Maximal Substrate Utilization Rates In Preterm Neonates

描述(申请人提供)：在这个国家，目前针对早产儿的营养策略导致出生后发育障碍，新生儿在出院时无法恢复。营养不良，特别是关键发育期蛋白质摄入不足，对神经发育和健康的长期结果产生不利影响。因此，努力优化营养支持，特别是在生命的头几周，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。这一建议的主要假设是，针对不同类型的婴儿和不同类型的出生后条件和疾病状态，有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，并最大限度地促进早产儿和重症新生儿的生长。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，以最大限度地增加极早产儿的蛋白质积累。具体目标1将检验这样一种假设，即相对较高的氨基酸摄入量在新生儿出生后立即开始，并通过密切监测营养摄入量维持在胎儿分娩率，与未监测的两种历史对照相比，将导致更好的生长结果。具体目标2将确定能量摄入量，在任何给定的氨基酸摄入量下，能量摄入量将优化蛋白质的积累。具体目标3将阐述在新生儿早期高血糖时给予外源性胰岛素对蛋白质增加和乳酸产生的代谢影响。具体目标4将开发方法学，以提高脆弱新生儿人群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。这位候选人已经发展出一套独特的研究经验和技能，将允许成功地对不稳定的早产儿进行复杂的营养调查。这位候选人在临床研究方面有广泛的资助记录，在以患者为中心的研究中指导见习医生。职业生涯中期临床研究人员奖将延长候选人在以患者为导向的研究方面的时间，以确定安全有效的早产儿和重症新生儿在出生后立即病程中促进合成代谢的策略，允许培训希望从事新生儿营养和代谢独立研究生涯的年轻研究人员，并推进候选人的职业目标，优化这一脆弱的婴儿群体的营养和代谢。

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.