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 Selection criteria: Published and unpublished randomised controlled trials (RCTs) comparing systemic oxytocin to placebo or no intervention for the prevention of PPH were included.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.

Background: Cervical ripening in labour induction using a combination of methods is gaining popularity, but the effectiveness and safety of this approach are not clear. Objective: To compare the effectiveness, perinatal and maternal safety of cervical ripening in the induction of labour (IOL) using a balloon catheter with concurrent low-dose vaginal misoprostol (combined group) versus low-dose vaginal misoprostol alone. Search Strategy: MEDLINE, Embase, Emcare, Scopus, Cochrane Library, WHO ICTRP and clinicaltrials.gov. Selection Criteria: Randomised controlled trials (RCTs), viable singleton gestation, no language restrictions, published and unpublished data. Data Collection and Analysis: Systematic search, screening for trustworthiness and study quality, and an individual participant data (IPD) meta-analysis were conducted. Main Results: Eight of 22 RCTs provided IPD, of which three were excluded due to trustworthiness concerns after IPD checking (604 women). Thirteen of 22 RCTs (59.1%) were identified as ‘ not meeting trustworthiness criteria’. This IPD meta-analysis included five RCTs (649 women): two had prospective, another two had retrospective trial registrations, and one RCT was unregistered. Vaginal delivery rate, composite adverse perinatal and maternal outcomes were comparable between the two groups in the IPD meta-analysis. Vaginal delivery rate, based on aggregate data from eight RCTs ‘meeting trustworthiness criteria’ (IPD and non-IPD), had an Odds Ratio (OR) of 1.07 (95% CI 0.68;1.68). In comparison, data from thirteen RCTs ‘not meeting trustworthiness criteria’ (IPD and non-IPD) showed an OR of 1.25 (95% CI 0.88;1.77). Conclusions: Based on trustworthy data, the effectiveness of the combined group and the low-dose vaginal misoprostol group is likely to be comparable. We are uncertain about the safety of using a balloon catheter with concurrent low-dose vaginal misoprostol due to low data retrieval and trustworthiness concerns among the underlying RCTs.