Pregnancy exposure registries, which are simple cohort studies, are useful for monitoring and quantifying the impact of medications on birth defect frequency. There are several factors which contribute to the decision to develop a pregnancy registry. These factors include the need for treatment of the indicated condition during pregnancy, a medication indication associated with birth defects, alternative therapies associated with birth defects, and background information about the medication itself (e.g. animal data).
As with many chronic conditions, epilepsy is treated chronically. Pregnancies in women with epilepsy are exposed to anticonvulsant medications from conception and throughout pregnancy. The literature shows that women with epilepsy and using anticonvulsant medications during pregnancy have an elevated risk of major birth defects compared with the general population (Samren, 1997; Canger et al., 1999), and some anticonvul-sants have been associated with an elevated frequency of specific major malformations (Omtzigt et al, 1992; Dravet, 1992; Arpino et al, 2000). Although there was no pre-clinical evidence of teratogenicity for lamotrigine, the Lamotrigine Pregnancy Registry was initiated to monitor for the possible elevated risk of birth defects. With the entry of a number of new medications into the armamentarium for treating epilepsy, anticonvul-sant exposure in pregnancy has become a growing issue. Prospective pregnancy exposure registries focusing on anticonvulsant exposures have been initiated in North America and in Europe with support from a number of pharmaceutical sponsors. Each registry enrolls exposures and follows the pregnancies prospectively to evaluate the pregnancy outcome, specifically major structural birth defects. Each registry is based on a different methodologic model. The North American Pregnancy Registry invites women with ongoing pregnancies to enroll themselves, and the European Anticonvulsant Registry works with epilepsy centers within multiple countries where clinicians enroll exposed pregnancies.
The Lamotrigine Pregnancy Registry, initiated in 1992, invites physicians throughout the world to enroll pregnancies exposed to lamotrigine. Physicians enroll exposed pregnancies anonymously before the outcome of the pregnancy is known. After the expected date of delivery, a follow-up form is sent to the physician requesting information on the pregnancy outcome. Birth defects are included if they meet the criteria for birth defects established by the Centre for Disease Control (CDC) in their birth defects monitoring program. An advisory committee consisting of independent experts in teratology, epidemiology and epilepsy semiannually review the data. As of September 2000, outcome data on 243 first-trimester exposures, 100 involving monotherapy, have been identified. The number of exposures is too small to make definitive conclusions about the risk of birth defects following lamotrigine exposure during pregnancy. However, to date the frequency of birth defects following monotherapy exposures, 3.0% (95% confidence interval 0.8%-9.2%), does not suggest a signal for concern.
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