Urinary metabolomic analysis to identify preterm neonates exposed to histological chorioamnionitis: A pilot study

Chorioamnionitis is a leading cause of preterm birth worldwide, with higher incidence at lower gestational ages. An early and reliable diagnosis of histological chorioamnionitis (HCA) in preterm infants may be helpful in guiding postnatal management, especially the administration of prophylactic antibiotics to prevent early-onset sepsis. The main aim of this study was to investigate metabolomic analysis of urines collected in the first 24 hours of life as diagnostic tool of HCA. Gestational age-, birth weight-, delivery mode- and sex- matched (1:2) preterm neonates (< 35 weeks' gestation) born to mothers with or without HCA were enrolled from an observational study. Gas chromatography-mass spectrometry (GC-MS)-based metabolomic analysis was performed on urine samples non-invasively collected in the first 24 hours of life. Univariate analysis, partial least square discriminant analysis (PLS-DA) and its associated variable importance in projection (VIP) score were performed. The most affected metabolic pathways were examined by Metabolite Sets Enrichment Analysis (MSEA). Fifteen cases (mean GA 30.2 ± 3.8 weeks, mean BW 1415 ± 471.9 grams) and 30 controls (mean GA 30.2 ± 2.9 weeks, mean BW 1426 ± 569.8 grams) were enrolled. Following univariate analysis, 29 metabolites had a significantly different concentration between cases and controls. The supervised PLS-DA model confirmed a separation between the two groups. Only gluconic acid, an oxidation product of glucose, was higher in cases than in controls. All other VIP metabolites were more abundant in the control group. Glutamate metabolism, mitochondrial electron transport chain, citric acid cycle, galactose metabolism, and fructose and mannose degradation metabolism were the most significantly altered pathways (P < 0.01). For the first time, urinary metabolomics was able to discriminate neonates born to mothers with and without HCA. The identification of specifically altered metabolic pathways may be helpful in understanding metabolic derangement following chorioamnionitis.