3 AEDs our Registry Helped to Identify as ‘Unsafe’ during Pregnancy

By Lewis B. Holmes, MD,
North American AED Pregnancy Registry Director

It’s been roughly 20 years since the North
American Antiepileptic Drug (AED) Pregnancy
Registry has been gathering data to answer an
important question – “Is my AED safe to take
during pregnancy?” Let us tell you about 3
AEDs our Registry helped learn more about so
we could answer that question:



Available since 1912, this was the first drug our team studied. Since it had been on the market for quite a while, most of the pregnant women who initially signed up for our Registry were taking this drug. This provided our researchers with a large enough sample to conclude that there was a direct correlation between taking phenobarbital and a greater risk of having a baby with heart and/or cleft lip/palate defects. Fortunately, the drug companies were not advertising the drug very aggressively (since it was so cheap) and the Registry saw a decline in the number of women using this drug.

Valproic Acid

Valproic Acid is another drug the Registry identified as increasing the chances for birth defects if taken while pregnant. Numerous defects were observed in babies born to women taking it, including defects in the heart, kidney, fingers and toes. Affected babies also had distinct facial features. Heart, cleft lip/palate birth defects, as well as spina bifida, can also be attributed to taking Valproic Acid.

Topiramate (Topamax®).

A third drug that is still being studied but has shown signs of increasing the risk of birth defects is Topiramate (Topamax®). The Registry is hoping to enroll more women taking this drug so that they can provide more solid evidence. So far, the data is showing the risk rate for having a child with certain birth defects doubles when the mother is taking this drug.

There are over 30 different anticonvulsant or antiepileptic drugs (AEDs) on the market in the United States and Canada.

“In 2021, the good news is that the information available, now, shows that the fetus exposed during pregnancy to either of five medications, specifically lamotrigine, levetiracetam, gabapentin, zonisamide and oxcarbazepine, has a very low risk of having a birth defect. More information is needed to be sure of this reassuring information on each of these medications,” explained Dr. Lewis B. Holmes, the North American AED Pregnancy Registry Director. “The good news about the other medications , including phenytoin, carbamazepine, topiramate, and phenobarbital, is that the risk to the exposed fetus is a two or three fold increase in that risk for birth defects. ( The baseline risk is 2% that a child born to healthy parents will have a birth defect. ) We need more information to be sure of those risks,” he added.

Even for these medications, those risks mean that the exposed fetus has at least a 90% or more chance of having no birth defects, says Dr. Holmes.

There is no good news about taking valproate during pregnancy, according to Dr. Holmes. The practicing neurologists recommend that no woman in the child-bearing age group be prescribed valproate. “The risk includes a 10% or greater chance for the infant to have serious birth defects, plus a decrease in IQ and an increased risk for autism……all very serious risks. So, we need help in enrolling all pregnant women who take antiepileptic medications (AEDs) for any reason, so we can be more certain of the risk they pose to the unborn infant. The earlier the woman enrolls, the more valuable her information is. We hope she will do that before she has had any prenatal screening, like blood tests or ultrasound.”

To volunteer to be part of this Registry during pregnancy, please click here.