Lamotrigine use in pregnancy and risk of orofacial cleft and other congenital anomalies

Helen Dolk*, Hao Wang, Maria Loane, Joan Morris, Ester Garne, Marie-Claude Addor, Larraitz Arriola, Marian Bakker, Ingeborg Barisic, Berenice Doray, Miriam Gatt, Karin Kallen, Babak Khoshnood, Kari Klungsoyr, Anna-Maria Lahesmaa-Korpinen, Anna Latos-Bielenska, Jan P. Mejnartowicz, Vera Nelen, Amanda Neville, Mary O'MahonyAnna Pierini, Anke Rissmann, David Tucker, Diana Wellesley, Awi Wiesel, Lolkje T. W. de Jong-van den Berg

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

45 Citaten (Scopus)
263 Downloads (Pure)


Objective: 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: This was a 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 nonchromosomal 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 nonchromosomal CA exposed to lamotrigine monotherapy with non-AED exposed pregnancies.

Results: There were 147 lamotrigine monotherapy-exposed babies with nonchromosomal CA. For all OC, ORadj was 1.31 (95% confidence interval [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 1 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.

Originele taal-2English
Pagina's (van-tot)1716-1725
Aantal pagina's10
Nummer van het tijdschrift18
StatusPublished - 3-mei-2016

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