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. Study design 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.