Objectives Micronutrients, especially iron, play a critical role in the developing infant brain. Yet, the causal effects of iron supplementation on neurocognitive functioning in a low-income anemic population of children have not been examined. This study sought to evaluate the effects of supplementation with iron syrup and iron-containing multiple micronutrient powders (MNPs) in Bangladeshi children on habituation to familiar sounds, a marker for healthy memory development, using auditory

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... -related brain potentials (ERPs). Methods This study was nested within the Benefits and Risks of Iron Supplementation in Children (BRISC) trial, a double blinded double dummy randomized controlled trial (RCT). At 8 months of age, 3300 children were randomized to receive 3 months of 1) iron syrup + placebo MNPs, or 2) MNPs (containing iron, retinol, zinc, and Vitamin C) + placebo iron syrup, or 3) placebo iron syrup and placebo MNPs. ERPs in response to an auditory roving oddball paradigm were measured in a random subset of 441 children at 3 months post-intervention (11 months of age) and 595 children after a further 9 months follow-up (20 months of age). ERP measures indexing aspects of habituation included the [deviant minus standard] difference waveform amplitude, N2 waveform amplitude, and the difference in deviant-evoked ERP amplitudes between the first and second half of the paradigm. Intention-to-treat analyses on ERP outcomes using linear models were used at 11 and 20 months of age separately. Results Baseline characteristics were balanced between treatment groups. Overall prevalence of anemia was 43.7% and iron deficiency was 28.4%. Intention-to-treat analyses indicated no significant treatment effects of iron or MNPs on the difference waveform amplitude at 11 months of age [mean difference (MD, 95% CI) iron vs placebo 0.24 (–1.03, 1.51); MNP vs placebo 0.59 (–0.70, 1.88)] and 20 months of age [(MD, 95% CI) iron vs placebo 0.50 (–0.62, 1.63); MNP vs placebo 0.24 (–0.89, 1.38)]. There were no differences by treatment arm for the other ERP measures. Conclusions Results from a rigorous prospectively powered sub-study of an RCT in an iron deficient population indicated no significant effects of supplementation with iron or MNPs on neural indices of habituation. Funding Sources NHMRC and The University of Melbourne.