Teratogenicity of mycophenolate confirmed in a prospective study of the European Network of Teratology Information Services

American Journal of Medical Genetics, Part A - Tập 158A Số 3 - Trang 588-596 - 2012
Maria Hoeltzenbein1, Élisabeth Éléfant2, Thierry Vial3, Victoriya Finkel‐Pekarsky4, Sally Stephens5, Maurizio Clementi6, Arthur Allignol7, Corinna Weber‐Schoendorfer1, Christof Schaefer1
1Pharmakovigilanzzentrum Embryonaltoxikologie, Charité Universitätsmedizin Berlin, Germany
2Centre de Référence sur les Agents Tératogènes, Paris, France
3Centre de Pharmacovigilance de Lyon, Lyon, France
4Israel Teratogen Information Service, Jerusalem, Israel
5UK Teratology Information Service, Newcastle upon Tyne, England
6Servizio Informazione Terologica, Padua, Italy
7Institut für Medizinische Biometrie und Medizinische Informatik, Freiburg, Germany

Tóm tắt

AbstractAfter maternal exposure to mycophenolate in pregnancy a high number of fetal losses and a specific pattern of birth defects consisting of microtia, cleft lip, and other anomalies have been reported. However, so far, prospective data on pregnancy outcome allowing quantitative risk assessment are missing. We report on 57 prospectively ascertained pregnancies after maternal therapy with mycophenolate (mycophenolate mofetil or mycophenolate sodium) identified by European Teratology Information Services (ETIS) through their risk consultation process. The outcome of these prospective pregnancies was as follows: 16 spontaneous abortions, 12 elective terminations of pregnancy (ETOP) (including two late terminations for multiple malformations consistent with mycophenolate embryopathy), and 29 liveborn infants. The probability of spontaneous abortion was about 45% (95% CI 29 to 66%) estimated using survival analysis technique. Six out of 29 live born infants had major congenital defects: Two with external auditory canal atresia (EACA) (with and without microtia), one with tracheo‐esophageal atresia, one with severe hydronephrosis, one with an atrial septal defect (ASD) and one with a myelomeningocele. Thus, at least four fetuses/infants of our prospective case series had a clinical phenotype consistent with mycophenolate embryopathy. Our results confirm a high incidence of major malformations (26%) after first trimester exposure to mycophenolate. Apart from exposure to mycophenololate, the underlying maternal disease and concomitant medication may also have contributed to the other poor pregnancy outcomes such as a high rate of spontaneous abortions, prematurity (62%), and low birth weight (31%). © 2012 Wiley Periodicals, Inc.

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American Journal of Medical Genetics, Part A

Tập 158A Số 3

588-596

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