Oral iron supplements for children in malaria-endemic areas.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 41510785 · doi:10.1002/14651858.CD006589.pub5
What was done
A systematic review and meta-analysis of individual and cluster-randomized controlled trials assessed oral iron supplementation (alone, with folic acid, or with antimalarials vs placebo/no treatment) in children aged under 18 years in hyperendemic or holoendemic malaria areas. Interventions supplied at least 80% of the Recommended Dietary Allowance for iron. Databases were searched to April 2024 (updated May 2025). The critical outcomes were clinical malaria, severe malaria, and all-cause mortality, evaluated using Cochrane RoB 1 and GRADE.
What was found
Forty trials (33,785 children) were included. Iron alone did not meaningfully alter clinical malaria risk (RR 0.93, 95% CI 0.87 to 1.00; 16 trials, 7,843 children; high certainty) and slightly reduced severe malaria (RR 0.90, 95% CI 0.81 to 0.98; 5 trials, 3,421 children; high certainty), with low-certainty evidence of no clear effect on mortality (RR 1.15, 95% CI 0.76 to 1.74; 20 trials, 8,809 children) or hospitalizations/visits (RR 0.99, 95% CI 0.95 to 1.04; 10 trials, 14,011 children). Iron plus folic acid showed no clear difference in severe malaria (RR 1.11, 95% CI 0.96 to 1.28; 2 trials, 17,575 children; low certainty) or mortality (RR 1.13, 95% CI 0.90 to 1.42; 5 trials, 18,034 children; low certainty). When grouped by healthcare infrastructure, iron (± folic acid) slightly reduced clinical malaria in areas with malaria prevention/management services (RR 0.91, 95% CI 0.84 to 0.97; 12 trials, 5,777 children; low certainty) but slightly increased it where services were absent (RR 1.15, 95% CI 1.02 to 1.30; 7 trials, 19,754 children; low certainty). Iron plus antimalarials substantially reduced clinical malaria (RR 0.54, 95% CI 0.43 to 0.67; 3 trials, 728 children; high certainty).
Why it matters
These findings support providing universal oral iron supplementation to children in malaria-endemic areas without prerequisite anaemia screening, provided effective malaria prevention and healthcare treatment services are in place.
Limits
Data on iron plus folic acid relied heavily on one large study (the Pemba trial) and omitted clinical malaria reporting. Subgroup findings regarding the absence versus presence of malaria services, as well as mortality and hospitalization endpoints, were supported only by low-certainty evidence.
Cited by
- contradicts Iron supplementation during infection increases mortality, and children given iron in high-pathogen developing areas are significantly more likely to die of infection.