Atopic outcomes in children with Down syndrome: a pilot sibling-matched case-control study.

Introduction: Atopic conditions such as wheezing, asthma, allergic rhinitis, and eczema are frequently reported in children with Down syndrome. Many previous studies have used unpaired analyses that do not account for shared familial and environmental factors. Sibling-matched designs offer a robust approach for addressing these limitations but require appropriate paired statistical methods. This study aimed to assess the feasibility of a sibling-matched design for studying atopic outcomes in children with Down syndrome and to propose an appropriate methodological and statistical framework for future larger-scale studies. Methods: This pilot sibling-matched case-control study included 34 children with Down syndrome and their unaffected siblings (34 complete sibling pairs). Binary outcomes included wheezing, severe wheezing, physician-diagnosed asthma, allergic rhinitis, and eczema. Descriptive prevalence was reported, and paired comparisons were performed using exact McNemar testing based on discordant sibling pairs. Results: Wheezing and physician-diagnosed asthma were numerically more frequent among children with Down syndrome than among their unaffected siblings, but the differences did not reach statistical significance. Statistical comparisons were driven by discordant pairs, illustrating the importance of paired analytical approaches in sibling-matched studies. Conclusions: This pilot study demonstrates the feasibility of sibling-matched designs for evaluating atopic outcomes in children with Down syndrome and highlights the importance of paired statistical methods for binary outcomes. The findings primarily serve to propose a methodological framework for future adequately powered sibling-matched studies rather than to draw definitive etiological conclusions.