Neonatal Azithromycin Administration and Growth during Infancy: A Randomized Controlled Trial

Observational studies have linked early-life antibiotic exposure to increased risk of obesity in children in high income settings. We evaluated whether neonatal antibiotic exposure led to changes in infant growth at 6 months of age in Burkina Faso. Neonates aged 8 to 27 days of age who weighed at least 2,500 g at the time of enrollment were randomized in a 1:1 fashion to a single oral 20-mg/kg dose of azithromycin or equivalent volume of placebo from April 2019 through December 2020. Weight, length, and mid-upper-arm circumference (MUAC) were measured at baseline and 6 months of age. Growth outcomes, including weight gain in grams per day, length change in millimeters per day, and changes in weight-for-age Z-score (WAZ), weight-for-length Z-score (WLZ), length-for-age Z-score (LAZ), and MUAC were compared among neonates randomized to azithromycin compared with placebo. Among 21,832 neonates enrolled in the trial, median age at enrollment was 11 days, and 50% were female. We found no evidence of a difference in weight gain (mean difference −0.009 g/day, 95% confidence interval [CI]: −0.16 to 0.14, P = 0.90), length change (mean difference 0.003 mm/day, 95% CI: −0.002 to 0.007, P = 0.23), or WAZ (mean difference −0.005 SD, 95% CI: −0.03 to 0.02, P = 0.72), WLZ (mean difference −0.01 SD, 95% CI: −0.05 to 0.02, P = 0.39), LAZ (mean difference 0.01, 95% CI: −0.02 to 0.04, P = 0.47), or MUAC (mean difference 0.01 cm, 95% CI: −0.02 to 0.04, P = 0.49). These results do not suggest that azithromycin has growth-promoting properties in infants when administered during the neonatal period. Trial registration: ClinicalTrials.gov NCT03682653.