Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry

作者：Torbjörn Tomson, Dina Battino, Erminio Bonizzoni, John J. Craig, Dick Lindhout, Emilio Perucca, Anne Sabers, Sanjeev V. Thomas, Frank J.E. Vajda, Francesca Faravelli, Chiara Pantaleoni, Elisabeth Robert‐Gnansia, Leonor Cabral‐Lim, Boštjan Čebular, Alejandro de Marinis, Reetta K. Kälviäinen, Ketevan Khomeriki, Gordana Kiteva-Trencevska, Silvia S. Kochen, Martin Kurthen, Gerhard Luef, Meritxell Martínez Ferri, Maja Milovanović, Karl Otto Nakken, Miri Y. Neufeld, Hideyuki Ohtani, Aline Russell, Vladimír Šafčák, Bettina Schmitz, Luigi Maria Specchio, Barbara Tettenborn, Eugène van Puijenbroek, Hsiang‐Yu Yu, Jana Zárubová, Claus Albretsen, Silje Alvestad, Noémi Becser Andersen, Luisa Antonini, Jens Arentsen, Dag Aurlien, Ismael Barzinji, Juan Luís Becerra, Natalia Bohórquez Morera, Martin J. Brodie, Eylert Brodtkorb, Laura Broglio, Elsebeth Bruun Christensen, Petr Bušek, Claudia Cagnetti, Maria Paola Canevini, Astrid Carius, María Dolores Castro Vilanova, Michela Cecconi, T-Y Chang, Jakob Christensen, Giovanni De Maria, Dieter Dennig, Brenda Diputado, Janne Marit Ertresvåg, Toni Escartin, Dominique Flügel, Birgitte Forsom Sondal, Nicoletta Foschi, Albertina Franza, Katsuyuki Fukushima, Antonio Gambardella, Iñigo Garamendi Ruiz, Helena Gauffin, Pia Gellert, Leif Gjerstad, Lisa M. Gordon, Katrine Haggag, Imad Halawa, Terttu Heikinheimo-Connell, Tim Hendgen, Zarouhi Hertz, Odo Hildenhagen, Stephanie Hödl, Ineke Hogenesch, Anette Huuse Farmen, Yushi Inoue, Stefan Juhl, Masaaki Kato, Germaine Kenou Van Rijckevorssel, Emily Kluck, Hana Krijtová, Eva Kumlien, Angelo Labate, Theresa Lasch, Hans Lindsten, Renata Listonova, Rasmus Lossius, Anders Lundgren, Kristina Malmgren, Iva Marečková, Daniela Marino, Peter A. Mattsson, Aileen McGonigal, Katarzyna Miesczanleh, Masahiro Mizobuchi, Barbara Mostacci, Birgit Müffelmann, Uden Navn, Anders Nilsson, Bernhard Oehl, Andrea Ortenzi, Judith Osseforth, Aldo Paggi, Eliana Pastor, Birthe Pedersen, Vaiva Petrenaite, Pietro Pignatta, Isabel Pires, Alessandra Pistelli, Jesús Antonio Riuz Gimenez, Raffaele Rocchi, Lone Rodam, Reina Roivainen, Gisela Rytířová, Christian Samsonsen, Gemma Sansa Fayos, Anna Maija Saukkonen, Alma Sikiric, David Sopelana Garay, Bernhard Jochen Steinhoff, Maria Strandberg, Torleiv Svendsen, Erik Taubøll, Kiyohito Terada, Marina Trivisano, Katherine L. Turner, Mogens Worm, Elias Zakharia, Elena Zambrelli, Morteza Zarifi-Oskoie · 发表于：The Lancet Neurology · 年份：2018 · DOI：10.1016/s1474-4422(18)30107-8 · 被引用次数：549 · 研究领域：Pharmacological Effects and Toxicity Studies、Pregnancy and Medication Impact、Epilepsy research and treatment

BACKGROUND: Evidence for the comparative teratogenic risk of antiepileptic drugs is insufficient, particularly in relation to the dosage used. Therefore, we aimed to compare the occurrence of major congenital malformations following prenatal exposure to the eight most commonly used antiepileptic drugs in monotherapy. METHODS: We did a longitudinal, prospective cohort study based on the EURAP international registry. We included data from pregnancies in women who were exposed to antiepileptic drug monotherapy at conception, prospectively identified from 42 countries contributing to EURAP. Follow-up data were obtained after each trimester, at birth, and 1 year after birth. The primary objective was to compare the risk of major congenital malformations assessed at 1 year after birth in offspring exposed prenatally to one of eight commonly used antiepileptic drugs (carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate, and valproate) and, whenever a dose dependency was identified, to compare the risks at different dose ranges. Logistic regression was used to make direct comparisons between treatments after adjustment for potential confounders and prognostic factors. FINDINGS: Between June 20, 1999, and May 20, 2016, 7555 prospective pregnancies met the eligibility criteria. Of those eligible, 7355 pregnancies were exposed to one of the eight antiepileptic drugs for which the prevalence of major congenital malformations was 142 (10·3%) of 13...