Wealthy communities have more cases of ASD - What can we learn from this?
Aspects of socioeconomic status (SES) such as household income, parental education, and neighborhood environment are strongly correlated with the health and development of children (Susser et al., 1985). For most chronic childhood disorders and developmental disabilities, the association with SES has a negative correlation: higher SES levels have lower prevalence of disorders (Victoria et al., 2003). In the case of autism spectrum disorders (ASD), however, evidence for association with SES has been in the opposite direction. In the earliest clinical notes from Dr. Kanner, he recorded a preponderance of “highly intelligent parents” (Kanner, 1943). In China, autism is often referred to as a “rich man’s disease.” Many clinical and population-based studies have reported positive associations between ASD and SES. Ecological analysis from grade schools have found positive associations between school district wealth and number of children receiving autism disability special education (Palmer et al., 2009). It appears that economically disadvantaged and minority populations have the least cases of autism. Interestingly, this correlation has only been found in developed countries (Becker, 2018). Understanding these relationships, and exceptions, may provide clues to the mechanisms that underlie disorders or point out disparities in access to services. This paper aims to explore possible causes for the links we see across SES and autism prevalence.
Ascertainment Bias
A compelling argument that has been explored by many researchers is that positive associations between SES and ASD prevalence is due to ascertainment bias (Cryan et al., 1996). Ascertainment bias is when the conclusions are skewed due to the method of data collection. For example, parents of high social class families have the necessary information and financial resources to find their way to specialized facilities for developmental concerns (Tsai et al., 1982) thus driving the number of diagnosed ASD cases up. If the SES gradient is found among children with a pre-existing ASD diagnosis (Durkin et al., 2010) it would support the hypothesis that the SES gradient is a result of ascertainment bias. It suggests that autism exists in every population at the same rates (one percent of the population according to the CDC, 2019). Access to diagnostic centers and lack of information for parents would be the reason we are underestimating prevalence in lower SES communities. Since most autism centers do not accept Medicaid nor have locations in rural or inner city areas, accessibility has been a huge issue for those who do not have socioeconomic advantage. On the other hand, evidence of a similar SES gradient among children meeting diagnostic criteria for ASD who have not previously been diagnosed or classified as having ASD suggests that the ASD-SES association is not entirely due to the ascertainment bias.
Durkins et al., found that the latter was the case in the largest US cross-sectional study done on the ASD-SES link. Hence, this suggests that there factors associated with socioeconomic advantage that might be causally associated with the risk of developing autism. Ascertainment bias alone is not a compelling argument to explain the significant associations found in these studies. Physical or environmental factors that affect children living in more advantaged environments could include immunological factors such as the hygiene hypothesis or biological factors like parental age.
Immune Link
An increasing number of studies have reported immune dysregulation or infection involved in the etiology of autism (Meltzer & Van De Water, 2017). Idiopathic ASD, when the origin is unknown, constitutes 85% of ASD cases and many have bowel inflammatory syndromes. Inflammation and the biological pathways that lead to inflammatory processes influence many disease states such as autism symptoms. Furthermore, inflammatory animal models of autism often replicate autism symptoms (Edmiston et al., 2017). The correlation may be explained by the Hygiene Hypothesis (Rook, 2007). This is a widely held theory that the etiology of many chronic inflammatory disorders have a more dense distribution in developed areas compared to less developed communities. It suggests that cleaner environmental conditions play a role in the increased prevalence of certain disorders. The correlation with SES in autoimmune or inflammatory disorders has generally been attributed to the lack of or aberrant prenatal or postnatal microbial exposure in the context of early immune system development, leading to immune dysregulation (Becker, 2018).
In many ways, the hygiene hypothesis seems counterintuitive since less clean, polluted environments correspond to lower levels of autism and other inflammatory disorders. Furthermore, it is common in western society to protect children from bacteria through extensive use of antibacterial soaps and isolation of children indoors when sick. These practices may be harmful in not allowing young immune systems to have a challenge in early neonatal or even childhood development (Yazdanbakhsh et al., 2002). Altered patterns of infant immune stimulation may hypersensitive the early immune system to inflammatory or cytokine responses affecting brain structure and function leading to autism (Becker, 2018). It has been well documented that immune cytokine molecules play a role in brain development (Silverstein et al., 1997) and our hygiene practices may affect brain structure and function, possibly leading to the development of autism. If this hypothesis holds merit, those with higher SES who spend more time and money on keeping their environments clean actually, to an extent, increase the risk of their children developing autism and related disorders. This is due to their lack of exposure to essential bacteria that trigger immune responses required for brain development.
A fascinating phenomenon tied to the Hygiene Hypothesis is the birth order effect on childhood disorders including autism, type 1 diabetes and atopy. It has been suggested that firstborn children are exposed to fewer infections early in life and due to the delayed immunologic challenge, they may be less likely to develop an autoimmune response responsible for healthy neurodevelopment (Rook, 2007). Moreover, a possible factor that could lead to observed birthother effect is exposure to potentially neurotoxic, fat-soluble chemicals accumulated in maternal tissue that have been passed to offspring transplacentally via breast milk (Iida et al., 1999). Due to the accumulation over a lifetime, the load of neurotoxins transmitted would be highest for firstborn children, especially combined with maternal age. The age of parents when they have their firstborn child, then, is another factor that can explain the ASD-SES link.
Parental Age
The possibility that autism is more common in children of older parents has generated considerable interest (Tsai et al., 1983). The risk of ASD has been found to be positively and independently associated with both maternal and paternal age. Firstborn offspring of two older parents were three times more likely to develop autism than were offspring of mothers aged 20–34 years and fathers aged <40 years (Durkin et al., 2008). The tendency for older parents of firstborn children to have higher levels of educational achievement and resources could further contribute to increased awareness thus an explanation of the more diagnosed of cases ASD in higher SES levels (Durkin et al., 2008).
Another possible explanation for this trend is the “stoppage” effect, a tendency for parents with one child with ASD not to have subsequent children because of high demands of parenting a child with disabilities. Or since they are more aware of the genetic susceptibility of their next children to also have ASD (Jones & Szatmari, 1988). Thus, parents with more education who have fewer children present a higher percentage of children of ASD in high SES populations. Older and more wealthy parents may have a greater social network in order to get screenings for autism since many centers are highly competitive to get a spot in. It has been found that, compared with younger parents, older parents are more aware of developmental abnormalities and better able to access diagnostic and special educational services (Durkin et al., 2008).
Finally, the association between advanced parental age and ASD may have a link to the role of infertility treatments and assisted reproductive technologies, the uses of which have increased in the past decade, especially by older women and men (Wright et al., 2007). It has been recorded that these technologies can lead to more adverse pregnancy outcomes, including those due to epigenetic effects (Ombelet et al., 2006). Infertility treatments such as in vitro fertilization cost anywhere between 10,000 to 200,000 USD for a successful pregnancy (Mohan, 2020). These methods of pregnancy are becoming increasingly popular especially for older parents with high SES levels. Thus, this may be a factor in the ASD-SES link.
Conclusion
The original assumption that the ascertainment bias is the cause of the differences we see in ASD and SES levels would mean there is no statistically significant SES gradient when analysis of studies are restricted to children with no pre-existing ASD. Durkin's et al. found this was not the case in the US. This suggested that the overall SES gradient may not be due to this bias, but have biological explanations . The Hygiene Hypothesis gives a unique perspective into the environment in which children in different SES levels are exposed to and therefore have different health outcomes. Patterns of behavior in high SES populations such as delayed birth of the first offspring and mode of pregnancy may have an effect on prevalence as well. Identifying such factors could lead to advances in our understandings of etiology and identification of autism and possible interventions.
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