Chronicling the story of maternal infection has not been easy. And for many other risk factors, reliable supporting evidence has been even harder to come by. Many scientists who have studied air pollution, for example, are convinced that it contributes to autism, but so far none have been able to prove it.
Governments typically monitor pollutant levels and make the data freely available, so “people don’t have to go out and collect air pollution data themselves to study it,” says Hertz. – Picciotto. His team analyzed air pollution and autism risk as part of the Childhood Autism Risks from Genetics and the Environment (CHARGE) study, a comprehensive, long-term study of autism risk factors in California-born preschoolers.
More than half a dozen studies, mostly based on US data, have shown that exposure to air pollution in utero or in the first years of life increases the risk of autism in children, says Amy Kalkbrenner, assistant professor of environmental health sciences at the University of Wisconsin-Milwaukee. Kalkbrenner has documented associations between air pollution and autism risk in North Carolina and West Virginia. Other researchers have found similar patterns in western Pennsylvania and among a nationwide cohort of 116,000 women participating in the Nurses’ Health Study II. “That level of consistency is unusual on the pitch,” Kalkbrenner says. “Seeing it in a different geographic area that has different seasonal patterns, different mixes of air pollution, gives more robustness to the results overall.”
The timing of exposure offers a plausible biological rationale. Two separate studies published earlier this year found that exposure to air pollution during the third trimester of pregnancy particularly increases the risk of autism. These months are crucial for brain development that seems to go awry in autism. “That kind of specificity greatly strengthens the argument for causation, that we’re really looking at something biological,” says Weisskopf, who led one of the studies based on the Nurses’ Health Study II data.
However, not all studies have found this link. An analysis of four large studies on child development in Europe, published in June, found no association between a mother’s exposure to air pollution during pregnancy and the level of related traits to her child’s autism.
“We have seen a lot [of results] in the United States, but I would like to see this in other parts of the world,” says lead researcher Monica Guxens, assistant research professor at the Environmental Epidemiology Research Center in Barcelona, Spain.
This analysis shows how difficult it can be to compare data between studies, Croen says. It’s possible that air pollution is linked to an autism diagnosis, the outcome measure in most US studies, but not to autism traits, measured in the European analysis. While only certain components of air pollution increase the risk, studies that measure different chemicals may also yield discordant results.
Before researchers can conclude that air pollution causes autism, they may need new types of evidence, such as better and more personalized measures of air pollution exposure. “Generally, this question of when to declare established causation is very interesting and confusing,” says Kalkbrenner. So far, studies have estimated exposure to air pollutants by cross-referencing a person’s home address with data from nearby government monitoring stations. But the approach is flawed. A person can live in an area with high levels of air pollution and work in an area with low levels, or vice versa. Designing studies in which pregnant women wear personal air quality monitors or identifying biomarkers in their blood that accurately reflect a person’s actual exposure to air pollution could provide this piece of the puzzle.
Finding new sources or new types of epidemiological data could also be helpful. “I would like to see what happens with the neurological development of children in areas with very high pollution levels, like China,” says Kalkbrenner. “It would also be nice to have access to data on ‘natural experiments’ where air pollutants have changed drastically over time.”
Researchers also need to better understand the precise toxic component in the air that contributes to developmental problems. Many studies involve fine particles less than 2.5 microns in diameter, but this category includes hundreds of toxic chemicals. “We had this pattern of positive results, but there was no exact overlap of which aspect of air pollution exposure was linked to autism risk,” says Newschaffer. “The lack of consistency there is always somewhat vexing.”
Finally, scientists will have to establish the mechanism by which any toxic component affects the brain and causes autism. Many scientists suspect inflammation or other pathways related to the immune system are involved. “Many of these same markers that we see altered in children with autism are also activated by exposure to air pollution,” says Heather Volk, assistant professor of mental health at the Johns Hopkins Bloomberg School of Public Health in Baltimore. , Maryland. . But so far, few animal studies or other labs have delved into the details of these mechanisms.
Without strong evidence from multiple types of studies, the link between air pollution and autism remains murky — and troubling. For one thing, air pollution is so prevalent that if it’s a true risk factor, it likely contributes to autism in a large number of children. On the other hand, it’s easy to show associations between air pollution and many conditions, and the link to autism in particular might be wrong. “It’s certainly plausible, it matches the literature for example on inflammation, all these little bits are there,” Lee says. “But putting them together to come up with the claim that air pollution is a causative risk factor for autism? I think we’re still a long way from being able to say that.