Comparing oxytocin alternatives for postpartum hemorrhage prevention in vaginal and caesarean births: a systematic review and meta-analysis

Abstract Background In this systematic review and meta-analysis, we aimed to explore the availability of alternatives to oxytocin for preventing postpartum haemorrhage (PPH) during vaginal births (VB) and caesarean births (CB). Methods We followed the Cochrane guidelines for the review, and reported the results using the PRISMA guidelines. Using a thorough search strategy, we retrieved original articles from SCOPUS, PubMed, Web of Science, and the Cochrane Library from January 2015 to February 2025. We analyzed the RCTs to compare Tranexamic Acid (TXA), carbetocin, and misoprostol with oxytocin for preventing PPH in both vaginal and caesarean births. The review's protocol has been officially registered with PROSPERO under the identifier CRD420251002602. Results A meta-analysis of 20 trials showed no statistically significant difference in reducing blood loss during vaginal births (SMD = − 0.21; 95% CI − 0.62 to 0.19; I2 = 96%). However, contrasting results were observed in cesarean births (SMD = − 0.82; 95% CI − 1.49 to − 0.16; p = 0.02). Correspondingly, no statistically significant difference was found in the occurrence of PPH in vaginal births (OR = 0.80; 95% CI 0.53 to 1.21; I2 = 98%), while significant variances were detected in cesarean births (OR = 0.58; 95% CI 0.43 to 0.80; I2 = 21%). Hemoglobin variation was notably lower in both vaginal and cesarean births (SMD = − 0.32; 95% CI − 0.49 to − 0.16; I2 = 93%) and (SMD = − 0.90; 95% CI − 1.52 to − 0.27; I2 = 96%), respectively. Conclusion Considering the substantial heterogeneity and mostly non-significant pooled results, the current findings should be viewed as indicative rather than conclusive. Further rigorous, well-designed randomized controlled trials are necessary to better define their effectiveness, optimize dosing, and identify patient groups most likely to benefit. Graphical abstract