In my clinical work, I often see parents struggle when placing their young children on epileptic medications. This hesitation is often in response to a common research finding indicating that some antiepileptic medications are associated with significant side-effects, including reduced cognitive capacity (although in most cases these side effects are not as severe as the risk posed by untreated epilepsy). But while many studies have explored the association between childhood use of antiepileptic drugs and cognitive performance, less is known about the effects of prenatal exposure to these drugs. Specifically, given that suspending their medication regime is not an option for many adults, it is important for expecting mothers and clinicians to understand which medications may pose the greatest risk to the fetus and which medications may be relatively safe.

Dr. Kimford Meador at Emory University in Atlanta recently published a study in the New England Journal of Medicine exploring the effects of several antiepileptic medications taken during pregnancy on the cognitive performance of the children when they were 3 years of age. The study included 309 children whose mothers were taking one of four medications during pregnancy, namely: carbamazepine, lamotrignine, phenytoin, or valproate.

The results:

Children of mothers who were taking valproate had significantly lower IQ at age 3 when compared to all other children in the study.

The IQ of the children taking the different medications were:

  • Carbamazepine = 98
  • Lamtrigine = 101
  • Phenytoin = 99
  • Valproate = 92
Antiepileptic drugs and cognitive functioning

Antiepileptic drugs and cognitive functioning

Two additional findings are worth noting:

  • The effect of valproate was dose dependent. That is, the higher the dose taken during pregnancy, the lower the IQ of the child during early childhood.
  • Maternal IQ was associated with child’s IQ (a very standard/common finding). Surprisingly however, this was not the case for mothers taking valproate. In this case, maternal IQ was not related to child IQ, suggesting that the use of the medication ‘overrode’ the natural intergenerational transmission of IQ scores.

The authors noted a number of limitations. Specifically, parents were not randomized to the medications, which means that the findings may be related to other characteristics that led to medication use. For example, mothers taking valproate were more likely than other mothers to have idiopathic generalized epilepsy. Therefore, it is possible that the relatively lower IQ levels observed in the children of these mothers were not at all associated with Valproate but instead were related to with having mothers with idiopathic generalized epilepsy.

One last related thought. Next week I will be in San Francisco at the annual meeting of the Association for Psychological Science (APS). One of the keynote speakers for the meeting is Dr. Richard E. Nisbett, a world-renown expert on education and intelligence. His talk will address the commonly held, but incorrect, belief that IQ is inflexible and entirely genetically determined. For clinicians conducting neuropsychological assessments this is a fact of our day-to-day work, and it applies most strongly to IQ scores during early childhood. That is, the IQ score obtained before the age of 7 is not stable (not highly associated with future IQ), and this variability is dependent upon environmental influences.

Considering this, the findings of valproate exposure during pregnancy have clinical implications in that early interventions may help these children improve their cognitive abilities and mitigate the possible effects of early valproate exposure.

The reference:  Meador, K., Baker, G., Browning, N., Clayton-Smith, J., Combs-Cantrell, D., Cohen, M., Kalayjian, L., Kanner, A., Liporace, J., Pennell, P., Privitera, M., Loring, D., & , . (2009). Cognitive Function at 3 Years of Age after Fetal Exposure to Antiepileptic Drugs New England Journal of Medicine, 360 (16), 1597-1605 DOI: 10.1056/NEJMoa0803531ResearchBlogging.org

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2 Responses to Fetal exposure to antiepileptic drugs: Effects on later cognitive function

  1. RAJ says:

    Prenatal exposure to valproate acid is one of the known teratogens associated with autism:

    http://www.ncbi.nlm.nih.gov/pubmed/10882750?

    Valproate acid is one of the generally accepted animal models for autism with numerous studies demonstrating how the exposure disrupts ealy brain development and induces behaviors in the offspring similar to the behaviors of autistic children.

    http://www.ncbi.nlm.nih.gov/pubmed/19460635?

    http://www.ncbi.nlm.nih.gov/pubmed/10840175?

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