Epigraph Vol. 10 Issue 1, Winter 2007-2008
Epilepsy and Pregnancy Registries
The risk that the medication can harm their children has been a major concern for all women with epilepsy considering pregnancy ever since the first reports on the possible teratogenic effects of antiepileptic drugs (AEDs) were published in the 1960s. Despite numerous studies since then, many of the major issues have remained unsolved, especially concerning to what extent AEDs differ in their teratogenic potential. This is explained by methodological shortcomings, and in particular small sample sizes of previous studies. Thousands of AED-exposed pregnancies are needed given the large number of treatment options and the, after all, low prevalence of birth defects in children of mothers with epilepsy medication. This paucity of data necessary for a rational management of epilepsy in women of childbearing potential prompted the establishment of epilepsy and pregnancy registries. Although slightly different in their methodology, the registries are typically prospective observational studies aimed at enrolling large numbers of pregnancies with exposure to AEDs and with the common objective to assess the risk for major congenital malformations associated with different types of treatment.
There are two major types of registries. Some are driven by the pharmaceutical industry and enroll exclusively pregnancies exposed to the manufacturer’s own specific product and thus lack a comparator to other AEDs. Independent registries that enroll pregnancies with all available AEDs are more informative since they provide comparisons among the various treatment options. There are four major national/regional and one international registry of this kind. EURAP, an international AED and pregnancy registry launched in Europe in 1999, now enrolls pregnancies through reporting physicians from 40 countries in Europe, Asia, Australia and South America. To date more than 11,000 pregnancies with AED exposure have been included in the central database. EURAP has so far only published data on seizure control during pregnancy, but the first analyses of comparative teratogenic risks are underway. The North American AED Pregnancy Registry, established in 1997, relies on self-enrollment of pregnant women from the U.S. and Canada. By November, 2007, more than 6,100 pregnancies had been enrolled. This registry has released data on malformation rates in association with Phenobarbital, Valproate, Lamotrigine and Carbamazepine. The UK Register, in function since 1996, recruits pregnant women through physicians, nurses and patient self-enrollment. A total of 6,200 pregnancies had been included by December, 2007. The UK Register published malformation rates for all types of exposures based on the first 3,607 prospective pregnancies. The Australian Register, founded in 1999, relies mainly on self-enrollment by eligible women. The methodology is otherwise similar to that of EURAP and the Australian Register contributes data to EURAP, but also publishes independently. By January, 2008, 1,300 pregnancies were enrolled. The Kerala Registry is a regional registry launched in southern India in 1999. The methodology is close to that of EURAP and the data are partly shared with this international registry. More than 1,000 pregnancies have been enrolled in the Kerala Registry.
These registries have all been very successful in enrolling pregnancies during the approximately ten years of function. New important information is beginning to emerge as a result of these efforts as recently reviewed (Tomson et al., 2007). However, so far useful information has been obtained only for the most commonly used AEDs and mainly concerning overall malformation rates with these exposures. It is now time for the registries to take the next steps: to provide meaningful data on more than the 3-4 most frequently used AEDs, to compare the risks for specific malformations, and to include potentially important confounding factors in the analyses. This would require even more enrolled pregnancies and thus continued support from the epilepsy community is absolutely necessary. The registries have demonstrated their ability for efficient patient enrollment, and it is essential to keep up this momentum in the coming years. We encourage all physicians who treat patients with epilepsy who are pregnant or are considering having a child to encourage their patients to participate in the registries. Below are contact details for the registries for those who are willing to contribute to this important work.
UK Register www.epilepsyandpregnancy.co.u
North American www.massgeneral.org/aed
Australian Register: Telephone number to coordinators +61 3 95947449
Kerala Registry: E-mail to coordinator: email@example.com
Department of Clinical Neuroscience
Department of Neurology
Karolinska University Hospital
SE 171 76 Stockholm
Telephone. +46 8 51773705
Fax: +46 8 51773757
Torbjörn Tomson is Professor of Neurology at the Karolinska Institute as well as the Chairman of EURAP, the International European Registry of Antiepileptic Drugs and Pregnancy.
Tomson T, Battino D, French J, Harden C, Holmes L, Morrow J, Robert-Gnansia E, Scheuerle A, Vajda F, Wide K, Gordon J, for the Epilepsy Therapy Development Project (ETDP) Work Group on Teratogenicity-Anatomical. Antiepileptic drug exposure and major congenital malformations: the role of pregnancy registries.
Epilepsy & Behavior. 2007;11:277-82.
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