Effects of daily iron supplementation in primary-school-aged children: Systematic review and meta-analysis of randomized controlled trials

Abstract

Background: Anemia is an important public health and clinical problem. Observational studies have linked iron deficiency and anemia in children with many poor outcomes, including impaired cognitive development; however, iron supplementation, a widely used prevent - ive and therapeutic strategy, is associated with adverse effects. Primary-school-aged children are at a critical stage in intellectual development, and optimization of their cognitive performance could have long-lasting individual and population benefits. In this study, we summarize the evidence for the benefits and safety of daily iron supplementation in primary-school-aged children. Methods: We searched electronic databases (including MEDLINE and Embase) and other sources (July 2013) for randomized and quasirandomized controlled trials involving daily iron supplementation in children aged 5-12 years. We combined the data using random effects meta-analysis. Results: We identified 16 501 studies; of these, we evaluated 76 full-text papers and included 32 studies including 7089 children. Of the included studies, 31 were conducted in low- or middleincome settings. Iron supplementation improved global cognitive scores (standardized mean difference 0.50, 95% confidence interval [CI] 0.11 to 0. 90, p = 0.01), intelligence quotient among anemic children (mean difference 4.55, 95% CI 0.16 to 8.94, p = 0.04) and measures of attention and concentration. Iron supplementation also improved age-adjusted height among all children and age-adjusted weight among anemic children. Iron supplementation reduced the risk of anemia by 50% and the risk of iron deficiency by 79%. Adherence in the trial settings was generally high. Safety data were limited. Interpretation: Our analysis suggests that iron supplementation safely improves hematologic and nonhematologic outcomes among primary-school-aged children in low- or middleincome settings and is well-tolerated.