Effects of iron supplementation on neural indices of habituation in Bangladeshi children.

Mohammed Imrul Hasan, Sm Mulk Uddin Tipu, Shamima Shiraji, Fahmida Tofail, Leila M Larson, Daniel Feuerriegel, Sabine Braat, Jerry Jin, Beverley-Ann Biggs, Jena D Hamadani, Katherine A Johnson, Stefan Bode, Sant-Rayn Pasricha

Journal: The American journal of clinical nutrition 2023;117(1):73-82

PMID: 36789946

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Plain Language Summary

Adversity during early life, including malnutrition, may influence the long-term cognitive development of children. Micronutrients, especially iron, may play a critical role in the developing infant brain The aim of this study was to determine the effects of supplementation with iron syrup and iron containing multiple micronutrient powders (MNPs) on neural indices of habituation in Bangladeshi children. This neurocognitive substudy was nested within the Benefits and Risks of Iron Supplementation in Children (BRISC) trial. BRISC was a 3-arm, double-blind, double-dummy, individual randomised, superiority trial. Children were randomly assigned to 1 of the 3 arms using a 1:1:1 allocation. Results showed that iron supplementation (provided through 2 different modes) did not affect neural indices of habituation. There wasn’t any identification of treatment effects for any of the outcomes measured, despite finding improvements in haemoglobin and ferritin concentrations for children given iron syrup or MNPs. Authors conclude that despite established links between iron availability and neurophysiological development, increased iron availability in children under one year of age does not lead to measurable changes in neural indices of habituation.

Abstract

BACKGROUND

Iron deficiency and anemia have been associated with poor cognition in children, yet the effects of iron supplementation on neurocognition remain unclear.

OBJECTIVE

We aimed to examine the effects of supplementation with iron on neural indices of habituation using auditory event-related brain potentials (ERPs).

METHODS

This substudy was nested within a 3-arm, double-blind, double-dummy, individual randomized trial in Bangladesh, in which 3300 8-mo-old children were randomly selected to receive 3 mo of daily iron syrup (12.5 mg iron), multiple micronutrient powders (MNPs) (including 12.5 mg iron), or placebo. Children were assessed after 3 mo of intervention (mo 3) and 9 mo thereafter (mo 12). The neurocognitive substudy comprised a randomly selected subset of children from the main trial. Brain activity elicited during an auditory roving oddball task was recorded using electroencephalography to provide an index of habituation. The differential response to a novel (deviant) compared with a repeated (standard) sound was examined. The primary outcome was the amplitude of the mismatch response (deviant minusstandard tone waveforms) at mo 3. Secondary outcomes included the deviant and standard tone-evoked amplitudes, N2 amplitude differences, and differences in mean amplitudes evoked by deviant tones presented in the second compared with first half of the oddball sequence at mo 3 and 12.

RESULTS

Data were analyzed from 329 children at month 3 and 363 at mo 12. Analyses indicated no treatment effects of iron interventions compared with placebo on the amplitude of the mismatch response (iron syrup compared with placebo: mean difference (MD) = 0.07μV [95% CI: -1.22, 1.37]; MNPs compared with placebo: MD = 0.58μV [95% CI: -0.74, 1.90]) nor any secondary ERP outcomes at mo 3 or 12, despite improvements in hemoglobin and ferritin concentrations from iron syrup and MNPs in this nested substudy.

CONCLUSION

In Bangladeshi children with >40% anemia prevalence, iron or MNP interventions alone are insufficient to improve neural indices of habituation. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12617000660381.

Address: Department of Health Promotion, Education, and Behavior, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia; Department of Infectious Diseases at the Peter Doherty Institute, The University of Melbourne, Melbourne, VIC, Australia. Electronic address: [email protected].; Melbourne School of Psychological Sciences, The University of Melbourne, Melbourne, VIC, Australia.; Maternal and Child Health Division, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia; Department of Infectious Diseases at the Peter Doherty Institute, The University of Melbourne, Melbourne, VIC, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Australia.; Department of Infectious Diseases at the Peter Doherty Institute, The University of Melbourne, Melbourne, VIC, Australia; Melbourne School of Psychological Sciences, The University of Melbourne, Melbourne, VIC, Australia.; Department of Infectious Diseases at the Peter Doherty Institute, The University of Melbourne, Melbourne, VIC, Australia; The Victorian Infectious Diseases Service, The Royal Melbourne Hospital, Melbourne, VIC, Australia.; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia; Diagnostic Hematology, The Royal Melbourne Hospital, Parkville VIC, Australia; Diagnostic Hematology and Clinical Hematology, The Peter MacCallum Cancer Centre and The Royal Melbourne Hospital, Parkville VIC, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia.

DOI: 10.1016/j.ajcnut.2022.11.023