Metabolomic profile of preterm newborn: associations with pre- and postnatal growth restriction

Background: Metabolomics is a science aimed to identify and interpret the metabolic profiles of a given biological system, namely the products of interaction between gene expression and environment. Among the "omic" sciences, it can be considered the closest one to phenotype. The impact of growth and nutrition in the very early stages of life is a topic of great interest, considering not only the immediate effect on development, but also on lifelong health. Ensuring an adequate nutritional intake and growth is even more crucial in preterm babies. Intrauterine growth restriction (IUGR) and extrauterine growth restriction (EUGR) are two conditions in which the fetus and the newborn respectively, are not able to achieve their genetically determined potential size. Nowadays reliable biomarker to assess the suitability of nutritional status and growth in preterm infants are lacking. Aim of the study: The aims of this study are to analyse and compare the metabolomic profile obtained by: 1) preterm infants diagnosed with IUGR during pregnancy versus preterm infants adequate for gestational age (AGA); 2) preterm infants who experienced EUGR and preterm infants who did not. Material and Methods: This prospective observational study has been conducted at the third level Neonatal Intensive Care Unit (NICU) of Padova. Premature neonates born between 23 and 32 weeks post-menstrual age (PMA) have been enrolled. For each subject urine samples have been collected at three time-point: within 72 hours of life, at 21 +/- 3 days of life and at 36 +/-1 weeks PMA. The urine samples underwent untargeted metabolomic analysis using mass spectrometry combined with ultra- performance liquid chromatography. For each enrolled subject all relevant clinical data during NICU stay have been captured. IUGR was diagnosed through review of obstetrical history of the mother; EUGR was diagnosed when weight at 36 weeks PMA was <10th %ile of the predicted value. The data obtained were analysed using multivariate and univariate statistical analysis tools. Results: 160 infants have been enrolled, with a median gestational age at birth of 195 days (interquantiles range: 185-207 days). Only urine samples collected within the first 48 hours of life were analysed (n=83). Among these 15 were collected from IUGR infants and were matched with 19 from AGA infants (controls). Untargeted metabolomic revealed evident clustering of the IUGR neonates versus the AGA ones. The metabolic derangements mainly involved were metabolism of tryptophan-serotonin and biosynthesis of steroid hormones. The comparison of urine samples collected from 9 infants with EUGR and 10 controls did not show any discriminant variables. Conclusions: Neonates with IUGR showed a distinctive urinary metabolic profile at birth. Although data are still preliminary, metabolomics is proving to be a promising tool to explore biochemical pathways involved in impaired fetal and neonatal growth.