NEW ORLEANS — Periconceptual folic acid supplementation appears to reduce by close to 20% the overall risk of congenital heart defects, a case-control study conducted in the Netherlands has shown.
This finding has important public health implications in light of the enormous number of babies born with congenital heart defects each year worldwide, Dr. Ingrid van Beynum said at the annual scientific sessions of the American Heart Association.
Indeed, congenital heart defects are the most common form of all birth defects. In the United States alone, 40,000 affected babies are born each year. Periconceptual folic acid supplementation at 400 mcg/day is already recommended for the prevention of neural tube defects, but surveys indicate many women do not follow this guidance. The added benefit of a reduced risk of congenital heart defects might be more persuasive, she said.
Consumption of folic acid-fortified foods typically gets a mother only one-quarter of the way to the recommended periconceptual 400 mcg/day, noted Dr. van Beynum of Radboud University Nijmegen (the Netherlands) Medical Centre.
She presented an analysis of a decade's worth of data from EUROCAT (European Surveillance of Congenital Anomalies), a comprehensive birth defects registry covering three Northern Dutch provinces.
In 1995, the year before the study period began, the Dutch government launched a major media campaign encouraging women to take 400 mcg/day folic acid starting 4 weeks before conception and to continue the supplements until 8 weeks afterward.
The cases comprised 611 mothers who gave birth to babies with isolated or complex heart defects unrelated to either a genetic abnormality or a syndrome; 2,401 mothers who gave birth to infants with noncardiac congenital malformations and a known chromosomal defect served as controls.
Diabetic mothers, those who had used folate antagonists, and mothers of babies with neural tube defects, limb reduction, hypospadias, or oral cleft palate were excluded from both groups in the analysis.
Of the Dutch mothers included in the study, 62% were regular users of folic acid supplements periconceptually; 38% were not. The incidence of any congenital heart defect was 28.5% in nonusers compared with 23.2% in users, for a highly significant 18.5% relative risk reduction in the women who took folic acid supplements.
After investigators adjusted in a multivariate model for potential confounders including the baby's year of birth, maternal age, smoking and alcohol consumption during pregnancy, and maternal body mass index and education level, the estimated relative risk reduction associated with maternal periconceptual folic acid supplements remained at 18%, owing to the fact that the prevalence of potential confounders in cases and controls was similar.
There was a particularly impressive 38% reduction in the adjusted risk of isolated septal heart defects in the folic acid group. Ventricular septal defects—the most common type of congenital heart defects—were reduced by 31%, while isolated atrial septal defects were decreased by 46%.
There were no significant differences between folic acid supplement users and nonusers in the incidence of right- or left-sided outflow obstruction or complex heart defects.
However, the 23% relative reduction in the risk of conotruncal heart defects among folic acid users might well have achieved statistical significance with a larger patient sample size, according to Dr. van Beynum.
Although a randomized, placebo-controlled, clinical trial is acknowledged to be the highest form of scientific evidence, a definitive randomized trial of periconceptual folic acid supplementation for the prevention of congenital heart defects would be ethically impossible because of the treatment's established effectiveness in preventing neural tube defects.
Data from EUROCAT and other comprehensive registries will have to do, she noted.
A ventricular septal defect is shown with myocardial motion imaging. Such defects were 31% less frequent in women who took periconceptual folic acid supplements. ©Elsevier, Textbook of Fetal Abnormalities, Twining, P., McHugo, J.M., Pilling, D.W., Churchill Livingstone, Edinburgh, 2000