Randomised study of effect of different doses of vitamin A on childhood morbidity and mortality

Objectives To determine whether the dose of vitamin A currently recommended by the World Health Organization or half this dose gives better protection against childhood morbidity and mortality. Design Randomised study. Setting A combined oral polio vaccine and vitamin A supplementation campaign in Guinea-Bissau, Africa. Participants 4983 children aged 6 months to 5 years. Interventions One of two doses of vitamin A (recommended and half); oral polio vaccine. Main outcome measures Mortality and morbidity at six and nine months. Results Mortality was lower in the children who took half the recommended dose of vitamin A compared with the full dose at both six months (mortality rate ratio 0.69, 95% confidence interval 0.36 to 1.35) and nine months (0.62, 0.36 to 1.06) of follow-up. There was a significant interaction between sex and dose, the lower dose being associated with significantly reduced mortality in girls (0.19, 0.06 to 0.66) but not in boys (1.98, 0.74 to 5.29). The lower dose of vitamin A was consistently associated with lower hospital case fatality in girls (0.19, 0.02 to 1.45). Paradoxically, in children aged 6-18 months, the low dose was associated with slightly higher morbidity. Conclusions Half the dose of vitamin A currently recommended by WHO may provide equally good or better protection against mortality but not against morbidity.