The Australian Brain and Cognition and Antiepileptic Drugs Study: IQ in School-Aged Children Exposed to Sodium Valproate and Polytherapy

Caroline Nadebaum, Vicki Anderson, Frank Vajda, David Reutens, Sarah Barton, Amanda Wood

Prenatal exposure to sodium valproate (VPA) and polytherapy has been linked with increased risk of birth defects and cognitive impairment in young children. We evaluated the cognitive impact of prenatal exposure to VPA and polytherapy in school-aged children. Fifty-seven children exposed to VPA (n = 23), polytherapy with VPA (n = 15), or polytherapy without VPA (n = 19) were assessed using the Wechsler Intelligence Scale for Children--Fourth Edition. Information on maternal epilepsy, pregnancy, and medical history was obtained prospectively through the Australian Pregnancy Register for Women with Epilepsy and Allied Disorders. All groups had elevated frequencies of Extremely Low (<70) or Borderline (70-79) Full-Scale IQ (15.8-40.0%). Verbal Comprehension and Working Memory scores in all groups fell significantly below the standardized test mean, while Perceptual Reasoning and Processing Speed scores were relatively intact. Multivariate analysis of covariance analysis revealed significant main effects of VPA on Verbal Comprehension and Working Memory, and of polytherapy on Verbal Comprehension and Processing Speed. Our results suggest that VPA has a dose-dependent negative impact on verbal intellectual abilities, and may also affect working memory. The possibility that inclusion of VPA in many polytherapy regimens may underlie reduced mean scores of polytherapy-exposed children is discussed.