Extrauterine Growth Restriction: What Is the Evidence for Better Nutritional Practices in the Neonatal Intensive Care Unit?



NAINR. 2014;14(3):92-98. 

In This Article

Early Administration of Amino Acids

The amount of amino acids administered in the early aggressive nutrition RCTs varied dependent upon investigator and the year in which the study was conducted. For example, the amount of protein administered in the study by Wilson et al.[16] was 0.5 g kg−1 day−1 and increased to a max of 2.5 g kg−1 day−1 whereas in the other two studies[17.,18.] protein was started in the range of 2.8 to 3.8 g kg−1 day−1. This same trend can be seen when reviewing the RCTs conducted on the early use of amino acids in premature infants (Table 1).

The variation in amino acid administration throughout the studies seen in Table 1 can be attributed to the fear of amino acid intolerance in premature infants. This fear of intolerance is due to the early parenteral nutrition formulations, which used hydrolyzed protein and crystalline amino acids. The early formulations that used hydrolyzed protein were associated with a number of problems and the early crystalline amino acid formulations were not designed for use in premature infants and were found to be associated with adverse outcomes when administered in high doses.[11] Some of these adverse outcomes were azotemia, hyperammonemia, metabolic acidosis and elevated blood urea nitrogen (BUN) levels.[7]

These adverse outcomes have contributed to the belief that early administration of amino acids is unsafe and potentially harmful in premature infants. However, Rivera et al.[19] Van Goudoever et al.[20] Thureen et al.[21] and TeBraake et al.[22] have shown in their studies with a combined 200 premature infants that early amino acid administration is safe and does not lead to the adverse outcomes of metabolic acidosis, azotemia, hyperammonemia or increased BUN levels. These findings are further supported by Trivedi and Sinn's 2013 systematic review in which early administration of amino acids was shown to promote positive nitrogen balance without causing acidosis or hyperammonemia.[23]

In addition to positive nitrogen balance early amino acid administration has been shown to promote adequate postnatal growth. In a 2006 study, Poindexter and associates did a secondary analysis of 1,018 ELBW infants who were enrolled in a previous RCT for parenteral glutamine supplementation. The purpose of the secondary analysis was to determine if early administration of amino acids resulted in improved growth and neurodevelopmental outcomes. The infants were stratified into two groups based on amino acid intake being > 3 g kg−1 day−1 by 5 days of age or not receiving at least 3 g kg−1 day−1 on any single day within the first 5 days of age. ELBW infants who received early amino acids had significant differences in their weight, length and head circumference at 36 weeks postconceptual age. Whereas, not receiving early amino acids increased the risk for EUGR four fold in ELBW infants.[24]

Strong evidence exists that administering amino acids at 3–4 g kg−1 day−1 directly after birth is not only safe but also leads to positive nitrogen balance. The administration of early amino acids at such a high rate leads to improved postnatal growth at 36 weeks postconceptual age, thus significantly reducing the risk of EUGR in ELBW infants.