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Differences in Brain Development in a High and Low Economic Setting1MNCHD&T, Bill & Melinda Gates Foundation, Seattle, WA, United States, 2Pediatrics, Brown University, Providence, RI, United States, 3University of Wisconsin at Madison, Madison, WI, United States
Synopsis
Adverse environmental conditions throughout infancy and childhood have potential to result in neurodevelopment delays and impaired cognitive outcomes. Children born in low and middle income countries (LMICs) often experience significant malnutrition, inadequate sanitation, and are exposed to poor water and air quality, all of which can affect brain and cognitive development. However, there are limited reports of brain growth in LMICs, with cognitive development often assessed indirectly through measures of physical growth (child height and weight). Here we present the first reports of brain volume growth in children from a low resource area of India. Relative to reference brain growth charts derived from a large cohort of healthy children in Providence RI, we find significant brain growth delay, particularly amongst girls. These results shine new light on the importance of living conditions on child brain health.
INTRODUCTION
An estimated 250 million children, or 25% of all children globally, under 5 years of age fail to meet their full developmental potential. Most of these children live in low and middle income countries (LMICs), where adverse living conditions such as malnutrition; infection and disease; inadequate sanitation; poor water and air quality; limited access to quality healthcare; and insufficient educational opportunities (including at-home parent-child interaction and play) are prevalent. Individually and in combination, these factors can result in physical stunting and waisting (i.e., failing to reach age appropriate height and weight standards) as well as delays in cognitive development. While measures of physical growth are easy to obtain in many of these rural and developing settings, assessments of cognitive development are challenged by the need to adapt standard assessments batteries for the local language and culture. Neuroimaging may provide a 'culturally agnostic' approach to measuring brain and cognitive growth and identifying children at risk for affected growth and delays. Here we investigated early brain development in 77 children from Lucknow, Uttar Pradesh (UP), India. UP suffers some of the worst human development indicators in India, with half of all children stunted or delayed. Brain and tissue volumes were compared against reference growth charts generated from data acquired from 946 healthy children from Providence, RI revealing significant developmental differences, particularly within the female UP children.METHODS
Data Acquisition & Methods: 946 T1-weighted volumetric datasets were acquired on 502, 0-12.5 year old children living in Providence, RI. These data were spatially normalised to a set of custom age-specific templates and and pre-computed whole-brain, white matter (WM), gray matter (GM) and CSF tissue masks were superimposed onto the individual images. Masks were then inverse transformed back to the child space and tissue volumes calculated. This approach allows tissue volumes to be calculated on infants <12 months of age whose images lack significant gray/white tissue contract. Matched T1 data were acquired from 77 children from UP India between 7 and 19 months of age and the same image analysis pipeline used.
Using quantile regression and the RI child data, gender-specific mean, +/- 1, and +/2 standard deviation reference growth curves were calculated for total brain, WM, GM, and CSF to which the UP child data was compared.
Child height and weight data were also collected for all UP children and associations between brain volume-for-age and physical growth were investigated.
RESULTS
Relative to the RI children, children from India showed significant volumetric reductions (below the 3rd percentile) in both white and grey matter volumes (Figure 1). Of note, CSF volume in the UP children was significantly greater than the children from the USA. This volumetric difference was particularly pronounced in the UP girls relative to UP boys, which may be related to the societal standing and care provided to girls relative to boys. We also found that child weight, though not height, was lower in India children, and we found a significant relationship between brain volume and weight (p=0.02) (Figure 2).
DISCUSSION
Results reveal, for the first time, significant brain volume reductions and 'brain stunting' in children born and growing up in the low resource setting of UP, India compared to the US. Of note, deficits appear to affect girls more severely than boys implying a potential cultural context with respect to cognitive delays. Of note, observed results appear in the absence of physical stunting. As physical growth is commonly used as a surrogate measure of neurodevelopment, these results carry implications for interventional studies that rely on physical height as a measure of cognition development and outcome.
Acknowledgements
No acknowledgement found.References
No reference found.Figures
