Chronic deficiency of essential micronutrients is the most common, preventable form of malnutrition in the developing world, affecting millions of infants, young children and pregnant women. Interest is growing in understanding effects of specific micronutrient deficiencies early in life, particularly iron and zinc, on child development. Adequate nutriture of both iron and zinc is necessary for optimal brain development and functioning. Deficiencies of either nutrient in fetal or early postnatal life may lead to irreversible neurocognitive dysfunction and impaired motor or behavioral development. Yet, experimental data are lacking to reveal either deficiency as a cause, or the developmental benefits of iron or zinc supplementation in undernourished populations. A unique opportunity exists in rural Nepal to examine effects of iron supplementation, with or without added zinc, during (i) pregnancy (in utero), (ii) early childhood and (iii) both periods on neurocognitive function in a cohort of 1750 children at 6-7 yr of age, the usual age at school entry. Recruited children will have participated in two, previous randomized controlled supplementation trials: one in which their mothers received either placebo or iron (+folic acid), with or without zinc daily from 1st trimester to 6 weeks post partum, and the second in which the children themselves were dosed daily with placebo, iron and/or zinc, in a 2x2 factorial design, when they were 12 to 35 months of age. -Thus, by preserving each original design, the proposed study will retain inferential strength of a 2-stage randomized trial. Over 18 months, children will be evaluated at home and in a clinic by standard tests of intelligence, motor function, affect and behavior. We will assess whether children in any of our supplementation groups show faster processing of information and greater inhibitory control, cognitive functions that rely on dopaminergic pathways, which in turn are sensitive to iron deficiency. However, it is also possible that the cumulative effect of supplementation could have a more general effect on intellectual functioning, which we assess independently. Socioeconomic status, home environment, and nutrition and hearth status will also be assessed. Analyses will evaluate child outcomes by original matemo-child supplement exposures. The study will fill critical gaps in knowledge and inform policy on the efficacy of selective micronutrient interventions in pregnancy and early childhood to improve school-aged cognition. ? ? ? ?
