Expanded Newborn Screening Metabolites as Potential Biomarkers of Extrauterine Growth Restriction in Very-Low-Birth-Weight Preterm Infants

Background: Expanded Newborn Screening (NBS) allows screening for more than 50 inborn errors of metabolism (IEMs), thanks to the use of tandem mass spectrometry (MS/MS). Beyond its primary diagnostic function, NBS offers a valuable opportunity to obtain comprehensive information regarding the nutritional status of each newborn. This aspect is particularly significant in very-low-birth-weight (VLBW) preterm infants, who are at increased risk of multiple perinatal complications. The objective of the present study was to leverage the extensive dataset generated from NBS samples of VLBW infants to explore potential correlations with longitudinal extrauterine growth restriction (EUGR). Methods: We retrospectively analyzed 155 VLBW newborns hospitalized in the neonatal intensive care unit (NICU) and screened at IRCCS Giannina Gaslini Children’s Hospital between May 2021 and December 2023. Forty-six NBS metabolites were evaluated at 48–72 h of life (T0), 30 days of life (T1), and at a body weight of 1800 g (T2). Results: Several metabolites showed significant differences between infants with and without longitudinal EUGR in the univariate analyses across the three sampling time points. However, after adjustment for multiple comparisons using the Benjamini–Hochberg procedure, no metabolite remained significantly associated with longitudinal EUGR. Conclusions: Although several metabolites initially appeared to be promising candidates, no independent metabolic signature of longitudinal EUGR was identified after adjustment for multiple testing. Nevertheless, the biological plausibility of several metabolic pathways potentially implicated in postnatal growth provides a rationale for future prospective studies with larger cohorts and more targeted metabolic panels to better elucidate the biological mechanisms underlying longitudinal EUGR.