title: Development of a Pipeline for Exploratory Metabolic Profiling of Infant Urine.
abstract: Numerous metabolic profiling pipelines have been developed to characterize the composition of human biofluids and tissues, the vast majority of these being for studies in adults. To accommodate limited sample volume and to take into account the compositional differences between adult and infant biofluids, we developed and optimized sample handling and analytical procedures for studying urine from newborns. A robust pipeline for metabolic profiling using NMR spectroscopy was established, encompassing sample collection, preparation, spectroscopic measurement, and computational analysis. Longitudinal samples were collected from five infants from birth until 14 months of age. Methods of extraction and effects of freezing and sample dilution were assessed, and urinary contaminants from breakdown of polymers in a range of diapers and cotton wool balls were identified and compared, including propylene glycol, acrylic acid, and tert-butanol. Finally, assessment of urinary profiles obtained over the first few weeks of life revealed a dramatic change in composition, with concentrations of phenols, amino acids, and betaine altering systematically over the first few months of life. Therefore, neonatal samples require more stringent standardization of experimental design, sample handling, and analysis compared to that of adult samples to accommodate the variability and limited sample volume.
authors.affiliation: Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London , South Kensington Campus, London SW7 2AZ, United Kingdom.
authors.forename: Frances
authors.initials: F
authors.lastname: Jackson
authors.affiliation: Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London , South Kensington Campus, London SW7 2AZ, United Kingdom.
authors.forename: Nancy
authors.initials: N
authors.lastname: Georgakopoulou
authors.affiliation: Metabometrix Ltd, Bioincubator, Prince Consort Road, South Kensington, London SW7 2AZ, United Kingdom.
authors.forename: Manuja
authors.initials: M
authors.lastname: Kaluarachchi
authors.affiliation: Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London , South Kensington Campus, London SW7 2AZ, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Kyriakides
authors.affiliation: Section of Neonatal Medicine, Department of Medicine, Imperial College London , Chelsea and Westminster Hospital Campus, London SW10 9NH, United Kingdom.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Andreas
authors.affiliation: Section of Neonatal Medicine, Department of Medicine, Imperial College London , Chelsea and Westminster Hospital Campus, London SW10 9NH, United Kingdom.
authors.forename: Natalia
authors.initials: N
authors.lastname: Przysiezna
authors.affiliation: Section of Neonatal Medicine, Department of Medicine, Imperial College London , Chelsea and Westminster Hospital Campus, London SW10 9NH, United Kingdom.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Hyde
authors.affiliation: Section of Neonatal Medicine, Department of Medicine, Imperial College London , Chelsea and Westminster Hospital Campus, London SW10 9NH, United Kingdom.
authors.forename: Neena
authors.initials: N
authors.lastname: Modi
authors.affiliation: Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London , South Kensington Campus, London SW7 2AZ, United Kingdom.|MRC-NIHR National Phenome Centre, Department of Surgery and Cancer, Imperial College London , Hammersmith Hospital Campus, London W12 0NN, United Kingdom.
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
authors.affiliation: Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London , South Kensington Campus, London SW7 2AZ, United Kingdom.
authors.forename: Anisha
authors.initials: A
authors.lastname: Wijeyesekera
authors.affiliation: Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London , South Kensington Campus, London SW7 2AZ, United Kingdom.|MRC-NIHR National Phenome Centre, Department of Surgery and Cancer, Imperial College London , Hammersmith Hospital Campus, London W12 0NN, United Kingdom.
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
mesh_terms: D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009682:Magnetic Resonance Spectroscopy; D055432:Metabolomics / Q000379:methods*; D018401:Sample Size; D013048:Specimen Handling / Q000379:methods / Q000592:standards; D014556:Urine / Q000737:chemistry*; D059349:Urine Specimen Collection / Q000592:standards*; D057188:Workflow
keywords: NMR spectroscopy; infant; metabolic profiling; metabonomics; pipeline development; urine