Urine NMR Metabolomics Profile of Preterm Infants With Necrotizing Enterocolitis Over the First Two Months of Life: A Pilot Longitudinal Case-Control Study

Objective: To investigate changes in the urine metabolome of very low birth weight preterm newborns with necrotizing enterocolitis (NEC) and feed intolerance, we conducted a longitudinal study over the first 2 months of life. The metabolome of NEC newborns was compared with two control groups that did not develop NEC: the first one included preterm babies with feed intolerance, while the second one preterm babies with good feed tolerance. Methods: Newborns developing NEC within the 3 weeks of life were identified as early onset NEC, while the remaining as late onset NEC. Case-control matching was done according to the gestational age (+/- 1 week), birth weight (+/- 200 g), and postnatal age. A total of 96 urine samples were collected and analyzed. In newborns with NEC, samples were collected before, during and after the diagnosis over the first 2 months of life, while in controls samples were collected as close as possible to the postnatal age of newborns with NEC. Proton nuclear magnetic resonance (H-1 NMR) spectroscopy was used for metabolomic analysis. Data were analyzed by univariate and multivariate statistical analysis. Results: In all the preterm newborns, urine levels of betaine, glycine, succinate, and citrate positively correlated with postnatal age. Suberate and lactate correlated with postnatal age in preterms with NEC and in controls with food intolerance, while N,N-dimethylglycine (N,N-DMG) correlated only in controls with good digestive tolerance. Preterm controls with feed intolerance showed a progressive significant decrease of N-methylnicotinamide and carnitine. Lactate, betaine, myo-inositol, urea, creatinine, and N,N-dimethylglycine discriminated late-onset NEC from controls with good feed tolerance. Conclusion: Our findings are discussed in terms of contributions from nutritional and clinical managements of patients and gut microbiota.