Neonatal Urine Metabolic Signature Reflects Multisystemic Adaptations Linked to Preterm Birth

Prematurity is associated with a higher risk of developing short- and long-term metabolic complications. However, the concrete mechanisms are not yet fully understood. The purpose of this study was to characterize early urinary metabolic adaptations linked to preterm birth. Urine samples collected at one month of age were compared between extremely and very preterm neonates (<32 weeks gestation) (n = 45) and term newborns (n = 96). Liquid chromatography coupled to mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) techniques were both applied and analyzed independently. Univariate analysis and multivariate analyses were utilized to assess the impact of preterm birth on the metabolites identified. Multiblock analysis was further used to evaluate the effect of prematurity on biological functions. A profound impact of prematurity was observed. Both experimental groups differed in the concentrations of 240 metabolites from the LC-MS dataset and 52 from the NMR one. Multivariate analyses confirmed a significant and important separation between groups. Finally, multiblock analysis identified six major biological outcomes affected by preterm birth: nitrogen metabolism, growth, neurochemical metabolism, microbiota metabolism, cell defense, and metabolic alterations. Most of the observed variations exhibited biological plausibility and were consistent with reported health complications associated with preterm birth. In conclusion, preterm birth is linked to a specific fingerprint in the urinary metabolome, reflecting metabolic adaptations in multiple systems occurring at one month of age.