Abstract

BackgroundThe efficacy of zinc combined with vitamin A or multiple micronutrients in preventing diarrhoea is unclear in African countries with high prevalence of HIV-exposed children. Potential modifying factors such as stunting need addressing.ObjectiveTo determine whether adding zinc, or zinc plus multiple micronutrients, to vitamin A reduces diarrhoea incidence, and whether this differs between strata of stunted or HIV-infected children.MethodsWe analyzed data from a randomized, controlled double-blinded trial (ClinicalTrials.gov NCT00156832) of prophylactic micronutrient supplementation to children aged 6–24 months. Three cohorts of children: 32 HIV-infected children, 154 HIV-uninfected children born to HIV-infected mothers, and 187 uninfected children born to HIV-uninfected mothers, received vitamin A, vitamin A plus zinc, or multiple micronutrients that included vitamin A and zinc. The main outcome was incidence of diarrhoea. Poisson regression was used in intent-to-treat analyses. Stratified analyses followed testing for statistical interaction between intervention and stunting.ResultsWe observed no significant differences in overall diarrhoea incidence among treatment arms. Stunting modified this effect with stunted HIV-uninfected children having significantly lower diarrhoea incidence if supplemented with zinc or multiple micronutrients compared to vitamin A alone (2.04 and 2.23 vs 3.92 episodes/year respectively, P=0.024). No meaningful sub-group analyses could be done in the cohort of HIV-infected children.ConclusionCompared with vitamin A alone, supplementation with zinc, and with zinc and multiple micronutrients, reduced diarrhoea morbidity in stunted rural South African children. Efficacy of zinc supplementation in HIV-infected children needs confirmation in studies that represent the spectrum of disease severity and age groups.

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