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Allergy. 2012 Aug;67(8):1041-59. doi: 10.1111/j.1398-9995.2012.02858.x. Epub 2012 Jun 19.

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

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Allergy & Respiratory Research Group, Centre for Population Health Sciences, Medical School, The University of Edinburgh, Edinburgh, UK.

Erratum in

  • Allergy. 2015 Apr;70(4):465.



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


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.


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.


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.

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