NITROGEN METABOLISM IN GROWTH RESTRICTED NEONATES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 限制胎儿生长可能会导致终身的生长发育变化，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。目前尚不清楚，在生命早期采取积极的喂养方法是否会改善严重发育受限婴儿的结局，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，与AGA相比，患有宫内生长受限(IUGR)的早产儿表现出氮代谢异常，包括蛋白质合成、氧化和分解代谢减慢。以前对营养代谢的研究没有显示出SGA和AGA婴儿之间持续不同的代谢模式，可能是因为SGA婴儿没有受到一致的生长限制。我们将通过研究一组已知为IUGR的SGA婴儿来解决这个问题，这些婴儿的胎儿研究表明，子宫内发育速度明显受限。然后，我们将在出生后第1天、第1周和第1个月结束时进行的研究中，使用示踪剂亮氨酸动力学测量来量化蛋白质代谢，以验证我们的假设，这些研究中AGA和IUGR婴儿的胎龄匹配，营养摄入量相对较高。此外，我们将通过间接量热法和双标记水技术来确定能量消耗，使用示踪剂方法来确定葡萄糖和甘油的周转率，使用我们已建立的技术来确定身体成分的变化，以及营养平衡。这项研究将首次全面研究长期接受积极营养摄入的IUGR婴儿的蛋白质代谢、身体成分和生长发育的变化，并将通过唯一识别表现出极端异常宫内生长速度的婴儿，最终确定IUGR和AGA婴儿是否存在显著的营养代谢差异。这些研究的结果可能会改变目前的喂养方式，并为未来对严重生长受限婴儿进行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.