Requested DocAlert: Effects of First-Trimester Lamotrigine Exposure: NEJM Journal Watch

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Effects of First-Trimester Lamotrigine Exposure

Risks for orofacial cleft and clubfoot were not increased in this case-control study.

Heightened risks for orofacial cleft and clubfoot have been reported with first-trimester exposure to lamotrigine. To investigate these risks further, investigators in a manufacturer-funded study analyzed data from a network of 21 European registries involving 10.1 million births from 1995 to 2011; the authors had previously linked lamotrigine to clubfoot in this network.

The overall rate of major malformations was 2.25%. There were 147 babies with nonchromosomal congenital anomalies (NCA) and exposure to lamotrigine monotherapy in the first trimester. The investigators examined rates of first-trimester exposure to lamotrigine monotherapy in babies with orofacial cleft or clubfoot and in those with other NCA. Analyses were adjusted for maternal age and specific registry.

Orofacial clefts were significantly associated with exposure to an anticonvulsant. However, there was no significant increase in lamotrigine exposure associated with orofacial clefts. The earlier link to clubfoot was not replicated in analyses of later registry data. The authors estimate that, at most, the excess risk of orofacial cleft would be less than 1 in every 550 lamotrigine-exposed babies.


In addition to industry funding, study weaknesses include the small number of lamotrigine-exposed babies with specific NCA, despite the large registry sample, and — for mental health clinicians — the fact that most women in these registries took anticonvulsants for seizures and not psychiatric disorders. Overall, though, the analyses add reassuring data on the potential risks of lamotrigine exposure during pregnancy and reinforce the safety of lamotrigine relative to other anticonvulsants.

Deborah Cowley, MD reviewing Dolk H et al. Neurology 2016 Apr 6.


Dolk H et al. Lamotrigine use in pregnancy and risk of orofacial cleft and other congenital anomalies. Neurology 2016 Apr 6; [e-pub].
[Free full-text Neurology article PDF | PubMed® abstract]

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