Carbetocin in the Prevention of Postpartum Hemorrhage after Vaginal Birth: A Systematic Review and Meta-analysis

Abstract Objective: To evaluate the safety and efficacy of carbetocin for reducing blood loss following vaginal delivery (VD). Methods: Databases, including MEDLINE, Scopus, Web of Science, EMBASE, Cochrane Library, Scopus, and clinical trial registries, were screened from inception to November 2024 using keywords related to carbetocin, postpartum hemorrhage (PPH), postpartum blood loss, and VD. Only randomized controlled trials included participants who underwent VD, totaling 19 studies including 69,884 women. Seventeen studies were published in English, one in Spanish, and one in Chinese. The extracted data included study location, number of participants and characteristics, intervention (including dose, route, and timing of administration), primary and secondary outcome parameters, and trial registration details. Results: Thirteen studies with 64,731 participants compared carbetocin to oxytocin. Blood loss in the first 24 h was assessed in ten trials (7403 participants), which reported a mean difference ( MD ) of −28.13 mL (95% confidence interval ( CI ): −51.76, −4.50; P = 0.020). The difference between antepartum and postpartum hemoglobin levels was measured in seven trials (2737 participants), which reported an MD of −0.39 g/dl (95% CI : −0.48, −0.29; P 500 mL and severe PPH > 1000 mL were reported in ten and seven studies (64,416 and 63,789 participants, respectively), with odds ratios ( OR s) of 0.99 (95% CI : 0.89, 1.10; P = 0.800) and 0.98 (95% CI : 0.89, 1.09; P = 0.720), respectively. The need for additional uterotonics was assessed in ten trials (34,852 participants), with an OR of 0.67 (95% CI : 0.49, 0.90; P = 0.008). Six studies (10,145 participants) compared carbetocin to syntometrine. Blood loss in the first 24 h was assessed in five trials (4853 participants), which reported an MD of −35.29 mL (95% CI : −75.68, 5.09; P = 0.090). The difference between the antepartum and postpartum hemoglobin levels was measured in four trials (860 participants), which reported an MD of −0.29 g/dl (95% CI : −0.48, −0.09; P = 0.004). PPH > 500 mL and severe PPH > 1000 mL were reported in five and four studies (4835 and 4733 participants, respectively), with OR s of 1.09 (95% CI : 0.96, 1.24; P = 0.170) and 0.93 (95% CI : 0.78, 1.09; P = 0.360), respectively. The need for additional uterotonics was calculated in five trials (4933 participants), with an OR of 0.93 (95% CI : 0.60, 1.46; P = 0.770). Conclusion: Carbetocin administration was associated with reduced blood loss during the first 24 h after VD, a less severe decrease in postpartum hemoglobin levels, and a reduced need for additional uterotonics compared with oxytocin administration. Registration: Registration number CRD42023492407