Protein supplementation delivered alone or in combination with presumptive azithromycin treatment for enteric pathogens did not improve linear growth in Bangladeshi infants: results of a cluster-randomized controlled trial

Background: Protein requirements established for healthy populations may be insufficient to support healthy growth in infants consuming largely cereal-based complementary foods and frequently exposed to enteric pathogens.

Objectives: This study aimed to assess independent and combined effects of protein supplementation and antibiotic treatment on linear growth of infants aged 6-12 mo.

Methods: We conducted a 2 × 4 factorial cluster-randomized trial in northwestern Bangladesh, allocating 566 clusters to masked azithromycin (10 mg/kg × 3 d) or placebo at 6 and 9 mo of age and unmasked delivery of an egg white protein-rich blended food supplement (250 kcal; 10 g added protein), a rice-based isocaloric supplement, egg, or nutrition education from 6 to 12 mo. We measured length at 6 and 12 mo. For this cluster-level intention-to-treat analysis of the 2 × 2 antibiotic and protein interventions, we used multiple linear or log-binomial regression with generalized estimating equations to assess changes in length-for-age z (LAZ) score and stunting (LAZ < -2), respectively.

Results: We enrolled 2055 infants (283 clusters) and included 1821 infants (281 clusters) with complete anthropometry data at 6 and 12 mo in our analysis. There were no significant interactions between the protein and antibiotic interventions for any outcomes. Independently, protein supplement did not improve LAZ (β: 0.05; 95% CI: 0.00, 0.11; P = 0.07) or reduce stunting (prevalence ratio: 1.12; 95% CI: 0.85, 1.49; P = 0.41) compared with the isocaloric supplement. The antibiotic intervention had no effect on LAZ (β: -0.05; 95% CI: -0.11, 0.01; P = 0.09) or stunting (prevalence ratio: 0.99; 95% CI: 0.75, 1.31; P = 0.96), relative to the placebo.

Conclusions: Supplementation to increase intakes of high-quality protein, provided with or without presumptive treatment for enteric pathogens, did not improve linear growth from 6 to 12 mo of age. This trial was registered at clinicaltrials.gov as NCT03683667.