IMPACT OF DEVELOPMENT ON PROTEIN UTILIZATION AND GROWTH

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心赠款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 表示子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 尽管在过去十年中，低出生体重儿（LBW）的营养管理有所改善，但大多数出生时体重1500 g的婴儿，即使出生时的胎龄大小合适，在出院时体重也低于或短于宫内标准的第10次妊娠（月经后约36周），许多婴儿在青春期和成年早期仍然很小。 虽然早期生长失败的后果尚不确定，但有证据表明，它可能导致该人群中发育缺陷的高患病率。 研究提出了测试的假设，有一个有限的时期，在此期间，人类婴儿能够最大限度地利用蛋白质的增长。 根据对婴儿的有限研究和对动物的急性研究，这一时期似乎包括妊娠后期和产后的前几个月，但尚未确定。 推论的假设，这也将在人类婴儿中进行测试，是最大限度地增加蛋白质摄入量在这一有限的时期内增强敏感性的蛋白质摄入量将改善生长，因此，减少随后的生长和神经发育缺陷的早产儿。 总的来说，拟定研究将确定是否存在一个有限的时间段，在此期间，人类新生儿可以最大限度地利用蛋白质摄入量进行生长（通过全身蛋白质周转测定），并将定义此时间段。 他们还将确定在这一有限时期内最大限度地摄入蛋白质是否会改善早期生长而不会造成不可接受的代谢后果，以及这种改善的生长是否会减少随后的生长和神经发育缺陷。 总的来说，本项目的研究结果预计将有助于进一步改善营养管理，从而改善低出生体重婴儿的结局。 这项研究所要解决的总体假设是，在生命早期有一个有限的时期，在此期间，新生儿能够独特地利用蛋白质摄入来促进生长。 如果这是真的，正如来自人类婴儿的数据以及来自啮齿动物和猪的急性喂养研究的数据所表明的那样，在这一有限时期内最大限度地摄入蛋白质将促进这一时期的生长，从而减少早产/低出生体重（LBW）婴儿的长期生长和神经发育缺陷。 这一假设将通过实现以下目标来解决： 1. 确定是否有一个有限的时期，在此期间，低出生体重婴儿对蛋白质摄入量的反应最大，如果有，确定这一时期; 2. 确定在这一（关键）时期较高的蛋白质摄入量是否能改善生长，而不会造成不可接受的代谢后果，并减少随后的LBW婴儿生长缺陷; 3. 确定在此（关键）时期摄入较高的蛋白质是否会改善LBW婴儿随后的神经发育表现。 具体目标 1. 从完全肠道摄入耐受时间起至足月后4个月，连续测量摄入约3 g和约4.0 g/kg-d蛋白质的LBW婴儿的全身蛋白质周转（使用1- 13 C-亮氨酸）、亮氨酸氧化和尿氮排泄。 在完全肠内喂养耐受后不久、出院时、月经后40周龄（足月）时、足月后2个月时和足月后4个月时进行测量。 对蛋白质摄入的最大反应的有限时期的结束将通过1- 13 C-亮氨酸氧化和尿氮排泄的增加来定义。 2. 监测低出生体重婴儿的生长（体重、身长、头围和皮褶厚度）和身体成分（DXA），直至足月后18个月，这些婴儿在足月后4个月内摄入上述蛋白质，在足月后4-9个月内摄入常规出院后配方奶粉，在足月后9-18个月内摄入常规婴儿饮食。 3. 确定在足月后4、12和18个月时按照特定目标2中所述喂养的婴儿的神经发育指数（学龄前儿童发育量表，第四版（PLS-4）;贝利婴儿发育量表-II（MDI和PDI）;皮博迪发育运动量表（PBMS））。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Despite improvements in nutritional management of low birth weight (LBW) infants over the past decade, most who weigh 1500g at birth, even if appropriate size for gestational age at birth, weigh less than and are shorter than the 10th percentiles of intrauterine standards at discharge (~36 wks post menstrual age) and many remain small as late as adolescence and young adulthood. While the consequences of the early growth failure are not known with certainty, there is evidence that it may contribute to the high prevalence of developmental deficits in this population. Studies are proposed to test the hypothesis that there is a finite period during which the human infant is capable of maximal utilization of protein for growth. Based on limited studies in infants and acute studies in animals, this period appears to encompass the latter part of gestation and the first few months post-term but it remains undefined. Corollary hypotheses, which also will be tested in human infants, are that maximizing protein intake during this finite period of enhanced sensitivity to protein intake will improve growth and, hence, reduce the subsequent growth and neurodevelopmental deficits of preterm infants. In toto, the proposed studies will determine if there is a finite period during which the human neonate can maximally utilize protein intake for growth as measured by whole body protein turnover and also will define this period. They also will determine if maximizing protein intake during this finite period improves early growth without imposing unacceptable metabolic consequences and if this improved growth reduces subsequent growth and neurodevelopmental deficits. Overall, the findings of this project are expected to contribute to further improvements in nutritional management and, hence, outcome of LBW infants. The overall hypothesis to be addressed by this study is that there is a finite period early in life during which the newborn is uniquely able to utilize protein intake for growth. if true, as suggested by data from human infants as well as data from acute feeding studies in rodents and swine, maximizing protein in take during this finite period will enhance growth during this period, thereby reducing the long-term growth and neurodevelopmental deficits of preterm/low birth weight (LBW) infants. This hypothesis will be addressed by achieving the following objectives: 1. To determine if there is a finite period during which the LBW infant responds maximally to protein intake and, if so, to define this period; 2. To determine if a higher protein intake during this (critical) period improves growth without imposing unacceptable metabolic consequences and decreases subsequent growth deficits of LBW infants; 3. To determine if a higher protein intake during this (critical) period improves subsequent neurodevelopmental performance of LBW infants. SPECIFIC AIMS 1. To measure whole body protein turnover (using 1-13C-leucine), leucine oxidation and urinary nitrogen excretion serially in LBW infants fed protein intakes of ~3 g and ~4.0 g/kg-d from the time full enteral intake is tolerated until 4 months post-term. measurements will be made shortly after full enteral feedings are tolerated, at hospital discharge, at 40 weeks post-menstrual age (term), at 2 months post-term and at 4 months post-term. The end of the finite period of maximal response to protein intake will be defined by increases in 1-13C-leucine oxidation and urinary nitrogen excretion. 2. To monitor, through 18 months post-term, growth (weight, length, head circumference and skinfold thicknesses) and body composition (DXA) of LBW infants fed the above protein intakes through 4 months post-term, a regular post-discharge formula from 4-to-9 months post-term and a regular infant diet from 9-to-18 months post-term. 3. To determine neurodevelopmental indices (Preschool Langueag Scale, Fourth edition (PLS-4); Bayley Scales of Infant Development-II (MDI and PDI); Peabody Developmental Motor Scales (PBMS) of infants fed as described in Specific Aim 2 at 4, 12 and 18 months post-term.