title: Risk of congenital anomalies after exposure to asthma medication in the first trimester of pregnancy - a cohort linkage study.
abstract: OBJECTIVE
  To examine the effect of maternal exposure to asthma medications on the risk of congenital anomalies.
  
  
  METHODS
  Meta-analysis of aggregated data from three cohort studies.
  
  
  METHODS
  Linkage between healthcare databases and EUROCAT congenital anomaly registries.
  
  
  METHODS
  519 242 pregnancies in Norway (2004-2010), Wales (2000-2010) and Funen, Denmark (2000-2010).
  
  
  METHODS
  Exposure defined as having at least one prescription for asthma medications issued (Wales) or dispensed (Norway, Denmark) from 91 days before to 91 days after the pregnancy start date. Odds ratios (ORs) were estimated separately for each register and combined in meta-analyses.
  
  
  METHODS
  ORs for all congenital anomalies and specific congenital anomalies.
  
  
  RESULTS
  Overall exposure prevalence was 3.76%. For exposure to asthma medication in general, the adjusted OR (adjOR) for a major congenital anomaly was 1.21 (99% CI 1.09-1.34) after adjustment for maternal age and socioeconomic position. The OR of anal atresia was significantly increased in pregnancies exposed to inhaled corticosteroids (3.40; 99% CI 1.15-10.04). For severe congenital heart defects, an increased OR (1.97; 1.12-3.49) was associated with exposure to combination treatment with inhaled corticosteroids and long-acting beta-2-agonists. Associations with renal dysplasia were driven by exposure to short-acting beta-2-agonists (2.37; 1.20-4.67).
  
  
  CONCLUSIONS
  The increased risk of congenital anomalies for women taking asthma medication is small with little confounding by maternal age or socioeconomic status. The study confirmed the association of inhaled corticosteroids with anal atresia found in earlier research and found potential new associations with combination treatment. The potential new associations should be interpreted with caution due to the large number of comparisons undertaken.
  
  
  CONCLUSIONS
  This cohort study found a small increased risk of congenital anomalies for women taking asthma medication.
authors.affiliation: Paediatric Department, Hospital Lillebaelt -Kolding, Kolding, Denmark.
authors.forename: E
authors.initials: E
authors.lastname: Garne
authors.affiliation: Paediatric Department, Hospital Lillebaelt -Kolding, Kolding, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Vinkel Hansen
authors.affiliation: Department Preventive Medicine, Wolfson Institute Preventive Medicine, Queen Mary University of London, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Morris
authors.affiliation: College of Human & Health Science, University of Swansea, Swansea, Wales, UK.
authors.forename: S
authors.initials: S
authors.lastname: Jordan
authors.affiliation: Medical Birth Registry of Norway, Norwegian Institute of Public Health and Department of Global Health and Primary Care, University of Bergen, Bergen, Norway.
authors.forename: K
authors.initials: K
authors.lastname: Klungsøyr
authors.affiliation: Medical Birth Registry of Norway, Norwegian Institute of Public Health and Department of Global Health and Primary Care, University of Bergen, Bergen, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Engeland
authors.affiliation: Congenital Anomaly Register and Information Service for Wales, Health Intelligence Division, Public Health Wales, Swansea, UK.
authors.forename: D
authors.initials: D
authors.lastname: Tucker
authors.affiliation: College of Human & Health Science, University of Swansea, Swansea, Wales, UK.
authors.forename: D S
authors.initials: DS
authors.lastname: Thayer
authors.affiliation: College of Human & Health Science, University of Swansea, Swansea, Wales, UK.
authors.forename: G I
authors.initials: GI
authors.lastname: Davies
authors.affiliation: Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
authors.forename: A-M
authors.initials: AM
authors.lastname: Nybo Andersen
authors.affiliation: Ulster University, Londonderry, UK.
authors.forename: H
authors.initials: H
authors.lastname: Dolk
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology*; D058186:Acute Kidney Injury / Q000453:epidemiology; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects*; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D000328:Adult; D000336:Aerosols / Q000009:adverse effects; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001006:Anus, Imperforate / Q000453:epidemiology; D001249:Asthma / Q000188:drug therapy*; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006330:Heart Defects, Congenital / Q000453:epidemiology; D006801:Humans; D007231:Infant, Newborn; D009664:Norway / Q000453:epidemiology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology*; D011261:Pregnancy Trimester, First; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology; D015995:Prevalence; D012042:Registries; D012107:Research Design / Q000706:statistics & numerical data; D012307:Risk Factors; D014852:Wales / Q000453:epidemiology
chemical_list: D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D000336:Aerosols; D018927:Anti-Asthmatic Agents
keywords: Asthma medication; congenital anomalies; first trimester exposure; inhaled beta-2 agonists; inhaled corticosteroids