Effect of daily iron supplementation on health in children aged 4-23 months: a systematic review and meta-analysis of randomised controlled trials

BACKGROUND: About 47% of preschool children worldwide are anaemic. Daily oral iron supplementation is a commonly recommended intervention for treatment and prevention of anaemia, but the efficacy and safety of iron supplementation programmes is debated. Thus, we systematically reviewed the evidence for benefit and safety of daily iron supplementation in children aged 4-23 months. METHODS: We searched Scopus and Medline, from inception to Feb 5, 2013, WHO databases, theses repositories, grey literature, and references. Randomised controlled trials that assigned children 4-23 months of age to daily oral iron supplementation versus control were eligible. We calculated mean difference (MD) or standard MD (SMD) for continuous variables, risk ratios for dichotomous data, and rate ratios for rates. We quantified heterogeneity with the I(2) test and synthesised all data with a random-effects model. This review is registered with the International Prospective Register of Systematic Reviews, number CRD42011001208. FINDINGS: Of 9533 citations identified by the search strategy, 49 articles from 35 studies were eligible; these trials included 42,306 children. Only nine studies were judged to be at low risk of bias. In children receiving iron supplements, the risk ratio for anaemia was 0·61 (95% CI 0·50-0·74; 17 studies, n=4825), for iron deficiency was 0·30 (0·15-0·60; nine studies, n=2464), and for iron deficiency anaemia was 0·14 (0·10-0·22; six studies, n=2145). We identified no evidence of difference in mental (MD 1·65, 95% CI -0·63 to 3·94; six studies, n=1093) or psychomotor development (1·05, -1·36 to 3·46; six studies, n=1086). We noted no significant differences in final length or length-for-age, or final weight or weight-for-age. Children randomised to iron had slightly lesser length (SMD -0·83, -1·53 to -0·12; eight studies, n=868) and weight gain (-1·12, -1·19 to -0·33) over the course of the studies. Vomiting (risk ratio 1·38, 95% CI 1·10-1·73) and fever (1·16, 1·02-1·31) were more prevalent in children receiving iron. INTERPRETATION: In children aged 4-23 months, daily iron supplementation effectively reduces anaemia. However, the adverse effect profile of iron supplements and effects on development and growth are uncertain. Adequately powered trials are needed to establish the non-haematological benefits and risks from iron supplementation in this group. FUNDING: Victoria Fellowship (Government of Victoria, Australia); CRB Blackburn Scholarship (Royal Australasian College of Physicans); Overseas Research Experience Scholarship, University of Melbourne