Titrated low‐dose vaginal and/or oral misoprostol to induce labour for prelabour membrane rupture: a randomised trial

Objective To evaluate the clinical effectiveness and safety of titrated low‐dose misoprostol for induction of labour (IOL) in the presence of prelabour rupture of membranes (PROM). Design Randomised controlled trial. Setting Maternity units in the UK (9) and Egypt (1). Population Women >34 weeks of gestation with PROM, singleton viable fetus and no previous caesarean section. Methods Subjects randomised to IOL with a titrated low‐dose misoprostol regimen (oral except if unfavourable cervix, where initial dose vaginal) or a standard induction method, namely vaginal dinoprostone followed by intravenous oxytocin if the cervix was unfavourable or intravenous oxytocin alone if the cervix was favourable. Main outcome measures Primary outcome measures were caesarean section and failure to achieve vaginal delivery within 24 hours. Analysis was by intention to treat. Results The trial did not achieve the planned sample size of 1890 due to failure in obtaining external funding. Seven hundred and fifty‐eight women were randomised (375 misoprostol and 383 standard). There were less caesarean section (14 versus 18%, relative risk [RR] 0.79; 95% CI 0.57–1.09) and less women who failed to achieve vaginal delivery within 24 hours in the misoprostol group (24 versus 31%, RR 0.79; 95% CI 0.63–1.00), but the differences were not statistically significant. Subgroup analysis showed that with unfavourable cervix, misoprostol may be more effective than vaginal dinoprostone. There was no difference in hyperstimulation syndrome. There were more maternal adverse effects with misoprostol, but no significant differences in maternal and neonatal complications. Conclusions Titrated low‐dose misoprostol may be a reasonable alternative for IOL in the presence of PROM, particularly in women with an unfavourable cervix. Safety and rare serious adverse events could not be evaluated in a trial of this size.