Declining malformation rates with changed antiepileptic drug prescribing: An observational study

Autores
Tomson, Torbjörn; Battino, Dina; Thomas, Sanjeev V.; Vajda, Frank; Kochen, Sara Silvia; Craig, John; Binozzoni, Erminio; Lindhout, Dick; Perucca, Emilio; Sabers, Anne
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objective Changes in prescribing patterns of antiepileptic drugs (AEDs) in pregnant women with epilepsy would be expected to affect the risk of major congenital malformations (MCMs). To test this hypothesis, we analyzed data from an international pregnancy registry (EURAP). Methods EURAP is an observational prospective cohort study designed to determine the risk of MCMs after prenatal exposure to AEDs. The Cochrane-Armitage linear trend analysis was used to assess changes in AED treatment, prevalence of MCMs, and occurrence of generalized tonic-clonic seizures (GTCs) over 3 time periods: 2000–2005 (n = 4,760), 2006–2009 (n = 3,599), and 2010–2013 (n = 2,949). Results There were pronounced changes in the use of specific AEDs over time, with a decrease in the use of valproic acid and carbamazepine and an increase in the use of lamotrigine and levetiracetam. The prevalence of MCMs with monotherapy exposure decreased from 6.0% in 2000–2005 to 4.4% in 2010–2013. The change over time in MCM frequency after monotherapy exposure showed a significant linear trend in the crude analysis (p = 0.0087), which was no longer present after adjustment for changes in AED treatment (p = 0.9923). There was no indication of an increase over time in occurrence of GTCs during pregnancy. Conclusions There have been major changes in AED prescription patterns over the years covered by the study. In parallel, we observed a significant 27% decrease in the prevalence of MCMs. The results of adjusting the trend analysis for MCMs for changes in AED treatment suggest that changes in prescription patterns played a major role in the reduction of teratogenic events.
Fil: Tomson, Torbjörn. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Battino, Dina. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Thomas, Sanjeev V.. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Vajda, Frank. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Kochen, Sara Silvia. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentina. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentina
Fil: Craig, John. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Binozzoni, Erminio. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Lindhout, Dick. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Perucca, Emilio. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Sabers, Anne. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Materia
Epilepsia
Neurologia
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/121432
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/121432
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Declining malformation rates with changed antiepileptic drug prescribing: An observational studyTomson, TorbjörnBattino, DinaThomas, Sanjeev V.Vajda, FrankKochen, Sara SilviaCraig, JohnBinozzoni, ErminioLindhout, DickPerucca, EmilioSabers, AnneEpilepsiaNeurologiahttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Objective Changes in prescribing patterns of antiepileptic drugs (AEDs) in pregnant women with epilepsy would be expected to affect the risk of major congenital malformations (MCMs). To test this hypothesis, we analyzed data from an international pregnancy registry (EURAP). Methods EURAP is an observational prospective cohort study designed to determine the risk of MCMs after prenatal exposure to AEDs. The Cochrane-Armitage linear trend analysis was used to assess changes in AED treatment, prevalence of MCMs, and occurrence of generalized tonic-clonic seizures (GTCs) over 3 time periods: 2000–2005 (n = 4,760), 2006–2009 (n = 3,599), and 2010–2013 (n = 2,949). Results There were pronounced changes in the use of specific AEDs over time, with a decrease in the use of valproic acid and carbamazepine and an increase in the use of lamotrigine and levetiracetam. The prevalence of MCMs with monotherapy exposure decreased from 6.0% in 2000–2005 to 4.4% in 2010–2013. The change over time in MCM frequency after monotherapy exposure showed a significant linear trend in the crude analysis (p = 0.0087), which was no longer present after adjustment for changes in AED treatment (p = 0.9923). There was no indication of an increase over time in occurrence of GTCs during pregnancy. Conclusions There have been major changes in AED prescription patterns over the years covered by the study. In parallel, we observed a significant 27% decrease in the prevalence of MCMs. The results of adjusting the trend analysis for MCMs for changes in AED treatment suggest that changes in prescription patterns played a major role in the reduction of teratogenic events.Fil: Tomson, Torbjörn. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Battino, Dina. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Thomas, Sanjeev V.. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Vajda, Frank. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Kochen, Sara Silvia. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentina. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; ArgentinaFil: Craig, John. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Binozzoni, Erminio. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Lindhout, Dick. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Perucca, Emilio. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Sabers, Anne. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaNLM (Medline)2019-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/121432Tomson, Torbjörn; Battino, Dina; Thomas, Sanjeev V.; Vajda, Frank; Kochen, Sara Silvia; et al.; Declining malformation rates with changed antiepileptic drug prescribing: An observational study; NLM (Medline); Neurology; 93; 9; 8-2019; 831-8401526-632XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1212/WNL.0000000000008001info:eu-repo/semantics/altIdentifier/url/https://n.neurology.org/content/93/9/e831.longinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:58:51Zoai:ri.conicet.gov.ar:11336/121432instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:58:51.642CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Declining malformation rates with changed antiepileptic drug prescribing: An observational study
title Declining malformation rates with changed antiepileptic drug prescribing: An observational study
spellingShingle Declining malformation rates with changed antiepileptic drug prescribing: An observational study
Tomson, Torbjörn
Epilepsia
Neurologia
title_short Declining malformation rates with changed antiepileptic drug prescribing: An observational study
title_full Declining malformation rates with changed antiepileptic drug prescribing: An observational study
title_fullStr Declining malformation rates with changed antiepileptic drug prescribing: An observational study
title_full_unstemmed Declining malformation rates with changed antiepileptic drug prescribing: An observational study
title_sort Declining malformation rates with changed antiepileptic drug prescribing: An observational study
dc.creator.none.fl_str_mv Tomson, Torbjörn
Battino, Dina
Thomas, Sanjeev V.
Vajda, Frank
Kochen, Sara Silvia
Craig, John
Binozzoni, Erminio
Lindhout, Dick
Perucca, Emilio
Sabers, Anne
author Tomson, Torbjörn
author_facet Tomson, Torbjörn
Battino, Dina
Thomas, Sanjeev V.
Vajda, Frank
Kochen, Sara Silvia
Craig, John
Binozzoni, Erminio
Lindhout, Dick
Perucca, Emilio
Sabers, Anne
author_role author
author2 Battino, Dina
Thomas, Sanjeev V.
Vajda, Frank
Kochen, Sara Silvia
Craig, John
Binozzoni, Erminio
Lindhout, Dick
Perucca, Emilio
Sabers, Anne
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Epilepsia
Neurologia
topic Epilepsia
Neurologia
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Objective Changes in prescribing patterns of antiepileptic drugs (AEDs) in pregnant women with epilepsy would be expected to affect the risk of major congenital malformations (MCMs). To test this hypothesis, we analyzed data from an international pregnancy registry (EURAP). Methods EURAP is an observational prospective cohort study designed to determine the risk of MCMs after prenatal exposure to AEDs. The Cochrane-Armitage linear trend analysis was used to assess changes in AED treatment, prevalence of MCMs, and occurrence of generalized tonic-clonic seizures (GTCs) over 3 time periods: 2000–2005 (n = 4,760), 2006–2009 (n = 3,599), and 2010–2013 (n = 2,949). Results There were pronounced changes in the use of specific AEDs over time, with a decrease in the use of valproic acid and carbamazepine and an increase in the use of lamotrigine and levetiracetam. The prevalence of MCMs with monotherapy exposure decreased from 6.0% in 2000–2005 to 4.4% in 2010–2013. The change over time in MCM frequency after monotherapy exposure showed a significant linear trend in the crude analysis (p = 0.0087), which was no longer present after adjustment for changes in AED treatment (p = 0.9923). There was no indication of an increase over time in occurrence of GTCs during pregnancy. Conclusions There have been major changes in AED prescription patterns over the years covered by the study. In parallel, we observed a significant 27% decrease in the prevalence of MCMs. The results of adjusting the trend analysis for MCMs for changes in AED treatment suggest that changes in prescription patterns played a major role in the reduction of teratogenic events.
Fil: Tomson, Torbjörn. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Battino, Dina. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Thomas, Sanjeev V.. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Vajda, Frank. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Kochen, Sara Silvia. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentina. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentina
Fil: Craig, John. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Binozzoni, Erminio. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Lindhout, Dick. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Perucca, Emilio. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Sabers, Anne. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
description Objective Changes in prescribing patterns of antiepileptic drugs (AEDs) in pregnant women with epilepsy would be expected to affect the risk of major congenital malformations (MCMs). To test this hypothesis, we analyzed data from an international pregnancy registry (EURAP). Methods EURAP is an observational prospective cohort study designed to determine the risk of MCMs after prenatal exposure to AEDs. The Cochrane-Armitage linear trend analysis was used to assess changes in AED treatment, prevalence of MCMs, and occurrence of generalized tonic-clonic seizures (GTCs) over 3 time periods: 2000–2005 (n = 4,760), 2006–2009 (n = 3,599), and 2010–2013 (n = 2,949). Results There were pronounced changes in the use of specific AEDs over time, with a decrease in the use of valproic acid and carbamazepine and an increase in the use of lamotrigine and levetiracetam. The prevalence of MCMs with monotherapy exposure decreased from 6.0% in 2000–2005 to 4.4% in 2010–2013. The change over time in MCM frequency after monotherapy exposure showed a significant linear trend in the crude analysis (p = 0.0087), which was no longer present after adjustment for changes in AED treatment (p = 0.9923). There was no indication of an increase over time in occurrence of GTCs during pregnancy. Conclusions There have been major changes in AED prescription patterns over the years covered by the study. In parallel, we observed a significant 27% decrease in the prevalence of MCMs. The results of adjusting the trend analysis for MCMs for changes in AED treatment suggest that changes in prescription patterns played a major role in the reduction of teratogenic events.
publishDate 2019
dc.date.none.fl_str_mv 2019-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/121432
Tomson, Torbjörn; Battino, Dina; Thomas, Sanjeev V.; Vajda, Frank; Kochen, Sara Silvia; et al.; Declining malformation rates with changed antiepileptic drug prescribing: An observational study; NLM (Medline); Neurology; 93; 9; 8-2019; 831-840
1526-632X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/121432
identifier_str_mv Tomson, Torbjörn; Battino, Dina; Thomas, Sanjeev V.; Vajda, Frank; Kochen, Sara Silvia; et al.; Declining malformation rates with changed antiepileptic drug prescribing: An observational study; NLM (Medline); Neurology; 93; 9; 8-2019; 831-840
1526-632X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1212/WNL.0000000000008001
info:eu-repo/semantics/altIdentifier/url/https://n.neurology.org/content/93/9/e831.long
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv NLM (Medline)
publisher.none.fl_str_mv NLM (Medline)
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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