Effects of maternal B12 supplementation on neurophysiological outcomes in children: a study protocol for an extended follow-up from a placebo randomised control trial in Bangalore, India

Shilpa Anand, Susan Thomas, Mahesh Jayachandra, Tinku Thomas, Tor Arne Strand, Anura V Kurpad, Christopher P Duggan, Krishnamachari Srinivasan, Shilpa Anand, Susan Thomas, Mahesh Jayachandra, Tinku Thomas, Tor Arne Strand, Anura V Kurpad, Christopher P Duggan, Krishnamachari Srinivasan

Abstract

Introduction: Vitamin 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 analysis: We 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 dissemination: The 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 number: NCT00641862.

Keywords: P300 and mismatch negativity; brain development; children; event related potentials; maternal vitamin B12 supplementation; neurophysiology.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
The Neuroelectrics ENOBIO system with the dry electrodes, electrode cap and the Neuroelectrics Instrument Controller device.
Figure 2
Figure 2
Event-related potentials: amplitude and latency.
Figure 3
Figure 3
Workflow of electrophysiological experiments along with information about system connections.
Figure 4
Figure 4
P300 stimuli and task. This figure shows the stimuli, the duration of the presentation of each stimuli and the inter-stimulus interval (ISI) of the P300 experiment. The three stimuli are presented at complete random in the ratio of 80:10:10 (standard:target:distraction).
Figure 5
Figure 5
Mismatch negativity (MMN) stimuli and task. This figure shows the stimuli, the duration of the presentation of each stimuli and the inter-stimulus interval of the MMN experiment. The two stimuli are presented at complete random in the ratio of 80:20 (standard:deviant).

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