May 03, 2016; 86 (18) ArticleOpen Access
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'Mahony, Anna Pierini, Anke Rißmann, David Tucker, Diana Wellesley, Awi Wiesel, Lolkje T.W. de Jong-van den Berg
First published April 6, 2016, DOI: https://doi.org/10.1212/WNL.0000000000002540
Helen Dolk
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
Hao Wang
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
Maria Loane
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
Joan Morris
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
Ester Garne
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
Marie-Claude Addor
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
Larraitz Arriola
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
Marian Bakker
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
Ingeborg Barisic
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
Berenice Doray
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
Miriam Gatt
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
Karin Kallen
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
Babak Khoshnood
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
Kari Klungsoyr
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
Anna-Maria Lahesmaa-Korpinen
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
Anna Latos-Bielenska
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
Jan P. Mejnartowicz
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
Vera Nelen
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
Amanda Neville
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
Mary O'Mahony
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
Anna Pierini
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
Anke Rißmann
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
David Tucker
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
Diana Wellesley
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
Awi Wiesel
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
Lolkje T.W. de Jong-van den Berg
From Ulster University (H.D., M.L.), Northern Ireland, UK; University of Groningen (H.W., L.T.W.d.J.-v.d.B.), the Netherlands; Barts and the London School of Medicine and Dentistry (J.M.), UK; Hospital Lillebaelt (E.G.), Kolding, Denmark; Registre Vaudois des Malformations (M.-C.A.), Lausanne, Switzerland; Public Health Division of Gipuzkoa (L.A.), Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; University Medical Centre Groningen (M.B.), the Netherlands; Children's University Hospital Zagreb (I.B.), Croatia; Registre des Malformations Congenitales D'Alsace (B.D.), University of Strasbourg, France; Department of Health Information and Research (M.G.), Malta; Swedish National Board of Health and Welfare (K. Kallen), Stockholm, Sweden; Institut National de la Sante et de la Recherche Medicale (B.K.), INSERM, Villejuif, France; Medical Birth Registry of Norway (K. Klungsoyr), Oslo; National Institute for Health & Welfare (A.-M.L.-K.), Helsinki, Finland; Poznan University of Medical Sciences (A.L.-B., J.P.M.), Poland; Provinciaal Instituut voor Hygiene (V.N.), Antwerp, Belgium; Center for Clinical and Epidemiological Research Ferrara (A.N.), Italy; Health Service Executive (M.O.), Kildare, Ireland; Institute of Clinical Physiology-National Research Council (IFC-CNR) (A.P.), Pisa, Italy; Otto-von-Guericke University Magdeburg (A.R.), Germany; Public Health Wales NHS Trust (D.T.), Congenital Anomaly Register and Information Service for Wales; Wessex Clinical Genetics Service (D.W.), Princess Anne Hospital, UK; and University Medical Center of Mainz Birth Registry Mainz Model (A.W.), Germany.
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'Mahony, Anna Pierini, Anke Rißmann, David Tucker, Diana Wellesley, Awi Wiesel, Lolkje T.W. de Jong-van den Berg
Neurology May 2016, 86 (18) 1716-1725; DOI: 10.1212/WNL.0000000000002540
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Abstract
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.
GLOSSARY
- AED=
- antiepileptic drug;
- CA=
- congenital anomaly;
- CI=
- confidence interval;
- EAC=
- external advisory committee;
- ICD-9/10=
- International Classification of Diseases–9/10;
- OC=
- orofacial cleft;
- OR=
- odds ratio;
- TOPFA=
- termination of pregnancy for fetal anomaly;
- VPA=
- valproic acid
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was paid by the authors.
Supplemental data at Neurology.org
- Received June 19, 2015.
- Accepted in final form January 26, 2016.
- © 2016 American Academy of Neurology
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.
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