title: Folic acid in pregnant women associated with reduced prevalence of severe congenital heart defects in their children: a national population-based case-control study.
abstract: OBJECTIVE
  Previous Hungarian intervention trials have shown an association between periconceptional folic-acid-containing multivitamin supplementation and significantly reduced risk of congenital heart defects (CHDs). These findings were confirmed in observational multivitamin studies in the USA, and studies in the Netherlands and China regarding folic acid. The objective of this observational population-based study was to estimate the possible preventive effect of folic acid supplementation for different CHDs during their critical period of development.
  
  
  METHODS
  Evaluation of medically recorded use of folic acid (calculated daily average 5.6mg) during the critical period of development of eight types of CHD (verified through autopsy reports or after catheter examination and/or surgical correction) in the population-based Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA), 1980-1996, containing 22,843 cases with congenital abnormalities and 38,151 population controls without any CHDs, including 5395 matched controls of 3567 live-born cases with various CHDs. A conditional logistic regression model was used to estimate the relative risk/protection [odds ratio (OR) with 95% confidence intervals (CI)] of folic acid in the mothers of cases with various types of CHD and their matched controls.
  
  
  RESULTS
  There was a significant decrease in the prevalence of cases with ventricular septal defect (OR 0.57, 95% CI 0.45-0.73), tetralogy of Fallot (OR 0.53, 95% CI 0.17-0.94), d-transposition of great arteries (OR 0.47, 95% CI 0.26-0.86) and atrial septal defect secundum (OR 0.63, 95% CI 0.40-0.98) in infants born to mothers who had taken high doses of folic acid during the critical period of CHD development.
  
  
  CONCLUSIONS
  The risk of development of certain types of CHD was significantly reduced in pregnant women who were supplemented with folic acid. Thus, CHDs should be included as a secondary assessment in neural-tube-defect preventive programs.
authors.affiliation: Foundation for the Community Control of Hereditary Diseases, Budapest, Hungary. Electronic address: czeizel@interware.hu.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Czeizel
authors.affiliation: Versys Clinics, Human Reproduction Institute, Budapest, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Vereczkey
authors.affiliation: Department of Obstetrics and Gynaecology, University of Pécs, Pécs, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Szabó
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006330:Heart Defects, Congenital / Q000453:epidemiology / Q000517:prevention & control*; D006344:Heart Septal Defects, Atrial / Q000453:epidemiology / Q000517:prevention & control; D006345:Heart Septal Defects, Ventricular / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D011247:Pregnancy; D011295:Prenatal Care; D015995:Prevalence; D013771:Tetralogy of Fallot / Q000453:epidemiology / Q000517:prevention & control; D014188:Transposition of Great Vessels / Q000453:epidemiology / Q000517:prevention & control; D014803:Vitamin B Complex / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D014803:Vitamin B Complex; D005492:Folic Acid
keywords: Congenital heart defect; Folic acid; Population-based case–control study; Tetralogy of Fallot; Ventricular septal defect; d-Transposition of great arteries