Robust early pregnancy prediction of later preeclampsia using metabolomic biomarkers.

Hdl Handle:
http://hdl.handle.net/10147/206248
Title:
Robust early pregnancy prediction of later preeclampsia using metabolomic biomarkers.
Authors:
Kenny, Louise C; Broadhurst, David I; Dunn, Warwick; Brown, Marie; North, Robyn A; McCowan, Lesley; Roberts, Claire; Cooper, Garth J S; Kell, Douglas B; Baker, Philip N
Affiliation:
Anu Research Centre, Department of Obstetrics and Gynaecology, University College, Cork, Cork University Maternity Hospital, Cork, Ireland. l.kenny@ucc.ie
Citation:
Hypertension. 2010 Oct;56(4):741-9.
Journal:
Hypertension
Issue Date:
31-Jan-2012
URI:
http://hdl.handle.net/10147/206248
DOI:
10.1161/HYPERTENSIONAHA.110.157297
PubMed ID:
20837882
Abstract:
Preeclampsia is a pregnancy-specific syndrome that causes substantial maternal and fetal morbidity and mortality. The etiology is incompletely understood, and there is no clinically useful screening test. Current metabolomic technologies have allowed the establishment of metabolic signatures of preeclampsia in early pregnancy. Here, a 2-phase discovery/validation metabolic profiling study was performed. In the discovery phase, a nested case-control study was designed, using samples obtained at 15+/-1 weeks' gestation from 60 women who subsequently developed preeclampsia and 60 controls taking part in the prospective Screening for Pregnancy Endpoints cohort study. Controls were proportionally population matched for age, ethnicity, and body mass index at booking. Plasma samples were analyzed using ultra performance liquid chromatography-mass spectrometry. A multivariate predictive model combining 14 metabolites gave an odds ratio for developing preeclampsia of 36 (95% CI: 12 to 108), with an area under the receiver operator characteristic curve of 0.94. These findings were then validated using an independent case-control study on plasma obtained at 15+/-1 weeks from 39 women who subsequently developed preeclampsia and 40 similarly matched controls from a participating center in a different country. The same 14 metabolites produced an odds ratio of 23 (95% CI: 7 to 73) with an area under receiver operator characteristic curve of 0.92. The finding of a consistent discriminatory metabolite signature in early pregnancy plasma preceding the onset of preeclampsia offers insight into disease pathogenesis and offers the tantalizing promise of a robust presymptomatic screening test.
Language:
eng
MeSH:
Adult; Biological Markers/*blood/metabolism; Case-Control Studies; Chromatography, High Pressure Liquid/methods; Cohort Studies; Female; Gestational Age; Humans; Mass Spectrometry/methods; Metabolomics/*methods; *Models, Biological; Multivariate Analysis; Pre-Eclampsia/*blood/metabolism; Predictive Value of Tests; Pregnancy; Prospective Studies; Reproducibility of Results; Risk Factors
ISSN:
1524-4563 (Electronic); 0194-911X (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorKenny, Louise Cen_GB
dc.contributor.authorBroadhurst, David Ien_GB
dc.contributor.authorDunn, Warwicken_GB
dc.contributor.authorBrown, Marieen_GB
dc.contributor.authorNorth, Robyn Aen_GB
dc.contributor.authorMcCowan, Lesleyen_GB
dc.contributor.authorRoberts, Claireen_GB
dc.contributor.authorCooper, Garth J Sen_GB
dc.contributor.authorKell, Douglas Ben_GB
dc.contributor.authorBaker, Philip Nen_GB
dc.date.accessioned2012-01-31T16:43:53Z-
dc.date.available2012-01-31T16:43:53Z-
dc.date.issued2012-01-31T16:43:53Z-
dc.identifier.citationHypertension. 2010 Oct;56(4):741-9.en_GB
dc.identifier.issn1524-4563 (Electronic)en_GB
dc.identifier.issn0194-911X (Linking)en_GB
dc.identifier.pmid20837882en_GB
dc.identifier.doi10.1161/HYPERTENSIONAHA.110.157297en_GB
dc.identifier.urihttp://hdl.handle.net/10147/206248-
dc.description.abstractPreeclampsia is a pregnancy-specific syndrome that causes substantial maternal and fetal morbidity and mortality. The etiology is incompletely understood, and there is no clinically useful screening test. Current metabolomic technologies have allowed the establishment of metabolic signatures of preeclampsia in early pregnancy. Here, a 2-phase discovery/validation metabolic profiling study was performed. In the discovery phase, a nested case-control study was designed, using samples obtained at 15+/-1 weeks' gestation from 60 women who subsequently developed preeclampsia and 60 controls taking part in the prospective Screening for Pregnancy Endpoints cohort study. Controls were proportionally population matched for age, ethnicity, and body mass index at booking. Plasma samples were analyzed using ultra performance liquid chromatography-mass spectrometry. A multivariate predictive model combining 14 metabolites gave an odds ratio for developing preeclampsia of 36 (95% CI: 12 to 108), with an area under the receiver operator characteristic curve of 0.94. These findings were then validated using an independent case-control study on plasma obtained at 15+/-1 weeks from 39 women who subsequently developed preeclampsia and 40 similarly matched controls from a participating center in a different country. The same 14 metabolites produced an odds ratio of 23 (95% CI: 7 to 73) with an area under receiver operator characteristic curve of 0.92. The finding of a consistent discriminatory metabolite signature in early pregnancy plasma preceding the onset of preeclampsia offers insight into disease pathogenesis and offers the tantalizing promise of a robust presymptomatic screening test.en_GB
dc.language.isoengen_GB
dc.subject.meshAdulten_GB
dc.subject.meshBiological Markers/*blood/metabolismen_GB
dc.subject.meshCase-Control Studiesen_GB
dc.subject.meshChromatography, High Pressure Liquid/methodsen_GB
dc.subject.meshCohort Studiesen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshGestational Ageen_GB
dc.subject.meshHumansen_GB
dc.subject.meshMass Spectrometry/methodsen_GB
dc.subject.meshMetabolomics/*methodsen_GB
dc.subject.mesh*Models, Biologicalen_GB
dc.subject.meshMultivariate Analysisen_GB
dc.subject.meshPre-Eclampsia/*blood/metabolismen_GB
dc.subject.meshPredictive Value of Testsen_GB
dc.subject.meshPregnancyen_GB
dc.subject.meshProspective Studiesen_GB
dc.subject.meshReproducibility of Resultsen_GB
dc.subject.meshRisk Factorsen_GB
dc.titleRobust early pregnancy prediction of later preeclampsia using metabolomic biomarkers.en_GB
dc.contributor.departmentAnu Research Centre, Department of Obstetrics and Gynaecology, University College, Cork, Cork University Maternity Hospital, Cork, Ireland. l.kenny@ucc.ieen_GB
dc.identifier.journalHypertensionen_GB
dc.description.provinceMunster-

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