Misoprostol Versus Oxytocin for the Prevention of Postpartum Haemorrhage: A Systematic Review and Meta-Analysis Including Individual Participant Data.

Abstract

Postpartum haemorrhage (PPH) is the leading cause of maternal mortality. Uterotonics are the mainstay of PPH prevention. To compare the efficacy of misoprostol and oxytocin for the prevention of PPH and to evaluate the trustworthiness of these randomised controlled trials (RCTs). Seven databases were searched for peer-reviewed literature meeting the inclusion criteria of RCTs comparing misoprostol and oxytocin for the prevention of PPH. Data were collected by two independent reviewers. Individual participant data (IPD) were meta-analysed for outcomes PPH ≥ 500 and ≥ 1000 mL. RCTs that did not share IPD were classified as trustworthy or not, and aggregate data were meta-analysed according to trustworthiness. Of 79 eligible RCTs, 10 (12.7%) provided IPD, of which 6 were included. Analysis of IPD showed PPH ≥ 500 mL to be significantly higher in the misoprostol than in the oxytocin group (2022 participants, aOR 1.84, 95% CI 1.43-2.34). For PPH ≥ 1000 mL, analysis of IPD showed that misoprostol and oxytocin were comparable (2022 participants, OR 1.14, 95% CI 0.68-1.91). Of the 69 studies that did not provide IPD, 23 (33.3%) were assessed as trustworthy. Analysis of trustworthy data (IPD and 23 aggregate data RCTs) showed no difference between misoprostol and oxytocin for PPH ≥ 500 mL (24 334 participants, OR 1.01, 95% CI 0.69-1.49), while misoprostol was associated with a significantly increased risk of PPH ≥ 1000 mL compared to oxytocin (25 249 participants, OR 1.36, 95% CI 1.16-1.59). Of 79 RCTs comparing misoprostol and oxytocin for the prevention of PPH, 36.7% met trustworthiness criteria. Oxytocin is comparable to misoprostol for preventing PPH and may be superior for preventing severe PPH.