Folic acid slashes risk of congenital heart defects: reduction of 54%

OB/GYN News, Dec 15, 2003 by Bruce Jancin

ORLANDO, FLA. -- Women who are of childbearing potential have a powerful new incentive to consume a folic acid-containing daily multivitamin: evidence from a large prospective cohort study that this reduces by 54% their risk of having a baby with a ventricular septal or conotruncal defect.

"This is the first real preventive strategy to reduce the risk of congenital heart disease," Cynthia Morris, Ph.D., observed in presenting the groundbreaking study results at the annual scientific sessions of the American Heart Association.

She reported on a National Institutes of Health-sponsored study involving 899 consecutive women who presented for routine prenatal care and 985 others referred for fetal echocardiography. Participants initiated prenatal care at about 10 weeks' gestation and averaged a dozen prenatal visits.

All underwent a detailed interview assessing pregnancy history, lifestyle, and nutrition. They were followed until their babies were 1 year old to identify all congenital heart defects.

A total of 43 infants had a conotruncal defect and 39 had an isolated ventricular septal defect, 73% of which were diagnosed prenatally. Seven affected fetuses were later aborted or were stillborn. Two children who had a chromosome 22 deletion were excluded from the study.

In a multivariate logistic regression analysis adjusting for age, race, binge drinking, smoking, and other potential confounders, women who took a daily folate supplement during the first 6 weeks of pregnancy-the period of cardiogenesis were 54% less likely to have an affected baby, said Dr. Morris of Oregon Health Sciences University, Portland.

A dose-response effect was evident, with supplements containing larger amounts of folate being more protective.

It appeared that a daily supplement containing at least 400 micrograms of folate was necessary to achieve a reduction in risk.

No benefit was associated with starting a folate supplement after 6 weeks' gestation or taking supplemental folate before, but not during, pregnancy.

A stored blood sample obtained at study enrollment from each mother who went on to deliver an infant with a congenital heart defect was later compared with samples from six matched controls. This nested case-control study showed that maternal plasma folate level was inversely associated with risk. Women with the highest plasma folate had roughly a 55% lower risk of having a baby with a congenital heart defect than mothers with the lowest plasma folate.

The presumed teratogen in these heart defects, as in neural tube defects, is homocysteine. Support for this theory comes from the finding in this study that women in the highest quartile for homocysteine were 2.28-fold more likely to have a child with a congenital heart defect than those in the lowest quartile, Dr. Morris continued.

Major medical organizations already recommend that women aged 15-45 years consume 400 micrograms/day of folic acid to reduce the risk of neural tube defects in their offspring, yet only about half do so regularly. Perhaps learning of the added benefit in terms of reduced risk of congenital heart defects, which occur far more frequently than neural tube defects, will persuade more women to do so.

"Clearly we're not doing what we need to do to get women to use a folic acid supplement.... This is a strategy that should be used by all women, and particulary by mothers who've previously had a child with a congenital heart defect," she stressed.

Her study was underway when mandatory folate fortification of the nation's food supply began in 1998.

Women who became pregnant after that point did seem less likely to have a baby with a congenital heart defect. But given the inconsistencies of individual dietary habits, food sources alone are viewed as an unreliable means of meeting the Institute of Medicine's recommended folate intake of 600 micrograms/day from both food and supplement sources during pregnancy.