{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:35:45Z","timestamp":1790825745730,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T00:00:00Z","timestamp":1559692800000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Stichting Panta Rhei"},{"name":"Christelijke Vereniging voor de Verpleging van Lijders aan Epilepsie"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To examine the behavioral functioning of children prenatally exposed to carbamazepine (<jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content>), lamotrigine (<jats:styled-content style=\"fixed-case\">LTG<\/jats:styled-content>), levetiracetam (<jats:styled-content style=\"fixed-case\">LEV<\/jats:styled-content>), or valproate (VPA) monotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In collaboration with the European Registry of Antiepileptic Drugs and Pregnancy (<jats:styled-content style=\"fixed-case\">EURAP<\/jats:styled-content>), the Dutch <jats:styled-content style=\"fixed-case\">EURAP<\/jats:styled-content> &amp; Development study was designed, a prospective observational study. Between January 2015 and March 2018, the Child Behavior Checklist and the Social Emotional Questionnaire were used to examine the nature and severity of behavioral problems. VPA\u2010exposed children were compared to children exposed to CBZ, LTG, or LEV, taking potential confounders into account. A direct comparison was also made between LTG and LEV, as these are first\u2010choice treatments for many women with epilepsy of childbearing potential.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 405 invited, 181 children were included; 26 were exposed to VPA, 37 to <jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content>, 88 to <jats:styled-content style=\"fixed-case\">LTG<\/jats:styled-content>, and 30 to LEV. For most children, both parents completed the behavioral questionnaires. Across all four antiepileptic drug (<jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>) exposure groups, high percentages of children with clinically relevant behavior problems were found, with behavioral problems occurring in 32% of <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>\u2010exposed children, 14% of <jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content>, 16% of <jats:styled-content style=\"fixed-case\">LTG<\/jats:styled-content>, and 14% of <jats:styled-content style=\"fixed-case\">LEV<\/jats:styled-content>. After controlling for potential confounders, VPA\u2010exposed children had significantly more social problems than those exposed to <jats:styled-content style=\"fixed-case\">LTG<\/jats:styled-content> (\u22122.8, 95% confidence interval [<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>] = \u22125.2 to \u22120.4; <jats:italic>P\u00a0<\/jats:italic>= 0.022) or <jats:styled-content style=\"fixed-case\">LEV<\/jats:styled-content> (\u22123.2, <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: \u22126.1 to \u22120.3; <jats:italic>P\u00a0<\/jats:italic>= 0.028), and significantly more attention problems than <jats:styled-content style=\"fixed-case\">LEV<\/jats:styled-content>\u2010exposed children (\u22123.7, <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: \u22126.7 to \u22120.8; <jats:italic>P\u00a0<\/jats:italic>= 0.013). <jats:styled-content style=\"fixed-case\">LTG<\/jats:styled-content>\u2010exposed children had significantly more attention deficit (\u22129.2, <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: \u221217.3 to 1.1; <jats:italic>P\u00a0<\/jats:italic>= 0.026), but significantly less anxious behavior when compared to <jats:styled-content style=\"fixed-case\">LEV<\/jats:styled-content>\u2010exposed children (9.0, <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 0.3\u201017.6; <jats:italic>P\u00a0<\/jats:italic>= 0.042).<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Compared to population norms, a high proportion of children of mothers with epilepsy exposed prenatally to monotherapy with four common <jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>s had clinical behavioral problems reported by parents. Different patterns were seen, with some but not all subscales raised for all <jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content> exposure groups. It is important that prenatally <jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>\u2010exposed children are regularly screened for behavioral problems so that appropriate help can be provided.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.15968","type":"journal-article","created":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T11:18:16Z","timestamp":1559733496000},"page":"1069-1082","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Behavioral problems in children of mothers with epilepsy prenatally exposed to valproate, carbamazepine, lamotrigine, or levetiracetam monotherapy"],"prefix":"10.1111","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0623-1929","authenticated-orcid":false,"given":"Yfke","family":"Huber\u2010Mollema","sequence":"first","affiliation":[{"name":"Stichting Epilepsie Instellingen Nederland (SEIN) Heemstede The Netherlands"},{"name":"Research Institute of Child Development and Education University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans J.","family":"Oort","sequence":"additional","affiliation":[{"name":"Research Institute of Child Development and Education University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9580-624X","authenticated-orcid":false,"given":"Dick","family":"Lindhout","sequence":"additional","affiliation":[{"name":"Stichting Epilepsie Instellingen Nederland (SEIN) Heemstede The Netherlands"},{"name":"Department of Genetics University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4288-1737","authenticated-orcid":false,"given":"Roos","family":"Rodenburg","sequence":"additional","affiliation":[{"name":"Stichting Epilepsie Instellingen Nederland (SEIN) Heemstede The 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