Metabolic subtypes and biomarkers in preterm and term neonates via targeted screening

Preterm infants exhibit metabolic immaturity, yet metabolic heterogeneity within this population remains underexplored. We performed targeted metabolomics on dried blood spots from 448 preterm (32-36 weeks) and 351 term neonates (37-40 weeks of gestation) using tandem mass spectrometry. Compared with term infants, preterm neonates showed significantly elevated tyrosine, leucine/isoleucine, arginine, and hydroxyoctadecenoylcarnitine (C18:1-OH), along with reduced glutamate (false discovery rate < 0.05). Multivariate analyses, including principal component analysis and partial least squares-discriminant analysis, identified three distinct metabolic clusters associated with gestational maturity and redox-related pathway signals. Pathway enrichment analysis highlighted disruptions in the urea cycle, ammonia recycling, purine metabolism, and mitochondrial fatty acid oxidation. Notably, C18:1-OH emerged as a key discriminatory metabolite and a potential biomarker of mitochondrial immaturity and altered fatty acid oxidation in preterm neonates. These findings support the presence of metabolically distinct subtypes within preterm infants and suggest that metabolomic profiling may contribute to precision neonatal risk stratification, although longitudinal validation is required.