title: Antibiotics in fetal and early life and subsequent childhood asthma: nationwide population based study with sibling analysis.
abstract: OBJECTIVE
  To investigate the association between exposure to antibiotics in fetal and early life and asthma in childhood, with adjustment for confounding factors.
  
  
  METHODS
  Nationwide prospective population based cohort study, including sibling control design.
  
  
  METHODS
  Swedish population identified from national demographic and health registers.
  
  
  METHODS
  493,785 children born 2006-10; 180,894 of these were eligible for sibling analyses.
  
  
  METHODS
  Asthma defined as having both an asthma diagnosis and dispensed asthma drugs. The association between antibiotic exposure and asthma was investigated in the whole cohort with Cox proportional hazard regression. A stratified proportional hazards model conditional on sibling group was used to adjust for shared factors within families. Confounding by respiratory infections was assessed by investigating whether specific groups of antibiotics were associated with asthma.
  
  
  RESULTS
  Antibiotic exposure in fetal life was associated with an increased risk of asthma in cohort analyses (hazard ratio 1.28, 95% confidence interval 1.25 to 1.32), but not in sibling analyses (0.99, 0.92 to 1.07). In cohort analyses, antibiotics used to treat respiratory infections in childhood were associated with a more pronounced increased risk of asthma (4.12, 3.78 to 4.50) than antibiotics used for urinary tract and skin infections (1.54, 1.24 to 1.92). In sibling analyses, the excess risks after exposure to antibiotics for respiratory infections decreased (2.36, 1.78 to 3.13) and disappeared for antibiotics for urinary tract and skin (0.85, 0.47 to 1.55).
  
  
  CONCLUSIONS
  Previous positive associations between exposure to antibiotics in fetal and early life and subsequent childhood asthma could have been caused by confounding by shared familial factors, in addition to confounding by respiratory infections.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, 17177 Stockholm, Sweden Anne.ortqvist@ki.se.
authors.forename: Anne K
authors.initials: AK
authors.lastname: Örtqvist
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, 17177 Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lundholm
authors.affiliation: Centre for Pharmacoepidemiology T2, Department of Medicine, Karolinska University Hospital, 17176 Stockholm, Sweden.
authors.forename: Helle
authors.initials: H
authors.lastname: Kieler
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, 17177 Stockholm, Sweden Department of Paediatrics, Örebro University Hospital, 70185 Örebro, Sweden.
authors.forename: Jonas F
authors.initials: JF
authors.lastname: Ludvigsson
authors.affiliation: Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Dag Hammarskjöldsväg 14B, Uppsala Science Park, Uppsala, Sweden.
authors.forename: Tove
authors.initials: T
authors.lastname: Fall
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, 17177 Stockholm, Sweden.
authors.forename: Weimin
authors.initials: W
authors.lastname: Ye
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, 17177 Stockholm, Sweden Astrid Lindgren Children's Hospital, Lung and Allergy Unit, Karolinska University Hospital, 17176 Stockholm, Sweden.
authors.forename: Catarina
authors.initials: C
authors.lastname: Almqvist
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001249:Asthma / Q000453:epidemiology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000453:epidemiology; D035781:Siblings; D017192:Skin Diseases, Bacterial / Q000188:drug therapy*; D013548:Sweden / Q000453:epidemiology; D014552:Urinary Tract Infections / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents