Urine metabolomic biomarkers for prediction of isolated fetal congenital heart defect.

Document Type

Article

Publication Date

12-2022

Publication Title

The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians

Abstract

OBJECTIVE: To identify maternal second and third trimester urine metabolomic biomarkers for the detection of fetal congenital heart defects (CHDs).

STUDY DESIGN: This was a prospective study. Metabolomic analysis of randomly collected maternal urine was performed, comparing pregnancies with isolated, non-syndromic CHDs versus unaffected controls. Mass spectrometry (liquid chromatography and direct injection and tandem mass spectrometry, LC-MS-MS) as well as nuclear magnetic resonance spectrometry,

RESULTS: A total of 222 metabolites were identified, of which 16 were overlapping between the two platforms. Twenty-three metabolite concentrations were found in significantly altered in CHD gestations on univariate analysis. The concentration of methionine was most significantly altered. A predictive algorithm combining metabolites (histamine, choline, glucose, formate, methionine, and carnitine) plus US four-chamber view achieved an AUC = 0.894; 95% CI, 0814-0.973 with a sensitivity of 83.8% and specificity of 87.8%. Enrichment pathway analysis identified several lipid related pathways that are dysregulated in CHD, including phospholipid biosynthesis, phosphatidylcholine biosynthesis, phosphatidylethanolamine biosynthesis, and fatty acid metabolism. This could be consistent with the increased risk of CHD in diabetic pregnancies.

CONCLUSIONS: We report a novel, noninvasive approach, based on the analysis of maternal urine for isolated CHD detection. Further, the dysregulation of lipid- and folate metabolism appears to support prior data on the mechanism of CHD.

Volume

35

Issue

25

First Page

6380

Last Page

6387

DOI

10.1080/14767058.2021

ISSN

1476-4954

PubMed ID

33944672

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