Maternal SARS-CoV-2 exposure and neonatal metabolic maturation during the first month of life: a longitudinal urinary metabolomics study

Abstract The first month of life is characterized by rapid metabolic adaptation as neonates transition from intrauterine to extrauterine life. Whether maternal SARS-CoV-2 infection influences these developmental trajectories remains largely unexplored. In this longitudinal study, we investigated urinary metabolic trajectories during the first month of life in 48 clinically stable full-term neonates, including 27 infants born to mothers who tested positive for SARS-CoV-2 at delivery and 21 unexposed controls. Samples were collected at 0–5 days (T0), 6–15 days (T1), and 19–37 days (T2) postpartum and analysed using 1 H NMR spectroscopy combined with multivariate statistics, covariate-adjusted regression models, and linear mixed-effects models. Across all infants, postnatal age emerged as the primary determinant of metabolic variation, with time-dependent changes involving energy metabolism, amino acid turnover, osmolyte regulation, and host–microbiota co-metabolism. The overall structure of the urinary metabolome was primarily shaped by postnatal maturation rather than maternal SARS-CoV-2 exposure, with exposed and unexposed infants displaying largely overlapping metabolic trajectories. A limited number of metabolic-specific differences were associated to maternal SARS-CoV-2 exposure, with transient deviations that were most evident during the second postnatal week. These changes were modest and not supported by stable correlation networks or enriched metabolic pathways. Overall, these findings indicate that early neonatal metabolic maturation is largely preserved in infants born to SARS-CoV-2–infected mothers, with only subtle and time-restricted modulation of a small subset of metabolites within an otherwise resilient developmental framework. This study highlights the value of longitudinal metabolomics for disentangling physiological maturation from exposure-related effects during early life.