Cochrane review: Oral iron supplementation for preventing or treating anaemia among children in malaria‐endemic areas
Authors: Ojukwu Juliana U , Okebe Joseph U , Yahav Dafna , Paul Mical 
Published: September 2010

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 searchedThe Cochrane Library(2009, issue 1); MEDLINE; EMBASE; LILACS andmetaRegister of Controlled Trials, all up to March 2009. We scanned references of included trials.

Selection criteria

Individually and cluster‐randomized controlled trials conducted in hypoendemic to holoendemic malaria regions and including children < 18 years. We included trials comparing orally administered iron with or without folic acid vs. placebo or no treatment. Iron fortification was excluded. Antimalarials and/or antiparasitics could be administered to either group. Additional micronutrients could only be administered equally to both groups.

Data collection and analysis

The primary outcomes were malaria‐related events and deaths. Secondary outcomes included haemoglobin, anaemia, other infections, growth, hospitalizations, and clinic visits. We assessed risk of bias using domain‐based evaluation. Two authors independently selected studies and extracted data. We contacted authors for missing data. We assessed heterogeneity. We performed fixed‐effect meta‐analysis and presented random‐effects results when heterogeneity was present. We present pooled risk ratios (RR) with 95% confidence intervals (CIs). We used adjusted analyses for cluster‐randomized trials.

Main results

Sixty‐eight trials (42,981 children) fulfilled the inclusion criteria. Iron supplementation did not increase the risk of clinical malaria (RR 1.00, 95% CI 0.88 to 1.13; 22,724 children, 14 trials, random‐effects model). The risk was similar among children who were non‐anaemic at baseline (RR 0.96, 95% CI 0.85 to 1.09). An increased risk of malaria with iron was observed in trials that did not provide malaria surveillance and treatment. The risk of malaria parasitaemia was higher with iron (RR 1.13, 95% CI 1.01 to 1.26), but there was no difference in adequately concealed trials. Iron + antimalarial was protective for malaria (four trials). Iron did not increase the risk of parasitological failure when given during malaria (three trials). There was no increased risk of death across all trials comparing iron versus placebo (RR 1.11, 95% CI 0.91 to 1.36; 21,272 children, 12 trials). Iron supplementation increased haemoglobin, with significant heterogeneity, and malaria endemicity did not affect this effect. Growth and other infections were mostly not affected by iron supplementation.

Authors' conclusions

Iron 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.

Plain Language Summary

Iron supplements for children living in malaria‐endemic countries

Children commonly develop anaemia (low haemoglobin) after birth. Anaemia is associated with several ill‐effects, including hindering motor development and learning skills, and it may have an adverse effect on immunity. Babies and children are therefore commonly given iron supplements to prevent or treat anaemia. In countries where malaria is prevalent, it has been suggested that iron supplementation increases the risk of malaria and deaths. The high dose of iron which is given as medicine may result in free iron circulating in the blood and available to the malaria parasite, which promotes its growth. We therefore aimed to assess the effects of iron administered to children living in countries where malaria is prevalent. We included only randomized controlled trials that compared iron given orally as a medicinal product (and not as food or drink fortification) with placebo or no treatment.

Iron did not increase the risk of malaria disease, indicated by fever and presence of parasites in the blood. The presence of parasites in the blood was slightly higher with iron overall, but not in trials with adequate randomization methods. There was no increased risk of death among iron‐treated children. Although more than 70 trials were identified for this review, malaria‐related outcomes and deaths were reported in only 16 and 11 trials, respectively. Iron supplementation increased haemoglobin by about 1 g/dL in areas where malaria is highly prevalent. At the end of follow up, which varied between two weeks and six months after the end of iron supplementation, the gain was smaller but still present at 0.4 g/dL. Iron did not increase the risk of respiratory infections, but episodes of diarrhoea were more frequent with iron when it was administered with zinc. Children given iron visited medical clinics less than children given placebo, but the rate of hospitalization was similar. Weight and height at the end of treatment were similar. Iron did not adversely affect rates of cure when given together with antimalarial treatment in three trials that examined this issue.

Our conclusions are that iron supplementation does not adversely affect children living in malaria‐endemic areas. The evidence shown in our review is limited by the lack of trials examining the relevant outcomes and the limited information allowing us to analyse factors that can affect our results, such as the children's baseline level of haemoglobin. Based on our review, routine iron supplementation should not be withheld from children living in countries where malaria is prevalent.