Effectiveness of intermittent iron and high-dose vitamin A supplementation on cognitive development of school children in southern Ethiopia: a randomized placebo-controlled trial.

BACKGROUND: Iron is an essential mineral whose deficiency results in cognitive alteration, impaired emotional behaviors, and altered myelination and neurotransmission. In animal models, it has been shown that vitamin A (VA) could affect cognition. OBJECTIVES: The study aimed to evaluate the effectiveness of intermittent iron and VA supplementation on cognitive development of schoolchildren, and to assess the interaction between these supplementations. METHODS: Considering a 2 × 2 factorial design, 504 children were randomly assigned to 1 of the 4 arms: placebo VA and placebo iron supplement; high-dose vitamin VA and placebo iron supplement; iron supplement and placebo VA; and iron and high-dose vitamin VA supplements. Cognitive development was assessed using Raven's Coloured Progressive Matrices, digit span, Tower of London, and visual search tasks. RESULTS: The mean [± standard deviation (SD)] age of the enrolled children was 9.6 (±1.6) y. One-fifth of the children had iron deficiency or anemia, whereas 2.9%, 3.9%, and 12.1% of children had low iron stores, iron deficiency anemia, and VA deficiency, respectively. Intermittent iron supplementation did not result in any significant improvement of children's cognitive development and had a negative effect on the performance index of the visual search task compared with placebo (-0.17 SD, 95% confidence interval: -0.32, -0.02). Effects were evident among children with stunting, thinness, or children coming from understimulating home environments. High-dose VA supplementation resulted in a significant improvement of digit span z-score with a mean difference of 0.30 SD (95% confidence interval: 0.14, 0.46) compared with placebo VA. VA had a more beneficial impact for girls, children infected with helminths, and those from food secure households. CONCLUSION: In a population where the prevalence of iron deficiency is low, intermittent iron supplementation did not have any or negative effect on the child's cognitive development outcomes. Conversely, VA supplementation improved the child's working memory. TRIAL REGISTRATION NUMBER: The study is registered at clinicaltrials.gov as NCT04137354 (https://clinicaltrials.gov/study/NCT04137354).

Effects of iron supplementation on cognitive development in school-age children: Systematic review and meta-analysis.

BACKGROUND: Iron deficiency is negatively associated with children's cognitive development. Evidence showed that iron supplementation improves cognitive development. Nearly 50% of anemia is caused by iron deficiency. Anemia affects more school-age children, at an age where their brain development continues. The aim of this systematic review and meta-analysis is to review the evidence from published randomized controlled trials to evaluate the effects of iron supplementation on cognitive development and function among school-age children. METHOD: Five databases including MEDLINE, EMBASE, Scopus, Web of Science and CENTRAL were used to search for articles on April 20th, 2021. The search was reconducted on October 13th, 2022 to retrieve new records. Studies were eligible if they included school children 6-12 years of age, were randomized controlled trials, and if they tested iron supplementation and measured cognitive development. RESULT: Thirteen articles were included in the systematic review. Overall, iron supplementation significantly improved intelligence (standardized mean difference, 95% confidence interval) (SMD 0.46, 95%CI: 0.19, 0.73, P<0.001), attention and concentration (SMD 0.44, 95%CI: 0.07, 0.81, P = 0.02) and memory (SMD 0.44, 95%CI: 0.21, 0.67, P <0.001) of school-age children. There was no significant effect of iron supplementation on school achievement of school-age children (SMD 0.06, 95%CI: -0.15, 0.26, P = 0.56). In a subgroup analysis, iron-supplemented children who were anemic at baseline had had better outcomes of intelligence (SMD 0.79, 95%CI: 0.41, 1.16, P = 0.001) and memory (SMD 0.47, 95%CI: 0.13, 0.81; P = 0.006). CONCLUSION: Iron supplementation has a significant positive effect on the intelligence, attention and concentration, and the memory of school-age children but there was no evidence on the effect of iron supplementation on their school achievement.