title: Cognition in school-age children exposed to levetiracetam, topiramate, or sodium valproate.
abstract: OBJECTIVE
  To investigate the effects of prenatal exposure to monotherapy levetiracetam, topiramate, and valproate on child cognitive functioning.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: From the Institute of Human Development (R.L.B. J.C.-S.), Department of Clinical Psychology (P.T.), and Centre for Women's Mental Health (R.S.), University of Manchester; Royal Manchester Children's Hospital (R.L.B.), Manchester; Department of Clinical Psychology (R.C.), University of Lancaster; Departments of Biostatistics (C.P.C., M.G.-F.) and Molecular and Clinical Pharmacology (G.A.B.), University of Liverpool; Neuropsychology Trauma Pathway (C.R.), Merseycare NHS Trust, Liverpool; Manchester Centre for Genomic Medicine (J.C.-S.), St Mary's Hospital, Manchester; and Department of Neurology (B.I., J.I.M.), Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK. Rebecca.bromley@manchester.ac.uk.
authors: Rebecca L
authors: RL
authors: Bromley
authors: From the Institute of Human Development (R.L.B. J.C.-S.), Department of Clinical Psychology (P.T.), and Centre for Women's Mental Health (R.S.), University of Manchester; Royal Manchester Children's Hospital (R.L.B.), Manchester; Department of Clinical Psychology (R.C.), University of Lancaster; Departments of Biostatistics (C.P.C., M.G.-F.) and Molecular and Clinical Pharmacology (G.A.B.), University of Liverpool; Neuropsychology Trauma Pathway (C.R.), Merseycare NHS Trust, Liverpool; Manchester Centre for Genomic Medicine (J.C.-S.), St Mary's Hospital, Manchester; and Department of Neurology (B.I., J.I.M.), Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.
authors: Rebecca
authors: R
authors: Calderbank
authors: From the Institute of Human Development (R.L.B. J.C.-S.), Department of Clinical Psychology (P.T.), and Centre for Women's Mental Health (R.S.), University of Manchester; Royal Manchester Children's Hospital (R.L.B.), Manchester; Department of Clinical Psychology (R.C.), University of Lancaster; Departments of Biostatistics (C.P.C., M.G.-F.) and Molecular and Clinical Pharmacology (G.A.B.), University of Liverpool; Neuropsychology Trauma Pathway (C.R.), Merseycare NHS Trust, Liverpool; Manchester Centre for Genomic Medicine (J.C.-S.), St Mary's Hospital, Manchester; and Department of Neurology (B.I., J.I.M.), Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.
authors: Christopher P
authors: CP
authors: Cheyne
authors: From the Institute of Human Development (R.L.B. J.C.-S.), Department of Clinical Psychology (P.T.), and Centre for Women's Mental Health (R.S.), University of Manchester; Royal Manchester Children's Hospital (R.L.B.), Manchester; Department of Clinical Psychology (R.C.), University of Lancaster; Departments of Biostatistics (C.P.C., M.G.-F.) and Molecular and Clinical Pharmacology (G.A.B.), University of Liverpool; Neuropsychology Trauma Pathway (C.R.), Merseycare NHS Trust, Liverpool; Manchester Centre for Genomic Medicine (J.C.-S.), St Mary's Hospital, Manchester; and Department of Neurology (B.I., J.I.M.), Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.
authors: Claire
authors: C
authors: Rooney
authors: From the Institute of Human Development (R.L.B. J.C.-S.), Department of Clinical Psychology (P.T.), and Centre for Women's Mental Health (R.S.), University of Manchester; Royal Manchester Children's Hospital (R.L.B.), Manchester; Department of Clinical Psychology (R.C.), University of Lancaster; Departments of Biostatistics (C.P.C., M.G.-F.) and Molecular and Clinical Pharmacology (G.A.B.), University of Liverpool; Neuropsychology Trauma Pathway (C.R.), Merseycare NHS Trust, Liverpool; Manchester Centre for Genomic Medicine (J.C.-S.), St Mary's Hospital, Manchester; and Department of Neurology (B.I., J.I.M.), Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.
authors: Penny
authors: P
authors: Trayner
authors: From the Institute of Human Development (R.L.B. J.C.-S.), Department of Clinical Psychology (P.T.), and Centre for Women's Mental Health (R.S.), University of Manchester; Royal Manchester Children's Hospital (R.L.B.), Manchester; Department of Clinical Psychology (R.C.), University of Lancaster; Departments of Biostatistics (C.P.C., M.G.-F.) and Molecular and Clinical Pharmacology (G.A.B.), University of Liverpool; Neuropsychology Trauma Pathway (C.R.), Merseycare NHS Trust, Liverpool; Manchester Centre for Genomic Medicine (J.C.-S.), St Mary's Hospital, Manchester; and Department of Neurology (B.I., J.I.M.), Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.
authors: Jill
authors: J
authors: Clayton-Smith
authors: From the Institute of Human Development (R.L.B. J.C.-S.), Department of Clinical Psychology (P.T.), and Centre for Women's Mental Health (R.S.), University of Manchester; Royal Manchester Children's Hospital (R.L.B.), Manchester; Department of Clinical Psychology (R.C.), University of Lancaster; Departments of Biostatistics (C.P.C., M.G.-F.) and Molecular and Clinical Pharmacology (G.A.B.), University of Liverpool; Neuropsychology Trauma Pathway (C.R.), Merseycare NHS Trust, Liverpool; Manchester Centre for Genomic Medicine (J.C.-S.), St Mary's Hospital, Manchester; and Department of Neurology (B.I., J.I.M.), Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.
authors: Marta
authors: M
authors: García-Fiñana
authors: From the Institute of Human Development (R.L.B. J.C.-S.), Department of Clinical Psychology (P.T.), and Centre for Women's Mental Health (R.S.), University of Manchester; Royal Manchester Children's Hospital (R.L.B.), Manchester; Department of Clinical Psychology (R.C.), University of Lancaster; Departments of Biostatistics (C.P.C., M.G.-F.) and Molecular and Clinical Pharmacology (G.A.B.), University of Liverpool; Neuropsychology Trauma Pathway (C.R.), Merseycare NHS Trust, Liverpool; Manchester Centre for Genomic Medicine (J.C.-S.), St Mary's Hospital, Manchester; and Department of Neurology (B.I., J.I.M.), Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.
authors: Beth
authors: B
authors: Irwin
authors: From the Institute of Human Development (R.L.B. J.C.-S.), Department of Clinical Psychology (P.T.), and Centre for Women's Mental Health (R.S.), University of Manchester; Royal Manchester Children's Hospital (R.L.B.), Manchester; Department of Clinical Psychology (R.C.), University of Lancaster; Departments of Biostatistics (C.P.C., M.G.-F.) and Molecular and Clinical Pharmacology (G.A.B.), University of Liverpool; Neuropsychology Trauma Pathway (C.R.), Merseycare NHS Trust, Liverpool; Manchester Centre for Genomic Medicine (J.C.-S.), St Mary's Hospital, Manchester; and Department of Neurology (B.I., J.I.M.), Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.
authors: James Irvine
authors: JI
authors: Morrow
authors: From the Institute of Human Development (R.L.B. J.C.-S.), Department of Clinical Psychology (P.T.), and Centre for Women's Mental Health (R.S.), University of Manchester; Royal Manchester Children's Hospital (R.L.B.), Manchester; Department of Clinical Psychology (R.C.), University of Lancaster; Departments of Biostatistics (C.P.C., M.G.-F.) and Molecular and Clinical Pharmacology (G.A.B.), University of Liverpool; Neuropsychology Trauma Pathway (C.R.), Merseycare NHS Trust, Liverpool; Manchester Centre for Genomic Medicine (J.C.-S.), St Mary's Hospital, Manchester; and Department of Neurology (B.I., J.I.M.), Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.
authors: Rebekah
authors: R
authors: Shallcross
authors: From the Institute of Human Development (R.L.B. J.C.-S.), Department of Clinical Psychology (P.T.), and Centre for Women's Mental Health (R.S.), University of Manchester; Royal Manchester Children's Hospital (R.L.B.), Manchester; Department of Clinical Psychology (R.C.), University of Lancaster; Departments of Biostatistics (C.P.C., M.G.-F.) and Molecular and Clinical Pharmacology (G.A.B.), University of Liverpool; Neuropsychology Trauma Pathway (C.R.), Merseycare NHS Trust, Liverpool; Manchester Centre for Genomic Medicine (J.C.-S.), St Mary's Hospital, Manchester; and Department of Neurology (B.I., J.I.M.), Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.
authors: Gus A
authors: GA
authors: Baker
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D002648:Child; D003072:Cognition Disorders / Q000139:chemically induced*; D003430:Cross-Sectional Studies; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D005500:Follow-Up Studies; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D010889:Piracetam / Q000009:adverse effects / Q000031:analogs & derivatives; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000503:physiopathology*; D000077236:Topiramate; D014635:Valproic Acid / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose; D000077287:Levetiracetam; D014635:Valproic Acid; D010889:Piracetam