A Cochrane review included 35 studies with a total of 31 955 children.
Overall, iron did not cause an excess of clinical malaria (RR 0.93, 95% CI 0.87 to 1.00; 14 trials, 7168 children). 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), 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). Iron supplementation does not cause an excess of severe malaria (RR 0.90, 95% CI 0.81 to 0.98; 6 trials, 3421 children). Any differences for deaths were no observed (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). Overall, iron resulted in fewer anaemic children at follow up, and the end average change in haemoglobin from base line was higher with iron.
No significant difference between iron alone and placebo was detected in clinical malaria (RR 0.99, 95% CI 0.90 to 1.09, 13 studies). 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 (RD +1.93 per 1000 children, 95% CI -1.78 to 5.64, 13 studies, n=17 898). 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, 3 studies) or deaths.