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 preventive 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 quasi-randomized 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 middle-income 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 middle-income settings and is well-tolerated.

Figure 1:

Flow diagram of identification of included studies. In total, 16 501 titles were identified, of which 43 references pertaining to 32 studies were eligible for inclusion in the systematic review.

Figure 2:

Forest plots for global cognitive performance and cognitive performance by anemia status. *Inverse variance, random effects. †Author-adapted scales included clerical task test, visual memory test, digit span test and maze test. Note: CI = confidence interval, TONI-II = Test of Non-verbal Intelligence, 2nd edition, SD = standard deviation, SMD = standardized mean difference, WISC = Wechsler Intelligence Scale for Children.

Figure 3:

Forest plot for height. Forest plot of the z scores for height. *Inverse variance, random effects. Note: CI = confidence interval, SD = standard deviation.