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.
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