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.


RESULTS
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.


CONCLUSIONS
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.
Sazawal
Sunil
S
Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205, USA.
Black
Robert E
RE
Ramsan
Mahdi
M
Chwaya
Hababu M
HM
Stoltzfus
Rebecca J
RJ
Dutta
Arup
A
Dhingra
Usha
U
Kabole
Ibrahim
I
Deb
Saikat
S
Othman
Mashavi K
MK
Kabole
Fatma M
FM
D018798:Anemia, Iron-Deficiency / Q000188:drug therapy; D046688:Child Mortality; D002675:Child, Preschool; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005492:Folic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D006397:Hematinics / Q000009:adverse effects / Q000627:therapeutic use*; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007223:Infant; D007501:Iron / Q000009:adverse effects / Q000627:therapeutic use*; D008288:Malaria / Q000517:prevention & control / Q000635:transmission*; D008297:Male; D011524:Protoporphyrins / Q000009:adverse effects / Q000627:therapeutic use*
D004791:Enzyme Inhibitors; D006397:Hematinics; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D005492:Folic Acid; D007501:Iron