Metabolomics Signatures and Subsequent Maternal Health among Mothers with a Congenital Heart Defect-Affected Pregnancy

Abstract

Congenital heart defects (CHDs) are the most prevalent and serious of all birth defects in the United States. However, little is known about the impact of CHD-affected pregnancies on subsequent maternal health. Thus, there is a need to characterize the metabolic alterations associated with CHD-affected pregnancies. Fifty-six plasma samples were identified from post-partum women who participated in the National Birth Defects Prevention Study between 1997 and 2011 and had (1) unaffected control offspring (n = 18), (2) offspring with tetralogy of Fallot (ToF, n = 22), or (3) hypoplastic left heart syndrome (HLHS, n = 16) in this pilot study. Absolute concentrations of 408 metabolites using the AbsoluteIDQ® p400 HR Kit (Biocrates) were evaluated among case and control mothers. Twenty-six samples were randomly selected from above as technical repeats. Analysis of covariance (ANCOVA) and logistic regression models were used to identify significant metabolites after controlling for the maternal age at delivery and body mass index. The receiver operating characteristic (ROC) curve and area-under-the-curve (AUC) are reported to evaluate the performance of significant metabolites. Overall, there were nine significant metabolites (p < 0.05) identified in HLHS case mothers and 30 significant metabolites in ToF case mothers. Statistically significant metabolites were further evaluated using ROC curve analyses with PC (34:1), two sphingolipids SM (31:1), SM (42:2), and PC-O (40:4) elevated in HLHS cases; while LPC (18:2), two triglycerides: TG (44:1), TG (46:2), and LPC (20:3) decreased in ToF; and cholesterol esters CE (22:6) were elevated among ToF case mothers. The metabolites identified in the study may have profound structural and functional implications involved in cellular signaling and suggest the need for postpartum dietary supplementation among women who gave birth to CHD offspring.