Infant Growth After Mass Administration of Azithromycin: Secondary Outcomes of a Cluster Randomized Clinical Trial.

Importance: Mass administration of azithromycin reduced child mortality in parts of sub-Saharan Africa. Promotion of infant growth may be an additional benefit of azithromycin treatment. Objective: To investigate whether the provision of mass administration of azithromycin for infants aged 1 to 11 months improves growth outcomes. Design, Setting, and Participants: This cluster randomized clinical trial conducted from December 1, 2020, to December 31, 2024, included 1151 villages in southwestern Mali. Villages were randomized in a 3:4:2 ratio to placebo, twice-yearly azithromycin, or quarterly azithromycin. Participants and study personnel were masked. The prespecified growth substudy, conducted from August 31, 2022, to July 31, 2023, was conducted in 59 villages in the Kita region. Eligible participants were infants aged 1 to 11 months, weighing 3.0 kg or more, with no macrolide allergy or severe illness. Anthropometric data were collected cross-sectionally from children aged 6 to 8 months and 12 to 14 months at 15, 18, 21, and 24 months after village enrollment. Interventions: Infants received a single oral dose of azithromycin, 20 mg/kg, at each quarterly visit: placebo at all rounds (control); azithromycin at 2 rounds from January to June and placebo at 2 rounds from July to December (twice-yearly azithromycin); or azithromycin at all rounds (quarterly azithromycin). Main Outcomes and Measures: Prespecified outcomes were weight and length; weight-for-age (WA), length-for-age (LA), weight-for-length (WL), and mid-upper-arm circumference (MUAC) z scores; and underweight, stunting, and wasting. Analysis was performed on an intention-to-treat basis. Results: A total of 1205 infants (mean age, 5.7 months [95% CI, 5.6-5.9 months]; 633 boys [52.5%]) were included in the trial at baseline. Among 1789 children (923 boys [51.6%]) assessed for growth, the mean anthropometric indices did not differ between the placebo, twice-yearly azithromycin, and quarterly azithromycin groups: weight, 7.8 kg (95% CI, 7.7-7.9 kg), 7.8 kg (95% CI, 7.7-7.9 kg), and 7.8 kg (95% CI, 7.7-7.9 kg), respectively; length, 70.2 cm (95% CI, 69.9-70.8 cm), 70.6 cm (95% CI, 70.2-70.9 cm), and 70.6 cm (95% CI, 70.1-71.0 cm), respectively; WA z score, -1.12 (95% CI, -1.23 to -0.95), -1.10 (95% CI, -1.19 to -0.98), and -1.12 (95% CI, -1.27 to -1.01), respectively; LA z score, -0.86 (95% CI, -1.06 to -0.70), -0.79 (95% CI, -0.93 to -0.65), and -0.78 (95% CI, -0.98 to -0.63), respectively; WL z score, -0.87 (95% CI, -1.00 to -0.68), -0.89 (95% CI, -1.01 to -0.77), and -0.95 (95% CI, -1.12 to -0.81), respectively; and MUAC z score, -0.30 (95% CI, -0.43 to -0.10), -0.24 (95% CI, -0.37 to -0.12), and -0.26 (95% CI, -0.41 to -0.10), respectively. The proportions of underweight, stunting, and wasting did not differ between groups. Conclusions and Relevance: In this prespecified analysis of secondary outcomes of a cluster randomized clinical trial of the provision of mass administration of azithromycin for infants aged 1 to 11 months, growth outcomes did not differ between azithromycin and placebo groups. These findings suggest that mass administration of azithromycin to infants is unlikely to promote growth. Trial Registration: ClinicalTrials.gov Identifier: NCT04424511.