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

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<body mass index≤37 kg/m2), resulted in an area under the receiver operating characteristic curve of 0.76 (95% confidence interval, 0.59–0.93; P=.023). The ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin ratio predicted neonatal outcomes with respective area under the receiver operating characteristic curve of 0.67 (95% confidence interval, 0.57–0.77; P=.005) and 0.78 (95% confidence interval, 0.63–0.93; P=.026) for neonatal composite morbidity and mortality scores of ≥3 or 4. In addition, the ratio of insulin-like growth factor-binding protein 4 to sex hormone binding globulin significantly stratified neonates with increased length of hospital stay (log rank P=.023). Conclusion We confirmed in an independent cohort the ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin ratio as a predictor of very preterm birth, with additional prediction of increased length of neonatal hospital stay and increased severity of adverse neonatal outcomes. Potential uses of the ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin predictor may be to risk stratify patients for implementation of preterm birth preventive strategies and direct patients to appropriate levels of care

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\u27 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\u27s exact test for neonatal morbidity/mortality (significance, p \u3c .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\u27 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

Traction versus 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 PROSPERO 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 (i.e. intervention) versus Foley catheter without traction (i.e. 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. Study appraisal and synthesis 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 (MD) with 95% confidence interval (CI). 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 Foley balloon had a similar time from induction to delivery, compared to no traction (MD 0.25, CI -0.78 to 1.27). No significant differences were found in the secondary outcomes. There was no difference in cesarean delivery between groups (RR 0.94, 95% CI 0.74 to 1.19). Foley catheter expulsion was faster in the tension group (MD -3.74, 95% CI -6.29 to -1.19) Conclusion: Adding traction to an intracervical Foley catheter during cervical ripening does not decrease time to delivery

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 \u3c24 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 \u3c37 weeks of gestation. Prespecified secondary outcomes included preterm birth at \u3c34 and \u3c28 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\u3c.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 \u3c37 (31% vs 38%; P=.28; relative risk, 0.81 [95% confidence interval, 0.54-1.20]), \u3c34 (9.6% vs 14.9%; P=.26; relative risk, 0.64 [95% confidence interval, 0.29-1.41]), or \u3c28 (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

Physical Exam Indicated Cerclage in Twin pregnancy: a Randomized Controlled Trial

Background: Twin pregnancies with dilated cervix in the second trimester are at increased risk of pregnancy loss and early preterm birth; currently there is no proven therapy to prevent preterm birth in this group of women. Objective: To determine if physical exam indicated cerclage reduces the incidence of preterm birth in asymptomatic women with twin gestations and cervical dilation diagnosed before 24 weeks of pregnancy. Study design: Multicenter, parallel-group, open-label, randomized controlled trial of women with twin pregnancy, and asymptomatic cervical dilation from 1-5 cm between 16 0/7 to 23 6/7 weeks were enrolled from 7/2015 to 7/2019 in 8 centers. Eligible women were randomized in a 1:1 ratio to either cerclage or no cerclage. We excluded women with: monochorionic-monoamniotic 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 <34 weeks. Secondary outcomes were preterm birth <32, <28 and <24 weeks, interval from diagnosis to delivery, and perinatal mortality. Data were analyzed as intention to treat. Results: After an interim analysis was performed, the Data Safety Monitoring Board recommended stopping the trial due to significant decrease of perinatal mortality in the cerclage group. We randomized 34 women, four were excluded due to expired informed consent. Seventeen women were randomized to physical exam indicated cerclage and 13 women to no cerclage. Four women randomized to cerclage did not receive the surgical procedure, while 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 cerclage vs no cerclage group, the incidence of preterm birth <34 weeks was significantly decreased: 12/17 (70%) vs 13/13 (100%) (RR: 0.71 95% CI 0.52-0.96), as well as preterm birth <32 weeks 11/17 (64.7%) vs 13/13 (100%) (RR: 0.65 95% CI 0.46-0.92), preterm birth <28 weeks 7/17 (41%) vs 11/13 (84%) (RR: 0.49 95% CI 0.26-0.89) and preterm birth <24 weeks 5/17 (30%) vs 11/13 (84%) (RR: 0.35 95% CI 0.16-0.75). The mean gestational age at delivery was later: 29.05±1.7 vs. 22.5±3.9 weeks (p<0.01); the mean interval from diagnosis of cervical dilation to delivery was longer: 8.3±5.8 vs. 2.9±3.0 weeks (p=0.02). Perinatal mortality was also significantly reduced in the cerclage group 6/34 (17.6%) vs 20/26 (77%), (RR: 0.22 95% CI 0.1-0.5). Conclusion: A combination of physical exam indicated cerclage, indomethacin, and antibiotics in asymptomatic twin pregnancies before 24 weeks significantly decreases preterm birth at all evaluated gestational ages. Most importantly, cerclage in this population is associated with a 50% decrease in very early preterm birth <28 weeks and with a 78% decrease in perinatal mortality

Outpatient versus inpatient management for superimposed preeclampsia without severe features: a retrospective, multicenter study

<p><b>Purpose:</b> To determine if women with preterm superimposed preeclampsia without severe features can be successfully and safely triaged to outpatient management.</p> <p><b>Materials and methods:</b> This was a multicenter, retrospective, cohort study of singleton pregnancies with superimposed preeclampsia without severe features diagnosed before 37 weeks managed outpatient versus inpatient at Thomas Jefferson University (Philadelphia, PA) and at University of Naples (Naples, Italy) from January 2008 to July 2015. The attending physician made the decision to manage outpatient or inpatient at his or her discretion. The primary outcome was composite maternal morbidity defined as development of at least one of the following: severe features, HELLP syndrome, placental abruption, eclampsia, postpartum hemorrhage, intensive care unit admission, or maternal death. Logistic regression, presented as adjusted odds ratio (aOR) with the 95% of confidence interval (CI) was performed.</p> <p><b>Results:</b> A total of 365 women with superimposed preeclampsia without severe features before 37 weeks were analyzed. 198 (54.2%) were managed outpatient, and 167 (45.8%) were managed inpatient. Women managed as outpatients had a similar rate of maternal morbidity compared to those managed as inpatients (36.4% versus 41.3%, aOR 0.82, 95%CI 0.55–1.17). Fetuses from women in the outpatient group had a significantly lower risk of small for gestational age (17.7% versus 29.3%; aOR 0.53, 95%CI 0.30–0.84), and lower risk of admission to neonatal intensive care unit (40.4% versus 47.9%; aOR 0.72, 95%CI 0.39–0.95) compared to women managed as inpatients.</p> <p><b>Conclusions:</b> Low risk women with superimposed preeclampsia without severe features can be triaged to outpatient management without increased maternal morbidity.</p