title: Congenital heart defects and maternal biomarkers of oxidative stress.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72211, USA. hobbscharlotte@uams.edu
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Hobbs
authors.forename: Mario A
authors.initials: MA
authors.lastname: Cleves
authors.forename: Weizhi
authors.initials: W
authors.lastname: Zhao
authors.forename: Stepan
authors.initials: S
authors.lastname: Melnyk
authors.forename: S Jill
authors.initials: SJ
authors.lastname: James
mesh_terms: D000328:Adult; D001131:Arkansas; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D004151:Dipeptides / Q000097:blood; D005260:Female; D005492:Folic Acid / Q000097:blood; D005978:Glutathione / Q000097:blood; D019803:Glutathione Disulfide / Q000097:blood; D006330:Heart Defects, Congenital / Q000097:blood* / Q000209:etiology / Q000517:prevention & control; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007231:Infant, Newborn; D008019:Life Style; D018384:Oxidative Stress / Q000502:physiology*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood* / Q000209:etiology / Q000517:prevention & control; D012042:Registries; D012307:Risk Factors; D012435:S-Adenosylhomocysteine / Q000097:blood; D025101:Vitamin B 6 / Q000097:blood
chemical_list: D015415:Biomarkers; D004151:Dipeptides; D006710:Homocysteine; C028505:cysteinylglycine; D025101:Vitamin B 6; D005492:Folic Acid; D012435:S-Adenosylhomocysteine; D005978:Glutathione; D019803:Glutathione Disulfide