The efficacy of a single dose of oral azithromycin in labour to prevent infections in infants and birthing parents in Fiji: secondary outcomes from a randomised controlled trial

INTRODUCTION: Our Bulabula MaPei trial of azithromycin administered during labour in Fiji found no evidence of a reduction in the primary endpoint of infant skin and soft tissue infections (SSTIs) at 3 months of age. Here, we determine the efficacy of this intervention on several secondary outcomes. METHODS: This randomised controlled trial included healthy pregnant adults presenting to hospital in labour. Prior to delivery, participants were randomly assigned a single dose of 2 g of oral azithromycin or placebo that were identical in appearance to mask treatment allocation, in a 1:1 ratio stratified by ethnicity. Cumulative incidence of infections and antibiotic prescription was compared using an intention-to-treat analysis of complete cases. Adverse events described as proportions by group at specified time points. RESULTS: From June 2019 to January 2022, we enrolled 2110 pregnant people and their infants (n=2122; azithromycin n=1059; placebo n=1063). At 3 months, the cumulative incidence of infant infections was 13.6% in the azithromycin group compared with 17.3% in the placebo group (risk ratio (RR) 0.79; 95% CI 0.63 to 0.99; p=0.038). Infections among birthing parents, including SSTIs, were reduced with the greatest effect 1 week postdelivery (infections: RR 0.31; 95% CI 0.13 to 0.71; p=0.006, SSTIs: RR 0.25; 95% CI 0.08 to 0.75; p=0.013) but with a diminishing effect up to 6 months postdelivery. There was no effect on the prescription of antibiotics at any time point. CONCLUSIONS: Intrapartum azithromycin prevents a variety of infections for birthing parents and infants up to 12 months post partum in Fiji. However, further research is required to identify target populations and better characterise potential impacts on antimicrobial resistance and the infant microbiome and resistome. TRIAL REGISTRATION NUMBER: NCT03925480.