What We Know About ASMs & Child Development

Studies examining the effects of anti-seizure medications (ASMs) on children exposed during pregnancy have primarily focused on two key outcomes:

  • Fetal malformations 
  • Adverse neurodevelopmental outcomes

Most research has found that the risks associated with exposure to ASMs are relatively low compared to exposure to other substances like thalidomide or fetal alcohol exposure.

However, some ASMs carry a higher risk than others. Clinicians need to consider these variations and weigh the potential risks and benefits of different ASMs when treating pregnant patients with epilepsy.

Diagram of Anti-seizure Medication and Pregnancy Risk

Diagram of anti-seizure medication and pregnancy risk

** = Neurodevelopmental risks are not yet known

Topics covered on this page include:

Neurodevelopmental Outcomes For Children Born To Parents Taking ASMs

Several studies have followed children exposed to ASMs during pregnancy.  These studies also found that: 

  • Lamotrigine exposure appears to carry a relatively low risk of adverse neurodevelopmental outcomes. 
  • Levetiracetam also carries a low risk, based on more limited data. 
  • The data on carbamazepine are mixed but generally suggest a low risk.
  • The data on topiramate are more mixed and suggest negative effects.
  • The data on valproic acid suggests highly elevated risk.

Valproic acid exposure during pregnancy was found to be associated with adverse neurodevelopmental outcomes (cognitive and behavioral)  in children when compared to children born to mothers without epilepsy and children born to mothers taking other anti-seizure medications. Specifically, children exposed to valproic acid during pregnancy may exhibit lower IQ, lower verbal abilities, and have an increased risk of autism and autism spectrum disorder. Moreover, these neurodevelopmental effects continue into the school-age years. Risk of major congenital malformations that exposure to valproic acid may impact is generally complete by 13 weeks of pregnancy.

We have limited data on the other seizure medications, and more research is needed to understand their effects on the neurodevelopment of children born to patients who take these medications during pregnancy.

ASMs & Major Congenital Malformations

Major congenital malformations (MCMs) are fetal abnormalities that impact daily health and function or require surgery. In the general population, pregnancies carry a background risk of 2-3% for MCMs. Examples include:

  • Spina bifida
  • Heart defects
  • Cleft lip/palate
  • Urogenital defects

Pregnancy registries have provided valuable insights into the risk of MCMs associated with ASMs by following patients from their early pregnancy stages. Among all ASMs:

  • Lamotrigine and levetiracetam have the lowest risk of malformations (e.g., IQ and brain function) based on data from these pregnancy registries. Risk of MCMs were within the range for children who were not exposed to any ASM during pregnancy.
  • Oxcarbazepine is also likely to have a low risk of malformations. 
  • Research suggests that carbamazepine is generally low-risk.
  • Data on topiramate are more mixed and suggest negative effects.
  • Data on zonisamide are mixed.
  • Valproic acid exposure is linked to the highest risk of MCMs

Anti-seizure Medications and Correlation to MCMs as Noted by Worldwide Pregnancy Registries

Bar graph of anti-seizure medications and their correlation to major congenital malformations as noted by world wide pregnancy registries.

NOTE: See Figure 1 in Teratogenicity of Antiepileptic Drugs as published in Current Opinion in Neurology for confidence intervals for each ASM (for three of the four pregnancy registries.) It is essential to reference these confidence intervals.

Importantly, the risk of MCMs appears to correlate with the dose and level of the medication. For example, a patient taking valproic acid at the dose of:

  • <700 mg a day has a 5.6% risk of MCMs
  • 700 - 1500 mg/day has a 10.4% risk of MCMs
  • >1500 mg/day has 24.2% risk of MCMs.

It is essential to recognize that even low-dose valproic acid presents some risk, along with potential risks of neurodevelopmental effects, as you can see in the above chart. Clinicians should be aware of these varying risks when treating pregnant individuals with epilepsy to optimize the health of the patient and their baby. 

Impact of ASMs on Fetal Growth

Certain ASMs can impact fetal growth differently. 

  • Topiramate and zonisamide exposure during pregnancy has been linked to a risk of infants being born small for their gestational age.
    • This effect is more significant for topiramate compared to zonisamide. 
  • Fetal exposure to topiramate is also associated with infants born with low birth weight, which carries greater long-term health risks.

Fetal growth monitoring can help identify any potential issues early on and is recommended for pregnant patients with epilepsy, especially those on these medications. Visit the pregnancy management page to see when this monitoring is recommended during pregnancy. 

Guide Your Patients

There are ASMs with a low risk of fetal malformations or adverse neurodevelopmental outcomes. These ASMs also present little risk to babies if parents take them while breastfeeding. It is important to be very clear with patients about the existing research, what it shows, and what we don’t yet know. This level of transparency adds to your credibility.

Patients considering pregnancy should be advised of the potential risks of certain ASMs on child development. However, patients should be reassured that there are options with little or no elevated risk to the fetus. Emphasize that they should not stop taking medication due to fear or perceived risk, as abrupt discontinuation can be harmful. Instead, a collaborative approach should be taken to assess the benefits and risks of ASMs for both the patient and the developing fetus. Ensure your patients are aware that a healthy pregnancy is achievable with planning for people with epilepsy.

Reviewed by: Page Pennell, MD FAES, August 2023