ACTIVITY AND RESPONSES TO NUTRIENT AND OXYGEN SUPPLY DURING DEVELOPMENT

Normal development of the human fetus and newborn depends on three factors; availability of a sufficient quantity of properly balanced nutrients, adequate oxygen supply and carbon dioxide removal and an appropriate balance between nutrient supply and metabolic gas exchange. Disruptions of these conditions lead not only to increased mortality in the perinatal period, but also to long-term morbidity ranging from subtle to severe neurobehavioral handicaps. Our long term goal is to understand how variations in nutrient balance in early life could impact on later health. As a first step we will identify relationships between acute perinatal disturbances of growth and development and physiologic control systems that t may become abnormal during later life, e.g. peripheral autonomic nervous system function and central neurotransmitter activity. Using experiments in low birth weight human infants, and human,ovine and baboon fetuses we will test two specific hypotheses. First, that increased dietary intake of carbohydrate is associated with tonic activation of the peripheral sympathetic nervous system, both biochemically and physiologically. Second, that variations in nutrient intake are capable of altering the ratio of the plasma concentration of tryptophan to the sum of the plasma concentrations of other large neutral amino acids and further, that increases in this ratio are associated with alterations of physiological and behavioral variables in a direction consistent with increased central serotonergic activity. These hypotheses will be tested by serially recording the physiologic and behavioral responses to prospective manipulations of nutrient intake. In addition to providing timely information about the effects of variations in nutritional management of the immature human, confirmation of these hypotheses would provide a theoretical model for the study of specific mechanisms through which nutritional experience in early life might "program" lifelong regulators of cardiovascular and metabolic functions.