Fetal growth restriction may produce life-long alterations in growth and development as well as increase the risk of diseases in adulthood such as diabetes, insulin-resistance and hypertension. It is not known if an aggressive feeding approach early in life might improve outcome in the severely growth restricted infant, particularly of early growth. This first requires understanding the specifics of abnormal nutrient metabolism and the qualitative and quantitative responses to feeding in these infants. We hypothesize that preterm SGA infants who had intrauterine growth restriction (IUGR) demonstrate abnormal nitrogen metabolism consisting of decreased rates of protein synthesis, oxidation and catabolism compared with AGA infants. Previous studies of nutrient metabolism have not shown consistently different metabolic patterns between SGA and AGA infants, probably because the SGA infants were not uniformly growth restricted. We will resolve this by studying a subgroup of SGA infants that are known to be IUGR based on fetal studies that demonstrate markedly restricted rates of in utero growth. We then will test our hypothesis using tracer leucine kinetic measurements to quantify protein metabolism in studies performed at the end of day 1, week 1 and month 1 of postnatal life, with both AGA and IUGR infants matched for gestational age and relatively high nutrient intake. In addition, we will determine energy expenditure by both indirect calorimetry and doubly labeled water techniques, glucose and glycerol turnover rates using tracer methodology, changes in body composition, and nutient balance using our established techniques. This study will be the first comprehensive study of changes in protein metabolism, body composition and growth in IUGR infants receiving aggressive nutrient intakes over an extended period of time, and will definitively determine if there are significant nutritional metabolic differences in IUGR versus AGA infants by uniquely identifying the infants who demonstrate the extreme of abnormal intrauterine growth rate. The results of these studies could alter current feeding practices and provide a rational basis for future nutritional intervention studies in severely growth restricted infants.
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