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January 21, 2014; 82 (3) Article

In utero exposure to levetiracetam vs valproate

Development and language at 3 years of age

R. Shallcross, R.L. Bromley, C.P. Cheyne, M. García-Fiñana, B. Irwin, J. Morrow, G.A. Baker
First published January 8, 2014, DOI: https://doi.org/10.1212/WNL.0000000000000030
R. Shallcross
From the Departments of Clinical Psychology (R.S.), Molecular and Clinical Pharmacology (R.L.B., G.A.B.), and Biostatistics (C.P.C., M.G.-F.), University of Liverpool; and the Department of Neurology (B.I., J.M.), Royal Group of Hospitals, Belfast, UK.
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R.L. Bromley
From the Departments of Clinical Psychology (R.S.), Molecular and Clinical Pharmacology (R.L.B., G.A.B.), and Biostatistics (C.P.C., M.G.-F.), University of Liverpool; and the Department of Neurology (B.I., J.M.), Royal Group of Hospitals, Belfast, UK.
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C.P. Cheyne
From the Departments of Clinical Psychology (R.S.), Molecular and Clinical Pharmacology (R.L.B., G.A.B.), and Biostatistics (C.P.C., M.G.-F.), University of Liverpool; and the Department of Neurology (B.I., J.M.), Royal Group of Hospitals, Belfast, UK.
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M. García-Fiñana
From the Departments of Clinical Psychology (R.S.), Molecular and Clinical Pharmacology (R.L.B., G.A.B.), and Biostatistics (C.P.C., M.G.-F.), University of Liverpool; and the Department of Neurology (B.I., J.M.), Royal Group of Hospitals, Belfast, UK.
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B. Irwin
From the Departments of Clinical Psychology (R.S.), Molecular and Clinical Pharmacology (R.L.B., G.A.B.), and Biostatistics (C.P.C., M.G.-F.), University of Liverpool; and the Department of Neurology (B.I., J.M.), Royal Group of Hospitals, Belfast, UK.
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J. Morrow
From the Departments of Clinical Psychology (R.S.), Molecular and Clinical Pharmacology (R.L.B., G.A.B.), and Biostatistics (C.P.C., M.G.-F.), University of Liverpool; and the Department of Neurology (B.I., J.M.), Royal Group of Hospitals, Belfast, UK.
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G.A. Baker
From the Departments of Clinical Psychology (R.S.), Molecular and Clinical Pharmacology (R.L.B., G.A.B.), and Biostatistics (C.P.C., M.G.-F.), University of Liverpool; and the Department of Neurology (B.I., J.M.), Royal Group of Hospitals, Belfast, UK.
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Citation
In utero exposure to levetiracetam vs valproate
Development and language at 3 years of age
R. Shallcross, R.L. Bromley, C.P. Cheyne, M. García-Fiñana, B. Irwin, J. Morrow, G.A. Baker
Neurology Jan 2014, 82 (3) 213-221; DOI: 10.1212/WNL.0000000000000030

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Abstract

Objective: To compare the cognitive and language development of children born to women with epilepsy (WWE) exposed in utero to levetiracetam (LEV) or sodium valproate (VPA) and control children born to women without epilepsy not taking medication during pregnancy.

Methods: The children, aged between 36 and 54 months, were recruited from the United Kingdom and assessed using the Griffiths Mental Development Scales and the Reynell Language Development Scale. Maternal demographic and epilepsy information was also collected for use in statistical regression. This is an observational study with researchers not involved in the clinical management of the mothers enrolled.

Results: After controlling for confounding variables, children exposed to LEV in utero (n = 53) did not differ from unexposed control children (n = 131) on any scale administered. Children exposed to VPA (n = 44) in utero scored, on average, 15.8 points below children exposed to LEV on measures of gross motor skills (95% confidence interval [CI] −24.5 to −7.1, p < 0.001), 6.4 points below on comprehension language abilities (95% CI −11.0 to −1.8, p = 0.005), and 9.5 points below on expressive language abilities (95% CI −14.7 to −4.4, p < 0.001).

Conclusion: The current study indicates that children exposed to LEV in utero were superior in their language and motor development in comparison to children exposed to VPA. This information should be used collaboratively between health care professionals and WWE when deciding on women's preferred choice of antiepileptic drug.

GLOSSARY

AED=
antiepileptic drug;
CI=
confidence interval;
GMDS=
Griffiths Mental Development Scales;
LEV=
levetiracetam;
LMNDG=
Liverpool and Manchester Neurodevelopment Group;
RDLS=
Reynell Developmental Language Scales;
SES=
socioeconomic status;
UKEPR=
UK Epilepsy and Pregnancy Registry;
VPA=
valproate;
WWE=
women with epilepsy

Footnotes

  • Coinvestigators are listed on the Neurology® Web site at www.neurology.org.

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 194

  • Supplemental data at www.neurology.org

  • Received April 11, 2013.
  • Accepted in final form September 3, 2013.
  • © 2014 American Academy of Neurology
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