OBJECTIVE: A systematic review and dose-response meta-analysis assessing the effect of different oxytocin prophylaxis doses on preventing postpartum hemorrhage after vaginal birth.
DATA SOURCES: MEDLINE, Embase, CINAHL, Web of Science, Global Health, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov (inception-June 9, 2025), along with reference lists of eligible trials.
STUDY ELIGIBILITY CRITERIA: Randomized controlled trials comparing different intravenous or intramuscular doses of prophylactic oxytocin, or a single prophylactic dose with no oxytocin, following vaginal birth were included.
STUDY APPRAISAL AND SYNTHESIS METHODS: Two authors independently evaluated studies for inclusion and risk of bias. A random-effects dose-response meta-analysis was conducted using a one-stage approach with a restricted maximum likelihood heterogeneity estimator and modeled using restricted cubic splines to detect departure from linearity. Certainty of evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluation methodology. Sufficient data were available to undertake a dose-response meta-analysis for blood loss ≥1000 mL, mean blood loss, blood transfusion, and use of additional uterotonics.
RESULTS: 13 studies involving 8961 participants were included, with oxytocin doses ranging from 2.5 to 80 IU. A J-shaped, nonlinear relationship was observed for blood loss ≥1000 mL, mean blood loss, and use of additional uterotonics. Doses of 4 to 10 IU resulted in 6 to 7 fewer individuals per 1000 experiencing blood loss ≥1000 mL (high certainty; risk with no oxytocin: 19 per 1000 individuals), likely 10 to 12 fewer individuals per 100 requiring additional uterotonics (moderate certainty; risk with no oxytocin: 26 per 100 individuals), but likely resulted in little to no difference in mean blood loss (moderate certainty). Lower doses (2.5-3 IU) likely reduced the risk of severe blood loss (moderate certainty) and may reduce additional uterotonic use (low certainty). At 20 IU, the risk of severe blood loss was probably reduced (moderate certainty), with possible diminishing returns at higher doses (low certainty). Additional uterotonics may increase at doses ≥20 IU (low certainty). No dose-response relationship was observed for blood transfusion.
CONCLUSION: Available evidence suggests the optimal range for oxytocin prophylaxis after vaginal birth is 4 to 10 IU, with lower doses within this range offering the best balance of efficacy and safety. However, limitations in the evidence base, including narrow dose ranges, under-representation of high-risk populations, and inconsistent reporting of safety outcomes, highlight the need for further research across clinical contexts.