乌鸦传媒

An analysis of an insurance claims database of 100 million patients has found clustering of autism spectrum disorder (ASD) and intellectual disability (ID) in counties across the U.S.

The clustering appears to be linked to environmental factors and, to a lesser extent, economic incentives at the state level that affect diagnosis, the researchers reported.

The researchers used male congenital malformations as a surrogate for parental exposures to environmental insults -- including pesticides, lead, sex hormone analogs, medication, and plasticizers, among others -- which are believed to play a role in the causation of ASD and ID.

"Adjusted for gender, ethnic, socioeconomic, and geopolitical factors, the ASD incidence rates were strongly linked to population-normalized rates of congenital malformations of the reproductive system in males -- an increase in ASD incidence of 283% for every percent increase in incidence of malformations (95% CI 91-576, P<6 x 10^-5)," wrote of the University of Chicago, and his co-authors March 13th in PLOS Computational Biology.

Congenital malformations in males affecting organs other than the reproductive system also appeared to be associated with an increase in both ASD (31.8% increased risk, 95% CI 12-52, P<6 x 10^-5) and ID (43% increased risk, 95% CI 23-67, P<6 x 10 ^-5).

Female reproductive malformations were also predictive of increased ASD and ID risk, the authors said, "but the magnitude of the statistical effect associated with this factor was much smaller."

The researchers also looked at the state-mandated rigor of ASD diagnosis that enables a child to be eligible for special education systems. Degree of rigor was predictive of decreased risk in ASD and ID incidence rates of 98.6% (95% CI 28-99.99, P=0.02475) and 99% (95% CI 68-99.99, P=0.00637), respectively.

The environmental effect was bigger, however. "The magnitude of influence of compound environmental predictors was approximately three times greater than that of state-level incentives," the researchers said.

"I suspected that connection between environmental status to rate of autism might exist, but the signal is much stronger than I expected," Rzhetsky told 乌鸦传媒 in an email.

The study was based on data taken from a large insurance claims database containing records for nearly 100 million Americans and census data that included county-level covariates that captured socioeconomic, demographic, and environmental effects.

The researchers created a statistical baseline frequency of ASD and ID and then looked at the actual rates of these disorders using the insurance records. Deviations from the baseline frequency were investigated for local influences, ranging from environmental exposure to ethnicity, income, and regional diagnostic stringency.

The population-adjusted incidence of viral infections in males was another environmental factor associated with ASD and ID incidence, the authors said, "although the specifics of the causal, biological mechanisms remain unresolved."

The incidence of the two diseases also appeared to vary across ethnic groups. Pacific Islanders, for instance, were at low risk for both ASD and ID.

Increases in per-capita income were weakly positively correlated with incidence of both diseases, and urbanization was also associated with higher risk. "A 1% increase in urbanization predicted about a 3% increase in ASD and ID incidence," the authors said.

This study provides evidence that, to understand the incidence of these disorders, "the scope of inquiry" should be routinely expanded to include environmental, demographics and socioeconomic factors, as well as government policies, the authors said. "Failure to do so," they said, "risks omitting important information about possibly strong confounders."

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