Live-Birth Bias and Observed Associations Between Air Pollution and Autism

A recent analysis found that exposure to air pollution during specific weeks of pregnancy was negatively associated with risk of autism spectrum disorder (ASD) when mutually adjusted for postnatal air-pollution exposure. In this commentary, we describe 2 possible selection-bias processes that might lead to such results, both related to live-birth bias (i.e., the inevitable restriction of the analyzed sample to live births). The first mechanism is described using a directed acyclic graph and relates to the chance of live birth being a common consequence of both exposure to air pollution and another risk factor of ASD. The second mechanism involves preferential depletion of fetuses susceptible to ASD in the higher air-pollution exposure group. We further discuss the assumptions underlying these processes and their causal structures, their plausibility, and other studies where similar phenomena might have occurred.