Background: Iron-deficiency anaemia is common during childhood. Iron supplementation has been claimed to increase the risk of malaria.
Objectives: To assess the effect of iron on malaria and deaths.
Search strategy: We searched The Cochrane Library, PUBMED, MEDLINE, LILACS; and trial registry databases, all up to June 2011. We scanned references of included trials.
Selection criteria: Individually and cluster randomized controlled trials conducted in hypoendemic to holoendemic malaria regions and including children below 18 years of age. We included trials comparing orally administered iron, iron with antimalarial treatment, or iron with folic acid versus placebo or no treatment. Iron fortification was excluded. Antihelminthics could be administered to either group. Additional micronutrients had to be administered equally to both groups.
Data collection and analysis: The primary outcomes were clinical (symptomatic) malaria, severe malaria, and death. Two authors independently selected the studies and extracted the data. We assessed heterogeneity and conducted subgroup analyses by the presence of anaemia at baseline, age, and malaria endemicity. We assessed risk of bias using domain-based evaluation. We performed a fixed-effect meta-analysis for all outcomes and random-effects meta-analysis for hematological outcomes. We adjusted analyses for cluster randomized trials.
Main results: Seventy-one trials (45,353 children) were included. For clinical malaria, no significant difference between iron alone and placebo was detected, (risk ratio (RR) 0.99, 95% confidence intervals (CI) 0.90 to 1.09, 13 trials). The results were similar in the subgroups of non-anaemic children and children below 2 years of age. There was no significant difference in deaths in hyper- and holoendemic areas, risk difference +1.93 per 1000 children (95% CI -1.78 to 5.64, 13 trials, 17,898 children). Iron administered for treatment of anaemia resulted in a larger increase in haemoglobin than iron given for prevention, and the benefit was similar in hyper- or holoendemic and lower endemicity settings. Iron and folic acid supplementation resulted in mixed results for severe malaria. Overall, the risk for clinical malaria was higher with iron or with iron plus folic acid in trials where services did not provide for malaria surveillance and treatment. Iron with antimalarial treatment significantly reduced malaria. Iron supplementation during an acute attack of malaria did not increase the risk for parasitological failure, (RR 0.96, 95% CI 0.74 to 1.24, three trials) or deaths.
Authors' conclusions: Iron alone or with antimalaria treatment does not increase the risk of clinical malaria or death when regular malaria surveillance and treatment services are provided. There is no need to screen for anaemia prior to iron supplementation.