The Beneficial Effects of Weekly Low-dose Vitamin A Supplementation on Acute Lower Respiratory Infections and Diarrhea in Ecuadorian Children

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Abstract
Background. Previous studies of large-dose vitamin A supplementation on respiratory morbidity have produced conflicting results in a variety of populations. The influence of malnutrition has not been examined in the majority of these trials. We hypothesized that weekly low-dose vitamin A supplementation would prevent respiratory and diarrheal disease morbidity and that malnutrition might influence the efficacy of vitamin A supplementation. Methods. In a randomized, double-blind, placebo-controlled field trial of 400 children, 6 to 36 months of age in a high Andean urban slum, half of the children received 10 000 IU of vitamin A weekly and half received placebo for 40 weeks. Children were visited weekly at home by physicians and assessed for acute diarrheal disease and acute respiratory infections. Results. Acute diarrheal disease and acute respiratory infection did not differ globally or by severity between supplement-treated and placebo groups. However, the incidence of acute lower respiratory infection (ALRI) was significantly lower in underweight (weight-for-age z score [WAZ] <−2 SD) supplement-treated children than in underweight children on placebo (8.5 vs 22.3 per 103 child-weeks; rate ratio: 0.38 [95% CI: 0.17–0.85]). ALRI incidence was significantly higher in normal-weight (WAZ >−2 SD) supplement-treated children than in normal-weight children on placebo (9.8 vs 4.4 per 103 child-weeks; rate ratio: 2.21 [95% CI: 1.24–3.93]). By logistic regression analysis the risk of ALRI was lower in underweight supplement-treated children than in underweight children on placebo (point estimate 0.148 [95% CI: 0.034–0.634]). In contrast, risk of ALRI was higher in normal-weight supplement-treated children (WAZ >−1 SD to mean) than in normal-weight children on placebo in the same WAZ stratum (point estimate: 2.51 [95% CI: 1.24–5.05]). The risk of severe diarrhea was lower in supplement-treated children 18 to 23 months of age than in children on placebo in this age group (point estimate: 0.26 [95% CI: 0.06–1.00]). Conclusions. Weekly low-dose (10 000 IU) vitamin A supplementation in a region of subclinical deficiency protected underweight children from ALRI and paradoxically increased ALRI in normal children with body weight over −1 SD. Protection from severe diarrhea was consistent with previous trials. Additional research is warranted to delineate potential beneficial and detrimental interactions between nutritional status and vitamin A supplementation regarding ALRI.