Relative Safety of Seizure Medications During Pregnancy

ARTICLE HIGHLIGHTS

  • The North American Antiepileptic Drug Pregnancy Registry recently reported its important new findings (Hernandez-Diaz, 2012).
  • The report compares the frequency of major malformations in the developing fetus in women taking an antiepileptic drug (AED) during their pregnancy. New and older AEDs are analyzed. Major malformations are serious medical problems that the fetus can develop during early development in the womb.
  • What is really important about this study: it describes the risks/safety of using the newer AEDs during pregnancy.
  • The study provides information about the relative risk/safety during pregnancy of 11 of the most commonly used AEDs. It looks at older AEDs, such as Dilantin and Depakote, and newer AED, such as Lamictal and Keppra. Prior to this study, there was not enough information available to say, with hardly any degree of confidence, which of the newer AEDs are the safest. This study describes a relatively large number of women exposed to AEDs during their pregnancies in order to compare the rates of problems with the fetal development- for both old and the new AEDs.
  • The study indicates that some of the newer AEDs may be safer during pregnancy than some of the older AEDs. Some of the relatively safer new AEDs:
    • Lamictal (generic = lamotrigine)
    • Keppra (generic = levetiracetam)
  • Depakote (generic= valproate) was associated with a 9.3% prevalence of major malformations- significantly higher than the relatively safer AEDs.
  • Take a look at the Table below—it lists the 11 AEDs and each AED’s prevalence of major malformations. A very valuable Table for clinicians and patients!
  • The website for the pregnancy registry:www.aedpregnancyregistry.org

INTRODUCTION

In 1963, one of the earliest reports describing a problem with fetal development in a woman taking an antiepileptic drug (AED) was published. The report described that the woman was taking mephenytoin, a medication similar to Dilantin, throughout her pregnancy. The child was found to have a low IQ, cleft palate, speech problems and a small head. Since that early report, it is clear that AEDs can be associated with an increased risk of medical problems with the developing fetus.

While seizure medications can cause problems for the developing baby, not taking seizure medications may result in more problems- a real double edged sword! Remember, intense seizures, especially generalized tonic-clonic seizures (= grand mal seizures) can result in serious problems for developing fetus. For most women with epilepsy, the safest strategy for their developing baby is to take a seizure medication.

In the old days, women with epilepsy were discouraged by some clinicians from going through a pregnancy—because of concerns about having a medically handicapped child. The latest data suggests that it is quite safe for the overwhelming number of women with epilepsy to consider pregnancy. Although the risk of having a medical problem may be higher than the general population, the increased risk may not be all that high and the majority of women with epilepsy can deliver healthy children. See the Table below for more details.

So, which AED should a woman take during her pregnancy? This is an extremely important question. The North American Antiepileptic Drug Pregnancy Registry recently reported its important new findings. These findings will be of great help in this important decision making process. The report compares the frequency of major malformations in the developing fetus in women taking an antiepileptic drug (AED) during their pregnancy. New and older AEDs are analyzed. Major malformations are serious medical problems that the fetus can develop during early development in the womb. Examples of major fetal malformations include cleft palate, spina-bifida and heart valve defects.

What is really important about this study: it compares the risk/safety of taking older and the newer AEDs during pregnancy. The study provides information for clinicians about the relative safety during pregnancy of 11 of the most commonly used AEDs. Prior to this study, there was not enough information available to say, with hardly any confidence, which of the newer AEDs is the safest. Past studies had too few women exposed to the newer AEDs to make conclusions. I am sure it makes sense-you need a large number of women exposed to an AED during their pregnancy to see what the problems are. You also need to compare women taking AEDs to controls (women going through their pregnancy not taking AEDs). This way, you can study what the problems are. That is why the North American Pregnancy Registry report is so important. This study describes a relatively large number of women exposed to AEDs during their pregnancies in order to compare the rates of problems with the fetal development- for both old and the new AEDs.

The study evaluated women from 1997 through 2011. 7,370 women were enrolled in the study. 4,899 women were taking only one seizure medication. The women taking only one AED are an important group—because they are only on one AED, it is easier to determine what problems are the result of the seizure medication. In contrast, if a woman is on three AEDs (Depakote, Dilantin and Keppra, for example), then it is harder to determine which AED is causing an identified problem. The study describes the rates of fetal malformations in women taking only one AED. These women are compared to controls (women not taking AEDs).

The following table summarizes some of the key findings (based on Table from North American Antiepileptic Drug Pregnancy Registry Spring 2012 newsletter). This is a great Table!:


AED

TOTAL MALFORMATIONS

ENROLLED PREGNANCIES
PREVALENCE OF MALFORMATIONS
Lamictal (=lamotrigine)

31

1562

2.0%

Tegretol (=carbamazepine)

31

1033

3.0%

Dilantin (=phenytoin)

12

416 2.9%
Keppra (=levetiracetam)

11

450 2.4%
Topamax (=topiramate)

15

359

4.2%

Depakote (=valproate)

30

323

9.3%

phenobarbital

11

199

5.5%

Trileptal (=oxcarbazepine)

4

182

2.2%

Neurontin (=gabapentin)

1

145

0.7%

Zonegran (=zonisamide)

0

90

0%

Klonopin (clonazepam)

2

64

3.1%

No AED (controls) 5 442

1.1%

www.aedpregnancyregistry.org

Take-away points:

  • Lamictal and Keppra appear to be safer, compared to some of the older AEDs (Depakote and Phenobarbital).
  • Depakote has a relatively higher rate of major malformations (9.3%). This does not mean that women should never take Depakote during pregnancy. Rather, other AEDs should be considered first, and Depakote should only be used if it is clearly needed for seizure control.
  • Topamax (a newer AED) was associated with a higher risk of cleft lip.
  • You may have noticed that Zonegran had no reported malformations. It should be noted, only 90 women were on Zonegran – this is too few patients to make a determination on the safety of Zonegran. More study is needed!
  • Please note- in the controls (women not taking AEDs) , 1.1% of patients had malformations.

CONCLUSIONS

The results of this study will be helpful as the clinician and patient consider going through a pregnancy on an AED. We encourage women with epilepsy who are considering pregnancy to have a detailed discussion with their healthcare provider—to optimally plan the pregnancy. The results from the North American Antiepileptic Drug Pregnancy Registry are a great addition to the literature (see their newsletter:www.aedpregnancyregistry.org for more information). The results of other pregnancy registries are going to be reported in the near future—and will further add to our understanding of this complicated and important topic!

REFERENCES

Hernandez-Diaz S, Smith CR, Shen A, et al. Comparative safety of antiepileptic drugs during pregnancy. Neurology 2012;78:1692-1699.

Mullers-Kupper vM. Embryopathy during pregnancy caused by taking anticonvulsants. Acta Paeddopsychiatr 1963;30:401-405.

The North American Antiepileptic Drug Pregnancy Registry Spring Newsletter: www.aedpregnancyregistry.org

Yerby MS, Battino D, Montouris GD. General principles: teratogenicity of antiepileptic drugs. In: Engel J, Pedley T, ed. Epilepsy: a comprehensive textbook. Philadelphia: LWW; p. 1213-1224.

LATEST UPDATE: 5/23/2012

Dr. White has been practicing as a full-time epileptologist since 1999. His practice focuses on optimizing the diagnosis and treatment of patients with seizure disorders. Dr. White’s special interests include patient education, improving the side-effect profile of seizure medications, and epilepsy surgery.

14 Responses to “Relative Safety of Seizure Medications During Pregnancy”

  1. I have been having seizures for about 24 years and am taking keppra and trileptal and am trying to have a baby has anyone taken trileptal during pregnancy and their baby came out just fine, i am really scared and have been reading that lamictal is one that is safer but am allergic to it, my neuro says i will be fine on trileptal and keppra, but am worried, if anyone has taken these 2 during pregnancy or has any advice please let me know. thanks!

  2. Hi,

    I feel you! I was soooooo worried the entire time I was pregnant. I was on high doses of both Trileptal and Keppra during my pregnancy and all the while having seizures. My son is now 5 and was born with no malformations! Eat right, exercise, try to have low stress (yoga or whatever destresses you) and do the best with the things you can control…All the best!

  3. I was well into my pregnancy before the lab tech discovered that I had a’ fetal Anamolity’ . Although I was on Tegretol, I ate right, exercised, took my prenatals and tried to live stress-free, and prayed a lot. I actually decreased my in take from 3 (500 mil) tablets a day to only one. Still, by baby was born with a condition called, “diaphragmatic hernia/ pulmonary hypoplasia”. She lived only a day (after the surgery) and died in my arms. My husband is ready for another child but I am livid. I don’t think I can go through that loss again. Still waiting for a ‘safe’ anti-seizure medication. Let me know too!

    • I feel for you. I have Juvenile Epilepsy, diagnosed at 19.(now 34) I had an uncle with seizures since 2, and my moms uncle died at 2. I am so paranoid about meds. getting switched around, and not on proper ones for my condition, and that they can cause more seizures, or birth defects. I had 2 healthy so far daughters off meds, and then a 3rd daughter last year off meds as well (I don’t think 2 seizures or 3 a year warrants meds since I have a strong aura of sickness before) I had 2 seizures while pregnant. one very early and one right before I was induced. My baby came home full term and healthy, but had a seizure at 4 days, spent a week in the NICU, and came home on phenobarbital, which seemed to help on her EEG, while docs still not sure what was going on, maybe birth trauma. They weaned her off at 3 months old. When she was 6 months old she died (this was 1 month ago) We still don’t know why. Some have thought SIDS/SUID might be related to a brain stem abnormality, or did she have a seizure? I was feeling icky that day, because I felt I was going to get my period and it was her morning nap time. I laid her down in a safe spot and laid down away from her…. I awoke wondering why she didn’t wake me up to find her not breathing/dead. I didn’t feel like I had a seizure…. After they told me she died, I freaked out and started having tons and tons of seizures, and ended up in the ICU. Like my body wanted to die….. losing a baby is very devastating. I feel responsible as her mom, as maybe she had a seizure, I should have had her monitored more, or I should have been monitored more, even though she was in a safe place. But being on meds causes its own added problems too, as does the gene pool. I am not sure I can have more kids either.. it is like PTSD I just don’t know what I could have done different, or even what happened yet. She looked like a perfect little angel, and they said expect no conclusion. They want me on meds, but the thought I might accidentally get pregnant and have another kid with problems is a lot to worry about.

    • So sorry for your lost I was on keppra and zonagran for 3 of my pregnancies. I always had a seizure at about six weeks but I think it was just do to a change in hormones. After that I did just fine and had no more. All three of my kids are healthy. I am now expecting my fourth child in December it was not planed I am on depikoate but my doctor is taking me off that and putting me on something else not sure what yet I hope this helps and may God bless you with your bundle of joy.

  4. I will be starting on keppra (newly diagnosed) in two weeks when I reach my second trimester. I’m freaking out :/ concerns that it will cause more seizures :/

  5. Hello! I have had epilepsy since I was 17 (24 now), and my husband and I have recently decided we want to try for children. My neurologist is switching me from Zonegran to Keppra (he says Keppra has a low risk of birth defects). Has anyone taken Keppra while pregnant, and if so, what was your experience like? And were your babies healthy? Just worried and wanting to make sure I do the healthiest thing possible for my future family…Thanks!

  6. Hello everyone,
    I have been reading some of your posts, I am on keppra and lamictal right now. My fiance and I do want to have babies, but I am nervous because of being on medication really. I am also on zoloft and buspar for anxiety and depression. It scares me because my neurologist said keppra was not good to get pregnant on. I am reading a few people have been on keppra and lamictal during pregnancy and they were just fine. I am just nervous as to what can happen or might.

  7. I have been on Lamictal and Keppra for 9 years now. I have tried to get pregnant for 9 years now and have had 2 miscarriages. It can really stab you in the heart when each of those children are born dead. Please keep me in your prayers. Dr. Agostini put me on Lamictal a high dose, and Keppra a high dose. Would that be too high then be high on the fetus?

  8. I just can’t believe that trying to get pregnant is so difficult and such a struggle. I can’t believe either that just about every one of the seizure medications I can think of comes with absolutely horrific side effects as well. So both issues are upsetting and going to be difficult to figure out a solution to. I just don’t know what else I can do or say to fix it!!!!!!!!!

  9. Dr.K.V.Seshaiah MD April 29, 2016 at 12:35 am

    Good useful ready reference

  10. Hi
    I have just found out I am 5 weeks pregnant and I am currently taking keppra and lamictal I’ve had multiple miscarriages whilst on these tablets and now I am scared the same is going to happen again. I am thinking about coming off the lamictal until I see my neurologist. I don’t want to risk another miscarriage and I know I will be fine on keppra alone for now as I’ve had to do it before for a different reason.
    Opinions please…

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