Oral iron supplements for children in malaria-endemic areas

Abstract

BackgroundIron-deficiency anaemia is common during childhood. Iron administration has been claimed to increase the risk of malaria.ObjectivesTo evaluate the effects and safety of iron supplementation, with or without folic acid, in children living in areas with hyperendemic or holoendemic malaria transmission.Search methodsWe searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library, MEDLINE (up to August 2015) and LILACS (up to February 2015). We also checked the metaRegister of Controlled Trials (mRCT) and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) up to February 2015. We contacted the primary investigators of all included trials, ongoing trials, and those awaiting assessment to ask for unpublished data and further trials. We scanned references of included trials, pertinent reviews, and previous meta-analyses for additional references.Selection criteriaWe included individually randomized controlled trials (RCTs) and cluster RCTs conducted in hyperendemic and holoendemic malaria regions or that reported on any malaria-related outcomes that included children younger than 18 years of age. We included trials that compared orally administered iron, iron with folic acid, and iron with antimalarial treatment versus placebo or no treatment. We included trials of iron supplementation or fortification interventions if they provided at least 80% of the Recommended Dietary Allowance (RDA) for prevention of anaemia by age. Antihelminthics could be administered to either group, and micronutrients had to be administered equally to both groups.Data collection and analysisThe primary outcomes were clinical malaria, severe malaria, and death from any cause. We assessed the risk of bias in included trials with domain-based evaluation and assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We performed a fixed-effect meta-analysis for all outcomes and random-effects meta-analysis for hematological outcomes, and adjusted analyses for cluster RCTs. We based the subgroup analyses for anaemia at baseline, age, and malaria prevention or management services on trial-level data.Main resultsThirty-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, altho...

Reducing anaemia in low income countries: control of infection is essential

“…Furthermore, iron increased Plasmodium parasitaemia risk by 11% (0-23%) during supplementation and by 23% (9-40%) in the post-supplementation period,11 supporting the cohort study findings described above. The consequent 2016 WHO guidelines therefore require that iron interventions be given only where strategies to prevent, diagnose, and treat malaria are operational; however, malaria control in settings where iron interventions may be recommended is often suboptimal (see below).…”

“…Updated 2016 WHO guidelines reintroduced daily iron supplementation as a second option (alongside micronutrient powders) in children, and based on an updated Cochrane review,11 reiterated that in malaria endemic areas iron provision to children “should be done in conjunction with public health measures to prevent, diagnose and treat malaria.” Guidelines further state that “provision of iron … should not be made to children who do not have access to malaria-prevention strategies (e.g. provision of insecticide-treated bednets and vector-control programmes), prompt diagnosis of malaria illness, and treatment with effective antimalarial drug therapy.”7…”

The effects of iron fortification and supplementation on the gut microbiome and diarrhea in infants and children: a review

“…A more recent systematic review (57) of studies that was done only in malaria-endemic areas included trials of both iron supplementation and fortification if they provided $80% of the Recommended Dietary Allowance by age in infants and children. For the comparison of iron treatment with placebo or no treatment (10 trials; w24,000 children), there was a significant 15% increase in diarrheal episodes per patient-month (risk ratio: 1.15; 95% CI: 1.06, 1.26) (57). Taken together, the available data suggest that oral iron supplements and iron-containing MNPs that are given to young children in low-resource settings modestly increase risk of diarrhea.…”

How I treat anemia in pregnancy: iron, cobalamin, and folate

“…104 In a 2016 Cochrane systematic review of 35 randomized controlled trials assessing iron supplementation in children living in areas with hyperendemic or holoendemic malaria transmission, iron did not cause an excess of clinical malaria. 105 This review did not include pregnant women. Provision of supplemental iron to pregnant women in malariaendemic areas has been controversial due to concerns that iron therapy may exacerbate infections.…”