Metabolomic analysis to predict the onset and severity of necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is the most devastating gastrointestinal (GI) emergency in preterm neonates. Untargeted metabolomics may allow the identification of biomarkers involved in NEC pathophysiology.

We conducted a prospective study including preterm infants born at < 34 gestational weeks (GWs) whose urine was longitudinally collected at birth (< 48 h, T0) and at 14 (T1) and 28 days (T2). Neonates were followed for their development of NEC, spontaneous intestinal perforation (SIP), or other GI conditions and compared to those of matched healthy controls. Urine samples were investigated by untargeted metabolomic analysis based on mass-spectrometry.

Thirty-five patients with NEC, 5 patients with SIP, 14 patients with other GI diseases and 113 controls were enrolled and selected for metabolomic analysis on the basis of their clinical characteristics and available samples. Considering urine samples at T0, the one-class classification approach was able to correctly classify 16/20 subjects (80%) who developed NEC, 3/3 (100%) who developed SIP and 5/7 subjects (71.4%) with other GI pathologies as not belonging to the control group. Neonates with surgical NEC had higher N-acetylaspartic acid, butyrylcarnitine and propionylcarnitine levels than did those with medical NEC. Considering the time evolution of the urinary metabolome, the NEC and control groups showed differences independently of the time point.

The urinary metabolome is closely associated with the underlying GI disease from birth. Urinary metabolic features characterize NEC patients from healthy controls until 28 days of life. The early urinary metabolome has the potential to predict surgical NEC. Future studies are needed to validate our results.