Serum and Urine Metabolomic Profiles in Children With Growth Retardation: An Exploratory ¹H-NMR Study

Growth retardation, defined by impaired anthropometric development relative to age-based population standards, may be accompanied by metabolic alterations. This study aimed to characterize serum and urine metabolomic profiles in children with growth retardation using exploratory ¹H-NMR spectroscopy. Thirty children with growth retardation and 24 controls were included in this cross-sectional study. Serum and urine samples were analyzed by ¹H-NMR spectroscopy, and annotated metabolites were evaluated using Chenomx, MetaboAnalyst, and R software. Clinical and laboratory variables were compared between groups. Metabolomic analysis included univariate comparisons, volcano plots, PCA, OPLS-DA, Spearman correlation analysis, age-adjusted regression, exploratory ROC analysis, and metabolite set enrichment analysis. The growth retardation group had lower age and BMI than controls, while serum iron and AST were higher. Volcano plot analysis showed a more distinct pattern of nominal metabolite alterations in serum than in urine. In serum, 3-hydroxybutyrate and glucuronate showed relative increases, whereas N-acetylgalactosamine, alanine, glutamate, and glucose showed relative decreases. In urine, metabolite differences were less pronounced. Multivariate analysis demonstrated a significant overall group effect in serum but not in urine. Within the growth retardation group, age was negatively correlated with serum 3-hydroxybutyrate and positively correlated with N-acetyl-L-aspartic acid, whereas several urinary metabolites showed negative correlations with age. After age adjustment, only 4-ethylbenzoic acid remained significant in serum after multiple testing correction. Exploratory ROC analysis identified N-acetylgalactosamine and 4-ethylbenzoic acid in serum and beta-alanine and creatinine in urine as the metabolites with the highest within cohort classification tendency. Children with growth retardation exhibited modest metabolic differences, with more consistent group-related alterations observed in serum than in urine. These findings mainly suggest changes related to energy metabolism, amino acid turnover, and intermediary metabolism. However, the results remain exploratory and require confirmation in larger, age-stratified and independently validated cohorts.