Folic Acid Supplementation In Women Of Child Bearing Age -- Just Do It

I was reminded today at our weekly department grand rounds of an extremely important topic that MS specialists often forget; the benefits of folic acid supplementation in pregnancy age women. We spend so much time discussing the use of disease modifying therapies in pregnancy that we often forget about other equally common and well-known risks. It has been known for decades that folic acid supplementation in doses above 0.4 mg per day reduces the risk of neural tube defects such as spina bifida. What women often do not know is that by the time their pregnancy is confirmed, it is often too late to start this supplementation, since neural tube closure is an early event in embryogenesis (first 25 days).  More importantly, at least 40 % of pregnancies are not planned in advance.

Why is this topic so important in woman of childbearing ages with MS?  Well, one of the most common class of medications used to treat MS related symptoms are the anti-epileptic drugs (AEDs) such as gabapentin, valproic acid, carbamazepine, lamotrigine, phenytoin, primidone and topiramate. We use these drugs to treat MS related pain syndromes, migraine headaches, mood disorders and even the main disorder for which they were developed, seizures. This class of medication, particularly valproic acid, has been associated with a number of major congenital malformations (MCM) and, more recently, disorders affecting behavior and learning including autism spectrum disorders. The risk is even higher with use of more than one of these medications at a time. While most of the data supporting the association of certain AEDs with birth defects come from Epilepsy Pregnancy Registries, there is little reason to believe that this data would not apply to women using these medications for other indications.

The reason for the increased risk of birth defects is clear with certain enzyme inducting AEDs such as phenytoin, carbamazepine and the barbiturates (primidone and phenobarbital), all of which cause a reduction in folic acid levels. For valproic acid it has been suggested that the drug interferes with folic acid metabolism. Other more recently introduced AEDs such as gabapentin, lamotrigine, oxcarbazepine and zonisamide have no significant effect on folic acid metabolism and the data on MCM is mixed. Yet most epilepsy specialists recommend folic acid supplementation in all women taking these drugs.

So what should you do with this information if you are (a woman) women of childbearing potential regardless of whether you are on birth control? (Birth control can fail)

1. Even if you are on no drugs, you should be taking at least 0.4 mg of folic acid a day if there is a chance you could become pregnant
2. If you are on an enzyme-inducing drug such as phenytoin, carbamazepine, primidone, or phenobarbital, you should strongly consider stopping the drug if a pregnancy is planned or take at least 1.0 mg of folic acid a day. Folic acid levels should be checked to make sure you are on enough supplementation and doses of Folic acid should be increased as needed.  This folic acid dosage requirement may increase during pregnancy as well.
3. Valproic acid should not be used unless absolutely necessary. 
4. If an AED is required, try to avoid the enzyme inducing drugs mentioned above, use the lowest dose required and take at least 0.8 mg a day of folic acid
5. If there is a history of birth defects involving neural tube closure in prior births, most experts recommend at least 5 mg per day of folic acid supplementation. Of course, women with a prior history of offspring with birth defects should be monitored in high-risk pregnancy clinics even before conception.
   

While the use of folic acid supplementation will not guarantee a child without birth defects, you can at least know you are doing something to reduce this risk. If you have daughters or grandchildren of childbearing ages, please pass this information along.

-- Rip Kinkel, MD