Comparing two counterfactual-outcome approaches in causal mediation analysis of a multicategorical exposure: An application for the estimation of the effect of maternal intake of inhaled corticosteroids doses on birthweight

Although medical research frequently involves an exposure variable with three or more discrete levels, detailed presentations of mediation techniques for dealing with multicategorical (multilevel) exposures are sparse. In this paper, we study two causal mediation approaches applicable to such a type of exposure for continuous mediator and outcome: the closed-form regression-based approach of Valeri and VanderWeele, and the marginal structural model-based approach of Lange, Vansteelandt, and Bekaert. While the consideration of multicategorical exposures is found explicitly addressed in the literature for the latter approach, this is, to our knowledge, not yet the case for the former. We first illustrate the application of the two aforementioned approaches to assess the dose-response relationship between maternal intake of inhaled corticosteroids and birthweight, where this relationship is potentially mediated by gestational age. More specifically, we provide a precise roadmap for the application of the regression-based approach and of the marginal structural model-based approach on our cohort of pregnancies. Expressions for the natural direct and indirect effects associated with our categorical exposure are provided and, for the regression-based approach, analytic formulas for standard error calculation using the delta method are presented for these effects. Second, a simulation study which mimics our data is presented to add to current knowledge on these causal mediation techniques. Results from this study highlight the relevance to assess robustness of mediation results obtained from multicategorical exposures, most notably for the least prevalent of exposure categories.