A new study from the Statens Serum Institut, in Denmark, has found a link between autism spectrum disorder (ASD) and circumcision in boys aged 0 to 9 years. Though no specific mechanism has been established, the team speculates that a malformed stress response, stemming from the procedure, may alter or delay brain development.

Just within the last decade, ASD rates have more than doubled in the U.S. Without a single cause to pin it to, science has seen a rush to draw links between the disorder and a range of environmental, social, and genetic factors. The best that ASD researchers can surmise at this point is it comes from some mix of the three, though in which proportions and at what time still remains unknown.

“Our investigation was prompted by the combination of recent animal findings linking a single painful injury to lifelong deficits in stress response and a study showing a strong, positive correlation between a country's neonatal male circumcision rate and its prevalence of ASD in boys,” said Professor Morten Frisch of the Statens Serum Institut, who led the research.

The team tracked more than 340,000 boys between 1994 and 2013. Nearly 5,000 cases of ASD were diagnosed during that time. Regardless of background, the team explains, “circumcised boys were more likely than intact boys to develop ASD before age 10 years.” What’s more, “risk was particularly high for infantile autism before age 5 years.”

Controversies surrounding circumcision are as fraught with uncertainty as the science behind the practice. Much of the data on circumcision is conflicting, as one study last year found the benefits outweighed the risks 100 to one and was, as the researchers put it, “equivalent to childhood vaccination.” A separate investigation put the chances of newborn boys getting a urinary tract infection at 50/50 if they stayed uncircumcised.

But while the U.S. circumcision rates are largely declining as the decades pass, worldwide the story is much different. Without access to the same anesthetics and trusted procedures, circumcision in foreign countries tends to earn a less favorable opinion among the public. By the World Health Organization’s most recent estimate, approximately 33 percent of the world’s males aged 15 years or older are circumcised. That number may be so low due to overwhelming beliefs that the practice equates to genital mutilation, while stateside it may be considered more comparable to dental braces.

In the latest study, Frisch and his colleague Jacob Simonsen relied on past research that suggests early pain in neonates has been shown to have long-lasting effects in pain perception, which crop up at greater rates in kids with ASD. “Possible mechanisms linking early life pain and stress to an increased risk of neurodevelopmental, behavioral, or psychological problems in later life remain incompletely conceptualized.” Frisch said. The findings are slightly complicated by earlier work that found autism emerges in utero, which suggests circumcision could only intensify a preexisting deficiency.

At any rate, the findings may hold great promise for other countries to adopt formal anesthetic protocol to avoid, or at least minimize, the pain children experience. “Given the widespread practice of non-therapeutic circumcision in infancy and childhood around the world,” Frisch concluded, “our findings should prompt other researchers to examine the possibility that circumcision trauma in infancy or early childhood might carry an increased risk of serious neurodevelopmental and psychological consequences.”

Source: Frisch M, Simonsen J. Ritual circumcision and risk of autism spectrum disorder in 0- to 9-year-old boys: national cohort study in Denmark. JRSM. 2015.