Prematurity is a risk factor for the development of chronic adult diseases. Metabolomics can correlate the biochemical changes to a determined phenotype, obtaining real information about the state of health of a subject at that precise moment. Significative differences in the metabolomic profile of preterm newborns compared to those born at term have been already identified at birth. An observational case–control study was performed at the University Hospital of Siena. The aim was to evaluate and compare the metabolomic profiles of young adults born preterm to those born at term. Urinary samples were collected from 67 young adults (18–23 years old) born preterm (mean gestational age of 30 weeks, n = 49), and at term of pregnancy (mean gestational age of 38 weeks, n = 18). The urinary spectra of young adults born preterm was different from those born at term and resembled what was previously described at birth. The Random Forest algorithm gave the best classification (accuracy 82%) and indicated the following metabolites as responsible for the classification: citrate, CH2 creatinine, fumarate and hippurate. Urine spectra are promising tools for the early identification of neonates at risk of disease in adulthood and may provide insight into the pathogenesis and effects of fetal programming and infants’ outcomes.

Oxidative stress is a central mechanism linking placental dysfunction, fetal injury, and neonatal disease, supporting the concept of a perinatal oxidative stress continuum that begins during abnormal placentation and may persist after birth. This narrative review explores the biological rationale and current experimental and clinical evidence for melatonin as a potential multitarget intervention across this continuum. Melatonin combines direct antioxidant activity with mitochondrial protection, anti-inflammatory and anti-apoptotic effects, and modulation of endogenous antioxidant defenses and redox homeostasis. Evidence from placental, fetal, and neonatal studies suggests potential protective effects in pregnancy complications and in neonatal conditions characterized by oxidative injury, including hypoxic–ischemic encephalopathy, bronchopulmonary dysplasia, necrotizing enterocolitis, neonatal sepsis, and retinopathy of prematurity. The review was informed by a non-systematic search of PubMed/MEDLINE, Scopus, Web of Science and Cochrane Library for relevant literature published up to 2026, including preclinical and clinical studies, systematic reviews, and relevant clinical trial registrations. Overall, although preclinical evidence is encouraging and early clinical studies suggest potential safety and biological activity, translation into clinical practice remains limited by heterogeneous study designs, dosing and timing regimens, and the lack of adequately powered randomized trials. Further research is needed to establish optimal dosing, timing, patient selection, pharmacokinetic–pharmacodynamic relationships, and long-term safety and efficacy.