AbstractObjective: To test previous signals of a risk of orofacial cleft (OC) and clubfoot with exposure to the antiepileptic lamotrigine, and to investigate risk of other congenital anomalies (CA). Methods: Population-based case- malformed control study based on 21 EUROCAT CA registries covering 10.1 million births 1995-2011, including births to 2005 in which the clubfoot signal was generated and a subsequent independent study population of 6.3 million births. A total of 226,806 babies with CA included livebirths, stillbirths and terminations of pregnancy following prenatal diagnosis. First trimester lamotrigine monotherapy exposure in OC cases and clubfoot cases was compared to other non-chromosomal CA (controls). Odds Ratios (OR) were adjusted for registry. An exploratory analysis compared the proportion of each standard EUROCAT CA subgroup among all babies with non-chromosomal CA exposed to lamotrigine monotherapy with non-AED exposed pregnancies.Results: There were 147 lamotrigine monotherapy exposed babies with non-chromosomal CA. For all OC, ORadj was 1.31 (95%CI 0.73-2.33); isolated OC 1.45 (95%CI 0.80-2.63); isolated cleft palate 1.69 (95%CI 0.69-4.15). Overall ORadj for clubfoot was 1.83 (95%CI 1.01-3.31), and 1.43 (95%CI 0.66-3.08) in the independent study population. No other specific CA were significantly associated with lamotrigine monotherapy.Conclusions:The risk of OC was not significantly raised and we estimate the excess risk of OC to be less than one in every 550 exposed babies. We have not found strong independent evidence of a risk of clubfoot subsequent to our original signal. Our study cannot assess the general malformation risk among lamotrigine exposed pregnancies.
- Drug Safety
- Congenital Anomalies