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.
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.
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.
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.