Newer-Generation Antiepileptic Drugs and the Risk of Major Birth Defects

Context Epilepsy during pregnancy is a therapeutic challenge. Since the 1990s, the number of licensed antiepileptic drugs has substantially increased, but safety data on first-trimester use of newer-generation antiepileptic drugs and birth defects are limited. Objective To study the association between fetal exposure to newer-generation antiepileptic drugs during the first trimester of pregnancy and the risk of major birth defects. Design, Setting, and Participants Population-based cohort study of 837 795 live-born infants in Denmark from January 1, 1996, through September 30, 2008. Individual-level information on dispensed antiepileptic drugs to mothers, birth defect diagnoses, and potential confounders were ascertained from nationwide health registries. Main Outcome Measures Prevalence odds ratios (PORs) of any major birth defect diagnosed within the first year of life by fetal exposure to antiepileptic drugs. Results Of the 1532 infants exposed to lamotrigine, oxcarbazepine, topiramate, gabapentin, or levetiracetam during the first trimester, 49 were diagnosed with a major birth defect compared with 19 911 of the 836 263 who were not exposed to an antiepileptic drug (3.2% vs 2.4%, respectively; adjusted POR [APOR], 0.99; 95% confidence interval [CI], 0.72-1.36). A major birth defect was diagnosed in 38 of 1019 infants (3.7%) exposed to lamotrigine during the first trimester (APOR, 1.18; 95% CI, 0.83-1.68), in 11 of 393 infants (2.8%) exposed to oxcarbazepine (APOR, 0.86; 95% CI, 0.46-1.59), and in 5 of 108 infants (4.6%) exposed to topiramate (APOR, 1.44; 95% CI, 0.58-3.58). Gabapentin (n=59) and levetiracetam (n=58) exposure during the first trimester was uncommon, with only 1 (1.7%) and 0 infants diagnosed with birth defects, respectively. Conclusion Among live-born infants in Denmark, first-trimester exposure to lamotrigine, oxcarbazepine, topiramate, gabapentin, or levetiracetam compared with no exposure was not associated with an increased risk of major birth defects. JAMA. 2011; 305(19): 1996-2002