1. Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry
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Birgitte Forsom Sondal, Zarouhi Hertz, Brenda Diputado, Meritxell Martinez Ferri, Odo Hildenhagen, Aldo Paggi, Gerhard Luef, Jakob Christensen, John Craig, Jana Zárubová, Gordana Kiteva-Trencevska, Raffaele Rocchi, Erik Tauboll, Lisa Gordon, Terttu Heikinheimo-Connell, Uden Navn, Ketevan Khomeriki, Iva Marečková, Erminio Bonizzoni, Michela Cecconi, Lone Rodam, Astrid Carius, Ineke Hogenesch, Katarzyna Miesczanleh, Angelo Labate, Eva Kumlien, Claus Albretsen, Torbjörn Tomson, Chiara Pantaleoni, David Sopelana Garay, Albertina Franza, Imad Halawa, Stefan Juhl, Emilio Perucca, Pia Gellert, Daniela Marino, Aline Russell, E. Kluck, Eylert Brodtkorb, Luigi Maria Specchio, Isabel Pires, Pietro Pignatta, Frank J.E. Vajda, Anette Huuse Farmen, Hans Lindsten, Boštjan Čebular, Maria Paola Canevini, Jens Arentsen, Francesca Faravelli, Bettina Schmitz, Noémi Becser Andersen, Birgit Müffelmann, Petr Bušek, T.-Y. Chang, Alma Sikiric, Judith Osseforth, Elias Zakharia, Elsebeth Bruun Christensen, Gemma Sansa Fayos, Vaiva Petrenaite, Alessandra Pistelli, Eliana Pastor, Hana Krijtová, Tim Hendgen, Leonor Cabral-Lim, Marina Trivisano, Hsiang-Yu Yu, Renata Listonova, Torleiv Svendsen, Vladimír Safcák, Nicoletta Foschi, Kristina Malmgren, Reetta Kälviäinen, Dag Aurlien, Martin J. Brodie, Maria Dolores Castro Vilanova, Anders Nilsson, Jesús Antonio Riuz Gimenez, Christian Samsonsen, Katsuyuki Fukushima, Maria Strandberg, Masaaki Kato, Giovanni De Maria, Katrine Haggag, Anna Maija Saukkonen, Maja Milovanovic, Masahiro Mizobuchi, Peter Mattsson, Bernhard Oehl, Anne Sabers, Juan Luis Becerra Cuñat, Mogens Worm, Antonio Gambardella, Miri Neufeld, Reina Roivainen, Kiyohito Terada, Janne Marit Ertresvåg, Birthe Pedersen, Gisela Rytířová, Claudia Cagnetti, Sanjeev V Thomas, Dick Lindhout, Silvia Kochen, Katherine Turner, Dieter Dennig, Luisa Antonini, Dina Battino, Laura Broglio, Aileen McGonigal, Helena Gauffin, Andrea Ortenzi, Ismael Barzinji, Hideyuki Ohtani, Rasmus Lossius, Elisabeth Robert-Gnansia, Morteza Zarifi-Oskoie, Leif Gjerstad, Barbara Tettenborn, Stephanie Hödl, Martin Kurthen, Barbara Mostacci, Alejandro De Marinis, Natalia Bohorquez Morera, Karl O. Nakken, Yushi Inoue, Germaine Kenou Van Rijckevorssel, Theresa Lasch, Iñigo Garamendi Ruiz, Silje Alvestad, Eugène van Puijenbroek, Anders Lundgren, Elena Zambrelli, Toni Escartin, Bernhard J. Steinhoff, Dominique Flügel, PharmacoTherapy, -Epidemiology and -Economics, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Tomson T, Battino D, Bonizzoni E, Craig J, Lindhout D, Perucca E, Sabers A, Thomas SV, Vajda F, EURAP Study Group, Bisulli F, and Tinuper P
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Pediatrics ,congenital heart malformation ,topiramate ,anticonvulsive agent ,oxcarbazepine ,Current Literature in Clinical Science ,phenobarbital ,cleft lip ,neural tube defect ,Epilepsy ,0302 clinical medicine ,newborn ,purl.org/becyt/ford/3.2 [https] ,fetus outcome ,030212 general & internal medicine ,Prospective cohort study ,Oxcarbazepine ,anticonvulsant therapy ,cleft palate ,adult ,phenytoin ,article ,longitudinal study ,Abnormalities, Drug-Induced ,polydactyly ,cohort analysis ,Kerala ,fetus ,female ,priority journal ,carbamazepine ,monotherapy ,perinatal death ,purl.org/becyt/ford/3 [https] ,Anticonvulsants ,Levetiracetam ,lamotrigine ,pregnancy ,medicine.drug ,Cohort study ,prospective study ,Topiramate ,medicine.medical_specialty ,levetiracetam ,congenital malformation ,prevalence ,first trimester pregnancy ,prenatal drug exposure ,Lamotrigine ,pregnancy termination ,live birth ,kidney malformation ,TERATOGENICIDAD ,Young Adult ,03 medical and health sciences ,male ,valproic acid ,medicine ,Humans ,fetus disease ,follow up ,human ,hypospadias ,Dose-Response Relationship, Drug ,business.industry ,EPILEPSIA ,Australia ,EMBARAZO ,multiple malformation syndrome ,Carbamazepine ,gastrointestinal malformation ,medicine.disease ,major clinical study ,United Kingdom ,Pregnancy Complications ,Logistic Models ,pregnant woman ,maternal age ,epilepsy ,Neurology (clinical) ,conception ,teratogenicity ,business ,Ireland ,030217 neurology & neurosurgery - Abstract
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 1381 pregnancies for valproate, 19 (6·5%) of 294 for phenobarbital, eight (6·4%) of 125 for phenytoin, 107 (5·5%) of 1957 for carbamazepine, six (3·9%) of 152 for topiramate, ten (3·0%) of 333 for oxcarbazepine, 74 (2·9%) of 2514 for lamotrigine, and 17 (2·8%) of 599 for levetiracetam. The prevalence of major congenital malformations increased with the dose at time of conception for carbamazepine (p=0·0140), lamotrigine (p=0·0145), phenobarbital (p=0·0390), and valproate (p
- Published
- 2018
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