Abstract
Growth failure in infants born preterm is a significant issue, increasing the risk of poorer neurodevelopmental outcomes and metabolic syndrome later in life. The aim of this study was to characterize patterns associated with urinary metabolites in extremely preterm and very preterm infants and to explore relationships with growth over time. Untargeted hydrogen-1 nuclear magnetic resonance ((1)H NMR) spectroscopy was used to characterize changes in urinary metabolites over time and explore relationships with growth and nutritional intake. Partial least-squares regression models were constructed to identify metabolic variation associated with age, growth, and nutrition. Biochemical aging differed between very (mean 29.4 weeks ± 1.08 gestational age; n = 21) and extremely (≤28 weeks gestational age; n = 33) preterm infants, but these differences were not apparent when urinary metabolites were aligned to postmenstrual age. Citrate was the only metabolite significantly positively associated with weight-for-age Z-score. At weeks 1 and 2, citrate was positively associated with gestational age and a greater increase in WAZ from birth to discharge. Biochemical aging aligned to chronological age differed between very and extremely preterm infants, but this variation was lost when aligned to postmenstrual age. Urinary citrate excretion in the first two weeks of life was associated with weight gain and may be a future modifiable biomarker to improve growth outcomes.