Metabolomic prediction of fetal congenital heart defect in the first trimester

  • Am J Obstet Gynecol. 2014 Sep;211(3):240.e1-240.e14. doi: 10.1016/j.ajog.2014.03.056.
Ray O Bahado-Singh  1 ,  Rebecca Ertl  2 ,  Rupasri Mandal  3 ,  Trent C Bjorndahl  3 ,  Argyro Syngelaki  2 ,  Beomsoo Han  4 ,  Edison Dong  3 ,  Philip B Liu  3 ,  Zeynep Alpay-Savasan  5 ,  David S Wishart  6 ,  Kypros H Nicolaides  2
Affiliations
  • 1. Department of Obstetrics and Gynecology, William Beaumont School of Medicine, Oakland University, Royal Oak, MI. Electronic address: [email protected].
  • 2. Harris Birthright Research Center for Fetal Medicine, King's College Hospital, London, England, UK.
  • 3. Department of Biological Sciences, Faculty of Science, University of Alberta, Edmonton, AB, Canada.
  • 4. Department of Computing Science, Faculty of Science, University of Alberta, Edmonton, AB, Canada.
  • 5. Department of Obstetrics and Gynecology, William Beaumont School of Medicine, Oakland University, Royal Oak, MI.
  • 6. Department of Biological Sciences, Faculty of Science, University of Alberta, Edmonton, AB, Canada; Department of Computing Science, Faculty of Science, University of Alberta, Edmonton, AB, Canada.
PMID: 24704061 DOI: 10.1016/j.ajog.2014.03.056
Abstract

Objective: The objective of the study was to identify metabolomic markers in maternal first-trimester serum for the detection of fetal congenital heart defects (CHDs).

Study design: Mass spectrometry (direct injection/liquid chromatography and tandem mass spectrometry) and nuclear magnetic resonance spectrometry-based metabolomic analyses were performed between 11 weeks' and 13 weeks 6 days' gestation on maternal serum. A total of 27 CHD cases and 59 controls were compared. There were no known or suspected chromosomal or syndromic abnormalities indicated.

Results: A total of 174 metabolites were identified and quantified using the 2 analytical methods. There were 14 overlapping metabolites between platforms. We identified 123 metabolites that demonstrated significant differences on a univariate analysis in maternal first-trimester serum in CHD vs normal cases. There was a significant disturbance in acylcarnitine, sphingomyelin, and Other metabolite levels in CHD pregnancies. Predictive algorithms were developed for CHD detection. High sensitivity (0.929; 95% confidence interval [CI], 0.92-1.00) and specificity (0.932; 95% CI, 0.78-1.00) for CHD detection were achieved (area under the curve, 0.992; 95% CI, 0.973-1.0).

Conclusion: In the first such report, we demonstrated the feasibility of the use of metabolomic developing biomarkers for the first-trimester prediction of CHD. Abnormal lipid metabolism appeared to be a significant feature of CHD pregnancies.

Keywords
congenital heart defects; maternal first-trimester serum; metabolomic markers.
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