METABOLIC CONSEQUENCES OF GROWTH FAILURE IN EXTREMELY LOW BIRTH WEIGHT INFANTS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。尽管存活率不断提高，但早产儿极低出生体重(ELBW)的生长结果仍然非常差。在这些接近足月妊娠的婴儿中，生长障碍几乎是普遍的。蛋白质损失率高和能量消耗增加而得不到足够的营养摄入，似乎是造成这种生长障碍的主要因素，可能会导致代谢变化，使生存优先于生长。本提案的目的是验证这样的总体假设，即宫外环境的营养不足会导致ELBW婴儿在蛋白质代谢、能量消耗、胰岛素敏感性和内皮功能方面的适应性反应，这些反应会持续整个婴儿时期。研究将在足月妊娠、4个月和18个月大的ELBW和正常对照组婴儿中进行。将追求以下具体目标：1.评估肠内喂养过程中的蛋白质动力学和蛋白质分解代谢，以及对整个婴儿期ELBW婴儿蛋白质摄入量增加的反应。2.测定低出生体重儿整个婴儿期的总能量消耗、静息能量消耗和活动能量消耗的比率。3.检测整个婴儿期极低出生体重儿的胰岛素敏感性。4.评估整个婴儿期极低出生体重儿的内皮功能。这些研究可能构成改善这些婴儿的临床和营养策略的基础，以及未来更彻底地探索这些适应的潜在机制的机会。

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. Despite continually improving survival rates, growth outcomes for premature extremely low birth weight (ELBW) infants remains exceptionally poor. Growth failure is nearly universal in these infants as they near term gestation. High rates of protein loss and elevated energy expenditures uncompensated by adequate nutritional intake appear to be primary factors in producing this growth failure, perhaps producing metabolic changes that prioritize survival over growth. The goal of the present proposal is to test the overall hypothesis that nutritional inadequacies of the extrauterine environment induce adaptive responses in protein metabolism, energy expenditure, insulin sensitivity, and endothelial function in ELBW infants which persist throughout infancy. Studies will be performed in ELBW and normal control infants at term gestation, 4 and 18 months of age. The following specific aims will be pursued: 1. To assess protein kinetics and protein catabolism during enteral feeding and in response to increased protein intake in ELBW infants throughout infancy. 2. To determine the rate of total energy expenditure, resting energy expenditure, and energy of activity in ELBW infants throughout infancy. 3. To examine insulin sensitivity in ELBW infants throughout infancy. 4. To evaluate endothelial function in ELBW infants throughout infancy. These studies may form the basis for improved clinical and nutritional strategies for these infants, as well as a future opportunity to more thoroughly explore the potential mechanisms underlying these adaptations.