{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T00:02:39Z","timestamp":1778976159279,"version":"3.51.4"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,5,16]],"date-time":"2020-05-16T00:00:00Z","timestamp":1589587200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Sodium valproate (VPA), the most effective antiepileptic drug for patients with genetic generalized epilepsy (GGE), is a potent human teratogen that increases the risk of a range of congenital malformations, including spina bifida. The mechanisms underlying this teratogenicity are not known, but may involve genetic risk factors. This study aimed to develop an animal model of VPA\u2010induced birth defects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used three different rat strains: inbred Genetic Absence Epilepsy Rats From Strasbourg (GAERS), a model of GGE with absence seizures; inbred Non\u2010Epileptic Controls (NEC); and outbred nonepileptic Wistars. Female rats were fed standard chow or VPA (20\u00a0g\/kg food) mixed in standard chow for 2\u00a0weeks prior to conception, and then mated with same\u2010strain males. Treatment continued throughout pregnancy. Fetuses were extracted via C\u2010section on gestational day 21 and examined for birth defects, including external assessment and spinal measurements.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>VPA\u2010exposed pups showed significant reductions in weight, length, and whole\u2010body development compared with controls of all three strains (<jats:italic>P\u00a0<\/jats:italic>&lt;\u00a0.0001). Gestational VPA treatment altered intravertebral distances, and resulted in underdeveloped vertebral arches between thoracic region T11 and caudal region C2 in most pups (GAERS, 100%; NEC, 95%; Wistar, 80%), more frequently than in controls (9%, 13%, 19%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Gestational VPA treatment results in similar developmental and morphological abnormalities in three rat strains, including one with GGE, indicating that the genetic underpinnings of epilepsy do not contribute markedly to VPA\u2010induced birth defects. This model may be used in future studies to investigate mechanisms involved in the pathogenesis of antiepileptic drug\u2013induced birth defects.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.16536","type":"journal-article","created":{"date-parts":[[2020,5,16]],"date-time":"2020-05-16T14:02:10Z","timestamp":1589637730000},"page":"1291-1300","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["A rat model of valproate teratogenicity from chronic oral treatment during pregnancy"],"prefix":"10.1111","volume":"61","author":[{"given":"Dana","family":"Jazayeri","sequence":"first","affiliation":[{"name":"Department of Medicine (Royal Melbourne Hospital) Melbourne Brain Centre University of Melbourne Parkville Victoria Australia"},{"name":"La Trobe Centre for Sport and Exercise Medicine Research School of Allied Health Human Services, and Sport La Trobe University Bundoora Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Braine","sequence":"additional","affiliation":[{"name":"Department of Medicine (Royal Melbourne Hospital) Melbourne Brain Centre University of Melbourne Parkville Victoria Australia"},{"name":"Department of Neuroscience Central Clinical School Monash University Melbourne Victoria Australia"},{"name":"Department of Neurology Alfred Hospital Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart","family":"McDonald","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Central Clinical School Monash University Melbourne Victoria Australia"},{"name":"Department of Neurology Alfred Hospital Melbourne Victoria Australia"},{"name":"Department of Physiology, Anatomy, and Microbiology School of Life Sciences La Trobe University Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Dworkin","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy, and Microbiology School of Life Sciences La Trobe University Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim L.","family":"Powell","sequence":"additional","affiliation":[{"name":"Department of Medicine (Royal Melbourne Hospital) Melbourne Brain Centre University of Melbourne Parkville Victoria Australia"},{"name":"Department of Neuroscience Central Clinical School Monash University Melbourne Victoria Australia"},{"name":"Department of Neurology Alfred Hospital Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Griggs","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy, and Microbiology School of Life Sciences La Trobe University Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5570-7538","authenticated-orcid":false,"given":"Frank J. 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