Published online April 1, 2008
PEDIATRICS Vol. 121 No. 4 April 2008, pp. 865-866 (doi:10.1542/10.1542/peds.2007-3804)

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LETTER TO THE EDITOR

Quality of Amino Acid Solutions for Preterm Infants

C. H. P. van den Akker, MSc
F. W. J. te Braake, MSc
W. W. Rövekamp-Abels, MD
J. B. van Goudoever, MD, PhD
Department of Pediatrics, Division of Neonatology
Erasmus MC, Sophia Children's Hospital
3000 CB, Rotterdam, the Netherlands

To the Editor.—

With great interest, we read the article by Clark et al¹ published in the December 2007 issue of Pediatrics. The authors concluded that higher doses of amino acid supplementation did not improve neonatal growth, and might even be unfavorable in terms of metabolic tolerance (increased blood amino acid and urea nitrogen levels).

However, we have some comments. Blood chemistry results, including amino acid concentrations, are reported for postnatal days 1, 7, and 28. Regrettably, no such information is provided for day 4, which shows a peak amino acid intake in the "high-dose group" and the largest difference in amino acid intake between groups. We also learn that, for most infants, the parenteral nutrition had been gradually replaced by enteral nutrition. Except for a single value on day 7, however, no information is given on the enteral nutrient (or protein) intakes in both groups for the remainder of the study period.

Referring to 1 of our previous studies,² the authors state that preterm neonates have immature metabolic pathways for using amino acids during catabolism and anabolism. In that study, however, we postulated that early amino acid administration in preterm infants results in increased protein synthesis without a concomitant decrease in proteolysis. We feel this mechanism should not be considered an immature metabolic pathway, but rather, a physiologic age-related response to nutrition. A similar phenomenon was observed in the ovine fetus.³

Amino acid concentrations were determined by using dried blood spots, as is also performed in metabolic screening programs. Consequently, concentrations are measured in whole blood, and thus cannot, as presented in Table 3 in Leichty et al,³ be expressed as in serum. Compared with the author's own reference values from healthy term neonates, alanine and glutamate were still lower in the "high-dose group," and arginine, leucine/isoleucine, methionine, ornithine, and valine were (slightly) higher. The authors designate these deviating values as abnormal concentrations. We point out, however, that caution should be exercised when comparing term with preterm infants. For example, valine concentrations are much higher in umbilical cord blood than after term birth.

Growth was assessed on day 28 in terms of increases in weight, length, and head circumference. The cumulative difference in parenterally administered amino acids between groups was 16.5 g/kg, which is 0.6 g amino acids per (kg/d) and can be converted to an extra tissue growth of 6 g per (kg/d) if used completely for this purpose. Yet, no difference in growth was observed. This would seem to imply that much of the intake was not used for anabolism, but was probably oxidized. The observed high urea concentrations point in this direction as well. These are, in our opinion, a sign of successful amino acid oxidation, rather than a sign of intolerance. One reason for amino acids to be oxidized is when not enough nonprotein calories are administered to facilitate protein synthesis, which is an energy-demanding process. Nevertheless, apart from the first week of life, this should not be the case in these infants. Another reason for a high amino acid oxidation rate is the use of amino acid solutions of suboptimal composition or quality. Amino acids are incorporated in proteins in a fixed ratio. If 1 of the (semi-)essential amino acids is lacking, all others cannot be used and will be oxidized. The solutions (trophamine and aminosyn) that were used contain hardly any or none of the semi-essential amino acid cysteine. Thus, the lack of cysteine might very well result in a high oxidation rate of all other amino acids, elevated free amino acid and urea concentrations, or the failure of growth improvement.

Indeed, in their randomized, controlled trial, Wilson et al⁴ infused a solution containing 6 times more cysteine than standard trophamine, and found improved growth with higher amino acid supplementation. Also Poindexter et al⁵ found improved growth after high-dose parenteral amino acid administration (with supplemented cysteine in a 20 times higher dose).

Taken together, we doubt whether the results obtained in this study validate the general conclusions at which the authors arrived.

REFERENCES

1. Clark RH, Chace DH, Spitzer AR; Pediatrix Amino Acid Study Group. Effects of two different doses of amino acid supplementation on growth and blood amino acid levels in premature neonates admitted to the neonatal intensive care unit: a randomized, controlled trial. Pediatrics. 2007;120 (6):1286 –1296[Abstract/Free Full Text]
2. van den Akker CH, te Braake FW, Wattimena DJ, et al. Effects of early amino acid administration on leucine and glucose kinetics in premature infants. Pediatr Res. 2006;59 (5):732 –735[CrossRef][Web of Science][Medline]
3. Liechty EA, Boyle DW, Moorehead H, Auble L, Denne SC. Aromatic amino acids are utilized and protein synthesis is stimulated during amino acid infusion in the ovine fetus. J Nutr. 1999;129 (6):1161 –1166[Abstract/Free Full Text]
4. Wilson DC, Cairns P, Halliday HL, Reid M, McClure G, Dodge JA. Randomised controlled trial of an aggressive nutritional regimen in sick very low birthweight infants. Arch Dis Child Fetal Neonatal Ed. 1997;77 (1):F4 –F11[Abstract/Free Full Text]
5. Poindexter BB, Langer JC, Dusick AM, Ehrenkranz RA; National Institute of Child Health and Human Development Neonatal Research Network. Early provision of parenteral amino acids in extremely low birth weight infants: relation to growth and neurodevelopmental outcome. J Pediatr. 2006;148 (3):300 –305[CrossRef][Web of Science][Medline]

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PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics

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This Article Extract Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by van den Akker, C. H. P. Articles by van Goudoever, J. B. Search for Related Content PubMed PubMed Citation Articles by van den Akker, C. H. P. Articles by van Goudoever, J. B. Related Collections Nutrition & Metabolism Social Bookmarking                         What's this?