Charlotte A Hobbs1, Mario A Cleves, Stepan Melnyk, Weizhi Zhao, S Jill James. 1. Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences and Arkansas Children's Hospital Research Institute, Little Rock, AR 72211, USA. hobbscharlotte@uams.edu
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.
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.
Authors: Mario A Cleves; Charlotte A Hobbs; Weizhi Zhao; Patrycja A Krakowiak; Stewart L MacLeod Journal: Paediatr Perinat Epidemiol Date: 2011-01-04 Impact factor: 3.980
Authors: Xinyu Tang; Mario A Cleves; Todd G Nick; Ming Li; Stewart L MacLeod; Stephen W Erickson; Jingyun Li; Gary M Shaw; Bridget S Mosley; Charlotte A Hobbs Journal: Am J Med Genet A Date: 2015-04-02 Impact factor: 2.802
Authors: S Jill James; Stepan Melnyk; Stefanie Jernigan; Mario A Cleves; Charles H Halsted; Donna H Wong; Paul Cutler; Kenneth Bock; Marvin Boris; J Jeffrey Bradstreet; Sidney M Baker; David W Gaylor Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2006-12-05 Impact factor: 3.568
Authors: Shimul Chowdhury; Charlotte A Hobbs; Stewart L MacLeod; Mario A Cleves; Stepan Melnyk; S Jill James; Ping Hu; Stephen W Erickson Journal: Mol Genet Metab Date: 2012-09-27 Impact factor: 4.797
Authors: Weizhi Zhao; Bridget S Mosley; Mario A Cleves; Stepan Melnyk; S Jill James; Charlotte A Hobbs Journal: Birth Defects Res A Clin Mol Teratol Date: 2006-04
Authors: Wendy N Nembhard; Xinyu Tang; Jingyun Li; Stewart L MacLeod; Joseph Levy; Gerald B Schaefer; Charlotte A Hobbs Journal: Am J Med Genet A Date: 2018-02-05 Impact factor: 2.802
Authors: Xianghu Qu; Haibo Jia; Deborah M Garrity; Kevin Tompkins; Lorene Batts; Bruce Appel; Tao P Zhong; H Scott Baldwin Journal: Dev Biol Date: 2008-03-06 Impact factor: 3.582