Given recent discussions within our group and with our colleague, Lewis Holmes, MD, chief of the Genetics and Teratology Unit at Massachusetts General Hospital for Children and director of the North American AED (Antiepileptic Drug) Pregnancy Registry, I wanted to expand upon a previous blog post. In the initial post, I wrote that women who take certain medications, like mood stabilizers or antiepileptic drugs, are advised to take increased doses of folic acid before pregnancy and throughout pregnancy.
Specifically, first trimester exposure to the anticonvulsant valproic acid has been associated with an increased risk of neural tube defects, as well as other structural abnormalities. This finding led to the recommendation that women on valproic acid should take an increased daily dose (4 mg) of folic acid. While research has not shown lamotrigine, a commonly prescribed mood stabilizer, to be associated with an increased risk of neural tube defects, the recommendation regarding folic acid supplementation has been broadened to include women taking any anticonvulsant. It is now recommended that women on antiepileptic drugs take 4 or 5 mg of folic acid daily before conception and during early pregnancy.
Research has shown that folic acid supplementation decreases the overall risk of neural tube defects in the general population, yet it has not been demonstrated that folic acid supplementation decreases the risk of neural tube defects or other malformations when given to women taking anticonvulsant drugs. It is hoped that the risk of neural tube defects and other structural defects may be decreased by supplementation with higher doses of folic acid; the 4-5 mg recommended daily dosage of folic acid has not been shown to be harmful to the pregnant woman or her fetus.
In addition to taking an increased daily dose of folic acid, all women who are planning to conceive or who are pregnant, should be taking a daily multivitamin tablet or prenatal vitamin which includes Vitamin B12. Recent studies have shown that multivitamin supplementation has decreased the rates of several different types of congenital malformations, including neural tube defects.
April Hirschberg, MD
Wilson RD et al. Pre-conceptional vitamin/folic acid supplementation 2007: the use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies. Obstet Gynaecol Can 2007;29(12): 1003-26.
Goh YI et al. Prenatal multivitamin supplementation and rates of congenital anomalies: a meta-analysis. J Obstet Gynaecol Can 2006;28(8): 680-9.
Hope you can give some advice on this…(I’m a psychiatrist so prescribe AEDs):
I looked up folate since you were recommending significantly higher doses, and found there are problems with too MUCH folate, as below [generally from http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-folate.html ].
1. Taking folic acid along with vitamin B12 may increase the risk of vitamin B12 deficiency. Caution is advised when taking both of these vitamins together. This article [ http://ods.od.nih.gov/factsheets/folate.asp ] cautioned against exceeding upper limit of folate (for 19yo and older it was 1000mcg/day) from triggering symptoms of vitamin B12 deficiency]
2. Supplemental folic acid might increase seizures in people with seizure disorders, particularly in very high doses.
3. Folic acid may mask the symptoms of pernicious, aplastic, or normocytic anemias caused by vitamin B12 deficiency and may lead to neurological damage. [this one I knew]
Given #1 above, I was worried about causing problems by giving folate in general (if we are to avoid more than 1mg of folate/day in adults, we would have to watch for the sum of doses between multivitamin + vitamin B complex before even getting to supplementing in women of childbearing years).
Worse is dosing women of childbearing years on AEDs–we’re being told to give much more than 1mg of folate a day, so seems we need to give even more B12…but how much?. And how often do we need to monitor B12?
Would love a CC to my email address since there’s no way to be notified of new posts here 🙂
Many thanks
Dear Dr. Green,
Thank you for your interest in our website. We appreciate your questions regarding folic acid and Vitamin B12 in reproductive age women.
Let me first clarify that no medical complications have been identified in healthy young women who took the folic acid vitamin supplement for the three months before and after conception. Furthermore, we recommend that the supplemental folic acid 4 mg/day be in the form of folic acid tablets and women should only take a multivitamin or prenatal vitamin which already contains vitamin B12. We are not recommending pregnant women take more than one multivitamin a day and we are not recommending additional vitamin B12 supplementation or the need for Vitamin B12 monitoring.
The NIH fact sheet you mention in your comment which suggested that increased folate may trigger symptoms of vitamin B12 deficiency was written in 1998, a more recent reference, listed below, states that “Folic acid 5 mg supplementation will not mask vitamin B12 deficiency (pernicious anemia), and investigations (examination or laboratory) are not required prior to initiating supplementation.”
You also mention that there was once a concern that folic acid supplementation increases seizures in people with seizure disorders, however, subsequent research has found that not to be the case.
I have provided a couple of references that our group has found helpful below.
Thank you for your thought provoking comments for they allowed me the opportunity to clarify my initial blog post. In summary, I would encourage you to recommend reproductive age women planning pregnancy, who are also on antiepileptic medications, to take folic acid supplementation in the three months before and after conception.
April Hirschberg, MD
Morrell MJ. Folic Acid and Epilepsy. Epilepsy Curr. 2002 Mar;2(2):31-34.
Wilson et al. Pre-conceptional vitamin/folic acid supplementation 2007: the use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies. J Obstet Gynaecol Can. 2007 Dec;29(12):1003-26.
I hv been TTC for the past 8 months and constantly taking folic acid for 3 months now and i cannot conceive. What do i do.