Carbetocin versus oxytocin in prevention of postpartum hemorrhage after cesarean delivery in high-risk women. A systematic review and meta-analysis

Archives of Gynecology and Obstetrics https://doi.org/10.1007/s00404-025-08014-6 REVIEW Carbetocin versus oxytocin in prevention of postpartum hemorrhage after cesarean delivery in high‑risk women. A systematic review and meta‑analysis Nour A. El‑Goly1 · Ahmed Mohamed Maged2 · Wafaa M. Kamal3 · Osama Hosny4 · Doaa Turki5 · Nadia M. Helmy2 Received: 29 January 2025 / Accepted: 17 March 2025 © The Author(s) 2025 Abstract Objectives To assess the value of carbetocin in prevention of postpartum hemorrhage (PPH) after Cesarean delivery (CD). Search strategy Screening of PubMed, Web Of Science, Scopus, register clinical trials registry and Google scholar from inception to December 2023. The keywords used included postpartum hemorrhage, intraoperative blood loss, postoperative blood loss, Cesarean delivery and their MeSH terms. Selection criteria All RCTs that compared carbetocin to oxytocin in women undergoing CD with risk factor for PPH. Fourteen studies including 3068 participants. Thirteen were written in English and one in Polish. Data collection and analysis The extracted data included location of the trial, number of centers involved in recruitment, the number of participants and their characteristics, details of the study groups and dose time and route of intervention and its comparator, primary and secondary outcome parameters and trial registration number and timing in relation to patients recruitment. The evaluated outcomes parameters included intraoperative and 1st 24 h post-operative blood loss, PPH, the hemoglobin changes after the procedure, the need for any additional uterotonic agents, surgical interventions or blood transfusion and drugs side effects. Main results Blood loss during the 1st 24 h after CD was evaluated in 11 studies with 2497 participants and revealed a mean difference (MD) of −111.07 with 95% CI of [−189.34 and −32.80 (P = 0.005, I2 97%). The hemoglobin changes after the operation was evaluated in 8 studies with 1646 participants and revealed a MD of −0.46 with 95% CI of −0.14 and −0.79 (P = 0.03, I2 96%). The incidence of PPH > 500 ml was reported in 8 studies with 1787 participants and revealed an Odd Ratio (OR) of 0.52 with 95%CI of [0.36, 0.77] (P < 0.001, I2 0%). The need for additional uterotonic agents was evaluated in 12 studies with 2663 participants and revealed an OR of 0.17 with 95% CI of 0.07 and 0.37 (P < 0.001, I2 88%). The need for blood transfusion was evaluated in 10 studies with 2439 participants and revealed an OR of 0.27 with 95% CI of 0.12 and 0.57 (P < 0.001, I2 20%). The need for additional interventions was evaluated in 3 studies with 1311 participants and revealed an OR of 0.67 with 95% CI of 0.28 and 1.60 (P = 0.37, I2 59%). Conclusion Carbetocin decreased the blood loss during the 1st 24 h after CD, post-operative hemoglobin drop, PPH the need for additional uterotonic agents and blood transfusion when compared to oxytocin. Keywords Carbetocin · Oxytocin · Cesarean delivery · Blood loss · Postpartum hemorrhage Introduction A million Cesarean deliveries (CDs) or more are carried on yearly in the United States being the most common surgical there [1]. World health organization reported an incidence of CD of 15% [2]. Although the rate of CD is increasing in both developed and developing countries, yet the incidence vary largely among different low income countries with a rate of 52% in Egypt and less than 5% in Somalia [3]. Extended author information available on the last page of the article CD provides a lower risk of maternal pelvic floor and neonatal birth injuries but carries a higher maternal surgical risk during the current and future pregnancies and a higher risk for development of neonatal respiratory distress [4]. The maternal morbidity during CD is double that occurs during vaginal delivery [5] with higher rates of hemorrhage, infections, anesthetic, thromboembolic complications, and even death [6]. Postpartum haemorrhage (PPH) occurs in more than 14 million women and accounts for 70 000 maternal deaths yearly [7]. It is defined as more than 500 and 1000-mL blood Vol.:(0123456789) Archives of Gynecology and Obstetrics loss during or within 24 h of VD and CD respectively [8]. Its risk is highest among low and middle income populations and the majority of maternal deaths in these countries are related to bleeding events as these counties lack the availability of high standard medical care [9]. The use of different uterotonic agents is recommended by WHO to prevent PPH in all deliveries [10]. The intravenous slow administration of 5 IU oxytocin is recommended by the Royal College of Obstetricians and Gynecologists after fetal extraction to ensure adequate contractions giving the advantages of rapid placental delivery and reduction of intraoperative and postpartum blood loss [11]. Oxytocin has many disadvantages. Its half life is short (4–10 min) so intravenous infusion is needed to achieve a prolonged action which necessitates continuous medical observation [12]. The other disadvantage is the requirement of a special storage and transport system with a 2–8 °C. This is particularly important in limited resource areas especially in countries with hot and humid environments [13]. In 1997, an oxytocin analog with heat stability that binds oxytocin receptors and results in prolonged uterine contractions were developed. Carbetocin starts its action within 2 min and its action is maintained for 1 h after administration. The uterine contractions induced by carbetocin is one and half times more strong than that caused by oxytocin. Carbetocin presents an excellent alternative to the traditional oxytocin in less developed areas with limited storage and transport facilities [14]. Objective To compare the safety and efficacy of carbetocin and oxytocin in prevention of PPH after CD in high-risk women. Methods The PRISMA guidelines of randomized controlled studies (RCTs) were followed in this systematic review. It was registered with CRD42023492407 number. Eligibility criteria, information sources, search strategy The search databases included PubMed, Web Of Science, Scopus, register clinical trials registry and Google scholar from inception to December 2023. The key words used included carbetocin, postpartum hemorrhage, Intraoperative blood loss, Postoperative blood loss, Cesarean delivery and their MeSH terms. All related clinical trials and reviews reference lists were checked for possible study inclusions. Study selection Study selection based on PICO format. Population included women underwent CD with high risk for development of postpartum hemorrhage. Intervention women received carbetocin injection. Comparator: studies comparing carbetocin to oxytocin alone or when combined with another uterotonic drugs as misoprostol. Outcomes: blood loss. Types of included studies: only RCTs without any language limitations. Cohort, case control studies, case series, reviews and editorial opinion were excluded. All dose (...truncated)