Earlier this year, HHS secretary RFK Jr. predicted that, “By September, we will know what has caused the autism epidemic and we’ll be able to eliminate those exposures.” Scientists have been researching autism for decades, including what factors are driving changes in diagnostic patterns. Promising such a major breakthrough in just six months is beyond ridiculous, and strongly implies that RFK Jr. thinks he already knows the answer.
What is that answer? He gives a clue in his statement – “those exposures”. RFK thinks that autism is dominantly caused by environmental exposures, despite mountains of evidence that autism is dominantly genetic. There are likely some contributing environmental factors, but they are not “the cause” of autism. We also know what RFK thinks is the king of evil environmental exposures – vaccines. This is why is quickly put together a bogus autism-vaccine study, almost certain to produce the results he desires.
But other environmental exposures are not off the hook, and any “big pharma” target is fair game. Recently the WSJ reported that RFK plans to claim that autism is linked to exposure to acetaminophen (Tylenol) during pregnancy. Well, it’s September, so I guess he feels he has to announce something. So let’s review what the science says about a potential link.
RFK has shown, over and over again, that he has no idea how to properly interpret the medical literature. He uses scientific evidence as the proverbial drunk uses a lamppost – for support rather than illumination. As regular readers here know, preliminary evidence is often all over the place, and also tends to favor false positives. You need careful analysis of research methodology, confounding factors, patterns of replication, detection of p-hacking, etc. in order to come to a reliable conclusion. Or – you can just cherry pick the inevitable studies that support your political agenda.
Sometimes, researchers will helpfully do this kind of analysis for you, with a high quality systematic review. That is, in fact, the entire point of a systematic review, and the good ones will cover all the factors I listed above. Better yet is looking at multiple systematic reviews to see if there is a solid consensus.
In the case of a potential link between Tylenol use in pregnancy and the risk of autism or other neurological developmental disorders (like ADHD), there are some preliminary studies showing a possible small risk, while others do not. This is a job for a good systematic review, and fortunately we have a recent high quality review to look at. The data came from the Swedish national database, which is extremely useful for such research. The review includes data on 185,909 children. They found a very small increased risk of neurodevelopmental disorders with Tylenol use in pregnancy, however this link disappeared when they did a sibling control analysis:
“Sibling control analyses found no evidence that acetaminophen use during pregnancy was associated with autism (HR, 0.98 [95% CI, 0.93-1.04]; RD, 0.02% [95% CI, -0.14% to 0.18%]), ADHD (HR, 0.98 [95% CI, 0.94-1.02]; RD, -0.02% [95% CI, -0.21% to 0.15%]), or intellectual disability (HR, 1.01 [95% CI, 0.92-1.10]; RD, 0% [95% CI, -0.10% to 0.13%]). Similarly, there was no evidence of a dose-response pattern in sibling control analyses. For example, for autism, compared with no use of acetaminophen, persons with low (<25th percentile), medium (25th-75th percentile), and high (>75th percentile) mean daily acetaminophen use had HRs of 0.85, 0.96, and 0.88, respectively.”
They conclude that earlier studies showing a possible link “may have been attributable to familial confounding.” In the end there is no link between Tylenol use in pregnancy and risk of autism, ADHD, or other neurodevelopmental conditions.
To understand this data a bit better, it is important to know that this is observational data. It is not ethical to expose subjects to a potential risk to see what happens. Therefore, we cannot randomize mothers to either take or not take Tylenol during pregnancy. We can just look at see what happens if mothers decide on their own to take it. This is an ethical way to gather data, and also allows for the collection of massive amounts of data (because you can just look at records or collect data, without having to carry out an elaborate experiment).
However, as we have pointed out here often, this also allows for the possibility of confounding factors. For example, what if mothers who have a fever for some reason are both more likely to take Tylenol and to have a child with a neurodevelopmental disorder? Researchers can try to correct for potential confounding factors.
With autism research, if you are looking at an environmental factor, it is standard procedure to control for genetic risk. One way to do that is with sibling control analysis. In order for an environmental factor to be considered a real and independent risk factor for autism, it must survive controlling for genetic risk, such as through sibling control analysis. In this systematic review, the potential link with Tylenol did not survive this analysis.
What this means is that there is very likely no link at all between Tylenol use in pregnancy and risk of autism, ADHD or neurodevelopmental disorder. Of course, data never proves a zero risk – it can only set limits on the potential size of the risk. So the scientific way of saying this is – the risk is below the threshold of statistical detection for existing data. But that data is now pretty robust, so any remaining potential risk is negligible.
We also have to recognize that untreated fever and pain during pregnancy is not risk free. In medicine, anything you do – or do not do – carries some risk. This is why all risk assessment is actually a risk vs benefit assessment. There very likely can be unintended consequences of scaring expectant mothers from treating pain or fever during pregnancy, with a risk that is somewhere between negligible and zero.
But that, of course, is RFK’s specialty – scaring people away from effective treatments with negligible risks based on his gross misreading of the scientific literature. We can expect more shenanigans to come.
