Congenital heart defects and abnormal maternal biomarkers of methionine and homocysteine metabolism ,

Abstract

Background: It is well established that folic acid prevents neural tube defects. Although the mechanisms remain unclear, multivitamins containing folic acid may also protect against other birth defects, including congenital heart defects. Objective: Our goal was to establish a maternal metabolic risk profile for nonsyndromic congenital heart defects that would enhance current preventive strategies. Design: Using a case-control design, we measured biomarkers of the folate-dependent methionine and homocysteine pathway among a population-based sample of women whose pregnancies were affected by congenital heart defects (224 case subjects) or unaffected by any birth defect (90 control subjects). Plasma concentrations of folic acid, homocysteine, methionine,S-adenosylmethionine (SAM),S-adenosylhomocysteine (SAH), vitamin B-12, and adenosine were compared, with control for lifestyle and sociodemographic variables. Results: After covariate adjustment, case subjects had higher mean concentrations of homocysteine (P < 0.001) and SAH (P < 0.001) and lower mean concentrations of methionine (P = 0.019) and SAM (P = 0.014) than did control subjects. Vitamin B-12, folic acid, and adenosine concentrations did not differ significantly between case and control subjects. Homocysteine, SAH, and methionine were identified as the most important biomarkers predictive of case or control status. Conclusions: The basis for the observed abnormal metabolic profile among women whose pregnancies were affected by congenital heart defects cannot be defined without further analysis of relevant genetic and environmental factors. Nevertheless, a metabolic profile that is predictive of congenital heart defect risk would help to refine current nutritional intervention strategies to reduce risk and may provide mechanistic clues for further experimental studies.