For decades, the discussion around autism has been a hotbed of misinformation, misinterpretation, and bad science, ranging from the long-discredited link between the neurodevelopmental condition and vaccines, to newer claims that going gluten-free and avoiding ultra-processed foods can reverse autistic traits.
On Monday night, this specter arose again in the Oval Office, as President Donald Trump announced his administration’s new push to study the causes of autism with claims that the common painkiller Tylenol, otherwise known as acetaminophen, can cause the condition. The FDA subsequently announced that the drug would be slapped with a warning label citing a “possible association.”
David Amaral, professor and director of research at the UC Davis MIND Institute, was among those watching in dismay as the president launched into a diatribe about Tylenol, repeatedly warning pregnant women not to take it, even to treat fevers.
“We heard the president say that women should tough it out,” says Amaral. “I was really taken aback by that, because we do know that prolonged fever, in particular, is a risk factor for autism. So I worry that this admonition to not take Tylenol is going to do the reverse of what they’re hoping.”
The speculation surrounding Tylenol stems from correlations drawn by some studies that have touted an association between use of the painkiller and neurodevelopmental disorders. One such analysis was published last month. The problem, says Renee Gardner, an epidemiologist at the Karolinska Institute in Sweden, is that these studies often reach this conclusion because they don’t sufficiently account for what statisticians describe as “confounding factors”—additional variables related to those being studied that might influence the relationship between them.
In particular, Gardner points out that pregnant women needing to take Tylenol are more likely to have pain, fevers, and prenatal infections, which are themselves risk factors for autism. More importantly, given the heritability of autism, many of the genetic variants that make women more likely to have impaired immunity and greater pain perception, and hence use painkillers like acetaminophen, are also linked to autism. The painkiller use, she says, is a red herring.
Last year, Gardner and other scientists published what is widely regarded within the scientific field as the most conclusive investigation so far on the subject, one that did account for confounding factors. Using health records from nearly 2.5 million children in Sweden, they reached the opposite conclusion to the president: Tylenol has no link to autism. Another major study of more than 200,000 children in Japan, published earlier this month, also found no link.
Doctors are worried that Trump’s claims will have adverse consequences. Michael Absoud, a pediatric neurodisability consultant and a researcher in pediatric neurosciences at King’s College London, says he fears that pregnant women will start using other painkillers with a less well-proven safety profile.
Gardner is concerned that it will also lead to self-blaming among parents, a flashback to the 1950s and ’60s, a time when autism was wrongly attributed to emotionally cold “refrigerator mothers.” “It’s making parents of children with neurodevelopmental conditions feel responsible,” she says. “It harks back to the early dark days of psychiatry.”
The press conference’s next announcement was that the FDA will be modifying the label of leucovorin—a modified version of vitamin B9, or folate, which is better known for its uses in protecting cancer patients from some of the toxic side effects of chemotherapy—so that this supplement can be used to treat autism.
Folate is well known for being crucial in the early stages of pregnancy to prevent the risk of neural defects in the developing baby, and some small studies have suggested that autistic children have deficiencies in folate metabolism, potentially caused by antibodies preventing this vital micronutrient from reaching their brains. One study suggested that these so-called autoantibodies may be present in approximately 70 percent of children with autistic spectrum disorder.
Amaral says that while replacing these deficiencies with leucovorin is an “interesting idea,” he is alarmed that it’s already being promoted as a potential treatment, stating that he’s only aware of a handful of small studies that have actually reported data on its use. The best evidence, he says, comes from a placebo-controlled clinical trial of 80 children published last year by pediatric neurologists in India, which reported slight improvements in some behavioral symptoms, particularly in children with the highest levels of autoantibodies impairing their folate metabolism.
“There is some indication that replacing the folate with leucovorin may actually prove beneficial to a subset of children,” says Amaral. “But a lot of the studies so far were unfortunately cherry-picking where they saw benefits. It needs to be tested properly through a large clinical trial of hundreds of kids, and then if it really works, let’s start promoting it. But don’t promote it before you know what’s going on.”
Absoud agrees that far more rigorous research is needed to confirm whether the antibodies being measured in some autistic children are truly impairing folate transport, and how prevalent they really are. Some of the studies linking these antibodies to brain folate deficiency and autism are small, he says, and their findings haven’t been replicated.
While the National Institutes of Health are reportedly planning confirmatory trials of leucovorin in autistic children, a concern among researchers WIRED spoke to is that the autism field has long been plagued by excessive hype and false dawns. Over his 25 years in the field, Amaral says he’s seen all kinds of autism treatment strategies being promoted, from removing heavy metals from the blood to hyperbaric oxygen. “And it turns out that so far, nothing has worked,” he says.
These thoughts are echoed by James McPartland, professor of child psychiatry and psychology at the Yale Child Study Center. “We want to make sure that promising leads are investigated soundly and rigorously, so we are making decisions for children that are informed by science,” he says. “It’s important because any family of an autistic person has a finite amount of time, energy, and money. Time spent pursuing any treatment is time spent not doing other things that could help.”
However, Amaral and McPartland welcome another part of the Trump administration’s plan—which is to delve deeper into the causes of autism through investigating the link between the genetic makeup of autistic people and their environmental exposures, otherwise known as their “exposome.”
In the wake of a new funding round opened earlier this year, the NIH are now funding 13 separate projects led by leading autism researchers examining whether the complex mixture of genetics and various environmental exposures—from diet to air pollution, pesticides, and heavy metals—can explain the rising prevalence of autism cases in recent years. The ultimate goal, Amaral says, is to try to figure out whether individuals with a specific genetic background respond differently to certain exposures than others, driving their autism risk.
Gardner says that it’s a potentially good approach, but her fear is how the findings will be interpreted by the administration.
“With autism, it’s not just one gene that influences the likelihood,” she says. “It’s a combination of many genes that opens the door for the environment to push a person’s tendencies one way or another. So you need an honest and clear evaluation of the data. And what happens if there are results coming out of this that don’t fit with what they’d like to see? Results that perhaps point to a very complex picture where we don’t have easy fixes. Based on what we saw last night, my concern would be how honestly they look at the data when it comes.”
