(Scanned from the applicant's description): A recent NICHD sponsored work shop reported that extremely low birth weight infants experience poor or no growth for the first several days to weeks of life. There is considerable evidence that these early growth deficits have long lasting effects including short stature and poor neurodevelopmental outcomes. The participants concluded that there was urgent need for research to evaluate short and long term metabolic, growth and neurodevelopmental responses of these infants to earlier and more aggressive nutritional management. Results of our recently completed enteral feeding studies highlighted important differences in the growth and nutritional status of VLBW infants. When compared to infants weighing 125 1-1600 g, infants weighing 750-1250 g at birth had significantly lower lengths and head circumference at discharge (weight 2200g). Preservation of weight gain in the face of slower linear growth and head growth is consistent with relative nitrogen deficiency; this interpretation is strengthened by the finding of lower plasma transthyretin concentrations in these infants. Furthermore, it took the smaller infants longer to achieve the desired enteral intakes and to regain birth weight. On the basis of these observations, we hypothesized that an early period of relative nitrogen deficiency underlies the growth failure seen in VLBW infants. To test this hypothesis we propose a randomized, prospective clinical trial to compare an aggressive early nutritional regimen providing 18 percent of energy intake as protein (P:E ratio of 4.5 g:l00 kcal) to a conventional regimen providing 12.5 percent of energy intake as protein (P:E ratio of 3.1 g:100 kcal) in appropriate for gestational age VLBW infants. The outcome of the nutritional intervention will be assessed by measurements of growth, rate and composition of weight gain and nutritional status made at the time parenteral nutrition is discontinued, and at discharge, as well as the neuro-developmental outcome at 18 months corrected age.
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