Effects of Supplementation With Iron Syrup or Iron-Containing Multiple Micronutrient Powders on Neural Indices of Cognitive Functioning in Bangladeshi Children

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 event-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.