PMID- 34096986 OWN - NLM STAT- MEDLINE DCOM- 20220113 LR - 20220716 IS - 2168-6157 (Electronic) IS - 2168-6149 (Print) IS - 2168-6149 (Linking) VI - 78 IP - 8 DP - 2021 Aug 1 TI - Two-Year-Old Cognitive Outcomes in Children of Pregnant Women With Epilepsy in the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs Study. PG - 927-936 LID - 10.1001/jamaneurol.2021.1583 [doi] AB - IMPORTANCE: The neurodevelopmental risks of fetal exposure are uncertain for many antiseizure medications (ASMs). OBJECTIVE: To compare children at 2 years of age who were born to women with epilepsy (WWE) vs healthy women and assess the association of maximum ASM exposure in the third trimester and subsequent cognitive abilities among children of WWE. DESIGN, SETTING, AND PARTICIPANTS: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational, multicenter investigation of pregnancy outcomes that enrolled women from December 19, 2012, to January 13, 2016, at 20 US epilepsy centers. Children are followed up from birth to 6 years of age, with assessment at 2 years of age for this study. Of 1123 pregnant women assessed, 456 were enrolled; 426 did not meet criteria, and 241 chose not to participate. Data were analyzed from February 20 to December 4, 2020. MAIN OUTCOMES AND MEASURES: Language domain score according to the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), which incorporates 5 domain scores (language, motor, cognitive, social-emotional, and general adaptive), and association between BSID-III language domain and ASM blood levels in the third trimester in children of WWE. Analyses were adjusted for multiple potential confounding factors, and measures of ASM exposure were assessed. RESULTS: The BSID-III assessments were analyzed in 292 children of WWE (median age, 2.1 [range, 1.9-2.5] years; 155 female [53.1%] and 137 male [46.9%]) and 90 children of healthy women (median age, 2.1 [range, 2.0-2.4] years; 43 female [47.8%] and 47 male [52.2%]). No differences were found between groups on the primary outcome of language domain (-0.5; 95% CI, -4.1 to 3.2). None of the other 4 BSID-III domains differed between children of WWE vs healthy women. Most WWE were taking lamotrigine and/or levetiracetam. Exposure to ASMs in children of WWE showed no association with the language domain. However, secondary analyses revealed that higher maximum observed ASM levels in the third trimester were associated with lower BSID-III scores for the motor domain (-5.6; 95% CI, -10.7 to -0.5), and higher maximum ASM doses in the third trimester were associated with lower scores in the general adaptive domain (-1.4; 95% CI, -2.8 to -0.05). CONCLUSIONS AND RELEVANCE: Outcomes of children at 2 years of age did not differ between children of WWE taking ASMs and children of healthy women. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01730170. FAU - Meador, Kimford J AU - Meador KJ AD - Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, California. FAU - Cohen, Morris J AU - Cohen MJ AD - Pediatric Neuropsychology International, Augusta, Georgia. FAU - Loring, David W AU - Loring DW AD - Department of Neurology, Emory University, Atlanta, Georgia. FAU - May, Ryan C AU - May RC AD - Emmes Company, Rockville, Maryland. FAU - Brown, Carrie AU - Brown C AD - Emmes Company, Rockville, Maryland. FAU - Robalino, Chelsea P AU - Robalino CP AD - Emmes Company, Rockville, Maryland. FAU - Matthews, Abigail G AU - Matthews AG AD - Emmes Company, Rockville, Maryland. FAU - Kalayjian, Laura A AU - Kalayjian LA AD - Department of Neurology, University of Southern California, Los Angeles. FAU - Gerard, Elizabeth E AU - Gerard EE AD - Department of Neurology, Northwestern University, Evanston, Illinois. FAU - Gedzelman, Evan R AU - Gedzelman ER AD - Department of Neurology, Emory University, Atlanta, Georgia. FAU - Penovich, Patricia E AU - Penovich PE AD - Minnesota Epilepsy Group, St Paul, Minnesota. FAU - Cavitt, Jennifer AU - Cavitt J AD - Department of Neurology and Rehabilitation Medicine, University of Cincinnati, Cincinnati, Ohio. FAU - Hwang, Sean AU - Hwang S AD - Northwell Health, Manhasset, New York. FAU - Sam, Maria AU - Sam M AD - Department of Neurology, Wake Forest University, Winston-Salem, North Carolina. FAU - Pack, Alison M AU - Pack AM AD - Department of Neurology, Columbia University, New York, New York. FAU - French, Jacqueline AU - French J AD - Department of Neurology, New York University, New York. FAU - Tsai, Jeffrey J AU - Tsai JJ AD - Department of Neurology, University of Washington, Seattle. FAU - Pennell, Page B AU - Pennell PB AD - Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. CN - Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs Investigator Group LA - eng SI - ClinicalTrials.gov/NCT01730170 GR - P50 HD103538/HD/NICHD NIH HHS/United States GR - U01 NS038455/NS/NINDS NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Research Support, N.I.H., Extramural PL - United States TA - JAMA Neurol JT - JAMA neurology JID - 101589536 RN - 0 (Anticonvulsants) SB - IM CIN - JAMA Neurol. 2021 Aug 1;78(8):911-913. PMID: 34096995 CIN - Am J Nurs. 2021 Sep 1;121(9):56. PMID: 34438431 MH - Adult MH - Anticonvulsants/*adverse effects/blood MH - Child, Preschool MH - Cognition Disorders/epidemiology/*etiology MH - Epilepsy/*complications/drug therapy MH - Female MH - Humans MH - Infant MH - Infant, Newborn MH - Language Development MH - Neurodevelopmental Disorders/*etiology MH - Pregnancy MH - Pregnancy Outcome MH - Pregnant Women MH - Prenatal Exposure Delayed Effects/diagnostic imaging/*psychology MH - Prospective Studies MH - Socioeconomic Factors PMC - PMC8185630 COIS- Conflict of Interest Disclosures: Dr Meador reported receiving research support from the National Institutes of Health (NIH), Eisai Co, Ltd, and Sunovion Pharmaceuticals Inc; travel support from Eisai Co, Ltd; and consulting for Eisai Co, Ltd, GW Pharmaceuticals, NeuroPace, Novartis AG, Supernus Pharmaceuticals, Inc, Upsher-Smith Laboratories, LLC, UCB SA, and VIVUS Inc, with fees paid to the university by The Epilepsy Study Consortium. Dr Loring reports receiving support for research from the National Institute of Mental Health (NIMH) and National Institute of Neurological Disorders and Stroke (NINDS), consulting for NeuroPace, receiving editorial stipends from Epilepsia and Neuropsychology Review, and receiving book royalties from Oxford University Press. Dr Gerard reported receiving research support from Sage Therapeutics, Inc, Sunovion Pharmaceuticals Inc, and Xenon Pharmaceuticals Inc; speaker fees from GW Pharmaceuticals and UCB SA; and travel funds from UCB SA. Dr Penovich reported receiving support for advisory and speakers bureau for Neurelis, Inc, SK Biopharmaceuticals, and UCB SA, and for advisory work for LVIS Corporation and Engage Therapeutics, Inc. Dr Cavitt reported receiving research support from the NINDS (MONEAD) and from GW Pharmaceuticals. Dr Sam reported receiving advisory board consulting fees for Aquestive Therapeutics. Dr Pack reported receiving royalties for the website UpToDate. Dr French reported receiving salary support at New York University from the Epilepsy Foundation and for consulting work and/or attending on behalf of the Epilepsy Study Consortium for Adamas Pharmaceuticals, Inc, Aeonian/Aeovian, Anavex Life Sciences Corp, Arvelle Therapeutics, Athenen Therapeutics/Carnot Pharma, Axovant Sciences, Baergic Bio, Inc, Biogen Inc, Biomotiv/Koutif, BioXcel Therapeutics, Inc, Blackfynn, Bloom Science, Bridge Valley Ventures LLP, Cavion, Cerebral Therapeutics, Cerevel Therapeutics, Crossject, CuroNZ Limited, Eisai Co, Ltd, Eliem Therapeutics, Encoded Therapeutics, Engage Therapeutics, Inc, Engrail Therapeutics, Epiminder, Epitel, Inc, Fortress Biotech Inc, Greenwich Biosciences, GW Pharmaceuticals, Idorsia Pharmaceuticals Ltd, Ionis Inc, Janssen Global Services, LLC, Johnson & Johnson Services, Inc, Knopp Biosciences, H Lundbeck A/S, Marinus, Mend Neuroscience, Merck, NeuCyte, Inc, Neurelis, Inc, Neurocrine, Novartis AG, Otsuka Pharmaceutical Development, Ovid Therapeutics Inc, Passage Bio, Inc, Pfizer Inc, Praxis, Redpin Therapeutics, Inc, Sage Therapeutics, Inc, Shire plc, SK Life Sciences, Inc, Sofinnova, SpringWorks Therapeutics, Inc, Stoke Therapeutics, Sunovion Pharmaceuticals Inc, Supernus Pharmaceuticals, Inc, Takeda Pharmaceutical Company Limited, UCB SA, West Therapeutic Development, LLC, Xenon Pharmaceuticals Inc, Xeris Pharmaceuticals, Inc, Zogenix, Inc, and Zynerba Pharmaceuticals, Inc; receiving research grants from Biogen Inc, Cavion, Eisai Co, Ltd, Engage Therapeutics, Inc, GW Pharmaceuticals, H Lundbeck A/S, Neurelis, Inc, Ovid Therapeutics, Inc, Pfizer Inc, SK Life Sciences, Inc, Sunovion Pharmaceuticals Inc, UCB SA, Xenon Pharmceuticals Inc, Zogenix, Inc, the Epilepsy Research Foundation, the Epilepsy Study Consortium, and the NINDS; serving on the editorial board of Lancet Neurology and Neurology Today; serving as chief medical/innovation officer for the Epilepsy Foundation, for which New York University receives salary support; and receiving travel reimbursement related to research, advisory meetings, or presentation of results at scientific meetings from the Epilepsy Study Consortium, the Epilepsy Foundation, Adamas Pharmaceuticals, Inc, Arvelle Therapeutics, Inc, Axovant Sciences, Biogen Inc, Blackfynn, Cerevel Therapeutics, Crossject, CuroNZ Limited, Eisai Co, Ltd, Engage Therapeutics, Inc, Idorsia Pharmaceuticals Ltd, H Lundbeck A/S, NeuCyte, Inc, Neurelis, Inc, Novartis AG, Otsuka Pharmaceutical Development, Ovid Therapeutics Inc, Pfizer Inc, Redpin Therapeutics, Inc, Sage Therapeutics, SK Life Sciences, Inc, Sunovion Pharmaceuticals Inc, Takeda Pharmaceutical Company Limited, UCB SA, Xenon Pharmaceuticals Inc, and Zogenix, Inc. Dr Tsai reported receiving research support from the NIH, SK Life Sciences, Inc, and Xenon Pharmaceuticals Inc. Dr Pennell reported receiving grants from the NIH during the conduct of the study, personal fees from the NIH for grant reviews, personal fees from the American Epilepsy Society and the American Academy of Neurology as speaking honoraria, personal fees from Medical Schools for speaking honoraria and travel, and personal fees from UpToDate for royalties outside the submitted work. No other disclosures were reported. FIR - Birnbaum, Angela IR - Birnbaum A FIR - Druzin, Maurice IR - Druzin M FIR - Finnell, Richard IR - Finnell R FIR - Holmes, Gregory IR - Holmes G FIR - McElrath, Frederick T IR - McElrath FT FIR - Nelson, Lorene IR - Nelson L FIR - Stowe, Zachary IR - Stowe Z FIR - Van Marter, Linda IR - Van Marter L FIR - Wells, Peter IR - Wells P FIR - Yerby, Mark IR - Yerby M FIR - Moore, Eugene IR - Moore E FIR - Ippolito, Dominic IR - Ippolito D FIR - Skinner, Julia IR - Skinner J FIR - Davis, Lisa IR - Davis L FIR - Shah, Nilay IR - Shah N FIR - Leung, Brenda IR - Leung B FIR - Friedman, Mark IR - Friedman M FIR - Loblein, Hayley IR - Loblein H FIR - Sheer, Traci IR - Sheer T FIR - Strickland, Suzanne IR - Strickland S FIR - Latif, Erin IR - Latif E FIR - Park, Yong IR - Park Y FIR - Acosta-Cotte, Delmaris IR - Acosta-Cotte D FIR - Ray, Patty IR - Ray P FIR - Cleary, Kirsten IR - Cleary K FIR - Echo, Joyce IR - Echo J FIR - Zygmunt, Annette IR - Zygmunt A FIR - Casadei, Camilla IR - Casadei C FIR - Dolan, Mary IR - Dolan M FIR - Ono, Kim IR - Ono K FIR - Bearden, Donald IR - Bearden D FIR - Ghilian, Christine IR - Ghilian C FIR - Teagarden, Diane IR - Teagarden D FIR - Newman, Melanee IR - Newman M FIR - McCabe, Paul IR - McCabe P FIR - Paglia, Michael IR - Paglia M FIR - Taylor, Cora IR - Taylor C FIR - Delucca, Rosemarie IR - Delucca R FIR - Blessing, Kristina IR - Blessing K FIR - Marter, Linda IR - Marter L FIR - Boyer, Katrina IR - Boyer K FIR - Hanson, Ellen IR - Hanson E FIR - Young, Amy IR - Young A FIR - Hickey, Paige IR - Hickey P FIR - Strauss, Jolie IR - Strauss J FIR - Madeiros, Hayley IR - Madeiros H FIR - Chen, Li IR - Chen L FIR - Allien, Stephanie IR - Allien S FIR - Sheldon, Yvonne IR - Sheldon Y FIR - Weinau, Taylor IR - Weinau T FIR - Barkley, Gregory L IR - Barkley GL FIR - Spanaki-Varelas, Marianna IR - Spanaki-Varelas M FIR - Thomas, Andrea IR - Thomas A FIR - Constantinou, Jules IR - Constantinou J FIR - Mahmood, Nazin IR - Mahmood N FIR - Wasade, Vibhangini IR - Wasade V FIR - Gaddam, Shailaja IR - Gaddam S FIR - Zillgitt, Andrew IR - Zillgitt A FIR - Anwar, Taimur IR - Anwar T FIR - Sandles, Carla IR - Sandles C FIR - Holmes, Theresa IR - Holmes T FIR - Johnson, Emily IR - Johnson E FIR - Krauss, Gregory IR - Krauss G FIR - Lawson, Shari IR - Lawson S FIR - Pritchard, Alison IR - Pritchard A FIR - Ryan, Matthew IR - Ryan M FIR - Coe, Pam IR - Coe P FIR - Reger, Katie IR - Reger K FIR - Pohlman, Jenny IR - Pohlman J FIR - Olson, Alisha IR - Olson A FIR - Schweizer, William IR - Schweizer W FIR - Morrison, Chris IR - Morrison C FIR - MacAllister, William IR - MacAllister W FIR - Clements, Tobi IR - Clements T FIR - Tam, Hima Bindu Tam IR - Tam HBT FIR - Cukier, Yael IR - Cukier Y FIR - Meltzer, Erica IR - Meltzer E FIR - Helcer, Jacqueline IR - Helcer J FIR - Lau, Connie IR - Lau C FIR - Grobman, William IR - Grobman W FIR - Coda, Joseph IR - Coda J FIR - Miller, Emily IR - Miller E FIR - Bellinski, Irena IR - Bellinski I FIR - Bachman, Elizabeth IR - Bachman E FIR - Krueger, Casey IR - Krueger C FIR - Seliger, Jordan IR - Seliger J FIR - DeWolfe, Jennifer IR - DeWolfe J FIR - Owen, John IR - Owen J FIR - Thompson, Matthew IR - Thompson M FIR - Hall, Cheryl IR - Hall C FIR - Labiner, David IR - Labiner D FIR - Maciulla, James IR - Maciulla J FIR - Moon, Jennifer IR - Moon J FIR - Darris, Kayla IR - Darris K FIR - Privitera, Michael IR - Privitera M FIR - Flood-Schaffer, Kellie IR - Flood-Schaffer K FIR - Jewell, George IR - Jewell G FIR - Mendoza, Lucy IR - Mendoza L FIR - Serrano, Enrique IR - Serrano E FIR - Salih, Yasin IR - Salih Y FIR - Bermudez, Christin IR - Bermudez C FIR - Miranda, Michelle IR - Miranda M FIR - Velez-Ruiz, Naymee IR - Velez-Ruiz N FIR - Figueredo, Pedro IR - Figueredo P FIR - Bagic, Anto IR - Bagic A FIR - Urban, Alexandra IR - Urban A FIR - Gedela, Satya IR - Gedela S FIR - Patterson, Christina IR - Patterson C FIR - Jeyabalan, Arundhathi IR - Jeyabalan A FIR - Radonovich, Krestin IR - Radonovich K FIR - Sutcliffe, Melissa IR - Sutcliffe M FIR - Beers, Susan IR - Beers S FIR - Wiles, Carrie IR - Wiles C FIR - Alhaj, Sandra IR - Alhaj S FIR - Stek, Alice IR - Stek A FIR - Perez, Sonia IR - Perez S FIR - Sierra, Rachel IR - Sierra R FIR - Miller, John W IR - Miller JW FIR - Mao, Jennie IR - Mao J FIR - Phatak, Vaishali IR - Phatak V FIR - Kim, Michelle IR - Kim M FIR - Cheng-Hakimian, Andrea IR - Cheng-Hakimian A FIR - DeNoble, Gina IR - DeNoble G FIR - Parker, Lamar IR - Parker L FIR - Morris, Melissa IR - Morris M FIR - Dimos, Jessica IR - Dimos J FIR - Miller, Danielle IR - Miller D EDAT- 2021/06/08 06:00 MHDA- 2022/01/14 06:00 PMCR- 2022/06/07 CRDT- 2021/06/07 12:25 PHST- 2021/06/08 06:00 [pubmed] PHST- 2022/01/14 06:00 [medline] PHST- 2021/06/07 12:25 [entrez] PHST- 2022/06/07 00:00 [pmc-release] AID - 2780605 [pii] AID - noi210027 [pii] AID - 10.1001/jamaneurol.2021.1583 [doi] PST - ppublish SO - JAMA Neurol. 2021 Aug 1;78(8):927-936. doi: 10.1001/jamaneurol.2021.1583.