• Kiattisak Kongwattanakul, Porjai Pattanittum, Apiwat Jongjakapun, Jen Sothornwit, Chetta Ngamjarus, Nampet Jampathong, Termtem Waidee, and Pisake Lumbiganon.
• Department of Obstetrics and Gynaecology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
• Cochrane Db Syst Rev. 2024 Oct 30; 10 (10): CD004904CD004904.

RationaleRetained placenta is a potentially life-threatening condition because of its association with postpartum haemorrhage. Manual removal of the placenta increases the likelihood of infectious complications of the uterine cavity. So, prophylactic antibiotics are recommended by some experts, and commonly administered to reduce these risks. However, the evidence supporting this decision is limited. This review aims to assess the effectiveness of prophylactic antibiotics for manual removal of retained placenta after vaginal birth.ObjectivesTo compare the effectiveness and adverse effects of routine prophylactic antibiotics for the manual removal of placenta after vaginal birth. To identify appropriate prophylactic antibiotic regimens.Search MethodsFor this update, we searched CENTRAL, MEDLINE, Embase, CINAHL, and two trials registries, in addition to screening the reference lists of retrieved studies and systematic reviews. The last search was 14 May 2024.Eligibility CriteriaAll randomised controlled trials and non-randomised studies comparing prophylactic antibiotics to no treatment or to another prophylactic antibiotic to prevent postpartum endometritis after manual removal of placenta after vaginal birth.OutcomesThe critical outcome in our review was postpartum endometritis. Other important outcomes were puerperal morbidity, perineal infection, duration of hospital stay, sepsis, any infection, blood loss, postpartum haemorrhage, secondary postpartum haemorrhage, readmission to hospital, adverse effects of the drugs, women's satisfaction, and neonatal outcomes, such as jaundice, sepsis, neonatal intensive care unit admission, et cetera.Risk Of BiasThe risk of bias was assessed at the outcome level. We used the Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool to assess the risk of bias in non-randomised studies.Synthesis MethodsWe carried out statistical analysis using Review Manager. We used a fixed-effect meta-analysis to synthesise the results, and GRADE to assess the certainty of the evidence.Included StudiesWe included four retrospective cohort studies with a total of 974 participants. Studies were conducted in Germany, Bulgaria, Norway, and Israel, between 1983 and 2017.Synthesis Of ResultsProphylactic antibiotics versus no antibiotics was the only comparison in our analysis. Postpartum endometritis We do not know whether prophylactic antibiotics have an impact on postpartum endometritis (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.48 to 1.85; 4 studies, 974 participants; very low-certainty evidence). Postpartum haemorrhage The evidence suggests that prophylactic antibiotics may result in little to no difference in postpartum haemorrhage (RR 1.00, 95% CI 0.78 to 1.29; 1 study, 325 participants; low-certainty evidence). Neonatal intensive care unit admission (NICU) The evidence suggests that prophylactic antibiotics may result in little to no difference in NICU admission of the neonate (RR 0.86, 95% CI 0.29 to 2.61; 1 study, 353 participants; low-certainty evidence). There were no data available for other important outcomes, including puerperal morbidity, perineal infection, duration of hospital stay, sepsis, any infection, blood loss, secondary postpartum haemorrhage, readmission to hospital, adverse effects of drugs, women's satisfaction, or neonatal outcomes of jaundice or sepsis.Authors' ConclusionsThere is very uncertain evidence supporting the use of prophylactic antibiotics for manual removal of placenta for preventing postpartum endometritis. The evidence suggests that prophylactic antibiotics result in little to no difference in postpartum haemorrhage or admission to a neonatal intensive care unit. There were no available data on other important outcomes. Multicentre, randomised controlled trials comparing antibiotic prophylaxis and placebo or no antibiotic, or one antibiotic and another, for manual removal of placenta in vaginal birth are needed to provide more robust evidence.FundingThis systematic review received support from the UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP).RegistrationProtocol and previous versions are available at https://10.1002/14651858.CD004904.pub3.Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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