title: Twins' risk of childhood asthma mediated by gestational age and birthweight.
abstract: BACKGROUND
  Children born with low gestational age (GA) or low birthweight (BW) are at increased risk of asthma. Twins as compared to singletons are on average more likely to be born with lower GA and BW and have been hypothesized to comprise a high-risk population for asthma. Many previous studies have not accounted for potential confounders or mediators.
  
  
  OBJECTIVE
  To investigate the association between twinship and childhood asthma or early life wheeze and identify potential mediators, such as GA/BW.
  
  
  METHODS
  The study population consisted of two cohorts including all children born in Sweden from 1 January 1993 to 1 June 2001 (n = 756,363 singletons, n = 22,478 twins) and 1 July 2005 to 31 December 2009 (n = 456,239 singletons, n = 12,872 twins). Asthma was defined using validated register-based outcomes of diagnosis or medication. The data were analysed using logistic (older cohort) and Cox regression (younger cohort). Adjusted models incorporated potential confounding or mediating factors including gestational age and birthweight.
  
  
  RESULTS
  In the younger cohort, the crude hazard ratio (HR) of asthma medication after 1.5 years of age was 1.12 (95% CI 1.01-1.23), and fully adjusted HR was 0.80, 95% CI 0.72-0.89. Crude HR of asthma diagnosis in the same age group was 1.14 (95% CI 0.99-1.30), fully adjusted 0.78 (0.68-0.98). Adjusted analyses in the older group yielded similar results.
  
  
  CONCLUSIONS
  Twins were at significantly higher unadjusted risk of asthma or early life wheeze compared to singletons in the younger, but not in the older cohort. Associations attenuated following adjustment for GA/BW, suggesting that GA/BW mediates the effect of twinship on asthma risk. After adjustments, twins were at lower risk of asthma outcomes, possibly due to unmeasured confounding.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: V
authors.identifier: http://orcid.org/0000-0002-8759-765X
authors.initials: V
authors.lastname: Ullemar
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Lundholm
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Lung and Allergy Unit, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Almqvist
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000453:epidemiology*; D001724:Birth Weight; D002648:Child; D005260:Female; D005865:Gestational Age; D006801:Humans; D008297:Male; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D014427:Twins
keywords: birthweight; child; epidemiology; gestational age; population-based birth cohort; risk factors; twinship