Metabolic profiling uncovers a phenotypic signature of small for gestational age in early pregnancy.

Hdl Handle:
http://hdl.handle.net/10147/206219
Title:
Metabolic profiling uncovers a phenotypic signature of small for gestational age in early pregnancy.
Authors:
Horgan, Richard P; Broadhurst, David I; Walsh, Sarah K; Dunn, Warwick B; Brown, Marie; Roberts, Claire T; North, Robyn A; McCowan, Lesley M; Kell, Douglas B; Baker, Philip N; Kenny, Louise C
Affiliation:
The Anu Research Centre, Department of Obstetrics and Gynaecology, University, College Cork, Cork University Maternity Hospital, Cork, Ireland.
Citation:
J Proteome Res. 2011 Aug 5;10(8):3660-73. Epub 2011 Jun 29.
Journal:
Journal of proteome research
Issue Date:
31-Jan-2012
URI:
http://hdl.handle.net/10147/206219
DOI:
10.1021/pr2002897
PubMed ID:
21671558
Abstract:
Being born small for gestational age (SGA) confers increased risks of perinatal morbidity and mortality and increases the risk of cardiovascular complications and diabetes in later life. Accumulating evidence suggests that the etiology of SGA is usually associated with poor placental vascular development in early pregnancy. We examined metabolomic profiles using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) in three independent studies: (a) venous cord plasma from normal and SGA babies, (b) plasma from a rat model of placental insufficiency and controls, and (c) early pregnancy peripheral plasma samples from women who subsequently delivered a SGA baby and controls. Multivariate analysis by cross-validated Partial Least Squares Discriminant Analysis (PLS-DA) of all 3 studies showed a comprehensive and similar disruption of plasma metabolism. A multivariate predictive model combining 19 metabolites produced by a Genetic Algorithm-based search program gave an Odds Ratio for developing SGA of 44, with an area under the Receiver Operator Characteristic curve of 0.9. Sphingolipids, phospholipids, carnitines, and fatty acids were among this panel of metabolites. The finding of a consistent discriminatory metabolite signature in early pregnancy plasma preceding the onset of SGA offers insight into disease pathogenesis and offers the promise of a robust presymptomatic screening test.
Language:
eng
MeSH:
Animals; Chromatography, Liquid; Female; Fetal Growth Retardation; Humans; Infant, Newborn; *Infant, Small for Gestational Age; Mass Spectrometry; Models, Animal; Multivariate Analysis; Pregnancy; Pregnancy Trimester, First/*metabolism; ROC Curve; Rats; Rats, Sprague-Dawley
ISSN:
1535-3907 (Electronic); 1535-3893 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorHorgan, Richard Pen_GB
dc.contributor.authorBroadhurst, David Ien_GB
dc.contributor.authorWalsh, Sarah Ken_GB
dc.contributor.authorDunn, Warwick Ben_GB
dc.contributor.authorBrown, Marieen_GB
dc.contributor.authorRoberts, Claire Ten_GB
dc.contributor.authorNorth, Robyn Aen_GB
dc.contributor.authorMcCowan, Lesley Men_GB
dc.contributor.authorKell, Douglas Ben_GB
dc.contributor.authorBaker, Philip Nen_GB
dc.contributor.authorKenny, Louise Cen_GB
dc.date.accessioned2012-01-31T16:43:04Z-
dc.date.available2012-01-31T16:43:04Z-
dc.date.issued2012-01-31T16:43:04Z-
dc.identifier.citationJ Proteome Res. 2011 Aug 5;10(8):3660-73. Epub 2011 Jun 29.en_GB
dc.identifier.issn1535-3907 (Electronic)en_GB
dc.identifier.issn1535-3893 (Linking)en_GB
dc.identifier.pmid21671558en_GB
dc.identifier.doi10.1021/pr2002897en_GB
dc.identifier.urihttp://hdl.handle.net/10147/206219-
dc.description.abstractBeing born small for gestational age (SGA) confers increased risks of perinatal morbidity and mortality and increases the risk of cardiovascular complications and diabetes in later life. Accumulating evidence suggests that the etiology of SGA is usually associated with poor placental vascular development in early pregnancy. We examined metabolomic profiles using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) in three independent studies: (a) venous cord plasma from normal and SGA babies, (b) plasma from a rat model of placental insufficiency and controls, and (c) early pregnancy peripheral plasma samples from women who subsequently delivered a SGA baby and controls. Multivariate analysis by cross-validated Partial Least Squares Discriminant Analysis (PLS-DA) of all 3 studies showed a comprehensive and similar disruption of plasma metabolism. A multivariate predictive model combining 19 metabolites produced by a Genetic Algorithm-based search program gave an Odds Ratio for developing SGA of 44, with an area under the Receiver Operator Characteristic curve of 0.9. Sphingolipids, phospholipids, carnitines, and fatty acids were among this panel of metabolites. The finding of a consistent discriminatory metabolite signature in early pregnancy plasma preceding the onset of SGA offers insight into disease pathogenesis and offers the promise of a robust presymptomatic screening test.en_GB
dc.language.isoengen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshChromatography, Liquiden_GB
dc.subject.meshFemaleen_GB
dc.subject.meshFetal Growth Retardationen_GB
dc.subject.meshHumansen_GB
dc.subject.meshInfant, Newbornen_GB
dc.subject.mesh*Infant, Small for Gestational Ageen_GB
dc.subject.meshMass Spectrometryen_GB
dc.subject.meshModels, Animalen_GB
dc.subject.meshMultivariate Analysisen_GB
dc.subject.meshPregnancyen_GB
dc.subject.meshPregnancy Trimester, First/*metabolismen_GB
dc.subject.meshROC Curveen_GB
dc.subject.meshRatsen_GB
dc.subject.meshRats, Sprague-Dawleyen_GB
dc.titleMetabolic profiling uncovers a phenotypic signature of small for gestational age in early pregnancy.en_GB
dc.contributor.departmentThe Anu Research Centre, Department of Obstetrics and Gynaecology, University, College Cork, Cork University Maternity Hospital, Cork, Ireland.en_GB
dc.identifier.journalJournal of proteome researchen_GB
dc.description.provinceMunster-

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