures. The primary outcome is a composite of fetal death or preterm delivery before 32 weeks' gestation. Secondary outcomes include maternal and neonatal morbidities. The PROMPT protocol may be viewed as a written agreement among the study investigators who make up the PROMPT consortium (PROSPERO ID# CRD42018067740). RESULTS: Results will be published in phases as the individual participating studies are concluded and published. Results of the first phase of singleton and twin pessary trials are expected to be available in late 2022. Updates are planned as participating trials are completed and published. KEY POINTS: · Short cervical length predicts preterm birth.. · Results of prior cervical pessary trials are mixed.. · Meta-analysis of pessary trials protocol..

Cervical Pessary for Prevention of Preterm Birth in Individuals With a Short Cervix: The TOPS Randomized Clinical Trial.

Importance: A short cervix as assessed by transvaginal ultrasound is an established risk factor for preterm birth. Study findings for a cervical pessary to prevent preterm delivery in singleton pregnancies with transvaginal ultrasound evidence of a short cervix have been conflicting. Objective: To determine if cervical pessary placement decreases the risk of preterm birth or fetal death prior to 37 weeks among individuals with a short cervix. Design, Setting, and Participants: We performed a multicenter, randomized, unmasked trial comparing a cervical pessary vs usual care from February 2017 through November 5, 2021, at 12 centers in the US. Study participants were nonlaboring individuals with a singleton pregnancy and a transvaginal ultrasound cervical length of 20 mm or less at gestations of 16 weeks 0 days through 23 weeks 6 days. Individuals with a prior spontaneous preterm birth were excluded. Interventions: Participants were randomized 1:1 to receive either a cervical pessary placed by a trained clinician (n = 280) or usual care (n = 264). Use of vaginal progesterone was at the discretion of treating clinicians. Main Outcome and Measures: The primary outcome was delivery or fetal death prior to 37 weeks. Results: A total of 544 participants (64%) of a planned sample size of 850 were enrolled in the study (mean age, 29.5 years [SD, 6 years]). Following the third interim analysis, study recruitment was stopped due to concern for fetal or neonatal/infant death as well as for futility. Baseline characteristics were balanced between participants randomized to pessary and those randomized to usual care; 98.9% received vaginal progesterone. In an as-randomized analysis, the primary outcome occurred in 127 participants (45.5%) randomized to pessary and 127 (45.6%) randomized to usual care (relative risk, 1.00; 95% CI, 0.83-1.20). Fetal or neonatal/infant death occurred in 13.3% of those randomized to receive a pessary and in 6.8% of those randomized to receive usual care (relative risk, 1.94; 95% CI, 1.13-3.32). Conclusions and Relevance: Cervical pessary in nonlaboring individuals with a singleton gestation and with a cervical length of 20 mm or less did not decrease the risk of preterm birth and was associated with a higher rate of fetal or neonatal/infant mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT02901626.

Outcomes associated with antibiotic administration for isolated maternal fever in labor.

BACKGROUND: The American College of Obstetricians and Gynecologists currently recommends that antibiotic treatment should be considered for women with isolated maternal fevers during labor. However, there is little known about the maternal and neonatal impact of antibiotic treatment in this scenario. OBJECTIVE: We sought to assess the outcomes in women with a nonsustained, isolated maternal fever treated with antibiotics and compare it with expectant management. STUDY DESIGN: This was a retrospective cohort study of laboring women with a singleton gestation at term and a single temperature of between 38.0°C and 38.9°C without other evidence of infection (leukocytosis >15,000/mm3, fetal tachycardia, malodorous amniotic fluid, suspected alternate source of infection) at a tertiary teaching hospital. A contemporaneously maintained, validated obstetrical database was used to identify women for our cohort. Women with rheumatologic or renal disease, nongestational diabetes, preterm labor, placental abruption, vaginal bleeding, HIV, malpresentation, and fetal anomalies were excluded. The primary outcome was a postpartum fever above 38.0°C. Secondary maternal outcomes were treatment for postpartum endometritis, uterine atony, postpartum hemorrhage, admission to the intensive care unit, and postpartum length of stay. Secondary neonatal outcomes were neonatal intensive care unit admission, 5-minute Apgar score of <7, 5-minute Apgar score of <4, neonatal intensive care unit length of stay, and neonatal antibiotic administration. The results were compared using univariable and multivariable analyses. RESULTS: From January 1, 2015, to December 31, 2018, 359 women were identified; 85 received antibiotics and 274 did not. The baseline characteristics were similar between the groups, except for gestational age at the time of delivery (39.2 weeks vs 39.5 weeks for the antibiotic and no antibiotic groups, respectively; P=.02). The incidence in postpartum fever showed a downward trend in the antibiotic group (10.59% for the antibiotic group vs 18.98% for the no antibiotic group; P=.07). Significantly fewer women in the antibiotic group were treated for postpartum endometritis (3.53% vs 11.31%; P=.03). Neonatal intensive care unit admission and neonatal antibiotic administration rates were higher in the antibiotic group (41.18% vs 17.88%; P<.001 and 36.47% vs 12.41%; P<.001, respectively). The incidence of 5-minute Apgar score of <7 was higher in the antibiotic group (8.25% vs 2.19%; P=.016). After controlling for age, gestational age, body mass index, group B streptococci status, delivery method, parity, administration of epidural, and receipt of acetaminophen, the odds for postpartum fever were reduced by a factor of 0.42 (95% confidence interval, 0.18-0.99) among women who received antibiotics when compared with those who did not receive antibiotics. Outcome results are presented in Table 2. CONCLUSION: Although there was a lower rate of treatment for endometritis among women who received antibiotics for a single isolated maternal fever, there was a higher rate of neonatal intensive care unit admissions and 5-minute Apgar score of <7. This indicates that there likely is maternal benefit associated with antibiotic use, however, there are concerns about the neonatal risk.

Early vs expectant artificial rupture of membranes following Foley catheter ripening: a randomized controlled trial.

BACKGROUND: Early amniotomy shortens the duration of spontaneous labor, yet there is no clear evidence on the optimal timing of amniotomy following cervical ripening. There are limited high-quality studies on the use of early amniotomy intervention following labor induction. OBJECTIVE: This study aimed to evaluate whether amniotomy within 1 hour of Foley catheter expulsion reduces the duration of labor among individuals undergoing combined misoprostol and Foley catheter labor induction at term. STUDY DESIGN: This was a randomized clinical trial conducted from November 2020 to May 2021 comparing amniotomy within 1 hour of Foley catheter expulsion (early artificial rupture of membranes) with expectant management. Randomization was stratified by parity. Labor management was standardized among participants. Individuals undergoing induction at ≥37 weeks with a singleton gestation and needing cervical ripening were eligible. Our primary outcome was time to delivery. Wilcoxon rank sum, Pearson chi-square, and Cox survival analyses with intent-to-treat principles were performed adjusting for age, body mass index, parity, mode of delivery, Bishop score, and the interaction between randomization group and parity. A sample size of 160 was planned to detect a 4-hour reduction in delivery time. RESULTS: A total of 160 patients (79 early artificial rupture of membranes, 81 expectant management) were randomized. Early artificial rupture of membranes achieved a faster median time to delivery than expectant management (early artificial rupture of membranes: 11.1 hours; interquartile range, 6.25-17.1 vs expectant management: 19.8 hours; interquartile range, 13.2-26.2; P<.001). A greater percentage of individuals in the early artificial rupture of membranes group delivered within 24 hours (86% vs 70%; P=.03). There was no difference in the cesarean delivery rate between the 2 groups (22% vs 31%; P=.25). Individuals delivered 2.3 times faster following early artificial rupture of membranes (hazard ratio, 2.3; 95% confidence interval, 1.5-3.4; P<.001). There were no significant differences in maternal and neonatal outcomes. CONCLUSION: Amniotomy within 1 hour of Foley catheter expulsion resulted in 2.3 times faster delivery than expectant management. Therefore, early artificial rupture of membranes should be considered in individuals undergoing mechanical cervical ripening at term.

Does Antenatal Progesterone Administration Modify the Risk of Neonatal Intraventricular Hemorrhage?

OBJECTIVE: Progesterone administration has been associated with improved neurological outcomes following traumatic brain injury in adults. However, studies examining the effect of progesterone on the risk of neonatal intraventricular hemorrhage (IVH) are inconsistent. We sought to determine if maternal administration of intramuscular 17-α-hydroxyprogesterone caproate (17-OHPC) is associated with decreased rates of IVH in infants born before 32-weeks gestation. STUDY DESIGN: This is a retrospective study of liveborn singleton deliveries between 20- and 32-weeks gestation at two large academic medical centers from January 1, 2012 to August 30, 2020. Data were extracted from hospital electronic medical record data warehouses using standardized definitions and billing and diagnosis codes. We evaluated receipt of 17-OHPC in the antepartum period and diagnosis of IVH (grade I-IV, per Volpe classification) during the neonatal delivery hospitalization encounter. Bivariate and multivariate analyses were performed to examine the association between 17-OHPC and neonatal IVH adjusting for potential confounders. Odds ratio (ORs) and 95% confidence intervals (CIs) were presented. RESULTS: Among 749 neonates born between 20- and 32-week gestation, 140 (18.7%) of their mothers had received antenatal 17-OHPC and 148 (19.8%) were diagnosed with IVH after birth. No significant association was observed between maternal 17-OHPC and neonatal IVH in unadjusted (OR 1.14, 95% CI 0.72-1.78) or adjusted analyses (adjusted odds ratio 1.14, 95% CI 0.71-1.84). Independent of exposure to 17-OHPC, as expected, infants born <28-weeks gestation or those with very low birthweight (<1,500 g) were at an increased risk of IVH (OR 2.32, 95% CI 1.55-3.48 and OR 2.19, 95% CI 1.09-4.38, respectively). CONCLUSION: Antenatal maternal 17-OHPC administration was not associated with the risk of neonatal IVH. Further research may be warranted to determine whether timing, route of delivery, and duration of progesterone therapy impact rates of neonatal IVH. KEY POINTS: · This study aimed to compare the frequency of intraventricular hemorrhage in preterm neonates exposed to antenatal 17-α-hydroxyprogesterone caproate to those not exposed.. · In neonates born at <32-weeks gestation, maternal use of progesterone is not associated with the risk of intraventricular hemorrhage.. · In contrast to preclinical and adult data, this study suggests that progesterone exposure is not associated with the prevention of neonatal brain injury..

Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Preterm birth remains a common cause of neonatal mortality, with a disproportionately high burden in low-income and middle-income countries. Meta-analyses of low-dose aspirin to prevent pre-eclampsia suggest that the incidence of preterm birth might also be decreased, particularly if initiated before 16 weeks of gestation. METHODS: ASPIRIN was a randomised, multicountry, double-masked, placebo-controlled trial of low-dose aspirin (81 mg daily) initiated between 6 weeks and 0 days of pregnancy, and 13 weeks and 6 days of pregnancy, in nulliparous women with an ultrasound confirming gestational age and a singleton viable pregnancy. Participants were enrolled at seven community sites in six countries (two sites in India and one site each in the Democratic Republic of the Congo, Guatemala, Kenya, Pakistan, and Zambia). Participants were randomly assigned (1:1, stratified by site) to receive aspirin or placebo tablets of identical appearance, via a sequence generated centrally by the data coordinating centre at Research Triangle Institute International (Research Triangle Park, NC, USA). Treatment was masked to research staff, health providers, and patients, and continued until 36 weeks and 7 days of gestation or delivery. The primary outcome of incidence of preterm birth, defined as the number of deliveries before 37 weeks' gestational age, was analysed in randomly assigned women with pregnancy outcomes at or after 20 weeks, according to a modified intention-to-treat (mITT) protocol. Analyses of our binary primary outcome involved a Cochran-Mantel-Haenszel test stratified by site, and generalised linear models to obtain relative risk (RR) estimates and associated confidence intervals. Serious adverse events were assessed in all women who received at least one dose of drug or placebo. This study is registered with ClinicalTrials.gov, NCT02409680, and the Clinical Trial Registry-India, CTRI/2016/05/006970. FINDINGS: From March 23, 2016 to June 30, 2018, 14 361 women were screened for inclusion and 11 976 women aged 14-40 years were randomly assigned to receive low-dose aspirin (5990 women) or placebo (5986 women). 5780 women in the aspirin group and 5764 in the placebo group were evaluable for the primary outcome. Preterm birth before 37 weeks occurred in 668 (11·6%) of the women who took aspirin and 754 (13·1%) of those who took placebo (RR 0·89 [95% CI 0·81 to 0·98], p=0·012). In women taking aspirin, we also observed significant reductions in perinatal mortality (0·86 [0·73-1·00], p=0·048), fetal loss (infant death after 16 weeks' gestation and before 7 days post partum; 0·86 [0·74-1·00], p=0·039), early preterm delivery (<34 weeks; 0·75 [0·61-0·93], p=0·039), and the incidence of women who delivered before 34 weeks with hypertensive disorders of pregnancy (0·38 [0·17-0·85], p=0·015). Other adverse maternal and neonatal events were similar between the two groups. INTERPRETATION: In populations of nulliparous women with singleton pregnancies from low-income and middle-income countries, low-dose aspirin initiated between 6 weeks and 0 days of gestation and 13 weeks and 6 days of gestation resulted in a reduced incidence of preterm delivery before 37 weeks, and reduced perinatal mortality. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Buccal vs vaginal misoprostol combined with Foley catheter for cervical ripening at term (the BEGIN trial): a randomized controlled trial.

BACKGROUND: Combining pharmacologic agents with mechanical ripening achieves the shortest time to labor; however, there is no clear evidence on route of drug administration. Buccal administration of misoprostol has shown greater patient acceptance but remains understudied. OBJECTIVE: This study aimed to evaluate the difference in time to delivery between buccal and vaginal administration of misoprostol along with a Foley catheter for induction of labor. STUDY DESIGN: The BEGIN trial (buccal vs vaginal misoprostol combined with Foley catheter for cervical ripening at term) was an institutional review board-approved, randomized clinical trial conducted from June 2019 to January 2020 comparing identical doses (25 µg) of buccal misoprostol and vaginal misoprostol along with a Foley catheter for induction of labor. Randomization was stratified by parity. Labor management was standardized among participants. Individuals undergoing induction of labor at ≥37 weeks with a singleton gestation and needing cervical ripening were included. Our primary outcome was time to delivery. Kruskal-Wallis, Pearson chi-squared, and Cox survival analyses with intent-to-treat principles were performed. A sample size of 216 was planned to detect a 4-hour reduction in delivery time. RESULTS: A total of 215 women (108 in the buccal drug administration group and 107 in the vaginal drug administration group) were randomized. The vaginal route of drug administration achieved a faster median time to delivery than the buccal route of drug administration (19.7 hours in the vaginal route vs 24.1 hours in the buccal route; P<.001). A greater percentage of women in the vaginal drug administration group delivered within 24 hours compared with the buccal drug administration group (65% vs 49%; P=.02). There was no difference in the cesarean delivery rate between the 2 groups (17% in the vaginal drug administration group vs 21% in the buccal drug administration group; P=.6). Individuals who received vaginal misoprostol with Foley catheter delivered 2 times faster than women who received buccal misoprostol with Foley catheter after censoring for cesarean delivery and adjusting for parity (hazard ratio, 2.13; 95% confidence interval, 1.44-3.17). There was no significant difference in maternal and neonatal outcomes. CONCLUSION: We found that vaginal administration of misoprostol was superior to buccal administration of misoprostol along with a Foley catheter for induction of labor. Furthermore, vaginal administration of misoprostol resulted in twice the chance of delivering earlier compared with buccal administration of misoprostol with no difference in cesarean delivery rates. Therefore, the vaginal route of administration of misoprostol should be preferred among individuals undergoing a combined pharmacologic and mechanical induction.

Text Messaging as a Means to Engage Patients in the Postpartum Period.

The use of electronic information and telecommunications technologies to support health systems has been increasingly recognized as an important tool in postpartum care. An emerging body of research has suggested that telehealth during the postpartum period may alleviate racial disparities and transportation barriers, while improving access to health resources. Thus, the purpose of this article is to describe current barriers to postpartum health, review prevalence and access to mobile devices, and current uses of text messaging in the postpartum period. We describe key areas of telemedicine utilization including lactation services, blood pressure monitoring, diabetes screening, mental health services, weight loss programs, and access to contraception in the postpartum period. Future research and clinical work should aim to further examine the use of telehealth among postpartum individuals.

Azithromycin vs erythromycin for the management of preterm premature rupture of membranes.

BACKGROUND: Preterm premature rupture of membranes complicates 2-3% of pregnancies. Many institutions have advocated for the use of azithromycin instead of erythromycin. This is secondary to national shortages of erythromycin, ease of administration, better side effect profile, and decreased cost of azithromycin as compared with erythromycin. OBJECTIVE: The objective of the study was to evaluate whether there are differences in the latency from preterm premature rupture of membranes to delivery in patients treated with different dosing regimens of azithromycin vs erythromycin. STUDY DESIGN: This is a multicenter, retrospective cohort of women with singleton pregnancies with confirmed rupture of membranes between 230 and 336 weeks from January 2010 to June 2015. Patients were excluded if there was a contraindication to expectant management of preterm premature rupture of membranes. Patients received 1 of 4 antibiotic regimens: (1) azithromycin 1000 mg per os once (azithromycin 1 day group); (2) azithromycin 500 mg per os once, followed by azithromycin 250 mg per os daily for 4 days (azithromycin 5 day group); (3) azithromycin 500 mg intravenously for 2 days, followed by azithromycin 500 mg per os daily for 5 days (azithromycin 7 day group); or (4) erythromycin intravenously for 2 days followed by erythromycin per os for 5 days (erythromycin group). The choice of macrolide was based on institutional policy and/or availability of antibiotics at the time of admission. In addition, all patients received ampicillin intravenously for 2 days followed by amoxicillin per os for 5 days. Primary outcome was latency from diagnosis of rupture of membranes to delivery. Secondary outcomes included clinical and histopathological chorioamnionitis and neonatal outcomes. RESULTS: Four hundred fifty-three patients who met inclusion criteria were identified. Seventy-eight patients received azithromycin for 1 day, 191 patients received azithromycin for 5 days, 52 patients received azithromycin for 7 days, and 132 patients received erythromycin. Women who received the 5 day regimen were younger and less likely to be non-African American, have hypertension, have sexually transmitted infection, or experienced substance abuse. There was no statistical difference in median latency time of azithromycin 1 day (4.9 days, 95% confidence interval, 3.3-6.4), azithromycin 5 days (5.0, 95% confidence interval, 3.9-6.1), or azithromycin 7 days (4.9 days, 95% confidence interval, 2.8-7.0) when compared with erythromycin (5.1 days, 95% confidence interval, 3.9-6.4) after adjusting for demographic variables (P = .99). Clinical chorioamnionitis was not different between groups in the adjusted model. Respiratory distress syndrome was increased in the azithromycin 5 day group vs azithromycin 1 day vs erythromycin (44% vs. 29% and 29%, P = .005, respectively). CONCLUSION: There was no difference in latency to delivery, incidence of chorioamnionitis, or neonatal outcomes when comparing different dosing regimens of the azithromycin with erythromycin, with the exception of respiratory distress syndrome being more common in the 5 day azithromycin group. Azithromycin could be considered as an alternative to erythromycin in the expectant management of preterm premature rupture of membranes if erythromycin is unavailable or contraindicated. There appears to be no additional benefit to an extended course of azithromycin beyond the single-day dosing, but final recommendations on dosing strategies should rely on clinical trials.

Term cesarean delivery in the first pregnancy is not associated with an increased risk for preterm delivery in the subsequent pregnancy.

BACKGROUND: Prior studies have reported an increased risk for preterm delivery following a term cesarean delivery. However, these studies did not adjust for high-risk conditions related to the first cesarean delivery and are known to recur. OBJECTIVE: The objective of the study was to determine whether there is an association between term cesarean delivery in the first pregnancy and subsequent spontaneous or indicated preterm delivery. STUDY DESIGN: This was a retrospective cohort study of women with the first 2 consecutive singleton deliveries (2007-2014) identified through a linked pregnancy database at a single institution. Women with a first pregnancy that resulted in cesarean delivery at term were compared with women whose first pregnancy resulted in a vaginal delivery at term. Exclusion criteria were known to recur medical or obstetrical complications during the first pregnancy. A propensity score analysis was performed by matching women who underwent a cesarean delivery with those who underwent a vaginal delivery in the first pregnancy. The association between cesarean delivery in the first pregnancy and preterm delivery in the second pregnancy in this matched set was examined using conditional logistic regression. The primary outcome was overall preterm delivery <37 weeks in the second pregnancy. Secondary outcomes included type of preterm delivery (spontaneous vs indicated), late preterm delivery (34-36 6/7 weeks), early preterm delivery (<34 weeks), and small-for-gestational-age birth. RESULTS: Of a total of 6456 linked pregnancies, 2284 deliveries were matched; 1142 were preceded by cesarean delivery and 1142 were preceded by vaginal delivery. The main indications for cesarean delivery in the first pregnancy were dystocia in 703 (61.5%), nonreassuring fetal status in 222 (19.4%), breech presentation in 100 (8.8%), and other in 84 (7.4%). The mean (SD) gestational ages at delivery for the second pregnancy was 38.8 (1.8) and 38.9 (1.7) weeks, respectively, for prior cesarean delivery and vaginal delivery. The risks of preterm delivery in the second pregnancy among women with a previous cesarean and vaginal delivery were 6.0% and 5.2%, respectively (adjusted odds ratio, 1.46, 95% confidence interval, [CI] 0.77-2.76). In an analysis stratified by the type of preterm delivery in the second pregnancy, no associations were seen between cesarean delivery in the first pregnancy and spontaneous preterm delivery (4.6% vs 3.9%; adjusted odds ratio, 1.40, 95% confidence interval, 0.59-3.32) or indicated preterm delivery (1.6% vs 1.4%; adjusted odds ratio, 1.21, 95% confidence interval, 0.60-2.46). Similarly, no significant differences were found in late preterm delivery (4.6% vs 4.1%; adjusted odds ratio, 1.13, 95% confidence interval, 0.55-2.29), early preterm delivery (1.6% vs 1.2%; adjusted odds ratio, 1.25, 95% confidence interval, 0.59-2.67), or neonates with birthweight less than the fifth percentile for gestational age (3.6% vs 2.2%; adjusted odds ratio, 1.26, 95% confidence interval, 0.52-3.06). CONCLUSION: After robust adjustment for confounders through a propensity score analysis related to the indication for the first cesarean delivery at term, cesarean delivery is not associated with an increase in preterm delivery, spontaneous or indicated, in the subsequent pregnancy.

Length of the second stage of labor and preterm delivery risk in the subsequent pregnancy.

BACKGROUND: Cervical injury is regarded as an important risk factor for preterm delivery. A prolonged second stage of labor may increase the risk of cervical injury that, in turn, may be associated with increased risk of spontaneous preterm delivery in the subsequent pregnancy. OBJECTIVE: We sought to evaluate whether the duration of the second stage of labor in a term primiparous singleton delivery is associated with an increased risk of singleton spontaneous preterm delivery (<37 weeks) in the second pregnancy. STUDY DESIGN: We carried out a retrospective cohort analysis of women with 2 consecutive pregnancies: a first term (≥37 weeks) delivery and second birth. Data were derived from a single institution's prospectively collected obstetrical database from January 2005 through January 2015. Duration of the second stage of labor was examined as a continuous variable, modeled based on nonparametric restricted cubic regression spline with 4 degrees of freedom. Second-stage duration was also examined as short (<30 minutes), normal (30-179 minutes), and prolonged, defined as ≥180 minutes. The association between the duration of the second stage of labor in the first term pregnancy and the risk for spontaneous preterm delivery in the second pregnancy was evaluated before and after adjusting for potential confounders based on the Cox proportional hazards regression model. Associations were expressed based on the adjusted hazard ratio and 95% confidence interval. RESULTS: In all, 6715 women met inclusion criteria. The hazard of spontaneous preterm delivery in the second pregnancy trended higher with both shorter and longer second-stage labors. The length of the second stage of labor in the first term delivery was categorized as short (<30 minutes) in 1749 (26.0%), normal (30-179 minutes) in 4551 (67.8%), and prolonged (≥180 minutes), in 415 (6.2%) women. Of these 6715 women with a first term delivery, 4.2% (n = 279) delivered spontaneously preterm in the second pregnancy. The risks of spontaneous preterm delivery among women with prolonged (≥180 minutes) second stage of labor and normal labor duration (30-179 minutes) were 5.4% (n = 22) and 3.5% (n = 158), respectively (adjusted hazard ratio, 1.81; 95% confidence interval, 1.15-2.84). This increased risk for prolonged second stage of labor was primarily seen among women who underwent a cesarean (hazard ratio, 3.38; 95% confidence interval, 1.09-10.49), but was imprecise among women who delivered vaginally (hazard ratio, 1.52; 95% confidence interval, 0.62-3.74). The risk of spontaneous preterm delivery among women with short second stage of labor (<30 minutes) in their first term pregnancy was 5.8% (n = 99; hazard ratio, 1.28; 95% confidence interval, 0.99-1.67). CONCLUSION: The risk of spontaneous preterm delivery in the second pregnancy was increased in women with a prolonged (≥180 minutes) second stage in the first term pregnancy. This risk was even greater among women who were delivered by cesarean in the first pregnancy.

Pain is an Independent Risk Factor for Failed Global Endometrial Ablation.

STUDY OBJECTIVE: To determine whether pain, as part of an indication for global endometrial ablation, is an independent risk factor for failure. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Academic-affiliated community hospital. PATIENTS: Women undergoing global endometrial ablation with radiofrequency ablation (RFA), hydrothermablation (HTA), or uterine balloon ablation (UBA) between January 2003 and December 2015. INTERVENTIONS: Procedure failure was defined as subsequent hysterectomy after the index ablation. MEASUREMENTS AND MAIN RESULTS: A total of 5818 women who underwent an endometrial ablation were identified, including 3706 with RFA (63.7%), 1786 with HTA (30.7%), and 326 with UBA (5.6%). Of the 5818 ablations, 437 (7.5%) involved pain (i.e., pelvic pain, dysmenorrhea, dyspareunia, lower abdominal pain, endometriosis, or adenomyosis) before ablation, along with abnormal uterine bleeding. Pain as part of the preoperative diagnoses before endometrial ablation was a significant risk factor for subsequent hysterectomy compared with all other diagnoses (19.2% vs 13.5%; p = .001). Consistent with previous studies, women who underwent ablation at an older age were less likely to fail, which held true even when one of the indications for ablation was related to pain (odds ratio, 0.96/year; 95% confidence interval, 0.95-0.97). When the pathology reports of women who underwent a hysterectomy were examined, women in the pain group had lower rates of adenomyosis than women without pain (38.1% vs 50.1%; p = .04). However, there was a trend toward a higher rate of endometriosis on pathology reports (14.3% vs 8.7%; p = .09) and even higher rates of visualized endometriosis identified by operative reports in women who had pain before their ablation (42.9% vs 15.8%; p < .001). Patients who had pain before their ablation were less likely to have myomas/polyps (p = .01). CONCLUSION: Pelvic pain before global endometrial ablation is an independent risk factor for failure.