Confounding and effect modification in studies of diet and childhood asthma and allergies

Objective: To propose a comprehensive set of confounders and effect modifiers that should be considered in epidemiologic investigations. 

Methods: Two reviewers independently critiqued studies included in a recent systematic review and extracted data on the confounders and effect modifiers that were considered and the approaches used to justify inclusion. 

Results: Of the 62 studies reviewed, 20 were cohort, 16 case-control, 25 cross-sectional studies, and one ecologic study. All cohort, cross-sectional, and ecologic studies had some adjustment for confounding or consideration of effect modification, but this was only the case for 7/16 (44%) case-control studies. Of the 53 studies that considered confounding or effect modification, 39/53 (74%) gave no justification for the inclusion of the variables considered. Studies that justified the inclusion of the variables did so based on empirical evidence (n = 10), conceptual justification (n = 7), or a combination of the two (n = 3). Confounding was handled mainly by using regression modeling, but some case-control studies utilized matching and anova. Ten studies handled effect modification by stratification, eight tested for interaction, and five used both strategies. 

Conclusions: We have found substantial shortcomings in the handling of confounding and effect modification in studies of diet and development of childhood asthma/allergies. Selection of variables should be based on conceptual considerations and empirical evidence. Using this approach, we have proposed a comprehensive set of confounders and effect modifiers that need to be considered in future studies.