Amino acid metabolism in newborns with sepsis
Objective. To analyze the main characteristics of amino acid metabolism disorders in newborns with sepsis. Patients and methods. This retrospective, controlled, non-randomized study was conducted in the City Neonatal Center and Ufa City Children's Clinical Hospital No 17 and lasted for 36 months. The study included 212 newborns, including 40 infants with sepsis (Group I), 132 infants with pneumonia (Group II), and 40 healthy infants (Group III, controls) followed up in the Republican Medical and Genetic Center of Ufa. The levels of amino acids were evaluated using tandem mass spectrometry with the Quattro micro MSMS system (Perkin Elmer, Finland). Data analysis was performed using the Statistica.6.1 software. We calculated parametric and nonparametric indicators; differences were considered significant at р < 0.05. We calculated Kullback information criterion (KIC) to assess the impact of each factor on the disease prognosis (at р < 0.01). Results. Infants from Group I had significantly higher levels of alanine, ornithine, phenylalanine, tyrosine, and valine along with lower levels of arginine, citrulline, cysteine, glycine, and valine/phenylalanine ratio than infants from Group II. Patients with sepsis demonstrated significantly decreased levels of alanine, citrulline, glycine, leucine, methionine, ornithine, proline, tyrosine (and some ratios of these amino acids) and increased level of succinylcholine, as well as increased methionine/phenylalanine, methionine/leucine, and ornithine/citrulline ratios compared to healthy controls. In contrast, newborns in Group II had significantly lower concentrations of alanine, citrulline, glycine, leucine, methionine, ornithine, phenylalanine, proline, tyrosine and valine along with an increased concentration of arginine compared to newborns in Group III. The levels of proline, tyrosine, and valine were found to be highly informative (KIC 5.28, 1.79, and 1.63 respectively); the levels of ornithine, arginine and citrulline were shown to be moderately informative (KIC 0.81, 0.68, and 0.64 respectively). We observed strong correlations (both positive and negative) between the levels of alanine, arginine, and citrulline and almost all blood parameters (including cell count, plasma glucose, and total protein) and a strong correlation between hemoglobin level and concentration of most amino acids (alanine, arginine, citrulline, leucine, methionine, ornithine, and phenylalanine). Conclusion. Changes in serum levels of proteinogenic (proline, tyrosine, valine, and arginine) and non-proteinogenic amino acids (citrulline and ornithine) characterize the metabolic profile of systemic inflammatory response and multiple organ dysfunction in newborns with sepsis. Screening assessment of serum amino acids in newborns will enable early identification of patients with a high risk of generalized infection and multiple organ dysfunction syndrome.