Finding
Should the former be true, it implies that adverse preand perinatal events are autism risk factors and may be amenable to prevention and intervention efforts.
Paper
Invited Commentary: Risk Factors for Autism—Perinatal Factors, Parental Psychiatric History, and Socioeconomic Status
Citations: 10
Full textAbstract
The paper by Larsson et al. (1) in this issue of the Journal adds to an accumulating body of evidence from relatively large, population-based observational studies (2, 3) suggesting that pregnancy complications and adverse birth outcomes are associated with subsequent risk of autism. As the struggle to understand the etiology of this devastating neurodevelopmental disorder continues, this growing literature offers promising opportunities for future research. In their discussion, Larsson et al. (1) touch on the challenge of determining whether an observed association between obstetric suboptimality and autism risk reflects an independent causal contribution or whether it arises merely as a by-product of genetic susceptibility. Should the former be true, it implies that adverse preand perinatal events are autism risk factors and may be amenable to prevention and intervention efforts. Prior to Larsson et al., few studies collected data informing this distinction between causal effects of obstetric suboptimality and genetic susceptibility (4, 5). As more large epidemiologic studies of autism risk factors are developed, careful consideration should be given to addressing this critical question. To foster this work, we present some simple causal diagrams (i.e., directed acyclic graphs (6)) to formalize and contrast competing causal models relating genetic susceptibility, obstetric suboptimality (the general term we will use to refer to adverse preor perinatal events), and autism. Figure 1 shows four basic causal diagrams; the arrows represent direct causal effects. These diagrams are obvious simplifications of a complex world. Such simplications can be useful to the extent that they do not omit important common causes of exposure and outcome, as well as important common causes of any mediating variable(s) and outcome. Model 1 depicts etiologic heterogeneity, with both genetic susceptibility and obstetric suboptimality having independent direct causal effects on the risk of autism. Although model 1 involves causal effects between both genetic susceptibility and obstetric suboptimality with autism, there is no causal relation between genetic susceptibility and suboptimality. Model 2 shows two epiphenomenon, or mediation, models in which genetic susceptibility is causally associated with an intermediate outcome that, in turn, is causally associated with a distal outcome. If genetic susceptibility led to the early pathologic changes underlying autism and these then reduced pregnancy optimality, it would be consistent with the first of the two epiphenomenon models. The second epiphenomenon model would apply if, for example, genetic susceptibility triggered a prenatal event that then caused autism. When either of these epiphenomenon models holds, crude associations will exist between all three variables. Model 3 illustrates shared risk factors, or confounding of the relation between obstetric suboptimality and autism due to genetic susceptibility. Under this model, genetic susceptibility is causally associated with both obstetric suboptimality and autism, but there is no causal association between obstetric suboptimality and autism. Model 4 depicts interdependency of causes or effectmeasure modification. Under this model, there is an association between obstetric suboptimality and autism only in the presence of genetic susceptibility. Table 1 summarizes key statistical associations expected under each of the alternative causal models presented in figure 1, assuming no selection bias, no measurement error, and no unmeasured confounding. If the true causal model were one of etiologic heterogeneity, then genetic susceptibility would be associated with autism even after adjusting for obstetric suboptimality. Similarly, obstetric suboptimality remains associated with autism even after adjustment for genetic susceptibility. Genetic susceptibility would not appear to be associated with obstetric suboptimality in crude
Authors
C. Newschaffer, S. Cole
Journal
American Journal of Epidemiology