Maximal Substrate Utilization Rates In Preterm Neonates

描述（由申请人提供）：在这个国家，目前对早产儿的营养策略导致新生儿在出院时无法恢复的产后生长衰竭。营养不良，特别是关键发育时期蛋白质摄入不足，会对长期神经发育和健康结果产生不利影响。因此，优化营养支持的努力，特别是在生命的最初几周，对于扭转这一弱势群体的营养相关不良后果至关重要。这一提议的首要假设是，对于不同类型的婴儿和不同类型的产后条件和疾病状态，存在各种营养和代谢策略，这些策略将优化合成代谢，减少发病率，最大化早产儿和危重新生儿的生长。本提案的基本研究目标是确定最佳的早期营养管理方法，以最大限度地增加极早产儿的蛋白质。特异性目标1将验证一个假设，即在新生儿初期开始相对较高的氨基酸摄入量，并通过密切监测营养摄入量在胎儿娩出率下维持，与未监测的两种历史对照相比，将导致更好的生长结果。特定目标2将确定能量摄入量，在任何给定的氨基酸摄入量下优化蛋白质的增加。特异性目标3将解决外源性胰岛素在新生儿早期高血糖对蛋白质增加和乳酸生成的代谢影响。具体目标4将制定方法，以提高易感新生儿群体蛋白质代谢研究的可接受性。该奖项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。该候选人已开发出一套独特的研究经验和技能，将允许在不稳定早产儿复杂的营养调查成功进行。候选人在资助临床研究和指导实习医生进行以病人为导向的研究方面有着广泛的记录。职业中期临床研究者奖将扩大候选人在以患者为导向的研究上的时间，以确定在早产和危重新生儿中安全有效的促进合成代谢的策略，并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者。并推进候选人的职业目标，优化这一弱势群体的婴儿营养和代谢。

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.