Does eczema in infancy cause hay fever, asthma, or both in childhood? Insights from a novel regression model of sibling data

Background: The atopic march hypothesis proposes that eczema precedes the development of asthma and allergic rhinitis. Objective: We sought to assess the evidence for a causal effect of infantile eczema on childhood hay fever, asthma, or both. Methods: We used parental reports on infantile eczema and childhood asthma and hay fever for 3778 pairs of 7-year-olds matched to their sibling closest in age within 2 years from the Tasmanian Longitudinal Health Study. We analyzed paired sibling data using a logistic regression model that allowed inference about a causal effect of a familial predictor on a child's outcome by examining the change in association with their cosibling's predictor after adjusting for their own predictor status. Results: Siblings were concordant for infantile eczema (tetrachoric correlation, 0.40). For having both hay fever and asthma by age 7 years, the association with cosibling's eczema was an odds ratio (OR) of 1.98 (95% CI, 1.37-2.86), which reduced after adjusting for own eczema to an OR of 1.65 (95% CI, 1.17-2.34). For having hay fever only, the association with cosibling's eczema was an OR of 1.68 (95% CI, 1.22-2.31) before and an OR of 1.59 (95% CI, 1.19-2.14) after adjusting for own eczema. There was no association between having asthma only and cosibling's eczema (OR, 1.00; 95% CI, 0.77-1.30). Conclusions: Eczema in infancy might have a causal effect on hay fever in children with and perhaps without asthma. The association of infantile eczema on asthma in children without hay fever, which might be early transient wheeze, is unlikely to be causal or familial. These findings have implications for hay fever prevention. (J Allergy Clin Immunol 2012;130:1117-22.)