Cognition in school-age children exposed to levetiracetam, topiramate, or sodium valproate

• Published in: Neurology Vol. 87; no. 18; p. 1943
• Main Authors: Bromley, Rebecca L, Calderbank, Rebecca, Cheyne, Christopher P, Rooney, Claire, Trayner, Penny, Clayton-Smith, Jill, García-Fiñana, Marta, Irwin, Beth, Morrow, James Irvine, Shallcross, Rebekah, Baker, Gus A
• Format: Journal Article
• Language: English
• Published: United States 01.11.2016
• Subjects: Adult; Anticonvulsants - adverse effects; Child; Cognition Disorders - chemically induced; Cross-Sectional Studies; Epilepsy - drug therapy; Female; Follow-Up Studies; Fructose - adverse effects; Fructose - analogs & derivatives; Humans; Levetiracetam; Male; Piracetam - adverse effects; Piracetam - analogs & derivatives; Pregnancy; Prenatal Exposure Delayed Effects - chemically induced; Prenatal Exposure Delayed Effects - physiopathology; Topiramate; Valproic Acid - adverse effects; Young Adult
• ISSN: 1526-632X
• DOI: 10.1212/WNL.0000000000003157

To investigate the effects of prenatal exposure to monotherapy levetiracetam, topiramate, and valproate on child cognitive functioning. This was a cross-sectional observational study. Children exposed to monotherapy levetiracetam (n = 42), topiramate (n = 27), or valproate (n = 47) and a group of children born to women who had untreated epilepsy (n = 55) were enrolled retrospectively from the UK Epilepsy and Pregnancy Register. Assessor-blinded neuropsychological assessments were conducted between 5 and 9 years of age. Information was collected on demographic and health variables and adjusted for in multiple regression analyses. In the adjusted analyses, prenatal exposure to levetiracetam and topiramate were not found to be associated with reductions in child cognitive abilities, and adverse outcomes were not associated with increasing dose. Increasing dose of valproate, however, was associated with poorer full-scale IQ (-10.6, 95% confidence interval [CI] -16.3 to -5.0, p < 0.001), verbal abilities (-11.2, 95% CI -16.8 to -5.5, p < 0.001), nonverbal abilities (-11.1, 95% CI -17.3 to -4.9, p < 0.001), and expressive language ability (-2.3, 95% CI -3.4 to -1.6, p < 0.001). Comparisons across medications revealed poorer performance for children exposed to higher doses of valproate in comparison to children exposed to higher doses of levetiracetam or topiramate. Preconception counseling should include discussion of neurodevelopmental outcomes for specific treatments and their doses and women should be made aware of the limited nature of the evidence base for newer antiepileptic drugs.