title: Use of asthma medication during pregnancy and risk of specific congenital anomalies: A European case-malformed control study.
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.
authors.affiliation: Paediatric Department, Hospital Lillebaelt Kolding, Kolding, Denmark. Electronic address: Ester.garne@rsyd.dk.
authors.forename: Ester
authors.initials: E
authors.lastname: Garne
authors.affiliation: Paediatric Department, Hospital Lillebaelt Kolding, Kolding, Denmark.
authors.forename: Anne Vinkel
authors.initials: AV
authors.lastname: Hansen
authors.affiliation: Department of Preventive Medicine, Wolfson Institute Preventive Medicine, Queen Mary University, London, United Kingdom.
authors.forename: Joan
authors.initials: J
authors.lastname: Morris
authors.affiliation: Paediatric Department, Hospital Lillebaelt Kolding, Kolding, Denmark.
authors.forename: Louise
authors.initials: L
authors.lastname: Zaupper
authors.affiliation: Service of Medical Genetics, Lausanne, Switzerland.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Addor
authors.affiliation: Children's Hospital Zagreb, Medical School University of Zagreb, Zagreb, Croatia.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Barisic
authors.affiliation: Directorate for Health Information and Research, Valletta, Malta.
authors.forename: Miriam
authors.initials: M
authors.lastname: Gatt
authors.affiliation: INSERM UMR 1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team (Epopé), Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lelong
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen and the Norwegian Institute of Public Health, Bergen, Norway.
authors.forename: Kari
authors.initials: K
authors.lastname: Klungsøyr
authors.affiliation: Department of Public Health, Health Service Executive South, Dublin, Ireland.
authors.forename: Mary
authors.initials: M
authors.lastname: O'Mahony
authors.affiliation: Provincial Institute for Hygiene, Antwerp, Belgium.
authors.forename: Vera
authors.initials: V
authors.lastname: Nelen
authors.affiliation: IMER (Emila Romagna Registry of Birth Defects), Azienda Ospedaliero-Universitaria di Ferrara, Ferrara, Italy.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Neville
authors.affiliation: CNR Institute of Clinical Physiology-National Research Council, Pisa, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Pierini
authors.affiliation: Congenital Anomaly Register & Information Service for Wales, Health Intelligence Division, Public Health Wales, Swansea, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Tucker
authors.affiliation: University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Hermien
authors.initials: H
authors.lastname: de Walle
authors.affiliation: Department of Paediatrics, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Awi
authors.initials: A
authors.lastname: Wiesel
authors.affiliation: Institute of Nursing and Health Research, Ulster University, Newtownabbey, United Kingdom.
authors.forename: Maria
authors.initials: M
authors.lastname: Loane
authors.affiliation: Institute of Nursing and Health Research, Ulster University, Newtownabbey, United Kingdom.
authors.forename: Helen
authors.initials: H
authors.lastname: Dolk
mesh_terms: D000305:Adrenal Cortex Hormones / Q000009:adverse effects* / Q000627:therapeutic use; D058666:Adrenergic beta-2 Receptor Agonists / Q000009:adverse effects* / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D016022:Case-Control Studies; D000013:Congenital Abnormalities / Q000453:epidemiology* / Q000209:etiology; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D016017:Odds Ratio; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011297:Prenatal Exposure Delayed Effects; D012306:Risk
chemical_list: D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D018927:Anti-Asthmatic Agents
keywords: Asthma medication; congenital anomalies; first trimester exposure; inhaled corticosteroids; inhaled β(2)-agonists; pregnancy