Effect of zinc supplementation on mortality in children aged 1-48 months: a community-based randomised placebo-controlled trial.

BACKGROUND: Studies from Asia have suggested that zinc supplementation can reduce morbidity and mortality in children, but evidence from malarious populations in Africa has been inconsistent. Our aim was to assess the effects of zinc supplementation on overall mortality in children in Pemba, Zanzibar. METHODS: We enrolled 42,546 children aged 1-36 months, contributing a total of 56,507 child-years in a randomised, double-blind, placebo-controlled trial in Pemba, Zanzibar. Randomisation was by household. 21 274 children received daily supplementation with zinc 10 mg (5 mg in children younger than 12 months) for mean 484.7 days (SD 306.6). 21,272 received placebo. The primary endpoint was overall mortality, and analysis was by intention to treat. This study is registered as an International Standard Randomised Clinical Trial, number ISRCTN59549825. FINDINGS: Overall, there was a non-significant 7% (95% CI -6% to 19%; p=0.29) reduction in the relative risk of all-cause mortality associated with zinc supplementation. INTERPRETATION: We believe that a meta-analysis of all studies of mortality and morbidity, will help to make evidence-based recommendations for the role of zinc supplementation in public health policy to improve mortality, morbidity, growth, and development in young children.

Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial.

BACKGROUND: Anaemia caused by iron deficiency is common in children younger than age 5 years in eastern Africa. However, there is concern that universal supplementation of children with iron and folic acid in areas of high malaria transmission might be harmful. METHODS: We did a randomised, placebo-controlled trial, of children aged 1-35 months and living in Pemba, Zanzibar. We assigned children to daily oral supplementation with: iron (12.5 mg) and folic acid (50 mug; n=7950), iron, folic acid, and zinc (n=8120), or placebo (n=8006); children aged 1-11 months received half the dose. Our primary endpoints were all-cause mortality and admission to hospital. Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59549825. FINDINGS: The iron and folic acid-containing groups of the trial were stopped early on Aug 19, 2003, on the recommendation of the data and safety monitoring board. To this date, 24 076 children contributed a follow-up of 25,524 child-years. Those who received iron and folic acid with or without zinc were 12% (95% CI 2-23, p=0.02) more likely to die or need treatment in hospital for an adverse event and 11% (1-23%, p=0.03) more likely to be admitted to hospital; there were also 15% (-7 to 41, p=0.19) more deaths in these groups. INTERPRETATION: Routine supplementation with iron and folic acid in preschool children in a population with high rates of malaria can result in an increased risk of severe illness and death. In the presence of an active programme to detect and treat malaria and other infections, iron-deficient and anaemic children can benefit from supplementation. However, supplementation of those who are not iron deficient might be harmful. As such, current guidelines for universal supplementation with iron and folic acid should be revised.