Intrapartum azithromycin to prevent maternal and neonatal sepsis and deaths: A systematic review with meta-analysis

Objectives: A systematic review with met-analysis was performed to summarise the evidence on the effect of intrapartum azithromycin on maternal and neonatal infections and deaths. Search strategy: PubMed, Scopus and Web of Science databases were searched in March 2023. Selection criteria: Randomised controlled trials comparing intrapartum single-dose of azithromycin with placebo. Data collection and analysis: Maternal infections, maternal mortality, neonatal sepsis, neonatal mortality. We used the random-effects Mantel–Haenszel method to calculate risk ratios (RR) with 95% confidence intervals (95% CI). We assessed risk of bias of the included studies and estimated the evidence certainty using the GRADE approach. Main results: After screening 410 abstracts, five studies with 44 190 women and 44 565 neonates were included. The risk of bias was low in four and had some concerns in one of the studies. The risk of endometritis was 1.5% in the azithromycin group and 2.3% in the placebo group (RR 0.64, 95% CI 0.55–0.75), and the evidence certainty was high. The respective risk for chorioamnionitis was 0.05% and 0.1% (RR 0.50, 95% CI 0.22–1.18; evidence certainty moderate). The wound infection rate was lower in the azithromycin group (1.6%) than in the placebo group (2.5%), RR 0.52 (95% CI 0.30–0.89; moderate certainty evidence). The maternal sepsis rate was 1.1% in the azithromycin group and 1.7% in the placebo group (RR 0.66, 95% CI 0.56–0.77; evidence certainty high). Mortality rates did not show evidence of a difference (0.09% versus 0.08%; RR 1.26, 95% CI 0.65–2.42; moderate certainty evidence). The neonatal mortality rate was 0.7% in the azithromycin group and 0.8% in the placebo group (RR 0.94, 95% CI 0.76–1.16; moderate certainty evidence). The neonatal sepsis rate was 7.6% in the azithromycin group and 7.4% in the placebo group (RR 1.02, 95% CI 0.96–1.09; moderate certainty evidence). Conclusions: Intrapartum administration of azithromycin to the mother reduces maternal postpartum infections, including sepsis. Impact on maternal mortality remains undecided. Azithromycin does not reduce neonatal sepsis or mortality rates.