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

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, Louise C. Kenny

Research output: Contribution to journalArticle

71 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3660-3673
Number of pages14
JournalJournal of Proteome Research
Volume10
Issue number8
DOIs
Publication statusPublished - 5 Aug 2011
Externally publishedYes

Keywords

  • fetal growth restriction
  • metabolic profiling
  • metabolomics
  • placental insufficiency
  • plasma
  • pregnancy
  • RUPP - reduced uterine perfusion pressure
  • small for gestational age
  • ultra performance liquid chromatography-mass spectrometry

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