Transcript (Part 3)

The following is the unedited transcript (Part 2 of 3) of the Tuesday, December 7, 2004, Pregnancy and AEDs briefing, "Birth Defects and Anticonvulsant Drugs: Emerging Data Points to Differing Levels of Risk."
Posted: December 7, 2004

Dr. [?]: Dr. Holmes, could you just give the audience an idea how much time it takes to register, and what's involved with each of the steps?

Dr. Holmes: Sure. This is a very reassuring story. She calls. She's sent a consent form that our hospital has agonized over and developed and approved, and she's sent the consent form. She reads that, signs it and sends it back. She has three interviews.

The initial enrollment interview can take as little as 10 or 12 minutes. Many of the women want to talk, so it takes longer than that. She's asked key information, is she a smoker, alcohol use, other medications, other diseases, that sort of thing. And then she has a short interview at 7 months, about 4, 5 minutes, and then she has a short interview after the baby's born, about two months after the baby's born. So it's a very quick easy process over the phone.

She is asked to give her written permission on forms that she sends in that we then send to the baby's doctor to get documentation. It's great to have her say what's wrong with the baby, but as you might guess, if I'm presenting to a neurologist the findings on Drug X they'd like to know that the pediatrician or the cardiologist agreed with her. And as you also I'm sure would agree, it's not easy for her to remember some of the lingo. She's going to get it right most of the time. And when we compare what she says to what the doctor says, it's about a 90 percent correlation, but everyone is going to believe our findings better if we have good, clear documentation.

So those are the steps. Sign the consent form, three interviews, give permission to get the information. It's all done over the phone. And we have been encouraged that the women themselves have been very responsive when we come back later with questions, and their doctors have also been very responsive, not everybody, but good cooperation.

Dr. [?]: I've had some patients do this, and they feel really pleased that they're able to contribute to help others, and that they hope that by volunteering this information, that this will be something that in a few years that other women won't have to agonize about whether or not they may be risking damage to their baby by taking this medication. So they really feel like they're doing a service to the public good by doing this.

Dr. [?]: Question from the phone?

Operator: Sara Wenn [ph] with the Epilepsy Foundation. Please state your publication. Sara Wenn, your line is open.

[No response.]

Operator: And no further questions from the phone.

Dr. [?]: Okay. We must have lost that one. Are there questions here in the audience?

Question: Dr. Holmes, yesterday in your scientific presentation you mentioned the importance of doctors being enthusiastic while avoiding coercion. I wonder if you could just give our reasons, who are physicians, you know, just some guidelines on how to gently encourage women to register.

Dr. Holmes: Sure. It actually would be repeating the things I just said. Assure her that this information is kept confidential, there's no way anyone can get into that and find out about her personally, that it is used in a carefully-guarded way, and it is used to provide information other folks need.

People commented at the session yesterday about why would anybody prescribe phenobarbital, and that is certainly a legitimate question to ask, and we took advantage of the historic fact that when we started this registry in 1997 there was probably a 4 or 5 percent sample of the women who enrolled who were taking phenobarbital. So even though the drug has been around since 1912, it was only in the last 10 years that the data came along showing there's some real problems with taking phenobarbital.

So the pitch I hope they give is that it's brief, it's user-friendly. She's talking to a woman. A lot of times women are concerned that they're not talking to a man. And the information is logical and relevant, and it's a brief process.

Dr. [?]: The other point I'd want to make is if a physician has a patient who is adamant that she does not want to participate in the registry and she is taking the medication Lamotrigine, the physician is able to enroll the patient in the Lamotrigine specific registry, and that also is a matter of just a very simple form, and it takes perhaps 10 minutes. So for women on Lamotrigine who do not choose to participate in the North American Registry, the physician has that option.

Question: Can I just ask [inaudible].

Dr. Holmes: Yes. The staff are all women, and the calls are—we get calls from nurses and doctors asking for information, but aside from those informational calls, the people enrolling are essentially all mothers themselves.

The reason why one might take phenobarbital is that it only costs a couple pennies a tablet to take phenobarbital, and if you have epilepsy and you don't have any insurance, it is a drug that just about anybody can afford to take. So it also is an effective anticonvulsant drug. So there are reasons why people might take that medication.

Yes? Phone call for a question?

Operator: We'll go to Jennifer Garrett with West County News. Please go ahead.

Question: Yes. You may have already said this earlier, but how many women are taking these medications? And a second question. For the women taking them for conditions other than epilepsy, do doctors prescribing them for say bipolar or migraines, are they aware of the serious side effects that could take place, or is there any way to maybe possibly reach those physicians?

Dr. [?]: Well, we hope—the answer to the question of how many women of child-bearing age are on these medications, we think that there are somewhere between 10 and 12 million prescriptions written in the United States every year for these drugs for that group of women.

Whether the physicians and the women are aware of the risk is not a point that we can know for sure, but the whole goal of this campaign and the reason why the Epilepsy Foundation and the American Epilepsy Society are working collaboratively, is because we are trying to inform two different audiences.

The Epilepsy Foundation is a voluntary health agency that works to try and educate consumers about epilepsy and its effects on life, and that would include the effects of anticonvulsive medication.

The American Epilepsy Society is a professional society that is an international body of physicians, researchers, nurses and other people working in the field of epilepsy. And so the very mission of the American Epilepsy Society is professional education. So we hope that the two organizations, by working together, can increase the professional awareness of the risk of these medications, as well as working to enlighten consumers about the risk and benefits of these medications.

Dr. [?]: But to use an example, the American Psychiatric Association has guidelines for treating bipolar disorder. They're very lengthy. They discuss many of the antiepileptic drugs, and nowhere in that guidelines document is there any mention of the potential trategenocity [ph] of these agents. So I would say the answer is no, these physicians are not aware of it, but the good news is, is that as soon as you start to tell them, they are very interested.

Dr. [?]: The recommendations by the American College of Obstetrics and Gynecology, as recently as about 15 years ago, thought that phenobarbital was the best drug, and they have now seen more recent data, and they've stopped that recommendation. But that just shows you that science is an ever-changing field, and the knowledge and the amount of scientific literature in the field of medicine is exploding, and so it's hard for people to keep up. And so we hope that by using these kinds of means of bringing this information to people and professionals, that we increase awareness so that we can prevent pregnancies that result in children with birth defects.

A question from the phone?

Operator: We'll go back to the line of Sara Wenn with the Epilepsy Foundation. Please state your publication.

Question: Hi, this is Sara, just have a couple of question, one about Lamotrigine. What are the malformations, or the serious malformations of that drug or the other drugs you're talking about?

Dr. [?]: Dr. Meador, would you like to answer that question?

Dr. Meador: Probably be better for [inaudible], but I will answer it.

Question: Let's do Lamotrigine first. I've got a daughter on that, and I was always told that was safe during pregnancy.

Dr. [?]: Well, let me just answer the question in general. We see defects in the heart, in midline closure defects like cleft palates, narrow tube defects. We see skeletal(?) defects. We see kidney and urogenital defects, and we see cerebral defects. There's a whole variety of different defects that are seen with these anti-convulsive drugs. Some of them are specific for drugs, like the narrow tube defects have been reported with (?) and with Carbamazepine, but the others are seen across the scope of the different drugs.

I don't think--I'm going to let Dr. Holmes comment on this. He's probably more, certainly more expert on this than I am.

Dr. Holmes: I think the things for your readers to know is that about 2 percent of infants at birth have a major malformation, so there's nobody whose risk is zero. And pregnancy registries have to continue a long time before you get information on specific drugs. I mentioned earlier that 555, enrolling 555 women would allow you to say that the frequency has gone from 2 percent to 4 percent with 80 percent confidence.

If you said, "I want you to tell me whether the frequency of cleft lip has gone up," well, you're looking at enrollment for a lot longer, because the baseline frequency of cleft lip is one in a thousand, instead of 2 percent, so it's going to take a lot longer to do that.

We do get clues and signals out of the case series of the really harmful drugs. And in the paper we're publishing in Neurology on valproate exposed children, it's repeating what's already been published many times. Heart defects are the most common birth defect, and they're heavily represented among these children. Spina bifida was the first major malformation identified in the valproate exposed pregnancies. Children having multiple birth defects is one of the sad consequences of valproate, especially at higher doses.

So we know some of the answer, but the sample sizes are going to have to get a lot bigger before we have really good malformation specific data.

Dr. [?]: Dr. Holmes, could you give, in the general population of healthy women, what are the most common major birth defects in order?

Dr. Holmes: Well, it varies by racial group, but roughly in that 2 percent, almost 1 percent is heart defects, a wide spectrum of defects. Many of those are known at birth, but some are not known until the children are older. Urinary tract abnormalities are very common. The spina bifida is probably a 1 in 800 frequency in Caucasians. I've already mentioned cleft lip at .1 percent. So the things that people know happen are part of that 2 percent. There's a small piece that's fatal. About a quarter of that 2 percent is fatal. And then a lot of fixable things like the clefts and the heart defects and the urinary tract abnormalities.

Dr. [?]: If there are no further questions, then maybe we can bring this to a close.

So I want to thank you for listening in on the phone and also for those of you here in the audience. My thanks go out to you on behalf of both the Epilepsy Foundation and the American Epilepsy Society.

So we hope that the message that you can bring to the public is the one of hope that most children born to women taking anticonvulsive drugs are healthy, that there are some specific risks, that there appear to be some medications that carry more risks than others, and that we need to have continued enrollment in these registries to learn with greater certainty the exact risks for each drug and combinations of medications.

Thank you very much, and I want to thank all the panelists for their time as well. Thank you.

[Applause.]

[End of briefing.]