Metabolic Subtypes and Biomarkers in Preterm and Term Neonates via Targeted Screening

Preterm infants exhibit metabolic immaturity, but heterogeneity within this population remains underexplored. We performed targeted metabolomics on dried blood spots from 448 preterm (32–36 weeks) and 351 term neonates using tandem mass spectrometry. Preterm infants showed elevated tyrosine, leucine/isoleucine, arginine, and hydroxyoctadecenoylcarnitine (C18:1-OH), with reduced glutamate (FDR < 0.05). Multivariate analyses (PCA, PLS-DA) revealed three metabolic clusters linked to gestational maturity and oxidative stress. Pathway analysis highlighted disruptions in the urea cycle, ammonia recycling, purine metabolism, and fatty acid oxidation. To our knowledge, this is the first study to identify C18:1-OH as a potential biomarker of mitochondrial dysfunction in preterm neonates. These findings suggest metabolic subtypes may guide precision interventions, though longitudinal validation is needed.