Alana Cavadino1, Lovisa Sandberg2, Inger Öhman2, Tomas Bergvall2, Kristina Star2,3, Helen Dolk4, Maria Loane4, Marie-Claude Addor5, Ingeborg Barisic6, Clara Cavero-Carbonell7, Ester Garne8, Miriam Gatt9, Babak Khoshnood10, Kari Klungsøyr11, Anna Latos-Bielenska12, Nathalie Lelong10, Reneé Lutke13, Anna Materna-Kiryluk12, Vera Nelen14, Amanda Nevill15, Mary O'Mahony16, Olatz Mokoroa17, Anna Pierini18, Hanitra Randrianaivo19, Anke Rissmann20, David Tucker21, Awi Wiesel22, Lyubov Yevtushok23, Joan K Morris24. 1. School of Population Health, the University of Auckland, Auckland, New Zealand. 2. Uppsala Monitoring Centre, Uppsala, Sweden. 3. Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden. 4. Institute of Nursing and Health Research, Ulster University, Newtownabbey, Northern Ireland, UK. 5. Department of Woman-Mother-Child, University Hospital Center CHUV, CH 1011, Lausanne, Switzerland. 6. Children's Hospital Zagreb, Centre of Excellence for Reproductive and Regenerative Medicine, Medical School University of Zagreb, Zagreb, Croatia. 7. Rare Diseases Research Unit, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region, Valencia, Spain. 8. Paediatric Department, Hospital Lillebaelt, Kolding, Denmark. 9. Malta Congenital Anomalies Registry, Directorate for Health Information and Research, Tal-Pietà, Malta. 10. Paris Registry of Congenital Malformations, Obstetrical, Perinatal and Paediatric Epidemiology Research Team, Centre for Biostatistics and Epidemiology, INSERM, UMR 1153, Paris, France. 11. Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway. 12. Department of Medical Genetics, Poznan University of Medical Sciences, Poznań, Poland. 13. Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands. 14. Department of Environment, PIH, Antwerp, Belgium. 15. IMER Registry (Emila Romagna Registry of Birth Defects), Center for Clinical and Epidemiological Research, University of Ferrara, Azienda Ospedaliero, Italy. 16. Department of Public Health, Health Service Executive-South, Cork, Ireland. 17. Basque Government, Department of Health, Public Health Division of Gipuzkoa, Donostia-San Sebastian, Spain. 18. Tuscany Registry of Congenital Defects (RTDC), Institute of Clinical Physiology, National Research Council/Fondazione Toscana Gabriele Monasterio, Pisa, Italy. 19. Unit of congenital malformations, REMACOR- Medical School University of La Réunion St Pierre, Sainte-Clotilde, France. 20. Malformation Monitoring Centre Saxony-Anhalt, Medical Faculty Otto-von-Guericke-University, Magdeburg, Germany. 21. Congenital Anomaly Register and Information Service for Wales, Public Health Wales Knowledge Directorate, Level 3, West Wing Block, Singleton Hospital, Sketty Lane, Swansea, UK. 22. Department of Pediatrics, Birth Registry Mainz Model, University Medical Center of Mainz, Mainz, Germany. 23. OMNI-Net Ukraine Birth Defects Program and Rivne Regional Medical Diagnostic Center, Rivne, Ukraine. 24. Population Health Research Institute, St George's, University of London, London, UK. jmorris@sgul.ac.uk.
Abstract
INTRODUCTION: Knowledge on the safety of medication use during pregnancy is often sparse. Pregnant women are generally excluded from clinical trials, and there is a dependence on post-marketing surveillance to identify teratogenic medications. AIMS: This study aimed to identify signals of potentially teratogenic medications using EUROmediCAT registry data on medication exposure in pregnancies with a congenital anomaly, and to investigate the use of VigiBase reports of adverse events of medications in the evaluation of these signals. METHODS: Signals of medication-congenital anomaly associations were identified in EUROmediCAT (21,636 congenital anomaly cases with 32,619 medication exposures), then investigated in a subset of VigiBase (45,749 cases and 165,121 exposures), by reviewing statistical reporting patterns and VigiBase case reports. Evidence from the literature and quantitative and qualitative aspects of both datasets were considered before recommending signals as warranting further independent investigation. RESULTS: EUROmediCAT analysis identified 49 signals of medication-congenital anomaly associations. Incorporating investigation in VigiBase and the literature, these were categorised as follows: four non-specific medications; 11 likely due to maternal disease; 11 well-established teratogens; two reviewed in previous EUROmediCAT studies with limited additional evidence; and 13 with insufficient basis for recommending follow-up. Independent investigations are recommended for eight signals: pregnen (4) derivatives with limb reduction; nitrofuran derivatives with cleft palate and patent ductus arteriosus; salicylic acid and derivatives with atresia or stenosis of other parts of the small intestine and tetralogy of Fallot; carbamazepine with atrioventricular septal defect and severe congenital heart defect; and selective beta-2-adrenoreceptor agonists with posterior urethral valve and/or prune belly. CONCLUSION: EUROmediCAT data should continue to be used for signal detection, accompanied by information from VigiBase and review of the existing literature to prioritise signals for further independent evaluation.
INTRODUCTION: Knowledge on the safety of medication use during pregnancy is often sparse. Pregnant women are generally excluded from clinical trials, and there is a dependence on post-marketing surveillance to identify teratogenic medications. AIMS: This study aimed to identify signals of potentially teratogenic medications using EUROmediCAT registry data on medication exposure in pregnancies with a congenital anomaly, and to investigate the use of VigiBase reports of adverse events of medications in the evaluation of these signals. METHODS: Signals of medication-congenital anomaly associations were identified in EUROmediCAT (21,636 congenital anomaly cases with 32,619 medication exposures), then investigated in a subset of VigiBase (45,749 cases and 165,121 exposures), by reviewing statistical reporting patterns and VigiBase case reports. Evidence from the literature and quantitative and qualitative aspects of both datasets were considered before recommending signals as warranting further independent investigation. RESULTS: EUROmediCAT analysis identified 49 signals of medication-congenital anomaly associations. Incorporating investigation in VigiBase and the literature, these were categorised as follows: four non-specific medications; 11 likely due to maternal disease; 11 well-established teratogens; two reviewed in previous EUROmediCAT studies with limited additional evidence; and 13 with insufficient basis for recommending follow-up. Independent investigations are recommended for eight signals: pregnen (4) derivatives with limb reduction; nitrofuran derivatives with cleft palate and patent ductus arteriosus; salicylic acid and derivatives with atresia or stenosis of other parts of the small intestine and tetralogy of Fallot; carbamazepine with atrioventricular septal defect and severe congenital heart defect; and selective beta-2-adrenoreceptor agonists with posterior urethral valve and/or prune belly. CONCLUSION: EUROmediCAT data should continue to be used for signal detection, accompanied by information from VigiBase and review of the existing literature to prioritise signals for further independent evaluation.
Authors: Anders Engeland; Tone Bjørge; Kari Klungsøyr; Vidar Hjellvik; Svetlana Skurtveit; Kari Furu Journal: Pharmacoepidemiol Drug Saf Date: 2018-06-19 Impact factor: 2.890
Authors: A Lupattelli; O Spigset; M J Twigg; K Zagorodnikova; A C Mårdby; M E Moretti; M Drozd; A Panchaud; K Hämeen-Anttila; A Rieutord; R Gjergja Juraski; M Odalovic; D Kennedy; G Rudolf; H Juch; A Passier; I Björnsdóttir; H Nordeng Journal: BMJ Open Date: 2014-02-17 Impact factor: 2.692