Journal of the International Neuropsychological Society

Research Articles

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

Caroline Nadebauma1a2, Vicki Andersona2a3a4, Frank Vajdaa5, David Reutensa6, Sarah Bartona1a2 and Amanda Wooda2a7a8 c1

a1 School of Psychology and Psychiatry, Monash University, Melbourne, Australia

a2 Critical Care and Neurosciences, Murdoch Childrens Research Institute, Melbourne, Australia

a3 Department of Psychology, Royal Children’s Hospital, Melbourne, Australia

a4 Department of Psychology, University of Melbourne, Melbourne, Australia

a5 Department of Medicine, The Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia

a6 Centre for Advanced Imaging, University of Queensland, Brisbane, Australia

a7 Department of Medicine, Southern Clinical School, Monash University, Melbourne, Victoria, Australia

a8 School of Psychology, University of Birmingham, United Kingdom


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. (JINS, 2011, 17, 000–000)

(Received June 15 2010)

(Revised October 06 2010)

(Accepted October 08 2010)

(Online publication November 19 2010)


c1 Correspondence and reprint requests to: Amanda Wood, School of Psychology, The University of Birmingham, Edgbaston, B15 2TT, UK. E-mail: