Objective: To determine, from the best available evidence, the effectiveness and safety of misoprostol administered vaginally or orally for third trimester cervical ripening or induction of labour.
Methods: Clinical trials of misoprostol used for cervical ripening or labour induction in the third trimester were identified from the register of randomised trials maintained by the Cochrane Pregnancy and Childbirth Group. All identified trials were considered for inclusion in the review according to a prespecified protocol. Primary outcomes were chosen to address clinical effectiveness (delivery within 24 hours) and safety (uterine hyperstimulation, caesarean section, serious maternal and neonatal morbidity) and were determined a priori. All meta-analyses were based on the intention-to-treat principle. In the absence of heterogeneity the summary statistics have been expressed as typical relative risk (RR) and 95% confidence interval (CI).
Results: Vaginal misoprostol: one small study showed that the use of misoprostol results in more effective cervical ripening and reduced need for oxytocin when compared with placebo. When compared with oxytocin, vaginal misoprostol was more effective for labour induction. The relative risk of failure to achieve vaginal delivery within 24 hours was 0.48 (95% CI 0.35 to 0.66). However, the relative risks for uterine hyperstimulation with and without fetal heart rate abnormalities were 2.54 (95% CI 1.12 to 5.77) and 2.96 (95% CI 2.11 to 4.14), respectively. In three out of four trials which studied women with intact membranes and unfavourable cervices, failure to achieve vaginal delivery within 24 hours was reduced with misoprostol when compared with other prostaglandins (RR 0.71, 95% CI 0.62 to 0.81). Vaginal misoprostol was associated with increased uterine hyperstimulation both without fetal heart rate changes (RR 1.67, 95% CI 1.30 to 2.14) and with associated fetal heart rate changes (RR 1.45, 95% CI 1.04 to 2.04). There was also an increase in meconium stained amniotic fluid following vaginal misoprostol (RR 1.38, 95% CI 1.06 to 1.79). Oral misoprostol: one small trial suggests that, when compared with placebo, oral misoprostol reduces the need for oxytocin and shortens the time between induction and delivery. Compared with other prostaglandins one small trial showed a reduced need for oxytocin with oral misoprostol. Two trials compared oral with vaginal misoprostol using different doses. No significant differences were evident.
Conclusions: Overall, misoprostol appears to be more effective than conventional methods of cervical ripening and labour induction. Although no differences in perinatal outcome were shown, the studies were not sufficiently large to exclude the possibility of uncommon serious adverse effects. In particular the increase in uterine hyperstimulation with fetal heart rate changes following misoprostol is a matter for concern. It is possible that, if sufficient numbers are studied, an unacceptably high number of serious adverse events including uterine rupture and asphyxial fetal deaths may occur. The data at present are not robust enough to address the issue of safety. Thus, though misoprostol shows promise as a highly effective, inexpensive and convenient agent for labour induction, it cannot be recommended for routine use at this stage. Lower dose misoprostol regimens should be investigated further.
PIP: The effectiveness and safety of misoprostol administered vaginally or orally for cervical ripening and labor induction in the third trimester of pregnancy were reviewed. Trials were identified from the register of randomized trials maintained by the Cochrane pregnancy and childbirth group. Findings showed that misoprostol doses ranging from 25 mcg 3-hourly to 50 mcg 4-hourly and 100 mcg 6- 12-hourly were more effective than oxytocin or dinoprostone recommended doses. The rate of cesarian section varied following vaginal misoprostol. However, there were increased rates of uterine hyperstimulation both with and without associated fetal heart rate changes. A lower dosage of vaginal misoprostol (25 mcg 6-hourly) was less effective than a higher one (25 mcg 3-hourly), with reduced rates of uterine hyperstimulation. Findings suggest that vaginal doses of 25 mcg misoprostol 3-hourly are more effective than conventional methods of cervical ripening and labor induction. The increase in uterine hyperstimulation with fetal heart rate changes following administration of misoprostol is a matter of concern. There is a possibility that an unacceptably high number of serious adverse events such as uterine rupture and asphyxial fetal deaths may occur if sufficient numbers are studied. Though misoprostol may show some promise as an effective agent for labor induction, it cannot be recommended for routine use. Lower-dose misoprostol regimens should be investigated further.