NITROGEN METABOLISM IN GROWTH RESTRICTED NEONATES

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。胎儿生长受限可能会导致生长和发育的终身改变，并增加成年后患糖尿病、胰岛素抵抗和高血压等疾病的风险。尚不清楚生命早期积极的喂养方法是否可以改善严重生长受限婴儿的结局，特别是早期生长。这首先需要了解这些婴儿营养代谢异常的具体情况以及对喂养的定性和定量反应。我们假设，早产SGA婴儿谁有宫内生长受限（IUGR）表现出异常的氮代谢，包括蛋白质合成，氧化和catalysts比阿加婴儿。以前的营养代谢研究并没有显示SGA和阿加婴儿之间的代谢模式始终不同，这可能是因为SGA婴儿的生长发育并不一致。我们将通过研究一组SGA婴儿来解决这个问题，这些婴儿是基于胎儿研究而被称为IUGR的，这些研究表明宫内生长速度明显受限。然后，我们将使用示踪亮氨酸动力学测量来验证我们的假设，以量化出生后第1天、第1周和第1个月结束时进行的研究中的蛋白质代谢，阿加和IUGR婴儿的胎龄和相对较高的营养摄入量相匹配。此外，我们将通过间接热量测定法和双标记水技术确定能量消耗，使用示踪方法确定葡萄糖和甘油周转率，使用我们建立的技术确定身体成分的变化和营养平衡。这项研究将是第一个全面的研究蛋白质代谢的变化，身体成分和生长的IUGR婴儿接受积极的营养摄入量在一段较长的时间，并将明确确定是否有显着的营养代谢差异IUGR与阿加婴儿唯一确定的婴儿谁表现出极端的异常宫内生长率。这些研究的结果可能会改变目前的喂养方法，并为未来严重生长受限婴儿的营养干预研究提供合理的基础。

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. 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 nutrient 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.