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Lamotrigine use in Pregnancy and Risk of Orofacial Cleft

Funding and timescale

The EUROCAT Central Database is supported in part by the European Commission's DG-Sanco (the Directorate General for Health and Consumers) Public Health Programmes (2004-2008 and 2008-2013).  Individual registries are supported by various sources of local public funding. Additional funding was obtained from GlaxoSmithKline (GSK) to conduct the original study assessing maternal first trimester exposure to the anti-epileptic drug (AED) Lamotrigine and risk of orofacial clefts in 2007 and five follow-up studies (2009-2013). 

About the Study

Following a US Federal Drugs Agency alert in 2006 concerning an increased risk of orofacial cleft associated with first trimester exposure to the new AED lamotrigine, the EUROCAT AED database was created in 2007 to evaluate this signal using EUROCAT data.

The original database included data from 19 registries covering a population of 4 million births, 1995-2005 and was compiled and co-ordinated from the Centre for Maternal, Fetal and Infant Research (Ulster University).  The database was used to conduct a case-control study evaluating the risk of orofacial clefts in relation to lamotrigine exposure.  The study found no evidence of a specific increased risk of isolated orofacial clefts relative to other malformations due to lamotrigine monotherapy.

  • [Dolk H, Jentink J, Loane M, Morris J, de Jong-van den Berg LTW and EUROCAT Antiepileptic Drug Working Group (2008), "Does Lamotrigine Use in Pregnancy Increase Orofacial Cleft Risk Relative to Other Malformations?", Neurology, Vol 71, pp 714-722].

In order to estimate the risk of orofacial clefts relative to other malformations more precisely and to explore whether lamotrigine exposure may be associated with other malformations, a follow-up study was commissioned by GSK.  This involved five yearly updates (2009, 2010, 2011, 2012, and 2013).  The final study included data from 21 registries and covered over 10 million births.  No evidence of an increased risk of orofacial clefts relative to other malformations associated with lamotrigine exposure in the first trimester was found.  This study is listed the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) register.

Aim of study

To investigate in an independent large dataset whether lamotrigine exposure in the first trimester of pregnancy is associated with an increased risk of orofacial clefts relative to other malformations.

Staff and collaborators

Centre for Maternal, Fetal and Infant Research, UU:

  • Prof Helen Dolk
  • Dr Maria Loane
  • Mrs Ruth Greenlees
  • Mrs Barbara Norton

Outside Ulster University:

  • Prof L de Jong-van den Berg, N Netherlands
  • Dr Hao Wang, N Netherlands
  • Prof Joan Morris, QMUL, UK
  • Dr Vera Nelen, Belgium
  • Dr Christine Verellen–Dumoulin Belgium
  • Dr Ingeborg Barisic, Croatia
  • Dr Ester Garne, Denmark
  • Dr Annukka Ritvanen, Finland
  • Dr Babak Khoshnood, France
  • Dr Bérénice Doray, France
  • Dr Awi Wiesel, Germany
  • Dr Anke Rißmann, Germany
  • Dr Mary O'Mahony, Ireland
  • Dr Elisa Calzolari, Italy
  • Dr Anna Pierini, Italy
  • Dr Miriam Gatt, Malta
  • Dr Marian Bakker, Netherlands
  • Dr Kari Klungsoyr, Norway
  • Dr Anna Latos-Bielenska, Poland
  • Dr Jan P Mejnartowicz , Poland
  • Dr Larraitz Arriola, Spain
  • Dr Karin Kallen, Sweden
  • Dr Marie-Claude Addor, Switzerland
  • David Tucker, United Kingdom
  • Dr Diana Wellesley, United Kingdom