In Baby Teeth, Links Between Chemical Exposure in Pregnancy and Autism

If you are a parent worrying through pregnancy, or maybe trying to make sense of your child’s neurodevelopmental problems, you aren’t always glad to see another story about a new study looking at possible environmental risk factors. From pesticides in the food to phthalates in the plastics to pollutant particles in the air, so many different exposures have been linked to problems in the developing fetal brain that parents can sometimes feel both bewildered and, inevitably, at fault for failing or having failed to take all possible precautions.

That’s a great pity, because the accumulating research is of tremendous value, particularly to families struggling with an autism diagnosis. But there’s an unfortunate tendency to treat each new study as a single explanatory solution to what is in fact a tremendously complicated and multifactorial issue.

Autism is “a very diverse condition — not all kids with autism are alike,” said Dr. Leonardo Trasande, the chief of the division of environmental pediatrics and an associate professor of pediatrics, environmental medicine and population health at New York University School of Medicine. “There are a lot of shades of gray and a lot of differential dysfunction,” probably related to different parts of the brain, he said.

Craig Newschaffer, director of the A.J. Drexel Autism Institute at Drexel University, said that while it’s very important for the public to be aware that there are environmental risk factors in the development of autism, “pointing a finger at mom is not the endgame of this kind of research. The endgame isn’t going to be about individual decision making, but more about informing policy.” He offers more information in his webinar, “Four Things to Know About Environmental Autism Risk Factors.”

“I very much agree this is not about blaming the parent in any way,” said Manish Arora, professor of environmental medicine and public health at Icahn School of Medicine at Mount Sinai. “It’s very hard to buy your way out of exposures; many exposures are present everywhere.”

From a research point of view, Arora said, one challenge has been to measure toxic chemicals and exposures during fetal development, and connect them with an outcome like autism, which is diagnosed years later. He has developed an innovative technique using baby teeth, which start to develop toward the end of the first trimester, and form a new layer each day, growing in what he called an “incremental archival manner.” The layers can capture traces of chemicals, so that they serve as “biologic hard drives,” records of what exposures occurred during fetal development, and when they occurred, in a manner similar to the rings on trees.

Using the teeth that children have shed between the ages of 6 and 12, Arora said, it’s possible to look back at exposures during fetal development, and at other aspects of early metabolism to see whether children who later go on to develop autism are biologically different early on. In a study published in Science Advances in May, scientists used this technique to compare early zinc and copper metabolism in children with autism with their siblings without autism.

Paul Curtin, an assistant professor of environmental medicine and public health at Mount Sinai who was first author on the study, said that in children with autism, regulation of zinc and copper metabolism shows differences beginning early in the course of fetal development. The point of the study was not to look at whether a child had been externally exposed to these metals, but rather at the internal metabolic rhythms of nutrients and possible toxins, at “what are the dynamics of zinc and copper metabolism, and how are those dysregulated in disease.”

Arora said this could lead to a biomarker for autism, a diagnostic test which could be administered before a child shows behavioral differences. Could finding ways to correct that disrupted pathway alter a child’s neurodevelopment?

“For the first time we have a biochemical pathway which, if we could modify, could have some effects,” Arora said. “If it turns out to be causal, there might be a therapeutic benefit — I doubt if this is the only pathway in autism, but if it is one of the more important ones, we might have something.”

Using baby teeth offers a remarkable new technique for looking back at all kinds of exposures during pregnancy. “Epidemiologists like myself are thrilled,” Newschaffer said. However, he said, “it’s very exciting but extremely early days.”

And there is never going to be one simple answer. “There are so many factors that likely contribute to the origins of autism,” Trasande said. “It’s impossible to point to any one factor for any one child,” he said. “We always speak about larger populations.”

From an epidemiologic point of view, Newschaffer said, the effects of any one exposure are likely to be of small magnitude for any one individual. The important gains in reducing autism would be seen at the population level, and therefore, the best response to the research about environmental risks would be policy change to protect the whole population.

But until those policy changes are enacted, individuals may still want to reduce their exposures and to be particularly careful during pregnancy, avoiding pesticides, for example, by buying organic produce, if that is economically feasible. “You can be a little more cautious during this time,” Newschaffer said. “The other way more generally to limit the effect of these chemicals on the brain is healthy diet and particularly iodine,” to protect the thyroid, Trasande said, since hypothyroidism, both in children and in mothers, is emerging as a possible contributing factor to autism. And after a child is born, “we can make sure families are eating healthier diets and having the best possible environment for raising their children.”

Newschaffer said that autism researchers had previously been surprised by the link between exposure to air pollution and autism. Over 25 epidemiologic studies have found an association between prenatal and early postnatal air pollution exposure and autism. Women who have higher air pollution exposures may be living in neighborhoods where there are other exposures, he said, but still, there is an emerging body of evidence to support the association.

“Air pollution” is a heterogeneous term, and different studies have suggested a range of pollutants as more closely linked. Other associations between prenatal risk factors and autism development are also complicated, Newschaffer said. There appears to be a connection with advanced parental age, both of the mother and of the father, and an association between autism and closely spaced pregnancies.

Autism risk is associated with a range of perinatal and neonatal complications, but as with air pollution, it’s not a simple picture, because there are many different complications and there is not one simple or consistent relationship. There could conceivably be some biological mechanism that might be activated by a range of different complications, Newschaffer said, but whatever the mechanism — and people have suggested inflammation, or hormone pathways — “having a complicated pregnancy does increase your risk of a child having autism.”

Still, he said, most pregnancies with complications do not result in a child with autism.

Trasande said he tells families that the strongest evidence we have of chemicals affecting the developing brain is about pesticides and flame retardants, which can be hard to avoid. People can reduce some exposures by eating organic produce, and opening windows to recirculate air and get rid of chemical dust, but it would take regulation to get some of these very persistent pollutants out of the home.

“The biggest impact here in autism and other environmentally driven conditions would be at the policy level,” Arora said. “We are exposing our populations to many chemicals which are untested.”