A major study published last year found no association between acetaminophen, an ingredient in Tylenol, and autism or ADHD when controlling for familial factors.Kylie Cooper/Reuters
Tylenol has long been the drug of choice for safely treating pain and fever during pregnancy. But it appears the Make America Healthy Again movement may be about to call this common wisdom into question.
Last week, sources told the Wall Street Journal that Robert F. Kennedy Jr. plans to announce Tylenol use in pregnancy as a potential cause of autism – a disorder that’s long been a fixation for the U.S. Health and Human Services Secretary.
An HHS spokesperson dismissed the news as “speculation.” But days later, the Atlantic reported that Mr. Kennedy is actively consulting with a fringe researcher who blames autism on children’s use of acetaminophen, the active ingredient in Tylenol and one of the world’s most popular household drugs.
The reports have ignited controversy and concern. They have also drawn fresh attention to studies that looked for a potential link between Tylenol use in pregnancy and neurodevelopmental disorders such as autism and ADHD – all with varying or conflicting results.
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To make sense of the scientific literature – and this confusing moment – The Globe and Mail spoke with four Canadian experts: Sura Alwan, a clinical teratologist and birth defects epidemiologist with the University of British Columbia; Lonnie Zwaigenbaum, a pediatrics professor and director of autism research with the University of Alberta; David Juurlink, head of clinical pharmacology and toxicology with Sunnybrook Health Sciences Centre in Toronto; and Tali Bogler, chair of family medicine obstetrics with Unity Health Toronto and a medical adviser to First Exposure, a resource that provides evidence-based information on health exposures during pregnancy.
These interviews have been edited and condensed for clarity and space.
What was your reaction when you saw recent headlines about Mr. Kennedy purportedly drawing a link between Tylenol use in pregnancy and autism?
Dr. Bogler: This is not the first time we’ve seen this [issue] in news outlets and on social media. And it’s so interesting to me that this sort of controversy lies solely in that realm – because we’re not debating it within clinical medicine and amongst most researchers.
Tylenol has long been considered safe during pregnancy. When and why did this start to be questioned by researchers?
Dr. Bogler: I would say about 10 years ago. And, you know, the rationale for conducting these studies is not wrong, right? Because we know acetaminophen is widely used, and we had no data at the time examining neurodevelopmental effects.
Dr. Zwaigenbaum: I think for a condition like autism, where we don’t know the causes – plus the fact that autism has been increasingly diagnosed over the past 10 or 20 years – it’s understandable that families will have questions and that researchers will be looking for possible associations.
So what does the current body of research tell us about a potential link?
Dr. Juurlink: It’s a mixed bag of mostly low-quality studies. The studies that find an association between acetaminophen used during pregnancy and autism are generally quite weak from a scientific perspective. They often rely on, for example, maternal recall of medications.
An important concept here is the phenomenon of recall bias. When a child is given a seemingly random diagnosis like autism, it’s normal to want to look for the cause: Why did this happen to my child? And a parent of a child with autism might be more likely to recall having used acetaminophen during pregnancy than the parent of a child who doesn’t have autism.
My read of this literature is that the best evidence out there suggests that there is, in fact, no causal link.
Dr. Alwan: The evidence points away from acetaminophen actually causing autism. Most studies that report a link show only very small increases in the risk, and those results are probably explained by other factors.
For example, pregnant women may take acetaminophen because they have frequent migraines or fevers – and both migraines and fevers themselves have the link to differences in child development. So the medication might look like the cause, but the underlying health issue could be what’s driving the association.
Dr. Bogler: Just because there’s a study, or there is an association, it does not mean causation. And evaluating the quality of studies is not a simple task.
A major study published last year analyzed medical records for nearly 2.5 million Swedish children to test whether acetaminophen use in pregnancy could be linked to autism or ADHD. What did it find?
Dr. Alwan: It observed no association with either autism or ADHD when controlling for familial factors.
Dr. Juurlink: What this study did that was special was take individual families into consideration. Families differ in genetic liability, health behaviours and other factors linked to both painkiller use and child neurodevelopment. So in this study, instead of comparing children from different families, they compared siblings within the same family. And when they did that, they found there was no increased risk, and that implies that the earlier signals [reported by other studies] were the result of genetics or environment or both, not the drug.
Does the Swedish study settle this question for you?
Dr. Juurlink: I would characterize this study as the largest and methodologically strongest study out there.
Dr. Bogler: I’m commonly advising on acetaminophen use in pregnancy and lactation. I can use this study to explain why I’m comfortable continuing to recommend acetaminophen use in pregnancy.
What does the current scientific literature tell us about what might actually cause autism?
Dr. Zwaigenbaum: We’ve recognized that there are genetic factors. We’ve known from twin studies dating back to the 1970s that if one twin was autistic it was much more likely that the second twin would also be autistic if they were identical rather than fraternal.
We also recognize that there are other factors, like prematurity or the difference between boys and girls, that shape autism beyond individual genes. And there are examples of environmental exposures that may increase the likelihood of autism. But we still don’t have all the answers.
In April, Mr. Kennedy promised to find the causes of autism by September, which is where we now find ourselves. What was your reaction to this?
Dr. Zwaigenbaum: Given the brilliant minds and the number of years that people have addressed this question, I had some healthy skepticism about whether these answers would suddenly materialize just because of that declaration. It seemed extremely improbable.
What are the stakes here, if pregnant people are scared off from taking acetaminophen?
Dr. Bogler: There’s harm in that. It’s really not fair, especially when there’s limited alternatives.
Not treating fever and pain is also associated with known risks to the developing fetus … birth defects, miscarriage and other long-term infant effects. So it’s important to treat fever in a pregnancy or during labour, and acetaminophen is still our recommended drug.
Dr. Alwan: The headlines are scaring women and the public on evidence that is weak and inconsistent. I’ve spoken to some women who have children that have autism, or they’re pregnant right now, and it’s a scary time for them. They’re frightened. And they shouldn’t be.
