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تسجيل مستخدم جديدBayesian kernel machine regression-causal mediation analysis
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Greater understanding of the pathways through which an environmental mixture operates is important to design effective interventions. We present new methodology to estimate the natural direct effect (NDE), natural indirect effect (NIE), and controlled direct effects (CDEs) of a complex mixture exposure on an outcome through a mediator variable. We implement Bayesian Kernel Machine Regression (BKMR) to allow for all possible interactions and nonlinear effects of 1) the co-exposures on the mediator, 2) the co-exposures and mediator on the outcome, and 3) selected covariates on the mediator and/or outcome. From the posterior predictive distributions of the mediator and outcome, we simulate counterfactuals to obtain posterior samples, estimates, and credible intervals of the mediation effects. Our simulation study demonstrates that when the exposure-mediator and exposure-mediator-outcome relationships are complex, BKMR-Causal Mediation Analysis performs better than current mediation methods. We applied our methodology to quantify the contribution of birth length as a mediator between in utero co-exposure to arsenic, manganese and lead, and childrens neurodevelopmental scores, in a prospective birth cohort in Bangladesh. Among younger children, we found a negative association between the metal mixture and neurodevelopment. We also found evidence that birth length mediates the effect of exposure to the metal mixture on neurodevelopment for younger children. If birth length were fixed to its $75^{th}$ percentile value, the effect of the metal mixture on neurodevelopment decreases, suggesting that nutritional interventions to help increase birth length could potentially block the harmful effects of the metal mixture on neurodevelopment.
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