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Child Growth Predicts Brain Functional Connectivity and Future Cognitive Outcomes in Urban Bangladeshi Children Exposed to Early Adversities

By Wanze Xie, Sarah K.G. Jensen, Mark Wade, Swapna Kumar, Alissa Westerlund, Shahria H. Kakon, Rashidul Haque, William A Petri, Charles A Nelson

Posted 22 Oct 2018
bioRxiv DOI: 10.1101/447722

Background: Faltered growth has been shown to affect 161 million children worldwide and derail cognitive development from early childhood. The neural pathways by which growth faltering in early childhood affects future cognitive outcomes remain unclear, which is partially due to the scarcity of research using both neuroimaging and sensitive behavioral techniques in low-income settings. We employed EEG to examine the association between growth faltering and brain functional connectivity and whether brain functional connectivity mediates the effect of early adversity on cognitive development. Methods: We recruited participants from an urban impoverished neighborhood in Dhaka, Bangladesh. One sample consisted of 85 children whose EEG and growth measures (height for age, weight for age, and weight to height) were collected at 6 months and cognitive outcomes were assessed at 27 months. Another sample consisted of 115 children whose EEG and growth measures were collected at 36 months and IQ scores were assessed at 48 months. Path analysis was used to test the effect of growth measures on cognitive outcomes through brain functional connectivity. Findings: Faltered growth was found to be accompanied by overall increased functional connectivity in the theta and low-beta frequency bands for the 36-month-old cohort. For both cohorts, brain functional connectivity was negatively predictive of later cognitive outcomes at 27 and 48 months, respectively. Faltered growth was found to have a negative impact on children's IQ scores in the older cohort, and this effect was found to be mediated by brain functional connectivity in the low-beta band. Findings: Faltered growth was found to be accompanied by overall increased functional connectivity in the theta and low-beta frequency bands for the 36-month-old cohort. For both cohorts, brain functional connectivity was negatively predictive of later cognitive outcomes at 27 and 48 months, respectively. Faltered growth was found to have a negative impact on children's IQ scores in the older cohort, and this effect was found to be mediated by brain functional connectivity in the low-beta band. Interpretation: The association found between growth measures and brain functional connectivity may reflect a broad deleterious effect of malnutrition on children's brain development. The mediation effect of functional connectivity on the relation between physical growth and later IQ scores provides the first experimental evidence that brain functional connectivity may mediate neural pathway by which biological adversity affects cognitive outcomes. Funding: Bill and Melinda Gates Foundation (OPP1111625)

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