title: Following healthy pregnancy by nuclear magnetic resonance (NMR) metabolic profiling of human urine.
abstract: In this work, untargeted NMR metabonomics was employed to evaluate the effects of pregnancy on the metabolite composition of maternal urine, thus establishing a control excretory trajectory for healthy pregnancies. Urine was collected for independent groups of healthy nonpregnant and pregnant women (in first, second, third trimesters) and multivariate analysis performed on the corresponding NMR spectra. Models were validated through Monte Carlo Cross Validation and permutation tests and metabolite correlations measured through Statistical Total Correlation Spectroscopy. The levels of 21 metabolites were found to change significantly throughout pregnancy, with variations observed for the first time to our knowledge for choline, creatinine, 4-deoxyerythronic acid, 4-deoxythreonic acid, furoylglycine, guanidoacetate, 3-hydroxybutyrate, and lactate. Results confirmed increased aminoaciduria across pregnancy and suggested (a) a particular involvement of isoleucine and threonine in lipid oxidation/ketone body synthesis, (b) a relation of excreted choline, taurine, and guanidoacetate to methionine metabolism and urea cycle regulation, and (c) a possible relationship of furoylglycine and creatinine to pregnancy, based on a tandem study of nonfasting confounding effects. Results demonstrate the usefulness of untargeted metabonomics in finding biomarker metabolic signatures for healthy pregnancies, against which disease-related deviations may be confronted in future studies, as a base for improved diagnostics and prediction.
authors.affiliation: CICECO-Department of Chemistry, Campus Universitário de Santiago, Universidade de Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Sílvia O
authors.initials: SO
authors.lastname: Diaz
authors.forename: António S
authors.initials: AS
authors.lastname: Barros
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Goodfellow
authors.forename: Iola F
authors.initials: IF
authors.lastname: Duarte
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: Maria do Céu
authors.initials: Mdo C
authors.lastname: Almeida
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gil
mesh_terms: D000144:Acids, Acyclic / Q000097:blood / Q000652:urine; D000328:Adult; D000596:Amino Acids / Q000097:blood / Q000652:urine; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002794:Choline / Q000097:blood / Q000652:urine; D003404:Creatinine / Q000097:blood / Q000652:urine; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome / Q000502:physiology*; D009010:Monte Carlo Method; D015999:Multivariate Analysis; D011247:Pregnancy / Q000097:blood / Q000652:urine*; D011264:Pregnancy Trimesters; D025341:Principal Component Analysis
chemical_list: D000144:Acids, Acyclic; D000596:Amino Acids; D015415:Biomarkers; D003404:Creatinine; D002794:Choline