Everything All at Once: On Choosing an Estimand for Multi-component Environmental Exposures.

Many research questions-particularly those in environmental health-do not involve binary exposures. In environmental epidemiology, this includes multivariate exposure mixtures with nondiscrete components. Causal inference estimands and estimators to quantify the relationship between an exposure mixture and an outcome are relatively few. We propose an approach to quantify a relationship between a shift in the exposure mixture and the outcome-either in a single timepoint or longitudinal setting. The shift in the exposure mixture can be defined flexibly in terms of shifting one or more components, including examining the interaction between mixture components, and in terms of shifting the same or different amounts across components. The estimand we discuss has a similar interpretation as a main effect regression coefficient. First, we focus on choosing a shift in the exposure mixture supported by observed data. We demonstrate how to assess extrapolation and modify the shift to minimize reliance on extrapolation. Second, we propose estimating the relationship between the exposure mixture shift and outcome completely nonparametrically, using machine learning in model fitting. This is in contrast to other common approaches, which employ parametric modeling for at least some relationships, which we would like to avoid, because parametric modeling assumptions in complex, nonrandomized settings are tenuous at best. We are motivated by longitudinal data on pesticide exposures among participants in the Center for the Health Assessment of Mothers and Children of Salinas Maternal Cognition cohort. We examine the relationship between longitudinal exposure to agricultural pesticides and risk of hypertension. We provide step-by-step code to facilitate the easy replication and adaptation of the proposed approach.