Abstract
BACKGROUND: Metabolomics, which involves profiling and comprehensive analysis of cellular metabolites, is a promising new tool for clinical diagnostic in neonatology. Urine is considered to be the most predictive of phenotypic outcome in neonatal conditions. Management of sick neonates could be improved with the availability of information on perinatal/neonatal maturational processes and their metabolic background. This study was carried out to compare metabolites identified in the urine sample obtained from term and preterm infants from the postnatal and neonatal intensive care unit (NICU) of University of Malaya Medical Centre. METHODS: Experiments were carried out to compare the metabolomic profiles between (I) collection of urine using urine bag and cotton ball from preterm infants, (II) urine collection at different time-points from preterm infants, (III) preterm and term infants, (IV) different birth weights of preterm infants and (V) between preterms with and without respiratory distress syndrome (RDS). Urine samples were stored at -40 °C freezer until analysis. Metabolites were extracted using cold methanol extraction. The extracted samples were analyzed on an Agilent 6540 Accurate-Mass LC/QTOF mass spectrometer. Qualitative analysis was done using MassHunter Professional Profiler. RESULTS: In relation to principle component analysis (PCA) plot, there were no observable differences between collection of urine using urine bag and cotton ball. Thus, urine samples were collected using cotton ball for all subsequent experiments. There were also no significant differences between the metabolomic profiles of week 1 and week 2 preterm infants. It was found that 47 metabolites and two biological pathways were found to differ significantly between preterm and term infants (P value <0.01). On the other hand, metabolomic profiles between preterm infants <1 kg and those >1 kg differed in 17 metabolites (P value <0.01). Importantly, 110 metabolites and 39 biological pathways differed significantly (P value <0.01) between metabolomic profiles of preterm infants with and those without RDS. CONCLUSIONS: Urine metabolomic profile is stable with time of collection over a period of 2 weeks but varies with birth weight and pathological conditions in preterm infants. It is of interest to note that there are significant differences in the urine metabolomics profile between preterm infants with and without RDS. Thus, urine metabolomics has the potential to be applied to the investigation of other pathological conditions in neonates.