METABOLOMIC PATTERNS OF PRETERM NEWBORNS WITH AND WITHOUT GROWTH RESTRICTION: MARKERS OF NUTRITIONAL AND CLINICAL STATUS

Background: the first thousand days of life are a critical period of time. The impact of growth restriction and nutritional issues in such early age could affect neurodevelopment and contribute to the onset of chronic adult diseases. This is especially true for preterm infants who experienced intrauterine growth restriction (IUGR) and for preterm infants who fail to thrive during the first weeks of life and develop extrauterine growth restriction (EUGR). These groups of premature babies are interesting populations to investigate with a metabolomic approach to optimize nutritional intakes. Aims of the study: to identify clinical, biochemical and nutritional parameters associated with the IUGR condition and looking for risk factors related to extra-uterine growth retardation; to analyse and compare the urinary metabolomic pattern at birth of preterm infants with and without growth restriction at 36 weeks of postmenstrual age or at discharge, searching for potential predictive biomarkers of growth failure in the very low birth weight infants (VLBWI); to compare the urinary metabolomic profile at birth of preterm infants who develop retinopathy of prematurity (ROP, a disease related also to suboptimal nutrition) compared to preterm infants who do not develop it. Materials and Methods: we enrolled preterm infants between 23 and 32 weeks of gestational age (GA) and/or with a birth weight <1500 g admitted to the Neonatal Intensive Care Unit (NICU) of the Department of Woman’s and Child’s Health of Padova University Hospital with early initiation of parenteral nutrition (PN). We collected clinical, biochemical and nutritional parameters from birth to 36 weeks of gestational age or discharge. Of a subgroup of patients with and without EUGR and with and without ROP we collected urinary samples within 48 hours of life and performed metabolomic analysis. Results: from 354 newborns enrolled, 75 IUGRs were paired with 75 non-IUGRs. IUGR infants had lower anthropometric parameters at birth and during hospitalisation, they continued parenteral nutrition longer and reached full enteral feeding later. They showed reduced phosphoremia and almost all of them had EUGR at 36 weeks of GA or at discharge. We found as risk factors of EUGR also in general population lower phosphoremia levels, poor energy and protein intake, prolonged parenteral nutrition and a delay in achieving full enteral feeding. For the metabolomic analysis 16 EUGR infants were selected and matched with 16 controls: they showed a different urinary metabolomic profile at birth, characterised especially by lower levels of anti-inflammatory and anti-oxidant metabolites. Furthermore 6 ROP infants were selected and matched with 6 controls: we found a different urinary metabolomic profile with lower level of L-histidine and L-homoserine in the ROP group, suggesting a pro-inflammatory state and an altered synthesis of the sphingolipids. Conclusions: growth restriction remains a serious problem in extremely preterm newborns, despite significant advancements in the nutritional care. EUGR is a complex and multifactorial condition but metabolomic analysis suggests a basal predisposition, which identification could be useful to tailor nutritional strategies. Similarly, ROP disease seems to be characterised by specific features in the metabolome at birth.