IMPACT OF DEVELOPMENT ON PROTEIN UTILIZATION AND GROWTH

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 尽管低出生体重(LBW)婴儿的营养管理在过去十年中得到了改善，但大多数出生时体重为1500克的婴儿，即使出生时的大小适合胎龄，体重也低于或低于出院时宫内标准的10%(月经后约36周)，而且许多人直到青春期和成年期都很小。虽然早期增长失败的后果尚不确定，但有证据表明，它可能导致这一人群中发育缺陷的高发。有人建议进行研究，以检验这一假设，即在有限的时期内，人类婴儿能够最大限度地利用蛋白质进行生长。根据对婴儿的有限研究和对动物的急性研究，这一时期似乎包括怀孕的后期和足月后的头几个月，但它仍然没有定义。也将在人类婴儿身上测试的推论是，在对蛋白质摄取的敏感度增强的有限时期内，最大限度地摄取蛋白质将促进生长，从而减少早产儿随后的生长和神经发育缺陷。总之，拟议的研究将确定是否存在一个有限的时期，在此期间，人类新生儿可以最大限度地利用蛋白质摄入量来促进生长，这是通过全身蛋白质周转来衡量的，并将定义这一时期。他们还将确定在这段有限的时间内最大限度地摄入蛋白质是否在不造成不可接受的代谢后果的情况下改善早期生长，以及这种改善的生长是否减少了随后的生长和神经发育缺陷。总体而言，预计该项目的结果将有助于进一步改善营养管理，从而有助于改善LBW婴儿的结局。 假设 这项研究要解决的总体假设是，在生命早期有一个有限的时期，在这段时期内，新生儿能够独特地利用蛋白质摄取来生长。如果是真的，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，在这一有限的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。 将通过实现以下目标来解决这一假设： 1.确定LBW婴儿对蛋白质摄入的最大反应是否存在一个有限的时间段，如果是，则定义该时间段； 2.确定在这一(关键)时期，较高的蛋白质摄入量是否在不造成不可接受的代谢后果的情况下改善生长，并减少LBW婴儿随后的生长缺陷； 3.确定在这一(关键)时期摄入更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.连续测定蛋白质摄入量为~3g/kg·d~(-1)和~4.0g/kg·d~(-1)的LBW婴儿从完全肠道耐受至足月后4个月的全身蛋白质周转(用1-13C-亮氨酸)、亮氨酸氧化和尿氮排泄。测量将在完全肠道喂养耐受后不久、出院时、经后40周(足月)、足月后2个月和足月后4个月进行。对蛋白质摄入的最大反应的有限时期的结束将被定义为1-13C-亮氨酸氧化和尿氮排泄的增加。 2.通过产后4个月、产后4个月、产后4个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月、产后9个月 3.于产后4个月、12个月和18个月测定神经发育指标(学龄前儿童语言发育量表第四版(PLS4)、贝利婴儿发育量表II(MDI和PDI)、Peabody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. 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 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. HYPOTHESIS 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.