Robust early pregnancy prediction of later preeclampsia using metabolomic biomarkers.
Authors
Kenny, Louise CBroadhurst, 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.ieIssue Date
2012-01-31T16:43:53ZMeSH
AdultBiological 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
Metadata
Show full item recordCitation
Hypertension. 2010 Oct;56(4):741-9.Journal
HypertensionDOI
10.1161/HYPERTENSIONAHA.110.157297PubMed ID
20837882Abstract
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
engISSN
1524-4563 (Electronic)0194-911X (Linking)
ae974a485f413a2113503eed53cd6c53
10.1161/HYPERTENSIONAHA.110.157297