There is increasing evidence that perinatal nutritional status may influence not only long term neurodevelopment but also the risk for cardiovascular and metabolic disease in adult life. Interestingly, the disease in question, coronary artery disease, hypertension, diabetes mellitus all share a dependence on the peripheral sympathetic nervous system (SNS). Thus, the interaction between nutrient intake and the SNS during early development appears to be a logical place to look for links between nutrition and the pathogenesis of metabolic and cardiovascular diseases. The overall hypothesis of our studies is that the tone and reactivity of the SNS are dependent on nutrient intake both acutely and over longer periods of time. As a result of systematic variations in SNS activity during early life, the resting level and responsiveness of the maturing SNS is permanently altered, leading to persistent differences in metabolic and cardiovascular regulation. To test this hypothesis we propose to compare cardiorespiratory activity, neurobehavioral organization, thermal regulation and catecholamines in VLBW infants receiving aggressive early nutrition regimen to a conventional regimen. We will also determine whether these same newborns, when examined in detail as infants, demonstrate physiologic, and neurobehavioral differences that can be related to early life nutrition. In parallel, hypotheses will be tested in the intra-uterine growth restricted that can be related to early life nutrition. In parallel, hypotheses will be tested in the intrauterine growth restricted (IUGR) fetal lamb. Specifically, we will systematically investigate the interaction nutrient supplementation of the IUGR fetus with oxygenation, glucose and insulin regulation and measures of SNS activity in cardiorespiratory activity, neurobehavioral organization, and systemic catecholamine release.
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