Behavioral Outcomes and Neurodevelopmental Disorders Among Children of Women With Epilepsy
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Published:2024-01-01
Issue:1
Volume:81
Page:19
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ISSN:2168-6149
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Container-title:JAMA Neurology
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language:en
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Short-container-title:JAMA Neurol
Author:
Cohen Morris J.1, Meador Kimford J.2, Loring David W.3, Matthews Abigail G.45, Brown Carrie45, Robalino Chelsea P.45, Birnbaum Angela K.6, Voinescu Paula E.7, Kalayjian Laura A.8, Gerard Elizabeth E.9, Gedzelman Evan R.3, Hanna Julie10, Cavitt Jennifer11, Sam Maria C.12, French Jacqueline A.13, Hwang Sean T.14, Pack Alison M.15, Pennell Page B.16, Druzin Maurice17, Finnell Richard17, Holmes Gregory17, McElrath Frederick T.17, Nelson Lorene17, Stowe Zachary17, Van Marter Linda17, Wells Peter17, Yerby Mark17, Moore Eugene17, May Ryan17, Ippolito Dominic17, Skinner Julia17, Davis Lisa17, Shah Nilay17, Leung Brenda17, Friedman Mark17, Loblein Hayley17, Sheer Traci17, Wang Yue17, Browning Nancy17, Arias Michelle17, Ayre Rebecca17, Blalock Temperance17, Hendrickson Linda17, Mathew Merin17, Nair Anjali17, Ogunsola Yinka17, Ott Chinh17, Zaia Renehan Phyllis17, Romano Sarah17, Schutte Dominic17, Shore Noble17, Vasudevan Vydhi17, Wilson Steffanie17, Winestone Jamie17, Zajdowicz Thad17, Strickland Suzanne17, Latif Erin17, Park Yong17, Acosta-Cotte Delmaris17, Ray Patty17, Cleary Kirsten17, Echo Joyce17, Zygmunt Annette17, Casadei Camilla17, Irobunda Ifemoa17, Chessky Anna17, Dolan Mary17, Ono Kim17, Bearden Donald17, Ghilian Christine17, Teagarden Diane17, Newman Melanee17, Bamps Yvan17, Wehunt Emilee17, McCabe Paul17, Paglia Michael17, Taylor Cora17, Delucca Rosemarie17, Blessing Kristina17, Dopko Joshua17, Boyer Katrina17, Hanson Ellen17, Young Amy17, Hickey Paige17, Strauss Jolie17, Madeiros Hayley17, Rozumny Brian17, Chen Li17, Allien Stephanie17, Sheldon Yvonne17, Weinau Taylor17, Shashkova Elizabeth17, Choe Melanie17, Barkley Gregory L.17, Spanaki-Varelas Marianna17, Thomas Andrea17, Constantinou Jules17, Mahmood Nazin17, Wasade Vibhangini17, Gaddam Shailaja17, Zillgitt Andrew17, Anwar Taimur17, Sandles Carla17, Holmes Theresa17, Johnson Emily17, Krauss Gregory17, Lawson Shari17, Pritchard Alison17, Ryan Matthew17, Coe Pam17, Reger Katie17, Pohlman Jenny17, Olson Alisha17, Steele Anna17, Lange Hadley17, Chang Patricia17, Ellis Sarah17, Schweizer William17, Morrison Chris17, MacAllister William17, Clements Tobi17, Riley Edward17, Smith Aaron17, Pleskovich Maria17, Tam Hima Bindu Tam17, Cukier Yael Cukier17, Meltzer Erica Meltzer17, Helcer Jacqueline Helcer17, Lau Connie Lau17, Baron Scott17, Colon Olivia17, Grobman William17, Coda Joseph17, Miller Emily17, Bellinski Irena17, Bachman Elizabeth17, Krueger Casey17, Seliger Jordan17, DeWolfe Jennifer17, Owen John17, Thompson Matthew17, Hall Cheryl17, Williams Valencia17, Moyana Anna17, Labiner David17, Maciulla James17, Moon Jennifer17, Darris Kayla17, Bahe Alicia17, Richards Scott17, Privitera Michael17, Flood-Schaffer Kellie17, Jewell George17, Mendoza Lucy17, Mcelroy Becky17, Serrano Enrique17, Salih Yasin17, Bermudez Christin17, Miranda Michelle17, Velez-Ruiz Naymee17, Figueredo Pedro17, Carns Danielle17, Harcourt Scott17, Ramirez Kristin17, Tedesco Silva Leticia17, Bagic Anto17, Urban Alexandra17, Gedela Satya17, Patterson Christina17, Jeyabalan Arundhathi17, Radonovich Krestin17, Sutcliffe Melissa17, Beers Susan17, Wiles Carrie17, Duran Sabrina17, Prince Dane17, Alhaj Sandra17, Stek Alice17, Perez Sonia17, Sierra Rachel17, Munoz Cynthia17, Miller John W.17, Mao Jennie17, Phatak Vaishali17, Kim Michelle17, Cheng-Hakimian Andrea17, DeNoble Gina17, Tsai Jeffrey17, Anthony-Fick Erin17, Steele Jennifer17, Parker Lamar17, Morris Melissa17, Dimos Jessica17, Oates Deanna17, Culbreth Danielle17,
Affiliation:
1. Pediatric Neuropsychology International LLC, Augusta, Georgia 2. Department of Neurology & Neurological Sciences, Stanford University, Palo Alto, California 3. Department of Neurology, Emory University School of Medicine, Atlanta, Georgia 4. Department of Biostatistics, The Emmes Company, Rockville, Maryland 5. Department of Project Leadership, The Emmes Company, Rockville, Maryland 6. Epilepsy Research and Education Program, Experimental & Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis 7. Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 8. Department of Neurology, University of Southern California, Los Angeles 9. Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Northwestern University, Chicago, Illinois 10. Adult Epilepsy, Minnesota Epilepsy Group, St Paul 11. Division of Epilepsy, Department of Neurology, University of Cincinnati, Cincinnati, Ohio 12. Department of Neurology, Wake Forest University, Winston-Salem, North Carolina 13. Department of Neurology and Comprehensive Epilepsy Center, New York University Comprehensive Epilepsy Center, New York 14. Department of Neurology, Northwell Health, Great Neck, New York 15. Department of Neurology, Columbia University, New York, New York 16. Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania 17. for the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) Investigator Group
Abstract
ImportanceThe association of fetal exposure to antiseizure medications (ASMs) with outcomes in childhood are not well delineated.ObjectiveTo examine the association of fetal ASM exposure with subsequent adaptive, behavioral or emotional, and neurodevelopmental disorder outcomes at 2, 3, and 4.5 years of age.Design, Setting, and ParticipantsThe Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational cohort study conducted at 20 epilepsy centers in the US. A total of 456 pregnant women with epilepsy or without epilepsy were enrolled from December 19, 2012, to January 13, 2016. Children of enrolled women were followed up with formal assessments at 2, 3, 4.5, and 6 years of age. Statistical analysis took place from August 2022 to May 2023.ExposuresExposures included mother’s epilepsy status as well as mother’s ASM blood concentration in the third trimester (for children of women with epilepsy). Women with epilepsy were enrolled regardless of ASM regimen.Main Outcomes and MeasuresThe primary outcome was the Adaptive Behavior Assessment System, Third Edition (ABAS-3) General Adaptive Composite (GAC) score among children at 4.5 years of age. Children of women with epilepsy and children of women without epilepsy were compared, and the associations of ASM exposures with outcomes among exposed children were assessed. Secondary outcomes involved similar analyses of other related measures.ResultsPrimary analysis included 302 children of women with epilepsy (143 boys [47.4%]) and 84 children of women without epilepsy (45 boys [53.6%]). Overall adaptive functioning (ABAS-3 GAC score at 4.5 years) did not significantly differ between children of women with epilepsy and children of women without epilepsy (parameter estimate [PE], 0.4 [95% CI, −2.5 to 3.4]; P = .77). However, in adjusted analyses, a significant decrease in functioning was seen with increasing third-trimester maximum ASM blood concentrations (PE, −7.8 [95% CI, −12.6 to −3.1]; P = .001). This decrease in functioning was evident for levetiracetam (PE, −18.9 [95% CI, −26.8 to −10.9]; P < .001) and lamotrigine (PE, −12.0 [95% CI, −23.7 to −0.3]; P = .04), the ASMs with sample sizes large enough for analysis. Results were similar with third-trimester maximum daily dose.Conclusions and RelevanceThis study suggests that adaptive functioning of children of women with epilepsy taking commonly used ASMs did not significantly differ from that of children of women without epilepsy, but there was an exposure-dependent association of ASMs with functioning. Thus, psychiatric or psychological screening and referral of women with epilepsy and their offspring are recommended when appropriate. Additional research is needed to confirm these findings.
Publisher
American Medical Association (AMA)
Subject
Neurology (clinical)
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