Epileptic Drugs Responsible for Risks in Pregnancy Not Epilepsy

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There are 38 countries participating in EURAP which is an international antiepileptic drug (AED) and pregnancy registry, 1999 to 2005. There are dramatic differences in AED use across countries. Exposure to second-generation AEDs range from 3.5% in India and 7.3% in Italy to 75% in Denmark. There was noticed an increase in use of AEDs over time. The use of lamotrigine increased from 9.9% of all pregnancies in women with epilepsy before 2001 to 29.6% after 2003.

There are many reasons given for the differences in AED use across countries. These include lack of evidence concerning the optimal treatment of epilepsy in women of childbearing age, as well as variation in country-specific traditions, medication costs, and drug promotion.

New research from Norway should help understand the risks associated with epilepsy, pregnancy, and the use of AEDs during pregnancy. The study, published in the September issue of Epilesia, used data from the compulsory Medical Birth Registry of Norway. From 1999 – 2005, there were 2,861 deliveries by women with epilepsy compared to all 369,267 non-epilepsy deliveries in the same period.

Of the 2861 epileptic women, 961 (34%) used AEDs and 1900 (66%) did not use antiepileptic drugs during pregnancy. The ones who did use AEDs were mostly on monotherapy (only one antiepileptic drug). AEDs used included carbamazepine, lamotrigine, valproate, oxcarbazepine, clonazepam, topiramate, phenytoin, phenobarbital, levetiracetam, gabapentin, and vigabatrin.

Dr. Gyri Veiby, of Haukeland University Hospital, Bergen, Norway, and colleagues found it is largely the drugs used to treat epilepsy and not the condition itself that increase the risk of adverse pregnancy and birth outcomes.

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Infants who were exposed to antiepileptic drugs were more often preterm, more often had birth weight <2500 g, head circumference <2.5 percentile, and low Apgar score compared to non-epilepsy controls.

There was no significant difference in the frequency of major congenital malformations between the epilepsy group and the control group (2.8% versus 2.5%, respectively). Significantly higher rates of major congenital malformations and any congenital malformations were found in infants exposed to either valproate (5.6%) or polytherapy (6.1%).

Cardiovascular malformations were more common in AED-exposed infants compared with controls, and especially for valproate exposure. In the untreated epilepsy group there was a higher occurrence of genital malformations and Down syndrome.

The researchers concluded, "Adverse pregnancy and birth outcome in women with epilepsy is mainly confined to antiepileptic drug-exposed pregnancies although some risks are associated also with untreated epilepsy."

Sources
Pregnancy, delivery, and outcome for the child in maternal epilepsy; Gyri Veiby, Anne K. Daltveit, Bernt A. Engelsen, Nils E. Gilhus; Epilepsia 2009;50:2130-2139. DOI: 10.1111/j.1528-1167.2009.02147.x

Utilization of antiepileptic drugs during pregnancy: Comparative patterns in 38 countries based on data from the EURAP registry; The EURAP Study Group; Epilepsia 2009; 50:2305-2309. DOI: 10.1111/j.1528-1167.2009.02093.x

Written by Ramona Bates MD
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