Targeted Metabolomic Analysis of Plasma Glycine, Serine, and Glutamic Acid in Neonatal Sepsis: A Case-Control Study Publisher



Mirnia K ; Sangsari R ; Mohebbi A ; Saeedi M ; Alhaddad MSO ; Vafaei E
Source: Archives of Clinical Infectious Diseases Published:2026

Abstract

Background: Amino acids are essential for immune function, and alterations in glycine, serine, and glutamic acid may contribute to neonatal sepsis. Objectives: To compare plasma levels of these amino acids between septic and healthy neonates using targeted metabolomic analysis. Methods: In this case–control study (2021 - 2022), 78 neonates with clinical symptoms of sepsis and 31 healthy controls matched for gestational age and birth weight were enrolled. Infants with metabolic, neurological, or congenital disorders, intrauterine growth restriction, or those receiving total parenteral nutrition were excluded. Amino acid concentrations were measured by liquid chromatography-tandem mass spectrometry (LC/MS/MS) with Multiple Reaction Monitoring (MRM). Results: Mean plasma glycine was 305.7±78 µmol/L in healthy neonates versus 245.8±71 µmol/L in septic neonates (P = 0.002). Serine was 121.9±33 µmol/L in healthy neonates versus 82.0±23 µmol/L in septic neonates (P < 0.001). Glutamic acid was 330.7±91 µmol/L in healthy neonates versus 249.5±84 µmol/L in septic neonates (P < 0.001). One‑way analysis of variance (ANOVA) confirmed significant group differences, with large effect sizes for serine (η2 = 0.33) and glutamic acid (η2 = 0.21). In multivariable logistic regression, lower serine [odds ratio (OR) = 0.924, 95% confidence interval (CI) 0.875–0.975, P = 0.004] and glutamic acid (OR = 0.992, 95% CI: 0.984 - 1.000, P = 0.046) remained independently associated with sepsis, while glycine was not significant. Conclusions: Serine and glutamic acid were independently associated with sepsis, supporting their potential as candidate biomarkers. Glycine, although reduced in septic neonates, was not independently predictive. These findings highlight the role of amino acid metabolism in neonatal sepsis and support further research into multi‑marker diagnostic approaches. Copyright © 2026, Mirnia et al.