Differential effects of antiepileptic drugs on neonatal outcomes

P. B. Pennell, A. M. Klein, N. Browning, G. A. Baker, J. Clayton-Smith, L. A. Kalayjian, J. D. Liporace, M. Privitera, T. Crawford, D. W. Loring, K. J. Meador, David Labiner, Jennifer Moon, Scott Sherman, Deborah T C Cantrell, Cheryl Silver, Monisha Goyal, Mike R. Schoenberg, Alison Pack, Christina PalmeseJoyce Echo, Kimford J. Meador, David Loring, Page Pennell, Daniel Drane, Eugene Moore, Megan Denham, Charles Epstein, Jennifer Gess, Sandra Helmers, Thomas Henry, Gholam Motamedi, Erin Flax, Edward Bromfield, Katrina Boyer, Barbara Dworetzky, Andrew Cole, Lucila Halperin, Sara Shavel-Jessop, Gregory Barkley, Barbara Moir, Cynthia Harden, Tara Tamny-Young, Gregory Lee, Patricia Penovich, Donna Minter, Layne Moore, Kathryn Murdock, Joyce Liporace, Kathryn Wilcox, Andres Kanner, Michael N. Nelson, William Rosenfeld, Michelle Meyer, Jill Clayton-Smith, George Mawer, Usha Kini, Roy Martin, Michael Privitera, Jennifer Bellman, David Ficker, Lyle Baade, Kore Liow, Gus Baker, Alison Booth, Rebecca Bromley, Miranda Casswell, Claire Barrie, Eugene Ramsay, Patricia Arena, Laura Kalayjian, Christianne Heck, Sonia Padilla, John Miller, Gail Rosenbaum, Alan Wilensky, Tawnya Constantino, Julien Smith, Naghme Adab, Gisela Veling-Warnke, Maria Sam, Cormac O'Donovan, Cecile Naylor, Shelli Nobles, Cesar Santos, Gregory L. Holmes, Maurice Druzin, Martha Morrell, Lorene Nelson, Richard Finnell, Mark Yerby, Khosrow Adeli, Peter Wells, Nancy Browning, Temperance Blalock, Todd Crawford, Linda Hendrickson, Bernadette Jolles, Meghan Kelly Kunchai, Hayley Loblein, Yinka Ogunsola, Steve Russell, Jamie Winestone, Mark Wolff, Phyllis Zaia, Thad Zajdowicz

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Offspring of women with epilepsy (WWE) on AEDs are at increased risks for major congenital malformations and reduced cognition. They may be at risk for other adverse neonatal outcomes. Women with epilepsy on carbamazepine (CBZ), lamotrigine (LTG), phenytoin (PHT), or valproate (VPA) monotherapy were enrolled in a prospective, observational, multicenter study of the neurodevelopmental effects of AEDs. The odds ratio for small for gestational age (SGA) was higher for VPA vs. PHT, VPA vs. LTG, and CBZ vs. PHT. Microcephaly rates were elevated to 12% for all newborns and at 12. months old, but normalized by age 24. months. Reduced Apgar scores occurred more frequently in the VPA and PHT groups at 1. min, but scores were near normal in all groups at 5. min. This study demonstrates increased risks for being born SGA in the VPA and CBZ groups, and transiently reduced Apgar scores in the VPA and PHT groups. Differential risks among the AEDs can help inform decisions about AED selection for women during childbearing years.

Original languageEnglish (US)
Pages (from-to)449-456
Number of pages8
JournalEpilepsy and Behavior
Issue number4
StatePublished - Aug 1 2012

Bibliographical note

Funding Information:
Dr. Pennell receives salary support for research from the National Institutes of Health, the Milken Family Foundation, and the Epilepsy Foundation. She has received travel reimbursement from the National Institutes of Health, the Milken Family Foundation, the Epilepsy Foundation, American Epilepsy Society, and the National EpiFellows Foundation. She has received an honorarium for speaking from Atlantic Health. She also serves as a volunteer member of the American Epilepsy Society Board of Directors, the Epilepsy Research Foundation, the Professional Advisory Board for the Epilepsy Foundation, and on the editorial boards for Epilepsy Currents. Autumn M. Klein, M.D., PhD has received research support from the American Epilepsy Society, the Epilepsy Foundation and Brigham and Women's Hospital, and payment from Digitrace for EEG interpretations. Nancy Browning, PhD has received salary support for research from the National Institutes of Health. Gus Baker, PhD has received educational grants from Epilepsy Research UK, Sanofi Aventis, and UCB, research support from the Medical Research Council and National Institutes of Health, and travel support from GlaxoSmithKline; he has received payment for serving as an expert witness in litigation related to neurodevelopmental effects of antiepileptic drugs and his institution has received compensation for his lectures from UCB. Jill Clayton-Smith, M.D. has received research support from the National Institutes of Health, the Manchester NIHR Biomedical Research Centre, and Action Medical Research, and has received payments to her institution for legal reports and for serving as an editor for the Clinical Dysmorphology journal. Laura A. Kalayjian, M.D. has received research support from the National Institutes of Health, and payment for lectures for GlaxoSmithKline. Joyce D. Liporace, M.D. has received research support from the National Institutes of Health and Marinus Pharmaceuticals, consulting honorarium from GlaxoSmithKline, and payment for lectures from UCB Pharma. Michael Privitera, M.D. has received research support from the National Institutes of Health, Eisai, UCB, American Epilepsy Society, Ortho McNeil, and payment to his institution for his lectures from UCB and GlaxoSmithKline, and travel reimbursement from the National Epifellows Foundation. Todd Crawford, M.S. has nothing to disclose. David W. Loring, PhD has received research support from the National Institutes of Health, Myriad Pharmaceuticals, SAM Technology, Novartis, and consultant fees from UCB Pharma and Neuropace. Dr. Meador reports receiving research support from the GlaxoSmithKline, EISAI Medical Research, Myriad Pharmaceuticals, Marinus Pharmaceuticals, NeuroPace, Pfizer, SAM Technology, Schwartz Biosciences, and UCB Pharma, the Epilepsy Foundation, and the NIH; received salary support to Emory University from the Epilepsy Consortium for research consultant work related for NeuroPace, Upsher-Smith, and Vivus; served as a consultant for Eisai, GlaxoSmithKline, Johnson and Johnson (Ortho Mc Neil), Medtronics Spherics, and UCB Pharma, but the money went to a charity of the company's choice; received travel support from Sanofi Aventis; and also serves on the Professional Advisory Board for the Epilepsy Foundation and the editorial boards for Cognitive and Behavioral Neurology, Epilepsy & Behavior, Neurology, and Journal of Clinical Neurophysiology.


  • Antiepileptic drugs
  • Apgar
  • Epilepsy
  • Microcephaly
  • Neonatal
  • Observational cohort study
  • Pregnancy
  • Seizures
  • Small for gestational age (SGA)

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