{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:36:03Z","timestamp":1790825763680,"version":"4.1.0"},"reference-count":46,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"\n Importance<\/jats:title>\n Antiseizure medications (ASMs) are potential teratogens commonly prescribed for multiple indications. ASM fetal exposure can impair neurodevelopment. Folate improves pregnancy outcomes, but higher doses may pose risks.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To compare the outcomes of 6-year-old children of women with epilepsy (WWE) vs those of healthy women (HW), and assess the association of outcomes to third-trimester ASM exposures.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n After informed consent, pregnant WWE and HW were enrolled from 2012 through 2016 in this prospective, multicenter, nonrandomized clinical trial. Children were assessed at 6 years of age (2019-2022). Participants were recruited from 20 US epilepsy centers. Study data were analyzed from August 2023 to August 2024.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Fetal ASM exposures.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The a priori main neurodevelopmental outcome was the blindly assessed Verbal Index Score in 6-year-old children. The Verbal Index Score is calculated as the mean of the scores from the Word Definitions and Verbal Similarities subtests from the Differential Ability Scales, Expressive One-Word Picture Vocabulary Test, Phonological Processing, Comprehension of Instructions, and Sentence Repetition subtests from the Neuropsychological Assessment and Peabody Picture Vocabulary Test. The 2 primary analyses (1) compared children of WWE and HW using linear regression and (2) examined the outcomes of fetal exposure via ASM blood concentrations. Analyses were adjusted for multiple potential confounding factors. Other outcomes and folate exposure-related outcomes were assessed.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 1123 pregnant women were screened, and 456 were enrolled (426 did not meet criteria, and 241 chose not to participate). A total of 298 children of WWE (mean [SD] age, 6.4 [4.2] years; 158 female [53.0%]; 140 male [47.0%]) vs 89 children of HW (mean [SD] age, 6.4 [4.2] years; 41 female [46.1%]; 48 male [53.9%]) did not differ on Verbal Index Score (parameter estimate, \u22120.6; 95% CI, \u22123.2 to 1.9;\n P<\/jats:italic>\n \u2009=\u2009.64). Exposure-dependent outcomes differed across ASMs. Assessment of other ASMs was limited because 232 of 298 WWE (78%) were taking lamotrigine or levetiracetam alone or in combination. Folate supplementation during the first 12 weeks of pregnancy had positive associations with cognition and behavior with no signal for risks at higher folate doses.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n Results of this prospective nonrandomized clinical trial suggest that verbal abilities in children of WWE vs HW did not differ. Exposure-dependent outcomes of ASMs highlight the importance of dosing high enough to protect the mother and fetus from seizures but low enough to protect the fetus. Folate supplementation early in pregnancy including higher doses was associated with improved cognitive and behavioral outcomes. Additional research is needed for ASMs with inadequate information on fetal exposure risks.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT01730170<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaneurol.2024.3982","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T11:32:24Z","timestamp":1732534344000},"page":"30","source":"Crossref","is-referenced-by-count":25,"title":["Neuropsychological Outcomes in 6-Year-Old Children of Women With Epilepsy"],"prefix":"10.1001","volume":"82","author":[{"given":"Kimford J.","family":"Meador","sequence":"first","affiliation":[{"name":"Department of Neurology & Neurological Sciences, Stanford Neuroscience Health Center, Stanford University School of Medicine, Palo Alto, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morris J.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Pediatric Neuropsychology International, Augusta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Loring","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail G.","family":"Matthews","sequence":"additional","affiliation":[{"name":"The Emmes Company, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie","family":"Brown","sequence":"additional","affiliation":[{"name":"The Emmes Company, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea P.","family":"Robalino","sequence":"additional","affiliation":[{"name":"The Emmes Company, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Carmack","sequence":"additional","affiliation":[{"name":"The Emmes Company, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela K.","family":"Birnbaum","sequence":"additional","affiliation":[{"name":"University of Minnesota, Minneapolis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula E.","family":"Voinescu","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth E.","family":"Gerard","sequence":"additional","affiliation":[{"name":"Northwestern University, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Kalayjian","sequence":"additional","affiliation":[{"name":"University of Southern California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan R.","family":"Gedzelman","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Hanna","sequence":"additional","affiliation":[{"name":"Minnesota Epilepsy Group, Roseville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Cavitt","sequence":"additional","affiliation":[{"name":"University of Cincinnati, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Sam","sequence":"additional","affiliation":[{"name":"Wake Forest University, Winston-Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Hwang","sequence":"additional","affiliation":[{"name":"Northwell Health, Great Neck, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison M.","family":"Pack","sequence":"additional","affiliation":[{"name":"Columbia University, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline A.","family":"French","sequence":"additional","affiliation":[{"name":"New York University Comprehensive Epilepsy Center, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey J.","family":"Tsai","sequence":"additional","affiliation":[{"name":"University of Washington, Seattle"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cora","family":"Taylor","sequence":"additional","affiliation":[{"name":"Geisinger Medical Center, Danville, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Page B.","family":"Pennell","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) Investigator Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"3","key":"noi240072r1","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/0892-0362(90)90092-Q","article-title":"Developmental neurotoxicity of anticonvulsants: human and animal evidence on phenytoin.","volume":"12","author":"Adams","year":"1990","journal-title":"Neurotoxicol Teratol"},{"issue":"16","key":"noi240072r2","doi-asserted-by":"publisher","first-page":"1597","DOI":"10.1056\/NEJMoa0803531","article-title":"Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs.","volume":"360","author":"Meador","year":"2009","journal-title":"N Engl J Med"},{"issue":"3","key":"noi240072r3","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/S1474-4422(12)70323-X","article-title":"Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study.","volume":"12","author":"Meador","year":"2013","journal-title":"Lancet Neurol"},{"key":"noi240072r5","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.yebeh.2018.04.009","article-title":"Changes in antiepileptic drug-prescribing patterns in pregnant women with epilepsy.","volume":"84","author":"Meador","year":"2018","journal-title":"Epilepsy Behav"},{"issue":"10","key":"noi240072r6","doi-asserted-by":"publisher","first-page":"e1083","DOI":"10.1212\/WNL.0000000000207580","article-title":"Utilization of antiseizure medications in women of childbearing age with epilepsy and nonepilepsy indications: a retrospective cohort study.","volume":"101","author":"Lawal","year":"2023","journal-title":"Neurology"},{"issue":"4","key":"noi240072r7","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1016\/j.ncl.2022.03.006","article-title":"Effects of maternal use of antiseizure medications on child development.","volume":"40","author":"Meador","year":"2022","journal-title":"Neurol Clin"},{"issue":"7","key":"noi240072r8","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1055\/a-1788-4791","article-title":"The obstetrical care and delivery experience of women with epilepsy in the MODEAD Study.","volume":"41","author":"McElrath","year":"2024","journal-title":"Am J Perinatol"},{"issue":"26","key":"noi240072r9","doi-asserted-by":"publisher","first-page":"2547","DOI":"10.1056\/NEJMoa2008663","article-title":"Changes in seizure frequency and antiepileptic therapy during pregnancy.","volume":"383","author":"Pennell","year":"2020","journal-title":"N Engl J Med"},{"issue":"4","key":"noi240072r10","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1001\/jamaneurol.2021.5487","article-title":"Antiseizure medication concentrations during pregnancy: results from the maternal outcomes and neurodevelopmental effects of antiepileptic drugs (MONEAD) study.","volume":"79","author":"Pennell","year":"2022","journal-title":"JAMA Neurol"},{"issue":"15","key":"noi240072r11","doi-asserted-by":"publisher","first-page":"e1573","DOI":"10.1212\/WNL.0000000000200958","article-title":"Prospective cohort study of depression during pregnancy and the postpartum period in women with epilepsy vs control groups.","volume":"99","author":"Meador","year":"2022","journal-title":"Neurology"},{"issue":"1","key":"noi240072r12","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1001\/jamaneurol.2023.4315","article-title":"Behavioral outcomes and neurodevelopmental disorders among children of women with epilepsy.","volume":"81","author":"Cohen","year":"2024","journal-title":"JAMA Neurol"},{"issue":"8","key":"noi240072r13","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1016\/S1474-4422(23)00199-0","article-title":"Cognitive outcomes at age 3 years in children with fetal exposure to antiseizure medications (MONEAD study) in the USA: a prospective, observational cohort study.","volume":"22","author":"Meador","year":"2023","journal-title":"Lancet Neurol"},{"issue":"8","key":"noi240072r14","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1001\/jamaneurol.2021.1583","article-title":"Two-year-old cognitive outcomes in children of pregnant women with epilepsy in the maternal outcomes and neurodevelopmental effects of antiepileptic drugs study.","volume":"78","author":"Meador","year":"2021","journal-title":"JAMA Neurol"},{"issue":"14","key":"noi240072r15","doi-asserted-by":"publisher","first-page":"e1502","DOI":"10.1212\/WNL.0000000000008687","article-title":"Fetal loss and malformations in the MONEAD study of pregnant women with epilepsy.","volume":"94","author":"Meador","year":"2020","journal-title":"Neurology"},{"issue":"12","key":"noi240072r16","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000209448","article-title":"Association of prenatal exposure to antiseizure medications with creative and executive function at age 4.5 years.","volume":"102","author":"Meador","year":"2024","journal-title":"Neurology"},{"issue":"2","key":"noi240072r17","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1001\/jamaneurol.2017.3897","article-title":"Association of folic acid supplementation during pregnancy with the risk of autistic traits in children exposed to antiepileptic drugs in utero.","volume":"75","author":"Bj\u00f8rk","year":"2018","journal-title":"JAMA Neurol"},{"issue":"9","key":"noi240072r18","doi-asserted-by":"publisher","first-page":"e811","DOI":"10.1212\/WNL.0000000000006073","article-title":"Verbal abilities in children of mothers with epilepsy: association to maternal folate status.","volume":"91","author":"Husebye","year":"2018","journal-title":"Neurology"},{"issue":"9","key":"noi240072r19","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1093\/nutrit\/nuy025","article-title":"Maternal oversupplementation with folic acid and its impact on neurodevelopment of offspring.","volume":"76","author":"Murray","year":"2018","journal-title":"Nutr Rev"},{"issue":"Pt 2","key":"noi240072r20","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1093\/brain\/awq352","article-title":"Foetal antiepileptic drug exposure and verbal vs nonverbal abilities at 3 years of age.","volume":"134","author":"Meador","year":"2011","journal-title":"Brain"},{"issue":"1","key":"noi240072r35","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/0378-3782(79)90022-7","article-title":"Comparative aspects of the brain growth spurt.","volume":"3","author":"Dobbing","year":"1979","journal-title":"Early Hum Dev"},{"issue":"4","key":"noi240072r38","doi-asserted-by":"publisher","first-page":"385","DOI":"10.2307\/2136404","article-title":"A global measure of perceived stress.","volume":"24","author":"Cohen","year":"1983","journal-title":"J Health Soc Behav"},{"issue":"3","key":"noi240072r39","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/S0022-3999(02)00330-6","article-title":"Test-retest reliability and validity of the Pittsburgh Sleep Quality Index in primary insomnia.","volume":"53","author":"Backhaus","year":"2002","journal-title":"J Psychosom Res"},{"issue":"11","key":"noi240072r40","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1001\/jamaneurol.2013.4290","article-title":"Early child development and exposure to antiepileptic drugs prenatally and through breastfeeding: a prospective cohort study on children of women with epilepsy.","volume":"70","author":"Veiby","year":"2013","journal-title":"JAMA Neurol"},{"issue":"8","key":"noi240072r41","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1001\/jamapediatrics.2014.118","article-title":"Breastfeeding in children of women taking antiepileptic drugs: cognitive outcomes at age 6 years.","volume":"168","author":"Meador","year":"2014","journal-title":"JAMA Pediatr"},{"issue":"4","key":"noi240072r42","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1001\/jamaneurol.2019.4443","article-title":"Antiepileptic drug exposure in infants of breastfeeding mothers with epilepsy.","volume":"77","author":"Birnbaum","year":"2020","journal-title":"JAMA Neurol"},{"issue":"11","key":"noi240072r43","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1001\/jamapediatrics.2020.3080","article-title":"Association of prenatal acetaminophen exposure measured in meconium with risk of attention-deficit\/hyperactivity disorder mediated by frontoparietal network brain connectivity.","volume":"174","author":"Baker","year":"2020","journal-title":"JAMA Pediatr"},{"issue":"12","key":"noi240072r44","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1177\/1060028015606469","article-title":"Association between prenatal acetaminophen exposure and future risk of attention deficit\/hyperactivity disorder in children.","volume":"49","author":"Hoover","year":"2015","journal-title":"Ann Pharmacother"},{"issue":"2","key":"noi240072r45","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1001\/jamapsychiatry.2019.3259","article-title":"Association of cord plasma biomarkers of in utero acetaminophen exposure with risk of attention-deficit\/hyperactivity disorder and autism spectrum disorder in childhood.","volume":"77","author":"Ji","year":"2020","journal-title":"JAMA Psychiatry"},{"issue":"6","key":"noi240072r46","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1097\/EDE.0000000000000540","article-title":"Prenatal use of acetaminophen and child IQ: a Danish cohort study.","volume":"27","author":"Liew","year":"2016","journal-title":"Epidemiology"},{"key":"noi240072r21","volume-title":"Differential Ability Scales","author":"Elliott","year":"2007","edition":"2nd ed"},{"key":"noi240072r22","volume-title":"Expressive One-Word Picture Vocabulary Test\u2013Fourth Edition (EOWPVT-4)","author":"Martin","year":"2010"},{"key":"noi240072r23","volume-title":"NEPSY-II: A Developmental Neuropsychological Assessment","author":"Korkman","year":"2007"},{"key":"noi240072r24","volume-title":"Peabody Picture Vocabulary Test","author":"Dunn","year":"2007","edition":"4th ed"},{"key":"noi240072r25","volume-title":"Developmental Test of Visuo-Motor Integration","author":"Beery","year":"2004","edition":"5th ed"},{"key":"noi240072r26","volume-title":"The Children\u2019s Memory Scale","author":"Cohen","year":"1997"},{"key":"noi240072r27","volume-title":"Behavior Rating Inventory of Executive Function","author":"Gioia","year":"2015","edition":"2nd ed"},{"key":"noi240072r28","volume-title":"Neuropsychological Test Manual","author":"Trites","year":"1977"},{"key":"noi240072r29","volume-title":"Wechsler Intelligence Scale for Children","author":"Wechsler","year":"2003","edition":"4th ed"},{"key":"noi240072r30","volume-title":"Adaptive Behavior Assessment System - II","author":"Harrison","year":"2003"},{"key":"noi240072r31","volume-title":"Behavior Assessment System for Children","author":"Reynolds","year":"2004","edition":"2nd ed"},{"key":"noi240072r32","volume-title":"Social Responsiveness Scale","author":"Constantino","year":"2012","edition":"2nd ed"},{"key":"noi240072r33","volume-title":"Parenting Stress Index","author":"Abidin","year":"1990","edition":"3rd ed"},{"key":"noi240072r34","volume-title":"Wide Range Achievement Test","author":"Wilkinson","year":"2006","edition":"4th ed"},{"key":"noi240072r36","volume-title":"Beck Depression Inventory Manual\u2013Revised","author":"Beck","year":"1996"},{"key":"noi240072r37","volume-title":"Beck Anxiety Inventory (BAI)","author":"Beck","year":"1990"},{"key":"noi240072r4","unstructured":"US Food and Drug Adminisration. FDA Drug safety communication: children born to mothers who took Valproate products while pregnant may have impaired cognitive development. Accessed June 20, 2023. https:\/\/www.fda.gov\/drugs\/drug-safety-and-availability\/fda-drug-safety-communication-children-born-mothers-who-took-valproate-products-while-pregnant-may"}],"container-title":["JAMA Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaneurology\/articlepdf\/2827125\/jamaneurology_meador_2024_oi_240072_1735932284.06304.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T11:02:05Z","timestamp":1736766125000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaneurology\/fullarticle\/2827125"}},"subtitle":["A Prospective Nonrandomized Clinical Trial"],"short-title":[],"issued":{"date-parts":[[2025,1,1]]},"references-count":46,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaneurol.2024.3982","relation":{},"ISSN":["2168-6149"],"issn-type":[{"value":"2168-6149","type":"print"}],"subject":[],"published":{"date-parts":[[2025,1,1]]}}}