Neural mechanisms of protective effects of early nutrition on the development of social-emotional difficulties among children in Ghana

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Project Summary An estimated 250 million children in low- and middle-income countries are at risk of not fulfilling their developmental potential, partly due to undernutrition. The long-term goal of this proposal is to inform evidence- based programs and policies to support children in Ghana and other low- and middle-income countries to grow and develop to their full potential. This proposal is to conduct a follow-up study of children at age 8-12 years whose mothers participated in a randomized control trial providing lipid-based nutrient supplements (LNS) to pregnant women from ≤ 20 weeks of gestation through 6 months postpartum and to their children from age 6 to 18 months (n = 440), comparing outcomes to control groups who received maternal micronutrient capsules during pregnancy and postpartum (n = 880). The objective is to examine the long-term effect of early nutrition on brain and nervous system development, while strengthening the research environment and capacity at the University of Ghana to conduct neurobehavioral and neuroimaging research. The specific aims are 1) To investigate the effect of LNS on social-emotional development at school age and in the context of children's home environments and 2) to investigate the potential neural mechanisms through which LNS buffers the effects of a disadvantaged environment on children's development of social-emotional difficulties. The hypotheses are that 1) children in the LNS group will have fewer social-emotional and behavioral problems, compared to children who did not receive LNS, 2) greater effects of LNS will be found in children from more disadvantaged home environments, and 3) intervention group differences in autonomic nervous system regulation and white matter integrity measured by diffusion tensor imaging will mediate group differences in social-emotional development. The rationale is based on the previous finding that children in the LNS group had fewer social-emotional difficulties at age 4-6 years, with greater effects of LNS in children from disadvantaged home environments, suggesting that early supplementation buffered the effect of a disadvantaged environment on the development of social-emotional difficulties in this sample, in which a high percentage of children had a social-emotional difficulties score in the abnormally high range. Nutrients contained in LNS, such as iron and essential fatty acids, are necessary for myelination of brain areas involved in social-emotional regulation and processing, which occurs rapidly during pregnancy and the first two years after birth. This study will be the first long-term follow-up study in Africa of a randomized trial of both pre-natal and post-natal nutritional supplementation covering most of the first 1000 days from conception to age two years, adding to evidence from only two other such studies, both conducted in Latin America (Guatemala and Colombia) in the 1970s. This study represents an unprecedented opportunity to examine the long-term effects of supplementation with both macro- and micro-nutrients during most of the first 1000 days using a randomized controlled design, and the underlying neural mechanisms of the effects of early nutrition on later behavior.