Gas chromatography-mass spectrometry based urinary metabolomics in very low birth weight premature infants

Abstract

Objective: To investigate the urinary metabolic spectrum and pathways in very low birth weight (VLBW) premature infants. Method: A prospective case-control study was conducted to collect and compare the data of VLBW premature infants and full term infants from the Sixth Affiliated Hospital of Sun Yet-Sen University in 2014. Within 24 hours after birth, urine specimens in each group were collected. Metabolites of urine samples including amino acid, fatty acid and organic acid were detected using the urease pre-processing and gas chromatography mass spectrometry (GC-MS) technology. Using the orthogonal partial least squares discriminant analysis (OPLS-DA), the biomarkers and differences between the two groups were found. The online metabolic pathway website was explored and multivariable analysis was conducted to investigate the valuable pathways and biomarkers related to the prematurity. Result: A total of 20 VLBW premature infants were enrolled, among whom 11 were male, 9 were female; and 20 full term infants were enrolled, among whom 9 were male, 11 were female. The urinary metabolites were established and compared between the VLBW premature and term infants. The investigation showed that the following nine pathways were enriched: amino-acyl-tRNA biosynthesis(P=0.000), lysine degradation(P=0.007), fatty acid biosynthesis(P=0.008), pyrimidine metabolism(P=0.014), pantothenate and CoA biosynthesis(P=0.022), valine, leucine and isoleucine biosynthesis(P=0.022), lysine biosynthesis(P=0.031), glycerolipid metabolism(P=0.046), and valine, leucine and isoleucine degradation(P=0.031). Almost all the metabolites decreased except for the glyceric acid exhibiting a higher content in the VLBW premature infant. 12 potential biomarkers were explored with the most significant covariance and correlation, within which stearic acid, palmiticacid, myristic acid, β-amino-isobutyric acid, and uric acid were lower, while myo-inositol, mannitol, glycine, glucose1, glucose2, glyceric acid and N-acetyl-tyrosine were higher in the VLBW premature group compared with the control group. Conclusion: There is a significant difference between the VLBW premature infants and full-term infants in the metabolic state and pathways. The urease pre-processing and GC-MS technology followed by the OPLS-DA and multivariable analysis to investigate VLBW premature infants' urinary metabolites is a valuable method to evaluate the patients' metabolism.