Carbetocin in the Prevention of Postpartum Hemorrhage after Vaginal Birth: A Systematic Review and Meta-Analysis.
Carbetocin may reduce blood loss after vaginal delivery compared to oxytocin, but the clinical significance of this finding is uncertain.
Where it sits
this study against the rest of the carbetocin corpusSummary and findings
This systematic review and meta-analysis evaluated the safety and efficacy of carbetocin in reducing blood loss after vaginal delivery in a total of 69,884 women across 19 studies. The findings indicated a mean difference in blood loss of -28.13 mL compared to oxytocin, with a p-value of 0.020. Additionally, carbetocin was associated with a reduced need for additional uterotonics.
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 < 0.001). PPH > 500 mL and severe PPH > 1000 mL were reported in ten and seven studies (64,416 and 63,789 participants, respectively), with odds ratios (ORs) 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 ORs 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.
Background
This paper addresses the clinical question of whether carbetocin is effective in reducing postpartum hemorrhage (PPH) following vaginal delivery (VD). Previous studies have shown varying results regarding the efficacy of carbetocin compared to traditional treatments like oxytocin. Understanding the effectiveness of carbetocin is critical for improving maternal health outcomes.
Methods
The study utilized a systematic review and meta-analysis design, screening databases from inception to November 2024. A total of 19 randomized controlled trials were included, with 69,884 women undergoing vaginal delivery. The primary outcome measures included blood loss in the first 24 hours and changes in hemoglobin levels, with secondary outcomes assessing the need for additional uterotonics.
Results
The primary endpoint showed a mean difference of -28.13 mL in blood loss within the first 24 hours when comparing carbetocin to oxytocin, with a 95% confidence interval of -51.76 to -4.50 and a p-value of 0.020. Additionally, the difference in hemoglobin levels was -0.39 g/dl, with a p-value of <0.001. The odds ratios for PPH > 500 mL and severe PPH > 1000 mL were 0.99 (p=0.800) and 0.98 (p=0.720), respectively.
Interpretation
While the findings suggest that carbetocin may reduce blood loss compared to oxytocin, the clinical significance of a mean difference of -28.13 mL should be interpreted cautiously, especially given the odds ratios for severe PPH did not show a statistically significant advantage. The variability in study designs and potential confounding factors limit the ability to draw definitive conclusions about the clinical efficacy of carbetocin.
Key findings
- -28.13 mL mean difference in blood loss vs oxytocin at 24 h, n=7403, p=0.020
- -0.39 g/dl mean difference in hemoglobin levels vs oxytocin, n=2737, p<0.001
- Odds ratio of 0.99 for PPH > 500 mL vs oxytocin, n=64416, p=0.800
- Odds ratio of 0.67 for need for additional uterotonics vs oxytocin, n=34852, p=0.008
- -35.29 mL mean difference in blood loss vs syntometrine at 24 h, n=4853, p=0.090
- -0.29 g/dl mean difference in hemoglobin levels vs syntometrine, n=860, p=0.004
Limitations
- Wide confidence intervals for some outcomes
- P-values indicating non-significance for severe PPH
- Variability in study designs and reporting
- Not all studies were published in English
- Potential publication bias in included studies