Complex interactions with infection and diet may explain seasonal growth responses to vitamin A in preschool aged Indonesian children

Objective: To explore the potential contribution of respiratory infections and vitamin A intakes to the seasonal effect of vitamin A supplementation on child growth. Methods: Data from a randomized double-blind placebo-controlled trial, in which a single high dose of vitamin A or placebo was given every 4 months to 1405 children aged 6-48 months were used for the analysis. In total, 4430 child-treatment cycles were examined, and for each cycle the children had their dietary intake, weight, and height assessed at the start and end. Linear regression models of the difference in height and weight during each treatment cycle were used and the within-child correlation was adjusted using the generalized estimating equations (GEE). Other covariables in the model included age, sex, percentage of days with acute lower respiratory infection and diarrhea, and cumulative doses of vitamin A. Results: This study showed that a significant effect of vitamin A supplementation on linear growth was observed in all seasons in children with a low burden of respiratory infections, that is, <21.5% of days with respiratory illness. In each season, the highest effect was found in children with a low burden of respiratory infections and low vitamin A intakes, that is, intakes <400 RE/day. Children with a high burden of respiratory infections or high vitamin A intakes benefited less from vitamin A supplementation for their linear growth than children with a low burden of respiratory infections and low vitamin A intakes. Finally, there was no benefit for linear growth from vitamin A supplementation in children with both a high burden of respiratory infections and high vitamin A intakes regardless of the season. Conclusions: The effect of vitamin A supplementation on growth is dependent on season. Respiratory infections and vitamin A intakes are important factors underlying the seasonal effect of vitamin A supplementation on growth.