Valproate and the risk for congenital malformations; is formulation and dosage regime important?

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dc.contributor.authorCampbell, J.
dc.contributor.authorCraig, John J.
dc.contributor.authorRussell, A.
dc.contributor.authorSmithson, W. Henry
dc.contributor.authorParsons, L.
dc.contributor.authorMorrison, P. J.
dc.contributor.authorLiggan, B.
dc.contributor.authorIrwin, B.
dc.contributor.authorDelanty, Norman
dc.contributor.authorHunt, S. J.
dc.contributor.authorMorrow, J.
dc.contributor.authorMawhinney, E.
dc.date.accessioned2018-10-08T10:25:01Z
dc.date.available2018-10-08T10:25:01Z
dc.date.issued2012-04
dc.date.updated2018-10-08T10:11:42Z
dc.description.abstractBackground: Use of valproate in pregnancy, especially in doses over 1000 mg a day, is known to be associated with a higher risk for major congenital malformations compared with other antiepileptic drugs. We sought to investigate whether the increased risk could be minimised by using controlled release or divided daily doses of valproate. Methods: The UK Epilepsy and Pregnancy Register is a prospective, observational and follow up study set up to determine the risks of major congenital malformations for infants exposed to antiepileptic drugs in utero. In this study we have extracted data for those pregnancies exposed to valproate in monotherapy. We have calculated malformation rates and relative risks as a function of valproate exposure. Results: Outcome data were available for 1109 pregnancies exposed to valproate in monotherapy. Exposure to 1000 mg a day or more of valproate was associated with almost double the risk of major congenital malformation compared with daily valproate doses below 1000 mg daily (8.86% vs 4.88%, RR: 1.7; 95% CI: 1.1â 2.9). There were no differences in the risks for malformations between standard release valproate and controlled release valproate preparations (RR: 1.11; 95% CI: 0.67â 1.83) or for those exposed to single or multiple daily administrations (RR: 0.99, 95% CI: 0.58â 1.70). Conclusion: Prescribing controlled release valproate or multiple daily administrations in pregnancy did not reduce the risk for malformations. Higher malformation rates observed with in utero exposure to valproate are more likely related to total daily dose, rather than peak serum levels.en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationMawhinney, E., Campbell, J., Craig, J., Russell, A., Smithson, W. Henry, Parsons, L., Morrison, P. J., Liggan, B., Irwin, B., Delanty, N., Hunt, S. J. and Morrow, J. (2012) 'Valproate and the risk for congenital malformations; is formulation and dosage regime important?', Seizure - European Journal of Epilepsy, 21(3), pp. 215-218. doi:10.1016/j.seizure.2012.01.005en
dc.identifier.doi10.1016/j.seizure.2012.01.005
dc.identifier.endpage218en
dc.identifier.issn1059-1311
dc.identifier.issued3en
dc.identifier.journaltitleSeizure -European Journal of Epilepsyen
dc.identifier.startpage215en
dc.identifier.urihttps://hdl.handle.net/10468/6989
dc.identifier.volume21en
dc.language.isoenen
dc.publisherElsevier B.V.en
dc.rights© 2012, British Epilepsy Association. Published by Elsevier Ltd. Open access under CC BY-NC-ND license.en
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectEpilepsyen
dc.subjectPregnancyen
dc.subjectAntiepileptic drugsen
dc.subjectValproateen
dc.subjectMajor congenital malformationsen
dc.titleValproate and the risk for congenital malformations; is formulation and dosage regime important?en
dc.typeArticle (peer-reviewed)en
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