Biomarkers for Isolated Congenital Heart Disease Based on Maternal Amniotic Fluid Metabolomics analysis

Abstract

Introduction: Congenital heart disease (CHD) is one of the most prevalence birth defects in the world. The pathogenesis of CHD is complex and unclear. With the development of metabolomics technology, the variations in metabolites may provide a new clue for CHD occurrence and may serve as a biomarker during pregnancy.Method: Maternal amniotic fluid (AF) samples during second and third trimester were utilized to analyze the metabolomics of CHD and normal fetuses. Differential comparison and randomForest were used to screen metabolic biomarkers. Results: A total of 2472 metabolites were detected and they were distributed differentially between the cases and controls. Setting the selection criteria of fold change (FC) ≥ 2, p value < 0.01 and the variable importance for the projection (VIP) ≥ 1.5, we screened out 118 differential metabolites. Within the prediction model by randomForest, PE(MonoMe(11,5)/MonoMe(13,5)), N-feruloylserotonin and 2,6-Di-tert-butylbenzoquinone were showed good prediction effect. Differential metabolites were mainly concentrated in aldosterone synthesis and secretion, drug metabolism, nicotinate and nicotinamide metabolism pathways, which may be related to the occurrence and development of CHD.Conclusion: This study provides a new database on CHD metabolic biomarkers and mechanism research. These results need to be further verified in larger samples.