Vaginal progesterone vs intramuscular 17-hydroxyprogesterone caproate for prevention of recurrent preterm birth: a randomized controlled trial.

BACKGROUND: Preterm birth is the leading cause of neonatal morbidity and mortality, and previous preterm birth is one of the strongest risk factors for preterm birth. National and international obstetrical societies have different recommendations regarding progesterone formulation for the prevention of recurrent preterm birth. OBJECTIVE: This study aimed to determine whether vaginal progesterone is superior to 17-hydroxyprogesterone caproate in the prevention of recurrent preterm birth in patients with singleton pregnancies who had a previous spontaneous preterm birth. STUDY DESIGN: This was an open-label multicenter pragmatic randomized controlled trial at 5 US centers of patients with singleton pregnancies at <24 weeks of gestation who had a previous spontaneous preterm birth randomized 1:1 to either 200 mg vaginal progesterone suppository nightly or 250 mg intramuscular 17-hydroxyprogesterone caproate weekly from 16 to 36 weeks of gestation. Based on the estimated recurrent preterm birth rate of 36% with 17-hydroxyprogesterone caproate, 95 participants were needed in each arm to detect a 50% reduction in preterm birth rate with vaginal progesterone, with 80% power and 2-sided alpha of 0.05. The primary outcome was preterm birth at <37 weeks of gestation. Prespecified secondary outcomes included preterm birth at <34 and <28 weeks of gestation, mean gestational age at delivery, neonatal morbidity and mortality, and measures of adherence. Analysis was by intention to treat. The chi-square test and Student t test were used as appropriate. P<.05 was considered significant. RESULTS: Overall, 205 participants were randomized; 94 participants in the vaginal progesterone group and 94 participants in 17-hydroxyprogesterone caproate group were included. Although gestational age at enrollment was similar, those assigned to vaginal progesterone initiated therapy earlier (16.9±1.4 vs 17.8±2.5 weeks; P=.001). Overall continuation of assigned formulation until delivery was similar (73% vs 69%; P=.61). There was no significant difference in preterm birth at <37 (31% vs 38%; P=.28; relative risk, 0.81 [95% confidence interval, 0.54-1.20]), <34 (9.6% vs 14.9%; P=.26; relative risk, 0.64 [95% confidence interval, 0.29-1.41]), or <28 (1.1% vs 4.3%; P=.37; relative risk, 0.25 [95% confidence interval, 0.03-2.20]) weeks of gestation. Participants in the vaginal progesterone group had a later mean gestational age at delivery than participants in the 17-hydroxyprogesterone caproate group (37.36±2.72 vs 36.34±4.10 weeks; mean difference, 1.02 [95% confidence interval, 0.01-2.01]; P=.047). CONCLUSION: Vaginal progesterone did not reduce the risk of recurrent preterm birth by 50% compared with 17-OHPC; however, vaginal progesterone may lead to increased latency to delivery. This trial was underpowered to detect a smaller, but still clinically significant, difference in the efficacy of preterm birth prevention. Patient factors that impact adherence and ability to obtain medication in a timely fashion should be included in counseling on progesterone selection.

Combination of Foley and prostaglandins versus Foley and oxytocin for cervical ripening: a network meta-analysis.

BACKGROUND: Trial and meta-analysis data revealed a reduction in time to delivery for Foley and prostaglandins or Foley and oxytocin vs Foley alone. However, there are limited data for the comparison of the 2 combination methods against each other. OBJECTIVE: This study aimed to determine whether Foley and prostaglandins or Foley and oxytocin decrease the time to vaginal delivery using a network meta-analysis. STUDY DESIGN: A network meta-analysis (PROSPERO CRD42018081948) was performed comparing Foley and prostaglandins (prostaglandin E1 or prostaglandin E2) vs Foley and oxytocin for cervical ripening. Foley alone and prostaglandins alone were used as nodes for indirect comparison. Database searches were performed from inception to March 2020 with data abstracted from published manuscripts. Eligibility criteria included randomized trials comparing Foley and oxytocin with Foley and prostaglandins (misoprostol or dinoprostone). Trials that compared Foley catheter or prostaglandins with a combination of Foley and prostaglandins or Foley and concurrent oxytocin were also included. Nulliparous and multiparous women were analyzed together. Foley catheters of any catheter material or size and >24 weeks' gestational age with a live fetus were included. Quasi-randomized, cohorts, and other combination methods for cervical ripening were not included. Prostaglandin E1 and prostaglandin E2 combined methods were analyzed separately in a planned subanalysis. The primary outcome was the mean time from induction to vaginal delivery in hours. Secondary outcomes included time from induction to delivery, delivery within 24 hours, cesarean delivery, chorioamnionitis, endometritis, epidural use, tachysystole, postpartum hemorrhage, meconium, neonatal intensive care unit admission, and 5-minute appearance, pulse, grimace, activity, and respiration score of <7. Data were analyzed as a network meta-analysis using multivariate meta-regression. RESULTS: A total of 30 randomized controlled trials with a total of 6465 women were considered eligible for inclusion in this network meta-analysis. When compared with Foley alone, the use of Foley-oxytocin reduced the time to vaginal delivery by 4.2 hours (mean duration, -4.2 hours; 95% confidence interval, -6.5 to -1.9). Foley-prostaglandins reduced the time to vaginal delivery compared with Foley but did not meet statistical significance (mean duration, -2.9 hours; 95% confidence interval, -5.7 to 0.0; P=.05). When compared head-to-head, there was no difference in the time to vaginal delivery between Foley-prostaglandins and Foley-oxytocin (mean duration, 1.3 hours; 95% confidence interval, -2.0 to 4.7). There was no difference in the rate of cesarean delivery, chorioamnionitis, epidural, tachysystole, postpartum hemorrhage, meconium, neonatal intensive care unit admissions, or 5-minute appearance, pulse, grimace, activity, and respiration score of <7 for Foley-prostaglandins vs Foley-oxytocin, although the rate of endometritis was high for Foley-prostaglandins. In the subanalysis by prostaglandin type, there was no difference in the time to vaginal delivery for Foley-misoprostol vs Foley-dinoprostone vs Foley-oxytocin. However, Foley-dinoprostone had a definite trend toward longer time to all deliveries compared with that of both Foley-misoprostol and Foley-oxytocin (P=.05). CONCLUSION: Time to vaginal delivery was similar when comparing Foley with combined misoprostol, combined dinoprostone, and combined oxytocin. Dinoprostone comparisons are limited by small sample size but suggest longer time to delivery compared with Foley and misoprostol or oxytocin. No significant differences were observed in maternal or neonatal adverse events except for endometritis, but this was limited by the sample size, varied reporting of studies used in the indirect comparisons, and definitions of infectious morbidity use in the studies.

Impact of the ACOG guideline regarding low-dose aspirin for prevention of superimposed preeclampsia in women with chronic hypertension.

BACKGROUND: Patients with chronic hypertension are at increased risk for superimposed preeclampsia. The 2016 American College of Obstetricians and Gynecologists guideline recommended initiating 81 mg of daily aspirin for all pregnant women with chronic hypertension to prevent superimposed preeclampsia. OBJECTIVE: (1) To evaluate the rates of implementation of the 2016 American College of Obstetricians and Gynecologists guideline over time; and (2) to evaluate the effectiveness of aspirin for the prevention of superimposed preeclampsia and other adverse maternal and neonatal outcomes in women with chronic hypertension before and after this guideline. STUDY DESIGN: This is a retrospective study of women with chronic hypertension who delivered at Thomas Jefferson University Hospital from January 2014 through June 2018. This cohort of women with chronic hypertension was divided into 2 groups, before and after the American College of Obstetricians and Gynecologists recommendation published in September 2016. Daily 81 mg of aspirin was initiated between 12 and 16 weeks. We excluded multiple gestations and incomplete records. The primary outcome was incidence of superimposed preeclampsia, and secondary outcomes were incidence of superimposed preeclampsia with or without severe features, small for gestational age, and preterm birth <37 weeks. Subgroup analysis based on risk stratification was evaluated in women with chronic hypertension requiring antihypertensive medication, history of preeclampsia, and pregestational diabetes. RESULTS: We identified 457 pregnant women with chronic hypertension, 203 in the post-American College of Obstetricians and Gynecologists group and 254 in the pre-American College of Obstetricians and Gynecologists group. Aspirin 81 mg was offered to 142 (70%) in the post-American College of Obstetricians and Gynecologists group and 18 (7.0%) in the pre-American College of Obstetricians and Gynecologists group. Maternal demographics were not significantly different. The overall incidence of superimposed preeclampsia was not significantly different: 87 (34.3%) vs 72 (35.5%), P=.79, in the pre- and post-American College of Obstetricians and Gynecologists guideline groups, respectively. Superimposed preeclampsia with severe features significantly increased: 32 (12.6%) vs 9 (4.4%), P<.01, whereas superimposed preeclampsia without severe features significantly decreased: 55 (21.7%) vs 63 (31.0%), P=.03. There were no significant differences in small for gestational age neonates or preterm birth <37 weeks incidences between groups. There were no significant differences in the subgroup analysis based on the severity of chronic hypertension requiring antihypertensive medication, history of preeclampsia, or pregestational diabetes. CONCLUSION: After the adoption of the American College of Obstetricians and Gynecologists guidelines in 70% of the cohort, superimposed preeclampsia, small for gestational age, and preterm birth were not significantly decreased after implementation of aspirin 81 mg initiated between 12 and 16 weeks of gestation.

Physical examination-indicated cerclage in twin pregnancy: a randomized controlled trial.

BACKGROUND: Women with twin pregnancies and a dilated cervix in the second trimester are at increased risk of pregnancy loss and early preterm birth; there is currently no proven therapy to prevent preterm birth in this group of women. OBJECTIVE: This study aimed to determine whether physical examination-indicated cerclage reduces the incidence of preterm birth in women with a diagnosis of twin pregnancies and asymptomatic cervical dilation before 24 weeks of gestation. STUDY DESIGN: Multicenter, parallel group, open-label, randomized controlled trial of women with twin pregnancies and asymptomatic cervical dilation of 1 to 5 cm between 16 weeks 0/7 days of gestation and 23 weeks 6/7 days of gestation were enrolled from July 2015 to July 2019 in 8 centers. Eligible women were randomized in a 1:1 ratio into either cerclage or no cerclage groups. We excluded women with monochorionic-monoamniotic twin pregnancy, selective fetal growth restriction, twin-twin transfusion syndrome, major fetal malformation, known genetic anomaly, placenta previa, signs of labor, or clinical chorioamnionitis. The primary outcome was the incidence of preterm birth at <34 weeks of gestation. Secondary outcomes were preterm births at <32, <28, and <24 weeks of gestation, interval from diagnosis to delivery, and perinatal mortality. Data were analyzed by intention-to-treat methods. RESULTS: After an interim analysis was performed, the Data and Safety Monitoring Board recommended stopping the trial because of a significant decrease in perinatal mortality in the cerclage group. We randomized 34 women, with 4 women being excluded because of expired informed consent. A total of 17 women were randomized to physical examination-indicated cerclage and 13 women to no cerclage. Whereas 4 women randomized to cerclage did not receive the surgical procedure, no women in the no cerclage group received cerclage. Maternal demographics were not significantly different. All women in the cerclage group also received indomethacin and antibiotics. When comparing the cerclage group vs the no cerclage group, the incidence of preterm birth was significantly decreased as follows: preterm birth at <34 weeks of gestation, 12 of 17 women (70%) vs 13 of 13 women (100%) (risk ratio, 0.71; 95% confidence interval, 0.52-0.96); preterm birth at <32 weeks of gestation, 11 of 17 women (64.7%) vs 13 of 13 women (100%) (risk ratio, 0.65; 95% confidence interval, 0.46-0.92); preterm birth at <28 weeks of gestation, 7 of 17 women (41%) vs 11 of 13 women (84%) (risk ratio, 0.49; 95% confidence interval, 0.26-0.89); and preterm birth at <24 weeks of gestation, 5 of 17 women (30%) vs 11 of 13 women (84%) (risk ratio, 0.35; 95% confidence interval, 0.16-0.75). The mean gestational age at delivery was 29.05±1.7 vs 22.5±3.9 weeks (P<.01), respectively; the mean interval from diagnosis of cervical dilation to delivery was 8.3±5.8 vs 2.9±3.0 weeks (P=.02), respectively. Perinatal mortality was also significantly reduced in the cerclage group compared with the no cerclage group as follows: 6 of 34 women (17.6%) vs 20 of 26 women (77%) (risk ratio, 0.22; 95% confidence interval, 0.1-0.5), respectively. CONCLUSION: In women with twin pregnancies and asymptomatic cervical dilation before 24 weeks of gestation, a combination of physical examination-indicated cerclage, indomethacin, and antibiotics significantly decreased preterm birth at all evaluated gestational ages. Most importantly, cerclage in this population was associated with a 50% decrease in early preterm birth at <28 weeks of gestation and with a 78% decrease in perinatal mortality.

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.

Cervical Ripening Using Foley Balloon with or without Oxytocin: A Systematic Review and Meta-Analysis.

OBJECTIVE: To assess available evidence regarding the use of oxytocin in conjunction with Foley balloon (FB) for cervical ripening. METHODS: Databases from MEDLINE (U.S. National Library of Medicine, 1980-May 12, 2017), MEDLINE (Ovid, 1980-June 30, 2017), the Cochrane Library Controlled Trials Register, ClinicalTrials.gov, and Web of Science were queried for studies on FB cervical ripening with or without oxytocin in pregnant women. Search terms included: "balloon dilatation" OR "mechanical methods" OR "mechanical method" OR "mechanical dilation" OR "mechanical dilatation" OR "mechanical dilations" OR "mechanical dilatations" OR "balloon" OR "Foley" AND "Pitocin" OR "oxytocin." All relevant references were reviewed. Literature for inclusion and methodological quality were reviewed based on the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. RESULTS: Out of 344 citations, six randomized clinical trials (1,133 patients) fulfilled our inclusion criteria. The pooled estimate showed that the cesarean delivery (CD) rate did not differ (relative risk [RR]: 0.91 (95% confidence interval [CI] [0.76-1.10]; p = 0.23) between patients who underwent preinduction cervical ripening with FB alone versus those who received oxytocin in addition to FB. Heterogeneity was not significant among studies (I 2 0.0%; p = 0.64). Furthermore, no differences in other outcomes such as composite and maternal outcomes were detected between these two groups. Compared with simultaneous use of oxytocin with FB, the Foley alone cervical ripening group had a longer induction to delivery time, and lower deliveries within 12 and 24 hours. Subgroup analysis showed that only multiparous women in the Foley alone group had lower rate of vaginal delivery within 24 hours (RR: 0.74, 95% CI [0.61-0.89], p = 0.002) along with a trend toward higher CD rates. CONCLUSION: Adding oxytocin to FB at the time of preinduction cervical ripening does not reduce cesarean rates nor improve maternal or neonatal outcomes. Multiparous women who received FB alone seem to have lower rates of vaginal deliveries within 24 hours, but these results should be interpreted with caution.

Increased single-balloon Foley catheter volume for induction of labor and time to delivery: a systematic review and meta-analysis.

INTRODUCTION: Induction of labor is a common intervention. The objective was to investigate whether larger Foley catheter volumes for labor induction decrease the total time from induction to delivery. MATERIAL AND METHODS: Randomized controlled trials comparing larger single-balloon volumes (60-80 mL) during Foley catheter cervical ripening with usual volume (30 mL) in women undergoing labor induction were identified by searching electronic databases (MEDLINE, Scopus, ClinicalTrials.gov, PROSPERO, EMBASE, Scielo and the Cochrane Central Register of Controlled Trials) from inception through 2017. The primary outcome was mean time from induction to delivery in hours. Secondary outcomes included time from induction to vaginal delivery, delivery within 24 h, time to Foley expulsion, cesarean section, chorioamnionitis, epidural use, hemorrhage, meconium staining, and neonatal intensive care unit admission. Meta-analysis was performed using the random effects model of DerSimonian and Laird (PROSPERO CRD42017058885). RESULTS: Seven randomized controlled trials including 1432 singleton gestations were included in the systematic review. Women randomized to larger volumes of balloon had a significantly shorter time from induction to delivery (mean difference 1.97 h, 95% CI -3.88 to -0.06). There was no difference in cesarean section between groups (16 vs. 18%, relative risk 0.84, 95% CI 0.6-1.17). A larger balloon volume was associated with a nonsignificant decrease in time from induction to delivery in multiparous (mean difference 2.67 h, 95% CI -6.1 to 0.76) and nulliparous women (mean difference 1.82 h, 95% CI -4.16 to 0.53). CONCLUSION: Balloon volumes larger than 30 mL during Foley catheter induction reduce total time to delivery by approximately 2 h.

Why the United States preterm birth rate is declining.

The preterm birth rate in the United States declined to 11.4% in 2013, the lowest level since 1997. Although the United States has one of the highest preterm birth rates in the developed world, we are improving this outcome and therefore improving the lives of thousands of infants. Demographic changes that may be responsible include a reduced teenage birth rate and fewer higher-order multiple births. Additionally, a public policy shift to prevent nonmedically indicated births at <39 weeks' gestation and smoking bans in several states have been associated with the reduced rate of preterm births. Last, interventions such as 17 hydroxyprogesterone caproate, vaginal progesterone, and the use of cerclage in selected populations probably are contributing to the reduction in preterm deliveries. However, a large portion of these births could still be prevented with greater access and implementation of our current interventions, the reduction of modifiable risk factors for preterm birth, and expanded reporting of outcomes and risk factors to facilitate research for both prevention and treatment.

Differential utilization of expanded genetic screening tests in patients of reproductive ages from private and academic practices.

OBJECTIVE: We sought to evaluate the types of genetic screening tests that are performed in women of childbearing ages in New Jersey. METHOD: Data from patients who had a reproductive genetics consultation between January 1, 2012, and July 31, 2012, were stratified according to the referring providers, i.e., those from academic or private practices, and descriptive analyses performed. Unconventional genetic screening was defined as any test ordered by the referring health care provider outside the recommendations from the American Congress of Obstetricians and Gynecologists or the American College of Medical Genetics and Genomics. RESULTS: Overall, 30% of 371 patients referred for a genetic consultation underwent unconventional screening. As compared to patients from academic practices, the relative rate of unconventional screening was 10-fold higher among patients from private practices, resulting in a relative 34-fold increase in the estimated cost in genetic screening (P<0.01). CONCLUSION: This set of preliminary observations highlight the need for further state, nationwide, and international studies to understand the financial, personal, and societal impact that this discrepancy health care system in the use of genetic carrier screening portends.

Induction of labor versus expectant management in patients with idiopathic polyhydramnios.

OBJECTIVE: To evaluate whether induction of labor is associated with lower risk of cesarean section compared to expectant management in patients with isolated polyhydramnios. STUDY DESIGN: This is a single-center, retrospective cohort study of patients with pregnancies complicated by idiopathic polyhydramnios, documented between 34 and 38 weeks gestation, who were delivered between July 2012 and February 2020. The primary outcome was cesarean delivery. Secondary outcomes included chorioamnionitis, endometritis, postpartum hemorrhage, preeclampsia/gestational hypertension, and composite neonatal morbidity. RESULTS: There were 194 patients included with idiopathic polyhydramnios - 115 underwent induction and 79 patients were expectantly managed. Planned induction was associated with a lower rate of CD compared with expectant management but did not meet statistical significance (19.1 % vs 30.4 %, aOR 0.51, 95 % CI 0.24, 1.05). A similar effect was seen when stratifying for parity: both nulliparous (9.1 % vs 16.3 %, aOR 0.59, 95 % CI 0.17, 1.98) and multiparous (32.7 % vs 47.2 %, aOR 0.45, 95 % CI 0.18, 1.15) patients had a lower CD rate when there was a planned induction, though neither group met statistical significance. No differences in maternal or fetal secondary outcomes were identified (chorioamnionitis, endometritis, postpartum hemorrhage, preeclampsia/gestational hypertension, composite neonatal morbidity). CONCLUSION: Lower rates of cesarean section were associated with labor induction for patients with isolated polyhydramnios, but confidence intervals did not reach statistical significance.

Development of a Maternal Equity Safety Bundle to Eliminate Racial Inequities in Massachusetts.

OBJECTIVE: The PNQIN (Perinatal-Neonatal Quality Improvement Network of Massachusetts) sought to adapt the Reduction of Peripartum Racial and Ethnic Disparities Conceptual Framework and Maternal Safety Consensus Bundle by selecting and defining measures to create a bundle to address maternal health inequities in Massachusetts. This study describes the process of developing consensus-based measures to implement the PNQIN Maternal Equity Bundle across Massachusetts hospitals participating in the Alliance for Innovation on Maternal Health Initiative. METHODS: Our team used a mixed-methods approach to create the PNQIN Maternal Equity Bundle through consensus including a literature review, expert interviews, and a modified Delphi process to compile, define, and select measures to drive maternal equity-focused action. Stakeholders were identified by purposive and snowball sampling and included obstetrician-gynecologists, midwives, nurses, epidemiologists, and racial equity scholars. Dedoose 9.0 was used to complete an inductive analysis of interview transcripts. A modified Delphi method was used to reach consensus on recommendations and measures for the PNQIN Maternal Equity Bundle. RESULTS: Twenty-five interviews were completed. Seven themes emerged, including the need for 1) data stratification by race, ethnicity and language; 2) performance of a readiness assessment; 3) culture shift toward equity; 4) inclusion of antiracism and bias training; 5) addressing challenges of nonacademic hospitals; 6) a life-course approach; and 7) selection of timing of implementation. Twenty initial quality measures (structure, process, and outcome) were identified through expert interviews. Group consensus supported 10 measures to be incorporated into the bundle. CONCLUSION: Structure, process, and outcome quality measures were selected and defined for a maternal equity safety bundle that seeks to create an equity-focused infrastructure and equity-specific actions at birthing facilities. Implementation of an equity-focused safety bundle at birthing facilities may close racial gaps in maternal outcomes.

Traction vs no traction in Foley catheter use for induction of labor: a systematic review and meta-analysis of randomized trials.

OBJECTIVE: Intracervical Foley catheter is a safe and effective method for cervical ripening. There are a variety of ways to modify this ripening method, including adding traction or tension to the catheter. The utility of this practice is uncertain. The aim of this systematic review and meta-analysis of randomized controlled trials was to investigate whether the placement of traction vs no traction on a Foley catheter during cervical ripening decreases total time from induction to delivery. DATA SOURCES: Electronic sources include MEDLINE, Scopus, ClinicalTrials.gov, the International Prospective Register of Systematic Reviews, SciELO, the Cochrane Central Register of Controlled Trials, and Google Scholar from inception through June 2020. STUDY ELIGIBILITY CRITERIA: Randomized trials comparing Foley catheter with traction (ie, intervention) vs Foley catheter without traction (ie, control) for cervical ripening were included in the meta-analysis. All types of traction were analyzed (weighted, taped to thigh) and whether the traction was placed only initially at Foley catheter placement or repeated throughout the ripening process. METHODS: The primary outcome was the mean time from induction to delivery in hours. Meta-analysis was performed using the random-effects model of DerSimonian and Laird to produce summary treatment effects in terms of mean difference with 95% confidence interval. Heterogeneity was measured using I-squared (Higgins I2). RESULTS: Three trials including 790 singleton gestations were identified as relevant and included in the systematic review. Women randomized to traction on the Foley balloon had a similar time from induction to delivery compared with no traction (mean difference, 0.25; confidence interval, -0.78 to 1.27). No significant differences were found in the secondary outcomes. There was no difference in cesarean delivery between groups (relative risk, 0.94; 95% confidence interval, 0.74-1.19). Foley catheter expulsion was faster in the tension group (mean difference, -3.74; 95% confidence interval, -6.29 to -1.19) CONCLUSION: Adding traction to an intracervical Foley catheter during cervical ripening does not decrease time to delivery.

Calculated blood loss at cesarean delivery in patients with preeclampsia with severe features on magnesium sulfate.

INTRODUCTION: Magnesium sulfate decreases the risk of eclampsia in patients with severe preeclampsia. There is a theoretical risk that magnesium sulfate increases the risk of intrapartum hemorrhage. We evaluated whether there was a quantitative difference in blood loss in patients receiving magnesium sulfate at the time of cesarean delivery (CD) compared to those who were not. MATERIALS AND METHODS: A retrospective cohort study was performed using a database of patients with preeclampsia with severe features or eclampsia. The primary outcome was calculated estimated blood loss (cEBL) compared between patients who received magnesium sulfate during CD and those who did not. cEBL was derived through a validated equation by multiplying the patient's blood volume by percent of blood volume loss. Secondary outcomes were hematocrit change, visual EBL (vEBL), hemorrhage, cEBL >1500mL, Apgar <7 at 5 min, and NICU admission. Exclusion criteria were incomplete records or negative cEBL, as well as blood transfusion prior to collection of a postpartum hematocrit. RESULTS: We identified 124 patients with preeclampsia with severe features or eclampsia at time of CD. There were 57 (46%) that received magnesium sulfate during CD and 67 (54%) in which magnesium was stopped during the CD. The mean differences for hematocrit value (0.8, 95% confidence interval (CI) -0.3 to 1.8) and cEBL (108, 95% CI -102 to 318) were not significantly different after adjusting for obesity and history of CD. CONCLUSION: Magnesium sulfate administration for seizure prevention in patients with preeclampsia with severe features at the time of CD does not appear to be associated with an increase in the cEBL.

Failure to Detect SARS-CoV-2 RNA in the Air During Active Labor in Mothers Who Recently Tested Positive.

The risk of potential SARS-CoV-2 transmission by infected mothers during labor and delivery has not been investigated in-depth. This work collected air samples close to (respiratory droplets) and more distant from (aerosol generation) unvaccinated patients who had previously tested positive for SARS-CoV-2 during labor within 5 days of a positive test. All but one of the patients wore masks during the delivery, and delivery was carried out in either birthing or negative pressure isolation rooms. Our work failed to detect SARS-CoV-2 RNA in any air samples for all of the six patients who gave birth vaginally, despite validation of the limit of detection of the samplers. In sum, this brief report provides initial evidence that the risk of airborne transmission of SARS-CoV-2 during labor may be mitigated by the use of masks and high ventilation rates common in many modern U.S. medical facilities; however more work is needed to fully evaluate the risk of SARS-CoV-2 transmission during labor and maternal pushing.

Neutralizing Antibodies and Cytokines in Breast Milk After Coronavirus Disease 2019 (COVID-19) mRNA Vaccination.

OBJECTIVE: To evaluate immune responses to coronavirus disease 2019 (COVID-19) mRNA-based vaccines present in breast milk and transfer of the immune responses to breastfeeding infants. METHODS: We enrolled 30 lactating women who received mRNA-based COVID-19 vaccines from January through April 2021 in this cohort study. Women provided serial milk samples, including milk expressed before vaccination, across 2-3 weeks after the first dose, and across 3 weeks after the second dose. Women provided their blood, spotted on cards (dried blood spots), 19 days after the first dose and 21 days after the second dose. Stool samples from the breastfed infants were collected 21 days after mothers' second vaccination. Prepandemic samples of milk, dried blood spots, and infant stool were used as controls. Milk, dried blood spots, and infant stool were tested by enzyme-linked immunosorbent assay for receptor-binding domain (RBD)-specific immunoglobulin (Ig)A and IgG. Milk samples were tested for the presence of neutralizing antibodies against the spike and four variants of concern: D614G, Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P.1). Levels of 10 cytokines were measured in milk samples. RESULTS: Milk from COVID-19-immunized women neutralized the spike and four variants of concern, primarily driven by anti-RBD IgG. The immune response in milk also included significant elevation of interferon-γ. The immune response to maternal vaccination was reflected in breastfed infants: anti-RBD IgG and anti-RBD IgA were detected in 33% and 30% of infant stool samples, respectively. Levels of anti-RBD antibodies in infant stool correlated with maternal vaccine side effects. Median antibody levels against RBD were below the positive cutoffs in prepandemic milk and infant stool samples. CONCLUSION: Humoral and cellular immune responses to mRNA-based COVID-19 vaccination are present in most women's breast milk. The milk anti-RBD antibodies can neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike and variants of concern. Anti-RBD antibodies are transferred to breastfed infants, with the potential to confer passive immunity against SARS-CoV-2.

Clinical and economic evaluation of a proteomic biomarker preterm birth risk predictor: cost-effectiveness modeling of prenatal interventions applied to predicted higher-risk pregnancies within a large and diverse cohort.

OBJECTIVES: Preterm birth occurs in more than 10% of U.S. births and is the leading cause of U.S. neonatal deaths, with estimated annual costs exceeding $25 billion USD. Using real-world data, we modeled the potential clinical and economic utility of a prematurity-reduction program comprising screening in a racially and ethnically diverse population with a validated proteomic biomarker risk predictor, followed by case management with or without pharmacological treatment. METHODS: The ACCORDANT microsimulation model used individual patient data from a prespecified, randomly selected sub-cohort (N = 847) of a multicenter, observational study of U.S. subjects receiving standard obstetric care with masked risk predictor assessment (TREETOP; NCT02787213). All subjects were included in three arms across 500 simulated trials: standard of care (SoC, control); risk predictor/case management comprising increased outreach, education and specialist care (RP-CM, active); and multimodal management (risk predictor/case management with pharmacological treatment) (RP-MM, active). In the active arms, only subjects stratified as higher risk by the predictor were modeled as receiving the intervention, whereas lower-risk subjects received standard care. Higher-risk subjects' gestational ages at birth were shifted based on published efficacies, and dependent outcomes, calibrated using national datasets, were changed accordingly. Subjects otherwise retained their original TREETOP outcomes. Arms were compared using survival analysis for neonatal and maternal hospital length of stay, bootstrap intervals for neonatal cost, and Fisher's exact test for neonatal morbidity/mortality (significance, p < .05). RESULTS: The model predicted improvements for all outcomes. RP-CM decreased neonatal and maternal hospital stay by 19% (p = .029) and 8.5% (p = .001), respectively; neonatal costs' point estimate by 16% (p = .098); and moderate-to-severe neonatal morbidity/mortality by 29% (p = .025). RP-MM strengthened observed reductions and significance. Point estimates of benefit did not differ by race/ethnicity. CONCLUSIONS: Modeled evaluation of a biomarker-based test-and-treat strategy in a diverse population predicts clinically and economically meaningful improvements in neonatal and maternal outcomes.

Preterm birth, defined as delivery before 37 weeks' gestation, is the leading cause of illness and death in newborns. In the United States, more than 10% of infants are born prematurely, and this rate is substantially higher in lower-income, inner-city and Black populations. Prematurity associates with greatly increased risk of short- and long-term medical complications and can generate significant costs throughout the lives of affected children. Annual U.S. health care costs to manage short- and long-term prematurity complications are estimated to exceed $25 billion.Clinical interventions, including case management (increased patient outreach, education and specialist care), pharmacological treatment and their combination can provide benefit to pregnancies at higher risk for preterm birth. Early and sensitive risk detection, however, remains a challenge.We have developed and validated a proteomic biomarker risk predictor for early identification of pregnancies at increased risk of preterm birth. The ACCORDANT study modeled treatments with real-world patient data from a racially and ethnically diverse U.S. population to compare the benefits of risk predictor testing plus clinical intervention for higher-risk pregnancies versus no testing and standard care. Measured outcomes included neonatal and maternal length of hospital stay, associated costs and neonatal morbidity and mortality. The model projected improved outcomes and reduced costs across all subjects, including ethnic and racial minority populations, when predicted higher-risk pregnancies were treated using case management with or without pharmacological treatment. The biomarker risk predictor shows high potential to be a clinically important component of risk stratification for pregnant women, leading to tangible gains in reducing the impact of preterm birth.

Intracervical Foley catheter with and without oxytocin for labor induction with Bishop score ≤3: a secondary analysis.

BACKGROUND: The combination method for cervical ripening with a Foley catheter and concurrent oxytocin administration has been shown to reduce the total time from induction to delivery when compared with a Foley catheter only in patients with an unfavorable cervix (Bishop score of <6). It is unclear if this is still effective for patients with a less favorable cervix as indicated by a Bishop score of ≤3. OBJECTIVE: This study aimed to determine if inducing labor with a Foley catheter and concurrent oxytocin administration reduced the total time from induction to delivery in subjects with a Bishop score of ≤3 compared with those who only received a Foley catheter without oxytocin for cervical ripening. STUDY DESIGN: This was a secondary analysis of a randomized, multicenter trial of patients with a live singleton pregnancy at ≥24 weeks' gestation undergoing labor induction with a Foley catheter and a Bishop score of <6. This analysis included patients with a Bishop score of ≤3. Exclusions included >1 cesarean delivery, unexplained bleeding, nonreassuring fetal tracing, major fetal anomalies, or other contraindications for vaginal delivery. The subjects were randomized to receive an intracervical Foley catheter only or with concurrent oxytocin infusion. The primary outcome for this analysis was the time from induction to delivery. Secondary outcomes included delivery at ≤12 hours, time to delivery ≤24 hours, cesarean delivery, total time of oxytocin infusion, need for additional ripening agents, postpartum hemorrhage, chorioamnionitis, and neonatal intensive care unit admission. RESULTS: A total of 322 patients were enrolled in the primary trial; 151 subjects had an initial Bishop score of ≤3 and were included in the secondary analysis (n=77 for Foley catheter with oxytocin and n=74 for the Foley catheter only). The demographics were similar in both groups. Those with a Bishop score of ≤3 who received a Foley catheter with concurrent oxytocin administration had a shorter time from induction to delivery than those patients who received a Foley catheter only for cervical ripening (21.3 vs 27 hours; P=.005). The group with a Foley catheter and oxytocin administered concurrently also had a shorter time from induction to delivery after adjusting for body mass index, parity status, and first Bishop score (21.5 vs 26.7 hours; P=.007). They also were more likely to deliver within 24 hours (74% vs 46%; P=.001) and not to require additional ripening agents (4% vs 15%; P=.04). Patients with the Foley catheter only method were more likely to receive additional ripening agents, but had fewer hours of oxytocin infusion (19.1 vs 12.4 hours; P<.001). There was no difference in the rate of delivery at ≤12 hours, cesarean delivery, postpartum hemorrhage, chorioamnionitis, and neonatal intensive care unit admission. CONCLUSION: Concurrent Foley catheter and oxytocin infusion significantly reduced the time from induction to delivery in patients with a Bishop score of ≤3 when compared with a Foley catheter only, particularly in multiparous patients.

Evidence-based labor management: induction of labor (part 2).

Induction of labor is indicated for many obstetrical, maternal, and fetal indications. Induction can be offered for pregnancy at 39 weeks' gestation. No prediction method is considered sensitive or specific enough to determine the incidence of cesarean delivery after induction. A combination of 60- to 80-mL single-balloon Foley catheter for 12 hours and either 25-µg oral misoprostol initially, followed by 25 µg every 2-4 hours, or 50 µg every 4-6 hours (if no more than 3 contractions per 10 minutes or previous uterine surgery), or oxytocin infusion should be recommended for induction of labor. Adding membrane stripping at the beginning of induction should be considered. Once 5-6 cm of cervical dilation is achieved during the induction of labor, consideration can be given to discontinue oxytocin infusion if in use at that time and adequate contractions are present. Induction with oxytocin immediately (as soon as feasible) or up to 12 hours of term prelabor rupture of membranes if labor is not evident is recommended. Outpatient Foley ripening can be considered for low-risk women. Cesarean delivery should not be performed before 15 hours of oxytocin infusion and amniotomy if feasible and ideally after 18-24 hours of oxytocin infusion.

Prenatal Depression and Risk of Short Interpregnancy Interval in a Predominantly Puerto Rican Population.

Background: Short interpregnancy interval (IPI) is associated with risk of adverse pregnancy outcomes; however, few studies have evaluated the role of depression as a risk factor for short IPI. Puerto Rican women in the United States experience disparities in adverse birth outcomes and have the highest birth rates. Methods: We analyzed the association between prenatal depressive symptoms and IPI in Proyecto Buena Salud, a prospective cohort of predominantly Puerto Rican women in Western Massachusetts (2006-2011). Depression was measured using the Edinburgh Postnatal Depression Scale (EPDS) in early, mid, and late pregnancy. We calculated follow-up time as the difference between the date of delivery of the index pregnancy and the last menstrual period of the subsequent pregnancy using medical records and billing data. We defined short IPI as ≤18 months. Results: Of 1262 eligible women, 35% (n = 440) had at least probable minor depression (EPDS scores ≥13) and 25% (n = 315) had probable major depression (EPDS scores ≥15). Participants were followed for a median of 3.7 years (interquartile range = 1.4-6.0 years) and 240 (20.6%) participants experienced a short IPI. After adjusting for risk factors, women with probable minor depression (adjusted odds ratio [aOR] = 1.39, 95% confidence interval [CI] = 1.02-1.88) and probable major depression (aOR = 1.42, 95% CI = 1.02-1.97) during pregnancy had increased odds of short IPI. Conclusions: Prenatal depressive symptoms were common in this Puerto Rican population and were associated with a modest increase in odds of short IPI. Further examination of the pathways through which mental health may affect IPI in vulnerable populations is warranted.

Performance of a proteomic preterm delivery predictor in a large independent prospective cohort.

BACKGROUND: Preterm birth remains a common and devastating complication of pregnancy. There remains a need for effective and accurate screening methods for preterm birth. Using a proteomic approach, we previously discovered and validated (Proteomic Assessment of Preterm Risk study, NCT01371019) a preterm birth predictor comprising a ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin. OBJECTIVE: To determine the performance of the ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin to predict both spontaneous and medically indicated very preterm births, in an independent cohort distinct from the one in which it was developed. STUDY DESIGN: This was a prospective observational study (Multicenter Assessment of a Spontaneous Preterm Birth Risk Predictor, NCT02787213) at 18 sites in the United States. Women had blood drawn at 170/7 to 216/7 weeks' gestation. For confirmation, we planned to analyze a randomly selected subgroup of women having blood drawn between 191/7 and 206/7 weeks' gestation, with the results of the remaining study participants blinded for future validation studies. Serum from participants was analyzed by mass spectrometry. Neonatal morbidity and mortality were analyzed using a composite score by a method from the PREGNANT trial (NCT00615550, Hassan et al). Scores of 0-3 reflect increasing numbers of morbidities or length of neonatal intensive care unit stay, and 4 represents perinatal mortality. RESULTS: A total of 5011 women were enrolled, with 847 included in this planned substudy analysis. There were 9 preterm birth cases at <320/7 weeks' gestation and 838 noncases at ≥320/7 weeks' gestation; 21 of 847 infants had neonatal composite morbidity and mortality index scores of ≥3, and 4 of 21 had a score of 4. The ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin ratio was substantially higher in both preterm births at <320/7 weeks' gestation and there were more severe neonatal outcomes. The ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin ratio was significantly predictive of birth at <320/7 weeks' gestation (area under the receiver operating characteristic curve, 0.71; 95% confidence interval, 0.55-0.87; P=.016). Stratification by body mass index, optimized in the previous validation study (22