Pregnancy Registries in Epilepsy


  • Ettore Beghi,

    1. Centro per l'Epilessia, Ospedale “San Gerardo,” Monza, and Istituto “Mario Negri,” Milano, Italy; and
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  • John F. Annegers,

    1. Health Science Center, University of Texas, Houston, Texas, U.S.A.
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  • for the Collaborative Group Pregnancy Registries in Epilepsy

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    • Dina Battino, Istituto Neurologico “C. Besta,” Milano, Italy; John Mumford, formerly International Therapeutic Area (CNS) Director, Merrel Dow, Winnersh, U.K.; Georgia Montouris, Comprehensive Epilepsy Care Center for Children and Adults, Memphis, TN, U.S.A.; and Martha Morrell, The Neurological Institute, Comprehensive Epilepsy Center, New York Presbyterian Hospital, NY, U.S.A.; James I. Morrow, Department of Neurology, The Royal Victoria Hospital, Belfast, Ireland; Emilio Perucca, Istituto di Farmacologia Medica, Università di Pavia, Italy; Sanjeev V. Thomas, Kerala Registry of Epilepsy and Pregnancy, SCTIMST, Trivandrum, India; Patricia Tennis, Director of Neurology and Psychiatry Epidemiology, Glaxo Smith Kline, Research Triangle Park, NC, U.S.A.; Torbjorn Tomson, Department of Neurology, Karolinska Hospital, Stockholm, Sweden; Frank Vajda, Director, Australian Centre for Clinical Neuropharmacology, University of Melbourne, Fitzroy, Victoria, Australia; Mark Yerby, North Pacific Epilepsy Research, Portland, OR, U.S.A.

Address correspondence and reprint requests to Dr. E. Beghi at Istituto “Mario Negri,” Via Eritrea, 62, 20157 Milano, Italy. E-mail:


Summary: The risk of major malformations in the offspring of mothers with epilepsy receiving antiepileptic drugs is 4–8% compared to 2–4% in the general population. Risk factors include daily dose and polytherapy. Selected drugs have been found to be associated with a higher risk of specific malformations (congenital heart defects and cleft palate with phenytoin and barbiturates; neural tube defects with valproate and carbamazepine). Although some of these findings are unquestionable, several questions are still unsolved, depending the characteristics of the target populations, the small samples of patients, and the design and limiting factors of the published reports. In the last decade, pregnancy registries have been activated by collaborative groups of physicians in Europe (EURAP), North America (NAREP), Australia and India (the latter two recently merged into EURAP), to enroll a large number of exposed women to be monitored prospectively with standardized methods, and by three pharmaceutical companies marketing lamotrigine, gabapentin and vigabatrin, as part of their post-marketing surveillance. Even though the structure of these registries and the target populations should theoretically result in the identification of a sufficient number of women exposed to different drugs and examined for the occurrence of malformations of any type and severity, the implementation of a common database with information from the existing registries may provide valuable information in a shorter time period. Although differences between some of the registries limit the possibility to pool data, a gradual development of a collaboration is highly desirable to discuss a list of design issues and assess to what extent and how data could be compared and organized.