Effect of routine prophylactic supplementation with iron and folic acid on preschool child mortality in southern Nepal: community-based, cluster-randomised, placebo-controlled trial.
BACKGROUND
Iron deficiency is widespread in the developing world and is especially common in young children who live on the Indian subcontinent. Supplementation with iron and folic acid alleviates severe anaemia and enhances neurodevelopment in deficient populations, but little is known about the risks of mortality and morbidity associated with supplementation.


METHODS
We did a community-based, cluster-randomised, double-masked, placebo-controlled, 2x2 factorial trial in children aged 1-36 months and residing in southern Nepal. We randomly assigned children daily oral supplementation to age 36 months with: iron (12.5 mg) and folic acid (50 microg; n=8337), zinc alone (10 mg), iron, folic acid, and zinc (n=9230), or placebo (n=8683); children aged 1-11 months received half the dose. Our primary outcome measure was all-cause mortality, and our secondary outcome measures included cause-specific mortality and incidence and severity of diarrhoea, dysentery, and acute respiratory illness. Analyses were by intention to treat. This study is registered at , number NCT00109551.


RESULTS
The iron and folic acid-containing groups of the study were stopped early in November, 2003, on the recommendation of the data and safety monitoring board; mortality in these groups did not differ from placebo and there was low power to detect positive or negative effects by the time enrollment was completed. We continued to enroll children to the placebo and zinc alone groups. 25,490 children participated and analyses are based on 29,097.3 person-years of follow-up. There was no difference in mortality between the groups who took iron and folic acid without or with zinc when compared with placebo (HR 1.03, 95% CI 0.78-1.37, and 1.00, 0.74-1.34, respectively). There were no significant differences in the attack rates for diarrhoea, dysentery, or respiratory infections between groups, although all the relative risks except one indicated modest, non-significant protective effects.


CONCLUSIONS
Daily supplementation of young children in southern Nepal with iron and folic acid with or without zinc has no effect on their risk of death, but might protect against diarrhoea, dysentery, and acute respiratory illness.
Tielsch
James M
JM
Center for Human Nutrition and the Sight and Life Institute, Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205, USA. jtielsch@jhsph.edu
Khatry
Subarna K
SK
Stoltzfus
Rebecca J
RJ
Katz
Joanne
J
LeClerq
Steven C
SC
Adhikari
Ramesh
R
Mullany
Luke C
LC
Shresta
Shardaram
S
Black
Robert E
RE
D018798:Anemia, Iron-Deficiency / Q000188:drug therapy* / Q000453:epidemiology; D046688:Child Mortality; D002675:Child, Preschool; D016000:Cluster Analysis; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D006397:Hematinics / Q000627:therapeutic use*; D006798:Housing; D006801:Humans; D007223:Infant; D007501:Iron / Q000627:therapeutic use*; D008297:Male; D009390:Nepal; D012923:Social Class
D006397:Hematinics; D005492:Folic Acid; D007501:Iron