Parenteral Nutrition for the High-Risk Neonate

Protein

The initial goal of parenteral nutrition is to minimize losses and preserve existing body stores, particularly for protein. Protein losses are significant if no parenteral amino acids are supplied, with losses being the highest in the most premature neonates. For example, a 26-week gestational age infant loses 1.5 g/kg/day of body protein when provided glucose alone over the first 2 days of life. This is compared to a term infant who loses only 0.7 g/kg/day of body protein over the same time period. Extremely preterm neonates given no amino acid supply lose 1.5% of their body protein per day compared to the fetal accretion rate of 2% per day. After only 3 days of no protein intake, an extremely preterm infant will accumulate a 10% protein deficit compared to the fetus over this same time period.

Fortunately, there is good evidence that early amino acid intake can improve nitrogen balance and help compensate for the high rate of protein loss. In addition, high versus low amino acid dosing has been shown to influence the nitrogen balance and decrease the risk for hyperglycemia; the influence on other outcomes, such as growth and neurodevelopment, however, is less clear. With regard to the side effects of various amino acid dosing strategies, some studies have found no correlation between blood urea nitrogen (BUN) and early as compared to late amino acid administration. Other studies, however, have shown a correlation between increased amino acid dosing and BUN concentrations during the first week of life. BUN levels, however, are not only influenced by protein intake but also fluid status and renal function. The available data indicate that providing parenteral amino acids at a rate of 2 to 3 g/kg/day as soon as possible after birth can preserve body protein stores in sick, premature, and VLBW neonates, even when given at low caloric intakes.

It is important to note that even though parenteral amino acid administration is beneficial at low caloric intakes, increasing caloric intake is likely to improve protein accretion. For example, even with a small increase in total calories from 49 to 62 kcal/kg/day over a short period, Vlaardingerbroek et al. demonstrated improved nitrogen balance with lipid supplement added to parenteral glucose and amino acids. Based on current data, a minimum intake of 30 to 40 kcal per 1 g amino acids is recommended to optimize protein accretion. However, additional energy beyond this amount is necessary to produce appropriate growth.

The ultimate goal of parenteral amino acid administration is to achieve a rate of protein accretion similar to that of the fetus. Based on a variety of studies measuring protein losses and balance, 3 to 4 g/kg/day of amino acids is a reasonable estimate of the parenteral protein requirements of VLBW neonates. Birth weight correlates with parenteral protein needs, with those neonates born less than 1000 g having estimated protein requirements of 3.5 to 4 g/kg/day. Estimates for term neonates are 2.5 to 3 g/kg/day. Parenteral protein intake recommendations for premature neonates are shown in Table 60.1 .

The composition of currently available amino acid solutions is shown in Table 60.2 . These amino acid solutions were designed to mimic plasma amino acid concentrations in healthy 30-day-old breastfed infants (TrophAmine, B. Braun Medical Inc.) or fetal or neonatal cord blood amino acid concentrations (Primene, Baxter Corporation). No convincing data exists to support the superiority of one neonatal amino acid solution over another.

Although the current neonatal amino acid solutions represent a substantial advance over previous mixtures, these solutions do not contain all amino acids. Glutamine, an amino acid supplied abundantly in breast milk and conditionally essential in premature neonates, is not included in any amino acid solutions due to instability (see Table 60.2 ). Meta-analysis of multiple studies investigating parenteral glutamine supplementation in premature neonates found no effect on mortality, invasive infection, or necrotizing enterocolitis. Tyrosine, a conditionally essential amino acid in neonates, has limited solubility, so little is included in current amino acid solutions. Some solutions, including TrophAmine and Premasol (Baxter Corporation) contain N-acetyltyrosine, a soluble tyrosine derivative with poor bioavailability. A variety of studies in premature neonates suggest the tyrosine supply may be suboptimal in current amino acid solutions. However, it is also important to note excess tyrosine supplementation should be avoided as elevated levels have been associated with negative neurodevelopmental outcomes. Cysteine, another conditionally essential amino acid in neonates, is not included in most amino acid solutions as it is not stable for long periods. However, a cysteine hydrochloride supplement that can be added to parenteral nutrition solutions prior to delivery is commercially available. Evidence suggests that cysteine hydrochloride supplementation of parenteral nutrition improves nitrogen retention in premature neonates. Cysteine supplementation of parenteral nutrition also improves the solubility of calcium and phosphorus. For these reasons, the addition of cysteine hydrochloride (30 to 40 mg/g of amino acids, up to a maximum of 120 mg/kg) is recommended. Cysteine hydrochloride can result in metabolic acidosis, but this can be countered by using acetate in the parenteral nutrition solution.