Metabolomic analysis of umbilical cord serum in small-for-gestational-age infants with a focus on linear growth

Small-for-gestational-age (SGA) infants exhibit considerable heterogeneity in growth trajectories and metabolic outcomes; however, the metabolic basis underlying distinct phenotypes remains poorly understood. In this study, we analyzed umbilical cord serum samples (term infants, n = 66; SGA infants, n = 18; controls, n = 48), using gas chromatography–mass spectrometry to explore nutritional metabolic profiles. A metabolomic analysis revealed that SGA infants had significantly lower levels of metabolites involved in galactose metabolism, lactose degradation, and the glucose–alanine cycle, indicating altered carbohydrate metabolism and energy homeostasis. Among SGA infants, those with both low weight and short length at birth (SGA-short) had significantly reduced glutamine concentrations in comparison to those with preserved length (SGA-tall). The SGA-short group also had a higher proportion of primiparous mothers. Glutamine is essential for fetal growth, particularly skeletal growth, and its deficiency may exacerbate linear growth impairment in the context of restricted intrauterine nutrition. These findings highlight the importance of metabolic subclassification in SGA infants and suggest that glutamine-related pathways could serve as potential biomarkers or therapeutic targets for infants at risk of postnatal growth failure.