Dose Comparison of Amino Acids on Growth in Premature Neonates

Overview

Malnutrition is a common problem in the neonatal intensive care unit. Recent studies indicate that prematurely born neonates commonly develop a severe nutritional deficit during the first weeks after birth, referred to as extrauterine growth restriction. Despite an increase in growth during the second month of hospitalization, many neonates are ultimately discharged home having grown inadequately. The early nutritional deficit affects weight gain as well as growth in length and head circumference. Growth measurements such as weight, length, and head circumference, however, are macroscopic measures of nutritional status and underestimate the physiologic consequences of prolonged nutritional deprivation. Energy and micronutrient deficiencies alter growth at a cellular and tissue level before macroscopic measures are altered. In the brain, for instance, energy is required for cell division and neuronal growth, glial cell function, and myelination. Energy deprivation may consequently alter neuronal function and growth, resulting in adverse neurodevelopmental outcomes. Immunocompetence also appears to be sensitive to the untoward effects of energy and nutritional deficiency. Malnourished neonates often exhibit immune deficiencies related to inadequate protein intake that compound an already immature immune system. Such immunodeficiency results in susceptibility to infectious agents that creates substantial morbidity and mortality to the course of intensive care for premature infants. A recent study suggests that postnatal malnutrition and growth restriction are inevitable if current recommended dietary intakes are followed. Multicenter studies show that variation in dietary intake accounts for 45% of the variation in growth. Hence, efforts have focused on determining whether nutritional deficiency and the observed growth restriction of premature infants can be prevented through the use of more optimal nutritional intake. In addition, inadequate protein support may be a primary cause for growth failure. Based on animal studies showing high in utero amino acid flux observed during the latter phase of gestation, Thureen et al have suggested the use of higher doses of amino acid supplementation in order to minimize growth restriction and improve outcomes of premature infants. However there are no large human trials that demonstrate that this approach promotes better growth or that it is safe. While small doses of amino acids may be inadequate to promote normal growth, high doses may lead to elevated serum amino acid levels and increase the occurrence of toxicity. Through the implementation of a multicenter, randomized trial and tandem mass spectrometry, the investigators propose to evaluate the effects of two distinct strategies of amino acid supplementation on serum amino acid profiles and growth of premature infants during the first 28 days of life.