title: UPLC-MS metabolic profiling of second trimester amniotic fluid and maternal urine and comparison with NMR spectral profiling for the identification of pregnancy disorder biomarkers.
abstract: We report on the first untargeted UPLC-MS study of 2nd trimester maternal urine and amniotic fluid (AF), to investigate the possible metabolic effects of fetal malformations (FM), gestational diabetes mellitus (GDM) and preterm delivery (PTD). For fetal malformations, considerable metabolite variations were identified in AF and, to a lesser extent, in urine. Using validated PLS-DA models and statistical correlations between UPLC-MS data and previously acquired NMR data, a metabolic picture of fetal hypoxia, enhanced gluconeogenesis, TCA activity and hindered kidney development affecting FM pregnancies was reinforced. Moreover, changes in carnitine, pyroglutamate and polyols were newly noted, respectively, reflecting lipid oxidation, altered placental amino acid transfer and alterations in polyol pathways. Higher excretion of conjugated products in maternal urine was seen suggesting alterations in conjugation reactions. For the pre-diagnostic GDM group, no significant changes were observed, either considering amniotic fluid or maternal urine, whereas, for the pre-PTD group, some newly observed changes were noted, namely, the decrease of particular amino acids and the increase of an hexose (possibly glucose), suggesting alteration in placental amino acid fluxes and a possible tendency for hyperglycemia. This work shows the potential of UPLC-MS for the study of fetal and maternal biofluids, particularly when used in tandem with comparable NMR data. The important roles played by sampling characteristics (e.g. group dimensions) and the specific experimental conditions chosen for MS methods are discussed.
authors.affiliation: CICECO-Department of Chemistry, Campus Universitário de Santiago, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Gonçalo
authors.initials: G
authors.lastname: Graça
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Goodfellow
authors.forename: António S
authors.initials: AS
authors.lastname: Barros
authors.forename: Sílvia
authors.initials: S
authors.lastname: Diaz
authors.forename: Iola F
authors.initials: IF
authors.lastname: Duarte
authors.forename: Konstantina
authors.initials: K
authors.lastname: Spagou
authors.forename: Kirill
authors.initials: K
authors.lastname: Veselkov
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Want
authors.forename: John C
authors.initials: JC
authors.lastname: Lindon
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Carreira
authors.forename: Eulália
authors.initials: E
authors.lastname: Galhano
authors.forename: Cristina
authors.initials: C
authors.lastname: Pita
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gil
mesh_terms: D000596:Amino Acids / Q000032:analysis; D000653:Amniotic Fluid / Q000737:chemistry*; D015415:Biomarkers / Q000652:urine; D001826:Body Fluids / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods; D016640:Diabetes, Gestational / Q000175:diagnosis / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism / Q000517:prevention & control*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D055442:Metabolome; D015999:Multivariate Analysis; D010920:Placenta / Q000737:chemistry; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism / Q000652:urine*; D011262:Pregnancy Trimester, Second / Q000378:metabolism* / Q000652:urine; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000596:Amino Acids; D015415:Biomarkers