Addition of Misoprostol to Double-Balloon Catheter for Cervical Ripening Associated with Improved Obstetric Outcomes

Introduction: Induction of labor (IOL) may be recommended in the setting of pregnancy complications, gestational age, maternal comorbidities, or electively after 39 weeks gestational age. If IOL is indicated but the cervix is determined to be unfavorable, cervical ripening agents like mechanical dilators and synthetic prostaglandin E1 medications can be used to promote cervical dilation, softening, and thinning to mimic the physiologic processes of spontaneous labor. The objective of this study was to compare labor outcomes of women who underwent cervical ripening with a double-balloon catheter alone or with the addition of concurrent misoprostol. We hypothesized that concomitant use of misoprostol and cervical ripening balloon (CRB) was associated with increased vaginal delivery rates compared to CRB use alone. Methods: This study was a retrospective cohort analysis. The Epic medical record system was used to identify all patients who underwent IOL at Eskenazi Hospital during the study period (January 1, 2021- December 31, 2023). Patients were included if they underwent induction that included the use of a balloon catheter for cervical ripening, with or without additional medications. Exclusion criteria included placenta previa, history of prior cesarean delivery, gestational age less than 34 weeks, or contraindications to vaginal delivery. Data was extracted from the electronic medical record by study investigators and entered into the password-protected REDCap data collection system. Broadly, data collected included patient demographics (e.g., AMA, gestational age, ethnicity, nulliparity, indication for IOL), labor characteristics (e.g., cervical exam at time of balloon placement and removal, fetal presentation at admission, medication use in relation to balloon placement and removal), and maternal and fetal outcomes (e.g., terbutaline use, delivery mode, estimated blood loss, 5-minute Apgar score, NICU admission). Descriptive statistics were calculated using Chi-Square for categorical variables and t-test for continuous variables. Unadjusted and adjusted logistic regression models were used to calculate odds ratios with 95% confidence intervals. All statistics were performed using SAS V9.4 (SAS Institute, Cary, NC). Results: Of 1714 patients identified during the study period, 327 charts were reviewed with 323 meeting criteria for analysis. All 323 patients underwent IOL with a double-balloon catheter; 204 (63.2%) received concurrent misoprostol, while 119 (36.8%) received no additional pharmacologic agents. Baseline characteristics including mean maternal age, number of patients of advanced maternal age (AMA), ethnicity, and indication for induction were similar between groups. Individuals who received misoprostol in addition to the double-balloon catheter tended to have a greater mean gestational age (38.4±1.56 vs. 37.9±1.86 weeks; p = 0.009) and were less likely to be nulliparous (43.6 vs. 59.7%; p = 0.005) compared to those without additional pharmacologic intervention. Patients who received concurrent misoprostol were significantly more likely to achieve vaginal delivery compared to those who received balloon catheter alone (84.3% vs. 60.5%, p < 0.0001). An unadjusted logistic regression demonstrated that treatment with balloon catheter and concurrent misoprostol was associated with reduced odds of cesarean delivery (OR 0.29, 95% CI: 0.17–0.48). This association remained significant after adjusting for nulliparity, indication for induction, birth weight, and AMA status (adjusted OR 0.32, 95% CI: 0.18–0.56). Patients who underwent cesarean delivery were more likely to be nulliparous (OR 3.69, 95% CI: 1.95-7.02), be AMA (OR 2.96, 95% CI: 1.37-6.40), have gestational or chronic hypertension (OR 1.99, 95% CI: 1.00-3.95), and deliver infants with higher birth weights (OR 2.22, 95% CI: 1.25-3.97). These risk factors for cesarean delivery have also been demonstrated in prior research. When stratified by delivery mode, there were no significant differences in rates of tachysystole (p = 0.68 for vaginal, p = 0.16 for cesarean), maternal complications (p = 0.82, p = 0.07), estimated blood loss (p = 0.14, p = 0.54), NICU admission (p = 0.15, p = 0.64), or low 5-minute Apgar scores (p = 0.52, p = 0.35) between patients who received both misoprostol and balloon catheter and those who received a balloon catheter alone. Discussion: Concurrent use of misoprostol and CRB during IOL was associated with increased vaginal delivery rate without a significant difference in NICU admission or obstetric complication rates. Patients who underwent cesarean delivery were more likely to be nulliparous, be AMA, have infants with higher birth weights, and have gestational or chronic hypertension, regardless of ripening technique used. Potential impacts of this study include providing evidence-based recommendations on cervical ripening practices as well as informing best practices for future studies on induction of labor.