The Impact of Antenatal Corticosteroids on the Metabolome of Preterm Newborns

Background. Antenatal corticosteroids (ACS) are commonly administered to women at risk of delivery, as they can reduce mortality and respiratory complications in newborns by inducing lung maturation. Various international guidelines recommend their use in pregnant women at high risk of preterm delivery. Despite antenatal corticosteroid prophylaxis is nowadays considered the standard of care, data regarding the optimal dosage, timing of administration and other variables such as pharmacokinetics and pharmacodynamics remain unknown. Metabolomics, the latest of the “omic” sciences, could help us in identifying specific metabolites or pathogenic pathways in newborns in order to personalize ACS prophylaxis and improve its effectiveness. Aim of the study. A prospective observational monocentric study was carried out in the Neonatal Intensive Care Unit of Padova University Hospital to analyze and compare variations in the urinary metabolome of newborns, as well as postnatal clinical outcomes among preterm infants, based on the timing of ACS administration in response to preterm labor onset in their mothers. Materials and methods. Singleton preterm newborns with a gestational age from 23 to 34 weeks, who necessitated respiratory resuscitation in the delivery room, were enrolled. A urine sample was obtained within 24 h from birth from each patient. Mass Spectrometry-based untargeted metabolomics analysis was then conducted. Demographic and clinical perinatal characteristics of the newborns were examined; multivariate and univariate analyses were conducted from the sample data. Results and conclusions. Urine samples were collected for 38 newborns requiring respiratory assistance at birth, divided into three groups based on the timing of maternal ACS administration: a complete course within the optimal time window (group O, 17 subjects), an incomplete course (i.e. only one dose of ACS) within 24 hours of delivery (group I, 11 subjects), a complete course more than 7 days before delivery (group C, 10 subjects). While no difference was found in urinary metabolomic profiles between group I and C, when compared to group I&C the group O exhibited elevated levels of cysteine, N-acetylglutamine, propionyl carnitine and 5-hydroxyindolacetic acid (metabolites with antioxidant and anti-inflammatory properties) while showing lower concentrations of dityrosine and pipecolic acid, suggesting a potential neuroprotective effect of correctly timed ACS. Future studies are needed to fully understand the biological roles of these metabolites in enhancing outcomes for preterm infants undergoing ACS, in order to maximize the efficacy of this treatment.