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(Abst. 3.243), 2001

EURAP: An International Pregnancy Registry for the Evaluation of the Comparative Teratogenic Effects of Antiepileptic Drugs.
Authors: T. Tomson, MD, Neurology, Karolinska Hospital, Stockholm, Sweden; D. Battino, MD, Neurological Institute, Carlo Besta, Milan, Italy; M. Beaussart, MD, University of Lille, Lille, France; E. Bonizzoni, PhD, Inst. of Medical Statistics and Biometry, University of Milan, Milan, Italy; J. Craig, MD, Institute of Neurology, National Hospital, London, United Kingdom; D. Lindhout, MD, Department of Medical Genetics, University of Utrecht, Utrecht, Netherlands; E. Perucca, MD, Department of Clinical Pha
Content: RATIONALE: Information on the comparative teratogenicity of old-generation antiepileptic drugs (AEDs) in humans is conflicting, and the teratogenic potential of newer generation AEDs is even less known. Based on these considerations, a multinational registry has been established aimed at determining the comparative risk of major foetal malformations following intake of old and new AEDs and their combinations during pregnancy.[br]METHODS: EURAP is a prospective registry set up originally in Europe and later extended to several other countries in Asia and Oceania. Women taking AEDs for any indication at the time of conception are eligible for inclusion, subject to their willingness to provide informed consent. To avoid selection bias, only pregnancies registered before foetal outcome is known and within week 16 of gestation contribute to the prospective study. Retrospective cases are also collected as they may provide valuable signals, but they are not included in the evaluation of comparative risk. Information on patients[scquote] demographics, underlying disease, seizure frequency, family history of malformations, drug therapy and a large set of other potential risk factors is obtained, and follow-up data are collected once at each trimester, at birth and at one year after delivery. Data are collected online, and rapid feedback between the central registry and reporting physicians or national co-ordinators allows rapid collection of any missing data and correction of any inconsistencies. Foetal outcome is recorded descriptively, and a central committee that is unaware of the type of drug exposure classifies and encodes the malformations.[br]RESULTS: Up to April 2001, a total of 96 centres in 17 countries have been actively contributing to the registry. Since its establishment in June 1999, the registry has enrolled a total of 716 pregnancies (340 over the past 6 months), 523 of which represent prospective cases, and enrolment rate is expanding rapidly. To date, less than 2% of registered pregnancies have been lost to follow-up. Among the 523 prospective pregnancies, carbamazepine (48%) has been the most common exposure, followed by valproic acid (29%), phenobarbital (16%) and lamotrigine (9%). Monotherapy accounted for 76% of recorded exposures. The first classification of the reported malformations is due on July 2001.[br]CONCLUSIONS: Intensive on-line interaction between the central registry, regional coordinators and reporting physicians has proven an effective means of ensuring efficient enrolment and follow-up on an international basis. Large collaborative registries utilizing rigorous inclusion criteria and careful data collection are invaluable if the much needed data on the comparative safety of AEDs during pregnancy are to be obtained.[br]Support: Scientific Advisory Board: Bernd Schmidt and Martin J Brodie[br]Supported by educational grants from GlaxoSmithKline, Janssen-Cilag, Pfizer, Sanofi-Synthelabo, and UCB SA.