{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T08:40:48Z","timestamp":1767861648247,"version":"3.49.0"},"reference-count":23,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2019,5,23]],"date-time":"2019-05-23T00:00:00Z","timestamp":1558569600000},"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":["Birth Defects Research"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>To evaluate pregnancy outcomes among women participating in the antiepileptic drug (AED) Levetiracetam Registry (LEV\u2010Registry), and to review the impact of using two other registries' outcome definitions on the number of major congenital malformations (MCMs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This US\u2010based prospective study (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link> NCT00345475) was overseen by an independent Expert Panel. Women exposed to levetiracetam at any time during pregnancy enrolled, directly, or via their healthcare provider. The primary outcome was prevalence of MCMs, defined according to a modified version of the Metropolitan Atlanta Congenital Defects Program criteria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 491 women enrolled, 465 (94.7%) had a documented outcome. Most (92.3%) received levetiracetam for epilepsy; 323 (69.4%) as monotherapy and 142 (30.5%) as polytherapy. With three twin pregnancies, there were 468 outcomes\u2014444 livebirths, 3 stillbirths, 19 miscarriages, and 2 terminations. Based on the MCM definition used by LEV\u2010Registry, 46 infants among 444 livebirths had MCMs resulting in 10.4% (95% CI 7.7, 13.6) for overall prevalence, 9.4% (95% CI 6.4, 13.2) with monotherapy, and 12.6% (95% CI 7.5, 19.4) with polytherapy. When MCM reports were reviewed independently by staff at EURAP (International Registry of AEDs) and North American AED Pregnancy Registry according to their respective criteria, only 22 and 7 infants of the 46, respectively, were classified as having MCMs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The LEV\u2010Registry Expert Panel did not find evidence suggestive of teratogenic association with prenatal exposure to levetiracetam. The substantial differences in which physical findings were considered MCMs highlight the major impact of pregnancy registry methodology on MCM prevalence estimates.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.1526","type":"journal-article","created":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T03:08:27Z","timestamp":1558667307000},"page":"872-887","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Levetiracetam Pregnancy Registry: Final results and a review of the impact of registry methodology and definitions on the prevalence of major congenital malformations"],"prefix":"10.1002","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9025-3276","authenticated-orcid":false,"given":"Angela E.","family":"Scheuerle","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Genetics and Metabolism University of Texas Southwestern Medical Center  Dallas Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0259-4848","authenticated-orcid":false,"given":"Lewis B.","family":"Holmes","sequence":"additional","affiliation":[{"name":"North American AED Pregnancy Registry MassGeneral Hospital for Children  Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica D.","family":"Albano","sequence":"additional","affiliation":[{"name":"Syneos Health (previously INC Research) Real World &amp; Late Phase  Raleigh North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Badalamenti","sequence":"additional","affiliation":[{"name":"UCB Pharma  Raleigh North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dina","family":"Battino","sequence":"additional","affiliation":[{"name":"Epilepsy Center, Department of Neurophysiology and Experimental Epileptology, IRCCS Besta Neurological Institute Foundation  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"Covington","sequence":"additional","affiliation":[{"name":"Evidera, Real World Evidence  Wilmington North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia","family":"Harden","sequence":"additional","affiliation":[{"name":"Department of Neurology Mount Sinai Health System  New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Miller","sequence":"additional","affiliation":[{"name":"UCB Pharma  Raleigh North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgia D.","family":"Montouris","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine  Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Pantaleoni","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurology Besta Neurological Institute Foundation  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Thorp","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of North Carolina  Chapel Hill North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azita","family":"Tofighy","sequence":"additional","affiliation":[{"name":"Synthesis  London United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Torbj\u00f6rn","family":"Tomson","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience Karolinska Institute  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda K.","family":"Golembesky","sequence":"additional","affiliation":[{"name":"UCB Pharma  Raleigh North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,5,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12302"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-4475-7"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.10111"},{"key":"e_1_2_10_5_1","volume-title":"Guidance for industry: Establishing pregnancy exposure registries","author":"Food and Drug Administration","year":"2002"},{"key":"e_1_2_10_6_1","volume-title":"Guidance for industry: Good pharmacovigilance practices and pharmacoepidemiologic assessment","author":"Food and Drug Administration","year":"2005"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182574f39"},{"key":"e_1_2_10_8_1","first-page":"S585","article-title":"International pregnancy registries for antiepileptic drug use","volume":"5","author":"Holmes L. 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