Metabolomic profiling of intrauterine growth-restricted preterm infants: a matched case-control study

Background: The biochemical variations occurring in intrauterine growth restriction (IUGR), when a fetus is unable to achieve its genetically determined potential, are not fully understood. The aim of this study is to compare the urinary metabolomic profile between IUGR and non-IUGR very preterm infants to investigate the biochemical adaptations of neonates affected by early-onset-restricted intrauterine growth.

Methods: Neonates born <32 weeks of gestation admitted to neonatal intensive care unit (NICU) were enrolled in this prospective matched case-control study. IUGR was diagnosed by an obstetric ultra-sonographer and all relevant clinical data during NICU stay were captured. For each subject, a urine sample was collected within 48 h of life and underwent untargeted metabolomic analysis using mass spectrometry ultra-performance liquid chromatography. Data were analyzed using multivariate and univariate statistical analyses.

Results: Among 83 enrolled infants, 15 IUGR neonates were matched with 19 non-IUGR controls. Untargeted metabolomic revealed evident clustering of IUGR neonates versus controls showing derangements of pathways related to tryptophan and histidine metabolism and aminoacyl-tRNA and steroid hormones biosynthesis.

Conclusions: Neonates with IUGR showed a distinctive urinary metabolic profile at birth. Although results are preliminary, metabolomics is proving to be a promising tool to explore biochemical pathways involved in this disease.

Impact: Very preterm infants with intrauterine growth restriction (IUGR) have a distinctive urinary metabolic profile at birth. Metabolism of glucocorticoids, sexual hormones biosynthesis, tryptophan-kynurenine, and methionine-cysteine pathways seem to operate differently in this sub-group of neonates. This is the first metabolomic study investigating adaptations exclusively in extremely and very preterm infants affected by early-onset IUGR. New knowledge on metabolic derangements in IUGR may pave the ways to further, more tailored research from a perspective of personalized medicine.