Young boys who were exposed in the womb to certain phthalate chemicals were more likely to have autism traits at ages 3 and 4, according to a new study published in Environmental Health Perspectives.
The researchers also report that mothers who had taken recommended doses of supplementary folic acid during their first trimester were less likely to have boys who later exhibited autism traits.
Lead author Youssef Oulhote, assistant professor of biostatistics and epidemiology at UMass Amherst's School of Public Health and Health Sciences, told EHN this apparent protective effect of folic acid was the "most important finding" of the study.
Folic acid is recommended for pregnant women to help prevent birth defects.
Roughly 1 in 59 U.S. children has autism spectrum disorder, according to the U.S. Centers for Disease Control and Prevention. The disorder—which is characterized by social problems, difficulty communicating or learning to speak, repetitive behaviors—is about four times more common in boys.
It's not clear what causes the disorder—but previous research has pointed to genetic conditions, older parents and premature births as risk factors.
Increasingly, however, scientists are looking at environmental exposures as a potential culprit. The new study does not prove that phthalates— widely used in certain plastics, personal care products, pharmaceuticals, food packaging, and medical devices— cause autism, however, it adds to a growing body of evidence that prenatal exposure to certain chemicals may impair social development and suggests folic acid may protect against some of these potential impacts.
"The rapid rise in prevalence over the past three decades cannot be explained solely by genetic factors," the authors wrote, adding the research "provides new insights regarding the potential neurotoxicity of phthalates and … supports earlier research showing increased susceptibility of the developing brain, especially the male fetal brain, to the impact of toxic chemicals."
From 2008 to 2011, Oulhote and colleagues measured 11 different phthalate metabolites—breakdown products of the compounds—in 2,000 Canadian women during their first trimester. They also asked the women about any supplementary folic acid they were taking.
After the women gave birth, 610 children at ages 3 and 4 were given assessment to tests on social cognition, social communication, social motivation, and repetitive behaviors.
Higher concentrations of certain phthalate metabolites were linked to higher scores in autistic traits for boys—but not for girls. For example, a doubling of concentrations of two phthalates was associated with roughly 60 percent higher scores on the tests for autistic traits.
"There was no link in kids from women who were taking enough [folic acid]," Oulhote said.
It's not clear how phthalates may impact brain and social development. Phthalates have previously been linked to changes in gene expression and DNA function, which is another pathway for the chemicals to impact children's brains.
The chemicals are also endocrine disruptors, meaning they alter the proper functioning of hormones. It's possible the chemicals could impact mothers' thyroid function or reduce the production of androgen hormones during pregnancy—both of which are crucial for babies' brain development, the researchers wrote. Oulhote added that some phthalates have already shown anti-androgenic effects. Androgen hormones regulate the development of male traits and reproduction.
Phthalates could also reduce testosterone in baby boys, which could also explain the difference the researchers saw between the sexes.
The children tested in the study are young and, just because they exhibited some autistic traits, doesn't mean they will be diagnosed with the disorder.
Walk for autism awareness in Richmond, Virginia, 2017. (Credit: Eli Christman/flickr)
"We do not know if these subtle effects associated with prenatal phthalate exposure will last after the preschool period," said child development specialist and study co-author Gina Muckle, professor at Université Laval and Quebec-CHU Research Center in Quebec City, Canada, in a statement.
The study was also limited in that it looked at mostly white, higher income mothers and children, the researchers only tested the women once for phthalates, and the tests to tease out autistic traits in the children are not always accurate and don't represent an autism diagnosis.
In addition, some studies in recent years looking at mid to late pregnancy have not found links between mothers' phthalate levels and autism traits in their children later in life. And some studies have even suggested that too much folic acid may be linked to autism.
However, the new study is not a complete outlier. A 2009 study of 4,779 children found that those who lived in homes with polyvinyl chloride flooring, a source of phthalates, were more likely to be diagnosed with autism. A 2010 study found links between higher levels of certain phthalate metabolites during mothers' third trimester and autism traits in 137 children ages 7 to 9.
A 2015 study found levels of two common phthalates (as well as another endocrine disrupting chemical, bisphenol-A or BPA) were significantly higher in children who had autism compared to children who did not.
Oulhote said a good way to push the research forward would be to measure these phthalates at different periods during pregnancy to get a fuller picture of the mothers' exposure.
"They're [phthalates] metabolized very quickly, so measurements show very recent exposure," he said, adding that additional future research should tease out how the chemicals impact sex steroid hormones or thyroid hormones in mothers and in fetuses.
In the meantime, Oulhote said the current study reinforces the importance of folic acid for pregnant women.
"We already know folic acid is important – before and during pregnancy to prevent neural tube defects," he said. "Here's evidence that folic acid may protect against effects of phthalates."
