Commentary
Prevention is always the best option and this research suggests, once again, that folic acid may offer even more benefits.
The study also shows that there was no clear difference in reduction of congenital heart defects based on either a 3-mg or 6-mg dose, except with atrial septal defect secundum. In that case, the 3-mg dose reduced risk by only 10%, compared with more than 40% at 6 mg. But the researchers were quick to point out that more research is needed to look at the dose-response relationship.
The 5.6-mg average daily dose is significant because it is far above the 0.4-mg level recommended by the Centers for Disease Control and Prevention and the level frequently prescribed for pregnant women – 0.8 mg to 1 mg.
We know that some women may benefit from more folic acid, such as women who have previously given birth to a child with neural tube defects. But there are more subgroups that could benefit from higher doses of folic acid, including women taking antifolate medications such as antiepileptic drugs, methotrexate, and sulfonamides. Women who don’t consume enough vegetables and don’t take a multivitamin could benefit from high doses, as well would obese women, smokers, and women with diabetes.
For years the concern has been that folic acid at higher levels could increase the risk for certain cancers, but the evidence there is uncertain. Additionally, that risk would be triggered only after years of exposure, while the benefits of high-dose folic acid could be achieved in a matter of months. I don’t think the evidence of harm is convincing enough to stop us from considering that high-dose folic acid could be used in the general population.
One of the encouraging aspects of using folic acid to prevent congenital heart defects is that the critical window for influencing malformations is larger than with neural tube defects. While folic acid must be given in the first 28 days of pregnancy to have a benefit, the window of opportunity is 1-2 months longer for cardiac malformations.
The bottom line is that high-dose folic acid to prevent congenital heart defects is a target ripe for further research. While randomized controlled trials aren’t possible, there are plenty of high-quality studies that could be conducted to provide clinicians with the information they need to prevent these devastating malformations.
Dr. Koren is professor of pharmacology and pharmacy at the University of Toronto. He is the founding director of the Motherisk Program. He received grant support to conduct studies on folic acid from Duchesnay. He has been a consultant to several companies that produce vitamins in the context of pregnancy, including Bayer. Email him at obnews@frontlinemedcom.com.