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We analyzed and compared variations in the urinary metabolome, as well as postnatal clinical outcomes among preterm infants, based on the timing of antenatal corticosteroid (ACS) administration in response to preterm labor onset in their mothers. This was a prospective observational study held in the Neonatal Intensive Care Unit, Department of Woman's and Child's Health, Padova University Hospital (Italy). A urine sample was obtained from each patient within 24 h of birth; Mass Spectrometry-based untargeted metabolomics analysis was then conducted. We searched for any significant disparities in the metabolomic profile of preterm newborns subjected to antenatal corticosteroid (ACS) treatment at varying timings; their correlation with clinical outcomes were also evaluated. The group receiving ACS within the optimal time window (1-7 days before delivery) exhibited elevated levels of cysteine, N-acetylglutamine, propionyl carnitine and 5-hydroxyindolacetic acid, coupled with a decrease in pipecolic acid. Clinically, this group demonstrated a reduced need for invasive ventilation ( p = 0.04). In conclusion, metabolomics analysis identified several metabolites that discriminated preterm infants whose mothers received ACS within the recommended time window. Elevated levels of cysteine and 5-Hydroxyindoleacetic acid, metabolites characterized by antioxidant and anti-inflammatory properties, were observed in these infants. This metabolic profile correlated with improved respiratory outcomes, as evidenced by a reduced necessity for invasive ventilation at birth.

Bronchopulmonary dysplasia (BPD) is a major complication of premature birth that significantly affects mortality and long-term morbidity in numerous immature infants. Corticosteroids are particularly suitable for treating BPD, as lung inflammation is central to its pathogenesis. Corticosteroids have considerable, fast beneficial effects on lung function in premature infants with lung disease, but they are also associated with several serious adverse effects, which may have a detrimental impact on long-term outcome. Dexamethasone is the most often used corticosteroid for systemic administration. Despite its value in preventing and treating BPD, its use is associated with several alarming short-term effects and, worst of all, with an increased rate of cerebral palsy in the long term. Dexamethasone nonetheless remains an important therapeutic option for infants with severe lung disease beyond the second to third week of life. Hydrocortisone is an important alternative to dexamethasone, as its use does not appear to be associated with any neurotoxic effects. Its efficacy in the prevention and treatment of BPD has yet to be clearly demonstrated, however. Inhaled corticosteroids might reduce lung inflammation with fewer systemic adverse effects; however, a recent, large randomized trial showed that inhaled budesonide was associated with an excess mortality, despite its beneficial respiratory effects. In another study, instilling budesonide together with surfactant in the trachea of intubated infants with severe respiratory distress appeared safe and achieved a significant reduction in the rate of BPD at 36 postmenstrual weeks. This important finding needs to be confirmed in a larger trial currently underway., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)