Metabolomic prediction of fetal congenital heart defect in the first trimester.
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).


METHODS
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).


CONCLUSIONS
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.
Department of Obstetrics and Gynecology, William Beaumont School of Medicine, Oakland University, Royal Oak, MI. Electronic address: raybahado-singh@beaumont.edu.
Ray O
RO
Bahado-Singh
Harris Birthright Research Center for Fetal Medicine, King's College Hospital, London, England, UK.
Rebecca
R
Ertl
Department of Biological Sciences, Faculty of Science, University of Alberta, Edmonton, AB, Canada.
Rupasri
R
Mandal
Department of Biological Sciences, Faculty of Science, University of Alberta, Edmonton, AB, Canada.
Trent C
TC
Bjorndahl
Harris Birthright Research Center for Fetal Medicine, King's College Hospital, London, England, UK.
Argyro
A
Syngelaki
Department of Computing Science, Faculty of Science, University of Alberta, Edmonton, AB, Canada.
Beomsoo
B
Han
Department of Biological Sciences, Faculty of Science, University of Alberta, Edmonton, AB, Canada.
Edison
E
Dong
Department of Biological Sciences, Faculty of Science, University of Alberta, Edmonton, AB, Canada.
Philip B
PB
Liu
Department of Obstetrics and Gynecology, William Beaumont School of Medicine, Oakland University, Royal Oak, MI.
Zeynep
Z
Alpay-Savasan
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.
David S
DS
Wishart
Harris Birthright Research Center for Fetal Medicine, King's College Hospital, London, England, UK.
Kypros H
KH
Nicolaides
D000328:Adult; D002853:Chromatography, Liquid; D005260:Female; D006330:Heart Defects, Congenital / Q000175:diagnosis*; D006801:Humans; D016015:Logistic Models; D009682:Magnetic Resonance Spectroscopy; D055432:Metabolomics / Q000379:methods*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D053719:Tandem Mass Spectrometry
congenital heart defects; maternal first-trimester serum; metabolomic markers