Preterm infants are susceptible to metabolic disruptions due to physiologically immature development, and early metabolic dysregulation may contribute to neurodevelopmental impairments that persist throughout infancy and beyond. This study aims to investigate the associations between preterm birth, neonatal metabolism, and later neurodevelopment, and to explore the potential mediating role of neonatal metabolism. In this prospective birth cohort of 9023 in China, linear regression analyses were employed in discovery and validation sets to identify metabolites associated with preterm birth. Metabolites were then categorized as extremely high (> 90th percentile) or low (< 10th percentile), and their associations with preterm birth were assessed using meta-analysis and logistic regression. Among 2086 infants with neurodevelopmental assessments at 1 year old, we applied restricted cubic splines and linear regression to evaluate associations between extreme metabolite levels and neurodevelopment. Mediation analysis was then performed to assess the potential mediating effects of neonatal metabolism. Preterm birth was associated with extremely low levels of four metabolites and extremely high levels of seven metabolites (e.g., 17-hydroxyprogesterone, alanine, and multiple carnitines/acylcarnitines), indicating perturbed neonatal metabolic profiles. Moreover, extremely high levels of free carnitine (C0) were associated with poorer cognition ( β = −0.47; 95% CI −0.75, −0.19) and receptive communication ( β = −0.32; 95% CI −0.61, −0.03), with C0 accounting for 10.3% of the relative effect on cognition and 7.2% on receptive communication among preterm infants. Conclusion : Preterm infants exhibit metabolic perturbations linked to suboptimal neurodevelopment at 1 year of age, offering compelling evidence for the biological mechanism underlying preterm birth outcomes. What is known: • Preterm birth is known to disrupt neonatal metabolism and to adversely affect neurodevelopment, but the underlying biological mechanisms remain controversial. What is new: • Preterm infants are prone to extreme metabolic perturbations, which are associated with subsequent suboptimal neurodevelopmental outcomes. • Free carnitine acted as a potential biomarker of the effects of preterm birth on suboptimal cognition and receptive communication.
Wang et al. (Wed,) studied this question.