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Type: Journal article
Title: Metabolic profiling uncovers a phenotypic signature of small for gestational age in early pregnancy
Author: Horgan, R.
Broadhurst, D.
Walsh, S.
Dunn, W.
Brown, M.
Roberts, C.
North, R.
McCowan, L.
Kell, D.
Baker, P.
Kenny, L.
Citation: Journal of Proteome Research, 2011; 10(8):3660-3673
Publisher: American Chemical Society
Issue Date: 2011
ISSN: 1535-3893
Statement of
Richard P Horgan, David I. Broadhurst, Sarah K. Walsh, Warwick B. Dunn, Marie Brown, Claire T. Roberts, Robyn A. North, Lesley M. McCowan, Douglas B. Kell, Philip N. Baker and Louise C. Kenny
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.
Keywords: small for gestational age; fetal growth restriction; placental insufficiency; RUPP − reduced uterine perfusion pressure; metabolomics; metabolic profiling; ultra performance liquid chromatography−mass spectrometry; pregnancy; plasma
Rights: Copyright © 2011 American Chemical Society
RMID: 0020111695
DOI: 10.1021/pr2002897
Appears in Collections:Obstetrics and Gynaecology publications

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