Neurobehavioral impacts in adolescence from early life nutrition supplementation: 10-year follow-up to a cluster randomized trial in Bangladesh - MODIFIED PROJECT SUMMARY Children in the USA and other contexts face poor nutrition and high rates of food insecurity, which have shown to be detrimental to their development. The provision of food-based combinations of macro- and micro-nutrients, such as small quantity lipid-based nutrient supplements (SQ-LNS), has emerged as a cost-effective solution to reducing child stunting, wasting, underweight, anemia, mortality, and suboptimal development. The expectation is that the health and neurobehavioral benefits in early life, when the brain is developing rapidly and is most sensitive to interventions, extend beyond childhood. Few studies, however, have examined the long-term impacts of exposure to enhanced nutrition with macro- and micro-nutrients during pregnancy and early childhood on adolescent neurobehavioral outcomes. To critically inform ongoing initiatives and maternal and child health interventions, follow-up studies of early life enhanced nutrition trials are required. This study will leverage an existing cohort of adolescents who participated in a rigorous community-based cluster-randomized trial that included provision of SQ-LNS during pregnancy and the first two years of life, the Rang-Din Nutrition Study (RDNS). In 2012, the RDNS enrolled 4011 women at ≤ 20 weeks gestation from 64 clusters. Nutrition supplementation was provided to women during pregnancy and the first 6 months postpartum and to their offspring from 6 to 24 months of age. Clusters were randomized to one of four study arms: 1) women and children both received SQ-LNS (LNS-LNS arm), 2) women receive iron and folic acid (IFA) and children received SQ-LNS (IFA-LNS arm), 3) women received IFA and children received micronutrient powders (IFA-MNP arm), and 4) women received IFA and children received no supplements (IFA-Control arm). Our study will follow the 3664 live-born children enrolled in the RDNS to examine the effect of early life nutrition supplementation on 13-14-year-old cognitive and socio-emotional outcomes, as well as autonomic nervous system function, functional brain activity, and brain structure. Our study has three aims. First, we will evaluate long-term differences in cognitive and socio-emotional outcomes among adolescents from the LNS-LNS arm, the IFA-LNS arm, the IFA-MNP arm, and the IFA-Control arm, using mixed-model intent-to-treat analyses. Second, we will evaluate the impact of the interventions on adolescent autonomic nervous system function using electrocardiography (ECG), functional brain activity using electroencephalography (EEG), and brain structure using magnetic resonance imaging (MRI). Third, we will evaluate the impact of the interventions on adolescent anthropometric outcomes (i.e., height, weight, body mass index, tricep skin fold thickness, arm fat area, and arm muscle area) and pubertal status. This study presents an efficient opportunity to study the long-term consequences of early life inputs in vulnerable households, the results of which will be valuable to designing health systems interventions to protect child health in settings across the USA. Poor nutrition is experienced by populations across the USA, particularly in low income and food insecure households. Poor nutrition in early life is important because it is a critical period biologically, socially, and behaviorally. Nutritional needs in pregnancy and early childhood are universal, as are developmental processes throughout childhood and adolescence.
