Background: Post-partum haemorrhage (PPH) is a common complication of labour. Objective: To assess the effectiveness of oxytocin in comparison to no treatment for the prevention of PPH. Selection criteria: Published and unpublished randomised controlled trials (RCTs) comparing systemic oxytocin to placebo or no intervention for the prevention of PPH were included. We did not apply language restrictions. Search Strategy: We identified RCTs from the Cochrane network meta-analysis on uterotonics for the prevention of PPH and updated the search via: Ovid MEDLINE, Embase via Ovid, Web of Science, CENTRAL, CINAHL Plus and clinicaltrials.gov. Data collection and analysis: An Individual participant data (IPD) meta-analysis. Main results: Of 14 eligible RCTs, four provided IPD (n=4,304; 51.7% received oxytocin and 48.4% received placebo or no intervention). Meta-analysis of IPD showed that oxytocin decreased the risk of PPH≥500 mL (aOR 0.59; 95% CI 0.46 to 0.74) and PPH≥1000 mL (aOR 0.51; 95%CI 0.32 to 0.80). Of ten RCTs that did not share data, seven met trustworthiness criteria while three did not. Trustworthy IPD and aggregate data from RCTs meeting trustworthiness criteria (n=6,003) showed that oxytocin significantly reduced the rate of PPH≥500 mL (aOR 0.53; 95%CI 0.45 to 0.62) and PPH≥1000 mL (aOR 0.59; 95%CI 0.48 to 0.71). Three RCTs not meeting trustworthiness criteria (n=1,027) reported a larger risk reduction of oxytocin for PPH≥500mL (aOR 0.37; 95%CI 0.03 to 4.03) and PPH≥1000mL (aOR 0.13; 95%CI 0.01 to 1.45). Conclusions : Prophylactic oxytocin reduces the risk of PPH≥500mL and PPH≥1000mL compared to no treatment. Studies not meeting trustworthiness criteria reported a larger effect, underlining the importance of integrity assessment in MA.

Background: Postpartum haemorrhage (PPH) is the leading cause of maternal mortality. Uterotonics are the mainstay of PPH prevention. Objectives: To compare the efficacy of misoprostol and oxytocin for the prevention of PPH, and to evaluate the trustworthiness of trials comparing these uterotonics. Search strategy and selection criteria: Seven databases were searched for peer-reviewed literature, meeting the inclusion criteria of randomized controlled trials (RCTs) comparing misoprostol and oxytocin for the prevention of PPH. Data Collection and Analysis: Data were collected by two independent reviewers. Individual participant data (IPD) was meta-analyzed for outcomes PPH≥500mL and PPH≥1000mL. RCTs that did not share IPD were classified as trustworthy or not and were included in an aggregate data meta-analysis according to trustworthiness. Main results: Of 79 eligible RCTs, ten (12.7%) provided IPD, of which six were included. Analysis of IPD showed PPH≥500mL to be significantly higher in the misoprostol than the oxytocin group (2,022 women, aOR 1.84, 95% CI 1.43- 2.34). For PPH≥1000mL, analysis of IPD showed misoprostol and oxytocin were comparable (2022 women, 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≥500mL (24,334 women, OR 1.01, 95% CI 0.69- 1.49), while misoprostol significantly increased the risk for PPH≥1000 (25,249 women, OR 1.36, 95% CI 1.16- 1.59). Conclusions: Of 79 RCTs comparing misoprostol and oxytocin for the prevention of PPH, 36.7% met trustworthiness criteria. Analysis of trustworthy data suggests oxytocin is superior to misoprostol for preventing PPH.