Ester Garne1, Anne Vinkel Hansen2, Joan Morris3, Louise Zaupper2, Marie-Claude Addor4, Ingeborg Barisic5, Miriam Gatt6, Nathalie Lelong7, Kari Klungsøyr8, Mary O'Mahony9, Vera Nelen10, Amanda J Neville11, Anna Pierini12, David Tucker13, Hermien de Walle14, Awi Wiesel15, Maria Loane16, Helen Dolk16. 1. Paediatric Department, Hospital Lillebaelt Kolding, Kolding, Denmark. Electronic address: Ester.garne@rsyd.dk. 2. Paediatric Department, Hospital Lillebaelt Kolding, Kolding, Denmark. 3. Department of Preventive Medicine, Wolfson Institute Preventive Medicine, Queen Mary University, London, United Kingdom. 4. Service of Medical Genetics, Lausanne, Switzerland. 5. Children's Hospital Zagreb, Medical School University of Zagreb, Zagreb, Croatia. 6. Directorate for Health Information and Research, Valletta, Malta. 7. INSERM UMR 1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team (Epopé), Paris, France. 8. Department of Global Public Health and Primary Care, University of Bergen and the Norwegian Institute of Public Health, Bergen, Norway. 9. Department of Public Health, Health Service Executive South, Dublin, Ireland. 10. Provincial Institute for Hygiene, Antwerp, Belgium. 11. IMER (Emila Romagna Registry of Birth Defects), Azienda Ospedaliero-Universitaria di Ferrara, Ferrara, Italy. 12. CNR Institute of Clinical Physiology-National Research Council, Pisa, Italy. 13. Congenital Anomaly Register & Information Service for Wales, Health Intelligence Division, Public Health Wales, Swansea, United Kingdom. 14. University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 15. Department of Paediatrics, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany. 16. Institute of Nursing and Health Research, Ulster University, Newtownabbey, United Kingdom.
Abstract
BACKGROUND: Pregnant women with asthma need to take medication during pregnancy. OBJECTIVE: We sought to identify whether there is an increased risk of specific congenital anomalies after exposure to antiasthma medication in the first trimester of pregnancy. METHODS: We performed a population-based case-malformed control study testing signals identified in a literature review. Odds ratios (ORs) of exposure to the main groups of asthma medication were calculated for each of the 10 signal anomalies compared with registrations with nonchromosomal, nonsignal anomalies as control registrations. In addition, exploratory analyses were done for each nonsignal anomaly. The data set included 76,249 registrations of congenital anomalies from 13 EUROmediCAT registries. RESULTS: Cleft palate (OR, 1.63; 95% CI, 1.05-2.52) and gastroschisis (OR, 1.89; 95% CI, 1.12-3.20) had significantly increased odds of exposure to first-trimester use of inhaled β2-agonists compared with nonchromosomal control registrations. Odds of exposure to salbutamol were similar. Nonsignificant ORs of exposure to inhaled β2-agonists were found for spina bifida, cleft lip, anal atresia, severe congenital heart defects in general, or tetralogy of Fallot. None of the 4 literature signals of exposure to inhaled steroids were confirmed (cleft palate, cleft lip, anal atresia, and hypospadias). Exploratory analyses found an association between renal dysplasia and exposure to the combination of long-acting β2-agonists and inhaled corticosteroids (OR, 3.95; 95% CI, 1.99-7.85). CONCLUSIONS: The study confirmed increased odds of first-trimester exposure to inhaled β2-agonists for cleft palate and gastroschisis and found a potential new signal for renal dysplasia associated with combined long-acting β2-agonists and inhaled corticosteroids. Use of inhaled corticosteroids during the first trimester of pregnancy seems to be safe in relation to the risk for a range of specific major congenital anomalies.
BACKGROUND: Pregnant women with asthma need to take medication during pregnancy. OBJECTIVE: We sought to identify whether there is an increased risk of specific congenital anomalies after exposure to antiasthma medication in the first trimester of pregnancy. METHODS: We performed a population-based case-malformed control study testing signals identified in a literature review. Odds ratios (ORs) of exposure to the main groups of asthma medication were calculated for each of the 10 signal anomalies compared with registrations with nonchromosomal, nonsignal anomalies as control registrations. In addition, exploratory analyses were done for each nonsignal anomaly. The data set included 76,249 registrations of congenital anomalies from 13 EUROmediCAT registries. RESULTS:Cleft palate (OR, 1.63; 95% CI, 1.05-2.52) and gastroschisis (OR, 1.89; 95% CI, 1.12-3.20) had significantly increased odds of exposure to first-trimester use of inhaled β2-agonists compared with nonchromosomal control registrations. Odds of exposure to salbutamol were similar. Nonsignificant ORs of exposure to inhaled β2-agonists were found for spina bifida, cleft lip, anal atresia, severe congenital heart defects in general, or tetralogy of Fallot. None of the 4 literature signals of exposure to inhaled steroids were confirmed (cleft palate, cleft lip, anal atresia, and hypospadias). Exploratory analyses found an association between renal dysplasia and exposure to the combination of long-acting β2-agonists and inhaled corticosteroids (OR, 3.95; 95% CI, 1.99-7.85). CONCLUSIONS: The study confirmed increased odds of first-trimester exposure to inhaled β2-agonists for cleft palate and gastroschisis and found a potential new signal for renal dysplasia associated with combined long-acting β2-agonists and inhaled corticosteroids. Use of inhaled corticosteroids during the first trimester of pregnancy seems to be safe in relation to the risk for a range of specific major congenital anomalies.
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Authors: Jorieke E H Bergman; L Renée Lutke; Rijk O B Gans; Marie-Claude Addor; Ingeborg Barisic; Clara Cavero-Carbonell; Ester Garne; Miriam Gatt; Kari Klungsoyr; Nathalie Lelong; Catherine Lynch; Olatz Mokoroa; Vera Nelen; Amanda J Neville; Anna Pierini; Hanitra Randrianaivo; Anke Rissmann; David Tucker; Awi Wiesel; Helen Dolk; Maria Loane; Marian K Bakker Journal: Drug Saf Date: 2018-04 Impact factor: 5.606
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Authors: Joanne E Given; Maria Loane; Johannes M Luteijn; Joan K Morris; Lolkje T W de Jong van den Berg; Ester Garne; Marie-Claude Addor; Ingeborg Barisic; Hermien de Walle; Miriam Gatt; Kari Klungsoyr; Babak Khoshnood; Anna Latos-Bielenska; Vera Nelen; Amanda J Neville; Mary O'Mahony; Anna Pierini; David Tucker; Awi Wiesel; Helen Dolk Journal: Br J Clin Pharmacol Date: 2016-07-07 Impact factor: 4.335