1. Academic Validation
  2. Metabolomic prediction of fetal congenital heart defect in the first trimester

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

Affiliations

  • 1 Department of Obstetrics and Gynecology, William Beaumont School of Medicine, Oakland University, Royal Oak, MI. Electronic address: raybahado-singh@beaumont.edu.
  • 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.
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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