A large Cochrane review of four randomized controlled trials involving over 42,000 pregnant women in labor evaluated whether prophylactic antibiotics could prevent maternal and neonatal infections. The findings showed that a single oral dose of antibiotics—primarily azithromycin—probably reduces maternal sepsis by 35%, while having little to no effect on maternal mortality, neonatal sepsis, neonatal mortality, or NICU admissions. Evidence on perineal wound infections and other maternal outcomes also showed minimal differences, and the overall risk of bias was low across most included trials.
Short-term increases in antibiotic-resistant organisms were noted in some maternal samples, but no persistent resistance was found at one year, and neonatal resistance was rare. The authors concluded that prophylactic antibiotics during labor may benefit maternal infection prevention but should be implemented cautiously due to uncertainty around long-term antimicrobial resistance. Further research is needed to clarify AMR effects and determine optimal antibiotic strategies, especially for diverse global populations.