Congenital heart defects and maternal biomarkers of oxidative stress

• Published in: The American journal of clinical nutrition 2005-09, Vol.82 (3), p.598-604
• Main Authors: Hobbs, Charlotte A, Cleves, Mario A, Zhao, Weizhi, Melnyk, Stepan, James, S Jill
• Format: Article
• Language: English
• Subjects: Adult; Amino acids; Arkansas; Biological and medical sciences; biomarkers; Biomarkers - blood; Birth defects; Cardiology. Vascular system; Case-Control Studies; congenital abnormalities; Congenital heart diseases. Malformations of the aorta, pulmonary vessels and vena cava; cysteine; Dipeptides - blood; Female; folic acid; Folic Acid - blood; glutathione; Glutathione - blood; Glutathione Disulfide - blood; Heart; Heart Defects, Congenital - blood; Heart Defects, Congenital - etiology; Heart Defects, Congenital - prevention & control; homocysteine; Homocysteine - blood; Humans; Infant, Newborn; Life Style; maternal effect; maternal nutrition; Medical sciences; Mothers; Oxidation; oxidative stress; Oxidative Stress - physiology; Pregnancy; pregnancy complications; Pregnancy Complications - blood; Pregnancy Complications - etiology; Pregnancy Complications - prevention & control; pyridoxine; Registries; Risk Factors; S-Adenosylhomocysteine - blood; Stress; Vitamin B 6 - blood; vitamin deficiencies
• ISSN: 0002-9165; 1938-3207
• DOI: 10.1093/ajcn/82.3.598

BACKGROUND: Women who have had pregnancies that were affected by nonsyndromic congenital heart defects have alterations in the homocysteine-methionine pathway that may indicate increased exposure to oxidative stress or reduced antioxidant defense or both. 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 transsulfuration pathway in a population-based sample of women whose pregnancies were affected by congenital heart defects (331 cases) and in a control group of women (125 controls). Plasma concentrations of reduced and oxidized glutathione, vitamin B-6, homocysteine, cysteine, cysteinylglycine (CysGly), and glutamylcysteine (GluCys) were compared between cases and controls after adjustment for lifestyle and sociodemographic variables. RESULTS: After covariate adjustment, cases had significantly lower mean plasma concentrations of reduced glutathione (P < 0.0001), GluCys (P < 0.0001), and vitamin B-6 (P = 0.0023) and significantly higher mean concentrations of homocysteine (P < 0.0001) and oxidized glutathione (P < 0.0001) than did controls. CONCLUSIONS: Biomarkers of oxidative stress involved in the transsulfuration pathway were significantly higher in women with pregnancies affected by congenital heart defects than in women without such a history. Further analysis of relevant biomarkers of oxidative stress and genetic and environmental factors is required to define the basis for the observed alterations. Identifying the nature and extent of alterations in biomarkers of oxidative stress may suggest primary intervention strategies and provide clues to a greater understanding of the pathogenesis of congenital heart defects.