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"It Matters to Get This Right"


By: Dr. William Parker

As many people have, WPLab followed the recent lawsuit alleging that acetaminophen exposure during pregnancy causes autism. The judge’s ruling was recently published. The judge threw out the expert testimony from the plaintiff’s team. Was that the right decision from a scientific perspective? Was the ruling by Judge Cotes fair?


Judge Denise Cotes said;

"It matters to get this right. It matters to parents, their children, and their health care providers. ASD and ADHD are neurological disorders that can have profound consequences for families and communities.”

We could not agree more.


As a scientist, I look at the details. Every little detail counts. My wife and my friends sometimes don’t like this, but I can’t help it. Reading through the Judge’s ruling, almost everything makes sense. Perfect sense. The evidence that acetaminophen exposure during pregnancy causes ASD is fairly weak. Based on everything else we know, heavy use of acetaminophen during pregnancy probably does cause some ASD, but it’s not likely a very high percentage of total cases. Most ASD is induced by acetaminophen after birth, with the time very near birth having the greatest risk. The broad strokes of the judge’s report definitely make sense. But some of the details of the report are very misleading. You would think that there is NO evidence that acetaminophen is harmful.  


Again, the lawsuit is all about safety during pregnancy, where evidence is limited. But, plenty of evidence tells us it’s truly not safe, and the judge’s report, for some reason, downplays some of that evidence.


Here’s a great example from the report:

“Of the six studies publishing risk ratios for prenatal, peripartum, or postpartum exposure and an ASD diagnosis, three found no association (Ji 2018, Leppert 2019, and Saunders 2019), one found an association only for ASD co-occurring with HKD (Liew 2016a), and one found a protective association among febrile women (Hornig 2018). While Ji 2020 did find an association, it has significant limitations.”


My first thought was “There is no way that is correct. I will check this out.” The part that is obviously not correct is the finding of “no association” between ASD and peripartum or postpartum use of APAP. Acetaminophen and ASD are always associated during this time period if the analysis has any validity whatsoever.


Here’s the breakdown of the facts pertinent to the judge’s statement:

  1. Liew 2016a, Hornig 2018, Leppert 2019, and Saunders 2019 are all looking at prenatal exposure only. That leaves only Ji 2018 and Ji 2020 as the two papers looking beyond pregnancy, according to the judge’s report.

  2. Somehow, the judge missed the landmark Schultz study. Shultz found a shockingly large association between post-partum use of APAP and regressive ASD.

  3. The judge decided that the study by Alemany 2021 did not count among the 6 studies because it was a meta-analysis and not original. However, it does contain original analyses, one of which is an analysis of the connection between ASD and post-partum acetaminophen use found in the Danish National Birth Cohort. The authors do find a positive association between ASD and post-partum acetaminophen use in that analysis. However, we have demonstrated that this association is possibly a profound underestimate of the connection between acetaminophen and ASD.  

  4. The Ji 2020 study, like the Schultz study, finds a shockingly large association between cord blood acetaminophen and ASD. The primary “significant limitation” of this study is that it is from the cord blood, so it only reflects acetaminophen use just prior to giving birth. This is obviously an important clue about what causes ASD, but since it doesn’t reflect in general what is going on during the majority of pregnancy, it doesn’t count very much for the lawsuit.

  5. Ji 2018 is the only study left mentioned in this portion of the judge’s report. Ji 2018 looked at acetaminophen levels in women one to three days after birth. Thinking about how that study was conducted, I would be surprised if there was no connection at all between acetaminophen and ASD. It’s covering only a tiny window in time (out of a 6-year time window), and it’s up to three days after the baby separated from the mother’s liver (at birth), so maybe the association won’t be great. But it should still exist, I would imagine. That’s because the time of birth is the most sensitive to the induction of ASD by acetaminophen. So, why did the judge say that it found “no association”, and what do the data actually show? It turns out that the half of the women with the highest levels of measurable acetaminophen or acetaminophen metabolites had almost double the risk of having a child with ASD compared to women with no acetaminophen. So, why did the judge’s ruling falsely say that this study found “no association”? The study did find almost double the risk using their most basic analysis. But, the risk wasn’t what we call “statistically significant” because something called the confidence interval crosses the line of no risk, which is 1.0. The confidence interval on the Ji 2018 paper connecting acetaminophen and ASD was 0.92 to 4.08 using the same approach that gave them almost double the risk. In other words, the half of women with the highest measurable acetaminophen levels COULD POSSIBLY BE more than 4-times more likely to have a child with ASD compared to women with no detectable acetaminophen levels. Or maybe they weren’t more likely at all to have a child with ASD, based strictly on this analysis. When we at WPLab see something like this, we think: “If the world’s most common drug MIGHT cause that much harm, we should look at it.” And when we did look at it, we see that the risk is indeed monumental, as we have discussed in many peer-reviewed papers. It also makes sense that the judge would dismiss the paper, since it might have little or even nothing to do with typical use of acetaminophen during pregnancy. But, the judge’s statement that acetaminophen use during the peripartum or postpartum period is not associated with ASD in that study is verifiably false. It is true that we can’t draw firm conclusions from that study, but it adds to the weight of evidence and should not be dismissed.


Also in the judge’s ruling, I found very odd commentaries about two published studies in laboratory animal models. A paper by Baker 2023 was dismissed as showing “ambiguous” results. Baker very clearly showed profound effects of acetaminophen on behavior, especially in males, similar to what we saw in our study at Duke University. The comment in the judge’s ruling focuses on a weaker (less certain) point in the data dealing with another aspect of behavior, for some reason.  A study by Harshaw 2022, in turn, is dismissed because the authors themselves state that “[a] key implication of our findings is that no simple conclusion regarding the relative safety vs. danger of [acetaminophen] early in life is yet possible.” The Harshaw study shows some long-term effects of acetaminophen exposure on behavior, none of which you would want to see happen in a child, and any of which would throw up red flags to a regulatory agency thinking of approving the drug for use in children. For example, Harshaw found that the effects of acetaminophen on social caution, particularly in males, were profound. This was made worse by the presence of mock inflammation (they used something called IL-1beta for this). Again, we found very similar results in my lab at Duke University. I can understand why the authors can’t conclude that acetaminophen is safe based solely on their study. I agree with them. But, fortunately, we have a lot of other evidence that tells us unequivocally that acetaminophen is not safe for neurodevelopment.


This is why we have spent so much time trying to help families, caregivers, parents, and future parents get access to information about what causes autism. We are here to research, educate, and inform, in order to provide hope for stopping the chemically-induced injuries of acetaminophen.


In this instance, Judge Cotes came to the same conclusion as we; it matters to get it right. This is why, in a recently published peer-reviewed paper, we outlined 5 categories of medical practice that need to change for children under 6 years of age.

 


Category 1: Acetaminophen should never be used in violation of current guidelines.  This includes treatment of temperatures that do not technically constitute a fever and administration more frequently or at higher doses than recommended. These practices are exceedingly common because the potential for the drug to cause harm is not widely recognized.



Category 2: Acetaminophen should not be used in situations where it is proven to lack effectiveness. This includes the treatment of pain of circumcision and perhaps the treatment of fevers to prevent febrile seizures. These practices are exceedingly common because the potential for the drug to cause harm is not widely recognized.



Category 3: Acetaminophen should not be used in situations where no evidence demonstrates long-term benefits of treatment or where evidence demonstrates a lack of long-term benefits. This includes the treatment of fevers and prophylactic treatments prior to labor and delivery. These practices are exceedingly common because the potential for the drug to cause harm is not widely recognized.



Category 4: Acetaminophen should not be used in situations where it is no longer recommended by governing medical bodies. This includes the treatment of patients receiving vaccinations and will hopefully include many more reasons for administration in the future. These practices are exceedingly common because the potential for the drug to cause harm is not widely recognized.



Category 5: Administration of acetaminophen under conditions where evidence indicates that it is or may be beneficial should not be continued without full disclosure of the drug’s long-term risks for neurodevelopment. All caregivers, including parents, should be made aware of evidence related to both benefits and risks so that they can make informed decisions.

 

It matters to get this right.


Please read the Judge's ruling for yourself or our guide to the connection between acetaminophen and autism, and continue the conversation with us.  



 

This blog described conclusions reached by a team of scientists and published in the journal Children. The information was provided to the medical and scientific community in the form or recommended changes to medical practice, and is not/was not intended to be personal medical advice. Individuals should seek the advice from a physician for any personal medical questions.

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