Effect of delayed misoprostol dosing interval for induction of labor: a retrospective study

Abstract

Background: Induction of labor occurs in greater than 22% of all pregnancies in the United States. Previous studies have shown that misoprostol is more effective for induction than oxytocin or dinoprostone alone. The World Health Organization recommends vaginal misoprostol 25mcg every 6 hours and the American Congress of Obstetricians and Gynecologists recommends 25mcg vaginal misoprostol every three to 6 hours. Although route of administration and dosage of misoprostol has been extensively studied, little is known about the optimal dosing interval of vaginal misoprostol.

Methods: The primary objective of this study is to determine the effect of delayed vaginal misoprostol dosing, defined as any interval longer than 4.5 h, on time to vaginal delivery. Our hypothesis is that the routine dosing interval of 4 hours shortens times to vaginal delivery compared to delayed dosing, even when adjusted for the time of delay. Secondary objectives include the effect of delayed vaginal misoprostol dosing on cesarean section rate, operative vaginal delivery rate, maternal outcomes, and neonatal outcomes. We conducted a retrospective chart review of 323 inductions of labor at one academic institution. The primary outcome was the proportion of patients who achieved a vaginal delivery within 24 h. The group who received all doses of misoprostol within a 4.5 h dosing window (Routine Dosing Interval Group) was compared with the group who had any dosing deviation (Delayed Dosing Interval Group).

Results: Of 133 included patients, 64 subjects received routine interval dosing and 69 subjects received delayed interval dosing. The vaginal delivery rates within 24 h were 56% (36/64) and 20% (14/69), respectively (P < 10^{- 4}). Spontaneous vaginal delivery rates were 86% (55/64) vs. 75% (52/69), respectively (P = .13). Kaplan Meier curves demonstrated statistically significant difference in time to vaginal delivery between groups, with a Cox Proportional Hazard ratio for routine dosing interval of 1.73 (P < 10^{- 5}) unadjusted and 1.34 (P = .01) when adjusted for dosing delay.

Conclusions: This retrospective study demonstrates a significant increase in delay-adjusted time to vaginal delivery when doses of vaginal misoprostol are delayed past 4.5 h.

Keywords: Cesarean section; Induction; Misoprostol; Multiparty; Nulliparity; Vaginal delivery.

Fig. 1

Selection of our study population based on exclusion and inclusion criteria

Fig. 2

Kaplan Meier Curves showing proportion of patients undelivered vs. time, by misoprostol dosing interval. Shaded areas represent the 95% confidence interval as calculated by the Kaplan Meier Curve Estimator. Crosses represent patients censored for cesarean delivery or vacuum assisted vaginal delivery. a demonstrates a significant difference in the hazard ratio even when delay of misoprostol administration was accounted for. b is stratified by parity, and Cox Proportional Hazard Ratio for each of the above covariates is significant, with P values less than 0.05 (see Table 3)