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.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 16413877 · doi:10.1016/S0140-6736(06)67962-2
What was done
A community-based, randomized, placebo-controlled trial was conducted among children aged 1–35 months in Pemba, Zanzibar. Participants were assigned to daily oral supplementation with iron (12.5 mg) and folic acid (50 µg; n=7,950), iron, folic acid, and zinc (n=8,120), or placebo (n=8,006); children aged 1–11 months received half the dose. Primary endpoints were all-cause mortality and hospital admission, analyzed by intention to treat across 25,524 child-years of follow-up.
What was found
The iron- and folic acid-containing arms were stopped early due to safety concerns. Children receiving iron and folic acid with or without zinc had a 12% increased risk of death or hospital treatment for an adverse event (95% CI 2–23%, p=0.02) and an 11% increased risk of hospital admission (95% CI 1–23%, p=0.03). All-cause deaths were 15% higher in these groups, which was not statistically significant (95% CI -7% to 41%, p=0.19).
Why it matters
This study demonstrated that universal, empirical iron and folic acid supplementation carries substantial risk of severe illness and hospitalization in areas with high malaria transmission. These findings led to major revisions of international guidelines on iron supplementation in malaria-endemic settings.
Limits
The trial was halted early for safety, resulting in reduced statistical power for the separate mortality endpoint. Subgroup findings regarding iron-deficient versus non-iron-deficient children discussed in the conclusion are not reported with quantitative data in the abstract.
Cited by
- partial Iron supplementation during infection increases mortality, and children given iron in high-pathogen developing areas are significantly more likely to die of infection.