ABSTRACT Background Deficiency of vitamin B-12 is common in pregnant Indian women. Assessment of neurophysiological measures using event-related potentials (ERPs) may yield additional information on the effects of maternal B-12 supplementation on child brain function. Objectives The objective of the study was to evaluate the effects of vitamin B-12 supplementation (50 μg daily orally) during pregnancy on the childhood ERP measures of positive waveform ∼300 ms after stimulus (P300) and mismatch negativity. Methods This study was a follow-up of children born to pregnant women who received oral vitamin B-12 supplements (n = 62) compared with children of pregnant women who received placebo (n = 70) from a randomized controlled trial. The mean ± SD child age was 72 ± 1 mo. We used the Enobio system to assess the ERP measures P300 and mismatch negativity. Results There were no significant differences in the primary outcomes, amplitudes, and latencies of the P300 results and the mismatch negativity between children in the supplementation and placebo groups. We combined the intervention and placebo groups for secondary analyses. On multiple variable regression analysis after adjusting for treatment group, intrauterine growth restriction, and home environment, P300 amplitude in children was significantly higher in the lowest tertile of third-trimester maternal methylmalonic acid (MMA) concentrations (β = 3034.04; 95% CI: 923.24, 5144.83) compared with the highest MMA tertile (β = 1612.12; 95% CI: −258.86, 3483.10, P = 0.005). Conclusions While no significant effects of maternal vitamin B-12 supplementation on children's ERP measures were seen at 72 mo, elevated maternal MMA concentrations in the third trimester were negatively associated with P300 amplitude in children. It may be worthwhile to study the impact of maternal and infant vitamin B-12 supplementation on childhood brain structure and function in longer and larger trials. The parent trial was registered at clinicaltrials.gov as NCT00641862.

IntroductionVitamin B12 deficiency is highly prevalent in pregnant Indian women. Neuropsychological tests have shown an association between low maternal vitamin B12 status and poorer cognitive performances in the offspring, although findings from these studies have been inconsistent. Vitamin B12 has an important role in the formation of myelin which is important for the transmission speed of neural impulses and myelination in the central nervous system has been linked to cognition. Assessing neurophysiological measures using event-related potentials (ERPs) in children may provide additional information on the effect of maternal vitamin B12 supplementation on offspring brain function. The study examines the effects of oral vitamin B12 daily supplements (50 µg) to pregnant Indian women on child neurophysiological function at 72 months.Methods and analysisWe previously conducted a double-blind, placebo-controlled study to examine the effects of maternal vitamin B12 supplementation on cognitive outcomes in their offspring using the Bayley scales of infant development, third edition. In this extended follow-up of the same cohort of mother-child dyad, we propose to use ERP to study the long-term impact of maternal B12 supplementation on brain function in children at 72 months of age. We intend to use P300 and mismatch negativity (MMN) as measures of neurophysiological outcomes. The primary outcome of this study will be child neurophysiological measures (as measured by amplitude and latency of P300 and MMN) assessed at 72 months of age in children whose mothers received vitamin B12 compared with neurophysiological status of children whose mothers received placebo.Ethics and disseminationThe study was approved by the Institutional Ethical Board of St. John’s Medical College and the Harvard School of Public Health Human Subjects Committee. Results obtained will be presented at national and international research meetings and published in peer-reviewed scientific journals.Trial registration numberNCT00641862.