Abstract: Thirty-five trials (31,955 children) met the inclusion criteria. Overall, iron does not cause an excess of clinical malaria (risk ratio (RR) 0.93, 95% confidence intervals (CI) 0.87 to 1.00; 14 trials, 7168 children, high quality evidence). Iron probably does not cause an excess of clinical malaria in both populations where anaemia is common and those in which anaemia is uncommon. In areas where there are prevention and management services for malaria, iron (with or without folic acid) may reduce clinical malaria (RR 0.91, 95% CI 0.84 to 0.97; seven trials, 5586 participants, low quality evidence), while in areas where such services are unavailable, iron (with or without folic acid) may increase the incidence of malaria, although the lower CIs indicate no difference (RR 1.16, 95% CI 1.02 to 1.31; nine trials, 19,086 participants, low quality evidence). Iron supplementation does not cause an excess of severe malaria (RR 0.90, 95% CI 0.81 to 0.98; 6 trials, 3421 children, high quality evidence). We did not observe any differences for deaths (control event rate 1%, low quality evidence). Iron and antimalarial treatment reduced clinical malaria (RR 0.54, 95% CI 0.43 to 0.67; three trials, 728 children, high quality evidence). Overall, iron resulted in fewer anaemic children at follow up, and the end average change in haemoglobin from base line was higher with iron. Iron treatment does not increase the risk of clinical malaria when regular malaria prevention or management services are provided. Where resources are limited, iron can be administered without screening for anaemia or for iron deficiency, as long as malaria prevention or management services are provided efficiently.

Plain-language summary: Cochrane researchers searched the available evidence up to 30 August 2015 and included 35 trials (31,955 children). Iron did not increase the risk of malaria, indicated by fever and the presence of parasites in the blood (high quality evidence). There was no increased risk of death among children treated with iron, although the quality of the evidence for this was low. Among children treated with iron, there was no increased risk of severe malaria (high quality evidence). Although it is hypothesized that iron supplementation might harm children who do not have anaemia living in malarial areas, there is probably no increased risk for malaria in these children (moderate quality evidence). In areas where health services are sufficient to help prevent and treat malaria, giving iron supplements (with or without folic acid) may reduce clinical malaria. In areas where these services are not available, iron supplementation (with or without folic acid) may increase the number of children with clinical malaria (low quality evidence). Overall, iron resulted in fewer anaemic children at follow up, and the end average change in haemoglobin from base line was higher with iron. Our conclusions are that iron supplementation does not adversely affect children living in malaria-endemic areas. Based on our review, routine iron supplementation should not be withheld from children living in countries where malaria is prevalent and malaria management services are available.