Neuropsychological effects of exposure to anticonvulsant medication in utero

Neurology. 2005 Mar 22;64(6):949-54. doi: 10.1212/01.WNL.0000154514.82948.69.


Objective: To investigate the long-term differential drug effects on cognitive functioning in school-aged children exposed to antiepileptic drugs (AEDs) in utero.

Methods: Mothers with epilepsy were recruited from specialist epilepsy clinics and obstetric clinics from the Liverpool and Manchester region. The mothers and their children were recruited without prior knowledge of their AED treatment during pregnancy or the health of the offspring. A battery of neuropsychological tests was applied to each mother-child pair in order to obtain a neuropsychological profile for each child.

Results: Neuropsychological investigation was performed on 249 children between the ages of 6 and 16. Children exposed to sodium valproate had a significantly lower verbal IQ when compared to children exposed to other antiepileptic drugs or not exposed at all. The same children were more likely to have an IQ below 69 and more likely to have memory impairment when compared to the other groups. The mothers' IQ, exposure to sodium valproate, and the number of tonic-clonic seizures during pregnancy were significant predictors of verbal IQ in this population.

Conclusions: This retrospective study highlights the potential harmful effects of sodium valproate exposure in utero on neuropsychological development.

MeSH terms

  • Adolescent
  • Anticonvulsants / adverse effects*
  • Brain / drug effects
  • Brain / growth & development
  • Brain / physiopathology
  • Child
  • Cognition Disorders / chemically induced*
  • Cognition Disorders / physiopathology
  • Cognition Disorders / psychology*
  • Cohort Studies
  • Epilepsy / drug therapy*
  • Female
  • Humans
  • Intellectual Disability / chemically induced
  • Intellectual Disability / physiopathology
  • Intellectual Disability / psychology
  • Intelligence / drug effects
  • Male
  • Memory Disorders / chemically induced
  • Memory Disorders / physiopathology
  • Memory Disorders / psychology
  • Neuropsychological Tests
  • Pregnancy
  • Prenatal Exposure Delayed Effects / physiopathology*
  • Prenatal Exposure Delayed Effects / psychology*
  • Retrospective Studies
  • United Kingdom
  • Valproic Acid / adverse effects


  • Anticonvulsants
  • Valproic Acid