This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The clinical care of sick newborn infants, particularly those with respiratory impairment, has improved dramatically during the past two decades. The introduction of Surfactant has played a major role in this development. Thus, neonatal research has focused primarily on the respiratory-cardio vascular system, while nutritional research has lagged behind. Newborn infants, especially those born very prematurely and those who are sick, are at risk of disturbed glucose metabolism and insufficient energy intake. Hyperglycemia is very common (prevalence 50-80%) in infants with birth weights below 1000g, especially those who are sick and who receive glucose infusion at rates exceeding the normal glucose turnover rates (6-8 mg/kg min). During the past several years we have studied glucose, lipid and protein metabolism in very premature infants (gestational age of less than 29 weeks) receiving parenteral nutrition addressing the issue of how to optimize the composition of total parenteral nutrition solutions in order to prevent both hypo- and hyperglycemia and insufficient energy intake. We have successfully set up methods to measure glucose production, gluconeogenesis, lipolysis, protein breakdown and protein oxidation. We have demonstrated that very premature infants receiving glucose at 3 mg/kg min (half their normal glucose turnover rate) are capable of producing glucose from both endogenous substrate stores and parenterally administered lipid and amino acid solution (TrophAmine). We showed that the components of the lipid emulsion (Intralipid) are more important than the parenteral amino acids in supporting gluconeogenesis. It has been demonstrated in critically ill adults and children, that hyperglycemia was associated with increased mortality. However, there is no information regarding the prevalence of hyperglycemia (the proposed protocol is not designed to address this issue) or the effects of glucose infusion rate on glucose, lipid and protein metabolism in newborn infants with respiratory illness such as IRDS, meconium aspiration or pneumothorax . In the proposed protocol, we will determine (in infants with gestational ages of 30 weeks and above with respiratory illness), the effects of 1) routine TPN (usually providing glucose at rates exceeding infant normal glucose turnover rate), and 2) reducing the glucose infusion rate to correspond to half normal glucose turnover rate (while providingthe appropriate supply of parenteral lipid and amino) on parameters of glucose, lipid and protein metabolism. Knowledge about the metabolic effects of routine and alternative nutritional approaches is a prerequisite for designing appropriate nutritional strategies.
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