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

Abstract

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.

Figure 1.

Results from a distributed-lag model representing polynomial time-dependent associations between weekly nitrogen dioxide exposure and risk of autism spectrum disorder among children born in central coastal Israel during 2005–2009 (reproduced with permission from Raz et al. (5)). The black line represents the time-varying function estimating risk of autism spectrum disorder with weekly exposures during 38 weeks of pregnancy (left) and the first 38 weeks of life (right), and the gray area around it represents its 95% confidence interval. These results are from a nonlinear distributed-lag model with 7 degrees of freedom. A linear association was assumed between the exposure and the outcome at each time point. Results were adjusted for year of birth, calendar month of birth, population group, paternal age, and census poverty index.

Figure 2.

A directed acyclic graph representing the bias resulting from conditioning on a collider. Conditioning on the collider, live birth, opens the backdoor path: Autism Spectrum Disorder (ASD) ← Unobserved (U) → Live Birth ← Air Pollution, therefore leading to selection bias.