Maximal Substrate Utilization Rates In Preterm Neonates

描述（由申请方提供）：目前，美国针对极早产儿的营养策略导致新生儿出生后生长失败，到出院时新生儿尚未恢复。营养不良，特别是在关键发育期蛋白质摄入不足，会对长期的神经发育和健康结果产生不利影响。因此，努力优化营养支持，特别是在生命的最初几周，对于扭转这一弱势群体中与营养有关的不良后果至关重要。该建议的总体假设是，对于不同类型的婴儿和不同类型的产后状况和疾病状态，有各种各样的营养和代谢策略，这些策略将优化早产儿和危重新生儿的营养，降低发病率并使其生长最大化。这项建议的基本研究目标是确定最佳的早期营养管理方法，将最大限度地增加极早产儿的蛋白质。具体目标1将检验以下假设：与未监测的两个历史对照相比，在新生儿期开始摄入相对较高的氨基酸并通过密切监测营养摄入维持在胎儿分娩率下，将导致生长结局改善。具体目标2将确定在任何给定氨基酸摄入量下优化蛋白质积累的能量摄入量。具体目标3将阐述外源性胰岛素给药对早期新生儿高血糖症蛋白质增加和乳酸产生的代谢影响。具体目标4将制定方法，以提高脆弱新生儿人群中蛋白质代谢研究的可接受性。该奖项中提出的这项工作建立在候选人过去在改善早期新生儿营养方面的里程碑式研究的基础上。候选人已经开发了一套独特的研究经验和技能，将允许在不稳定的早产儿中成功进行复杂的营养调查。候选人在临床研究和指导实习医生进行以患者为导向的研究方面都有广泛的记录。职业生涯中期临床研究者奖将扩大候选人在出生后立即进行的以患者为导向的研究，以确定早产儿和危重新生儿的安全有效的促合成代谢策略，允许培训希望在新生儿营养和代谢方面从事独立研究的年轻研究人员，并推进候选人优化这一弱势婴儿群体的营养和新陈代谢的职业目标。

DESCRIPTION (provided by applicant): Current nutritional strategies for very preterm infant in this country are resulting in postnatal growth failure from which the neonate does not recover by the time of hospital discharge. Undernutrition, particularly insufficient protein intake during critical development periods adversely affects long-term neurodevelopmental and health outcomes. Efforts to optimize nutritional support, therefore, particularly in the first weeks of life, are critical to reversing nutritionally related adverse outcomes in this vulnerable population. The overarching hypothesis of this proposal is that there are a variety of nutritional and metabolic strategies for different types of infants and different types of postnatal conditions and disease states that will optimize anabolism, reduce morbidity and maximize growth in very preterm and critically ill neonates. The fundamental research goal of this proposal is to determine optimal early nutritional management approaches that will maximize protein accretion in extremely premature neonates. Specific Aim 1 will test the hypothesis that relatively high amino acid intake initiated in the immediate neonatal period and sustained at fetal delivery rates through close monitoring of nutrient intake will result in improved growth outcomes compared when compared to both historical controls that are not monitored. Specific Aim 2 will determine the energy intake that will optimize protein accretion at any given amino acid intake. Specific Aim 3 will address the metabolic effects of exogenous insulin administration in early neonatal hyperglycemia on protein accretion and lactate production. Specific Aim 4 will develop methodology to increase acceptability of protein metabolism studies in vulnerable neonatal populations. This work proposed in this award builds on the candidate's past landmark research in improving early neonatal nutrition. The candidate has developed a unique set of research experiences and skills that will allow for successful conduct of complex nutritional investigations in unstable preterm neonates. The candidate has an extensive record of both funding in clinical investigation and mentoring trainee physicians in patient-oriented research. A mid-career clinical investigator award would expand the time the candidate has for patient-oriented research on determining safe and efficacious anabolism-promoting strategies in very preterm and critically ill neonates during the immediate postnatal course, allow for training of young investigators who wish to pursue independent research careers in neonatal nutrition and metabolism, and advance the candidate's career goals of optimizing nutrition and metabolism in this vulnerable population of infants.