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, Anne-Marie Lahesmaa-Korpinen, Anna Latos-Bielenska, Jan Mejnartowicz, Vera Nelen, Amanda Neville, Mary O'MahonyAnna Pierini, Anke Rissmann, David Tucker, Diana Wellesley, Awi Wiesel, Lolkje de Jong-van den Berg

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)1716-1725
Issue number18
Early online date6 Apr 2016
Publication statusPublished (in print/issue) - 3 May 2016


  • Lamotrigine
  • Drug Safety
  • Congenital Anomalies


Dive into the research topics of 'Lamotrigine use in pregnancy and risk of orofacial cleft and other congenital anomalies'. Together they form a unique fingerprint.

Cite this