Labour induction with prostaglandins: a systematic review and network meta-analysis

Abstract

Objectives: To assess the effectiveness and safety of prostaglandins used for labour induction.

Design: Systematic review with Bayesian network meta-analysis

Data sources: The Cochrane Pregnancy and Childbirth Group's Database of Trials (which incorporates the results of a broad generic search for all pregnancy and postpartum trials). Sources included are CENTRAL, Medline, Embase, NHS Economic Evaluation Database, CINAHL, relevant journals, conference proceedings, and registries of ongoing trials.

Eligibility criteria for selecting studies: Randomised clinical trials of prostaglandin or prostaglandin analogues used for third trimester cervical ripening or labour induction versus placebo or no treatment, alternative prostaglandin dose or administration, or a different type of prostaglandin. We included studies recruiting women with a viable fetus, but had no other restrictions relating to indication for labour induction or language of publication. Outcomes assessed were serious neonatal morbidity (trialist defined) or perinatal death; serious maternal morbidity (trialist defined) or death; vaginal delivery not achieved within 24 hours, caesarean section, and uterine hyperstimulation with fetal heart rate changes.

Results: 280 randomised clinical trials were included (48 068 women) in the review. Maternal and neonatal mortality and serious morbidity were rarely reported and are summarized narratively. Unresolved inconsistency was observed for the hyperstimulation outcome. Relative to placebo, the odds of failing to achieve a vaginal delivery were lowest for vaginal misoprostol (≥50 µg) (odds ratio 0.06 (95% credible interval 0.02 to 0.12)), with a 39% absolute probability of event (95% credible interval 1% to 94%). Compared with placebo, odds of caesarean section were lowest for titrated oral misoprostol solution (<50 µg) (odds ratio 0.65 (0.49 to 0.83)), with an absolute probability of event of 15% (3% to 40%).

Conclusions: Low dose(<50 µg) titrated oral misoprostol solution had the lowest probability of caesarean section, whereas vaginal misprostol (≥50 µg) had the highest probability of achieving a vaginal delivery within 24 hours. These findings have important implications for a series of current national and international guidelines for induction of labour and future research in this area.

Systematic review registration: PROSPERO 2013:CRD42013005116.

Fig 1 Prisma diagram of study selection for network meta-analysis

Fig 2 Networks of eligible comparisons for five outcomes: vaginal delivery not achieved within 24 hours, caesarean section, uterine hyperstimulation, serious neonatal morbidity or perinatal death, and serious maternal morbidity or death. The width of the lines is proportional to the number of trials comparing each pair of treatments, and the size of each node is proportional to the number of randomised participants (sample size)

Fig 3 Odds ratios and 95% credible intervals from network meta-analysis of failure to achieve vaginal delivery within 24 hours. An odds ratio >1 favours control (that is, fewer events occur with control than with active treatment), while an odds ratio <1 favours the active treatment (fewer undesirable events occurred with the active treatment)

Fig 4 Ranking for each of the 12 prostaglandin treatments for vaginal delivery not achieved within 24 hours and caesarean section. Ranking indicates the probability of being the best treatment, the second best, the third best, etc. For comparability across outcomes, rankings are based on the sensitivity analysis having excluded studies at high risk of bias

Fig 5 Odds ratios and 95% credible intervals from network meta-analysis of caesarean section. An odds ratio >1 favours control (that is, fewer events occur with control than with active treatment), while an odds ratio <1 favours the active treatment (fewer undesirable events occurred with the active treatment)