Dilapan-S versus Standard Methods for Cervical Ripening in Term Pregnancies: An Individual Patient Data Meta-Analysis.

Abstract

Objectives: Dilapan-S is a cervical ripening agent approved by the FDA that has been found to be just as effective as other agents and can be utilized for outpatient ripening. No large-scale studies have been conducted to compare cesarean delivery rates between Dilapan-S and other ripening methods. Our objective was to combine these trials to compare cesarean delivery rates for Dilapan-S with other cervical ripening methods, overall and in sub-groups.

Data sources: The time period for this study was from January 1994 to April 2023. Ovid MEDLINE, Embase via Ovid, Ovid Emcare, CINAHL Plus, ClinicalTrials.gov, euclinicaltrialsregister.eu, and Scopus were searched. The study was conducted according to the Preferred Reporting Item for Systematic Reviews guidelines and was registered with PROSPERO (CRD42023423573).

Study eligibility criteria: This was a systematic review and meta-analysis of individual patient data (IPD) from randomized controlled trials comparing Dilapan-S to other mechanical or pharmacologic cervical ripening methods for labor induction in singleton gestations. The main outcome measure assessed was the cesarean delivery (CD) rate in comparing Dilapan-S to alternative methods. Secondary maternal outcomes included changes in Bishop score post-intervention, vaginal delivery without complications, postpartum hemorrhage, cervical ripening issues, uterine infection, and patient satisfaction. Secondary neonatal outcomes were Apgar score <7 at 5 minutes, arterial cord pH <7.1, meconium presence, NICU admission and length of stay, hypoxic-ischemic encephalopathy, intraventricular hemorrhage, infant infection, and infant death. This study exclusively included randomized controlled trials (RCTs) involving participants who underwent labor induction during the third trimester of a singleton pregnancy. At least one group within these trials received Dilapan-S for the purpose of cervical ripening. Trials were excluded if induction occurred prior to 37 weeks of gestation or if cervical ripening was deemed unnecessary.

Study appraisal and synthesis: Two reviewers independently selected studies, assessed the risk of bias using the Cochrane Risk of Bias Tool for randomized controlled trials, and extracted the data. Pre-specified subgroup analysis was performed for parity, BMI, Bishop score, and gestational age. Pooled odds ratios (ORs) adjusted for maternal age and parity with 95% confidence intervals (CI) were calculated using frequentist and Bayesian approaches.

Results: Four randomized controlled trials were identified, with 1731 women included (1036 allocated to Dilapan-S; 695 to alternative cervical ripening methods). CD rates were 28% and 30% with Dilapan-S and other methods, respectively. There was no difference in maternal age and parity-adjusted CD rates between Dilapan-S and other methods (OR 1.03, 95% CI 0.8-1.3). Bayesian inference indicated a 95% probability of being non-inferior (5% margin) and a 4.5% probability of being inferior to other methods. Subgroup analysis demonstrated significant interaction with parity with a 99% probability of lowering cesarean rates among multiparous women treated with Dilapan-S (RR 0.61, 95% CrI 0.4-0.9) compared to a 6% probability of benefit among nulliparous women (RR 1.13, 95% CrI 0.97-1.33). Pain levels ≥ 4 were significantly lower in the Dilapan-S group (46% vs. 62%; OR 0.5, 95% CI 0.40-0.64). Complication rates during cervical ripening (uterine hypertonus, uterine tachysystole, non-reassuring fetal heart tracing, and others) were also lower in the Dilapan-S group (19% vs. 47%; OR 0.28, 95% CI 0.28-0.37). Higher patient satisfaction was reported with Dilapan-S.

Conclusion: Dilapan-S was at least non-inferior and marginally superior in lowering cesarean rates compared to other pre-induction cervical ripening agents. Parity impacted efficacy, with multiparous women benefiting the most.