(P04-010-25) Urinary Metabolites Associated With Growth Failure in the Preterm Infant

Objectives: Postnatal growth failure (GF) in preterm infants is linked to higher morbidities and poor neurodevelopmental outcomes. The study aims to identify urinary biomarkers in infants with GF.

Methods: 54 infants < 32 weeks’ gestation were selected from an existing data biorepository at the NICU, Beth Israel Deaconess Medical Center in Boston, MA from October 2009 to October 2012 (IRB approved at BIDMC). Infants were included if urine samples were available for at least two of the three study timepoints.

Maternal and infant data were collected from electronic medical records. Growth was assessed from birth to discharge with velocity defined as change in z-scores (weight) over time. Infants were divided into growth velocity tertiles and designated as adequate growth (AG), moderate growth failure (MGF), or high growth failure (HGF) (birth-to-discharge mean Δz-score of -0.30, -0.86, -1.39, respectively). Urine samples were collected at postnatal ages of 2, 3, and 6 weeks. Samples were analyzed by Metabolon (Durham, NC). Differential metabolites as a function of growth status were determined using ANOVA followed by post-hoc analysis. Statistical significance was defined as p< 0.05 and corrected for multiple comparisons.

Results: At 2 weeks, compared to infants with AG, infants with HGF showed decreased urinary secondary bile-salt lipid metabolites, namely 12-dehydrocholate, 3-dehydrocholate, 7-ketodeoxycholate (p = 0.008, 0.03, 0.03, respectively). In contrast at 6 weeks, primary bile-salt lipid metabolites were increased in HGF versus AG, suggesting delayed lipid metabolism in the early postnatal period may correlate with early high growth failure. Importantly, these differences were independent of maternal and infant clinical data and nutritional intake as these variables were not different between groups (p ≥0.05).

Conclusions: Urinary metabolomic profiles distinguish postnatal growth patterns in preterm infants. Lack of differences in maternal, clinical, and nutritional profiles support that endogenous drivers of metabolism determine nutrient utilization and overall growth. Gut microbiota, which convert primary to secondary bile acids, may influence these metabolic patterns and thus postnatal growth.

Funding Sources: Massachusetts Life Science Center
Weill Cornell Medicine