“To be clear, while an association between acetaminophen and autism has been described in many studies, a causal relationship has not been established . . . .”  That is not your DDL bloggers speaking (although we did add the emphasis).  It is not a drug manufacturer speaking, nor any particular doctor or researcher speaking.  It is not even an expert retained by the defense in litigation speaking. 

No, this is the position of the United States Food & Drug Administration, as stated two weeks ago in a Notice to Physicians.  The Notice also said that “there are contrary studies in the scientific literature” and that “acetaminophen is the safest over-the-counter alternative in pregnancy among all analgesics and antipyretics.”  We are also told by people who know that the FDA updated its website less than two months ago to say, “To date, FDA has not found clear evidence that appropriate use of acetaminophen during pregnancy causes adverse pregnancy, birth, neurobehavioral, or developmental outcomes.” 

So there you have it.  The federal government’s position is that acetaminophen used during pregnancy has not been shown to cause autism.  Yet, we as a nation were treated to our President holding a press conference to inform pregnant women that acetaminophen “can be associated with a very increased risk of autism” (which is not true) and telling them “don’t take Tylenol” unless they “can’t tough it out” (which no doctor would say). 

We do not cover politics, but we do cover prescription drugs, and we write today to remind you that we have been through this before.  Plaintiffs in the acetaminophen MDL have been claiming that acetaminophen use during pregnancy causes autism since before that MDL was created in 2022.  More to the point, the district judge presiding over that MDL ruled nearly two years ago that the plaintiffs had presented no reliable expert opinion that prenatal exposure to acetaminophen can cause autism spectrum disorder or ADHD.  In re Acetaminophen ASD-ADHD Prods. Liab. Litig., 707 F. Supp. 3d 309 (S.D.N.Y 2023). 

It was a detailed and exceptionally thorough order, which we covered here and here.  The plaintiffs’ expert epidemiologist was superbly qualified (currently Dean of the Harvard School of Public Health).  But even the best of us cannot make chicken salad out of chicken feathers, and there simply is no accepted causal relationship between prenatal acetaminophen and autism.  As the MDL judge noted, acetaminophen use by pregnant women is common, and autism and attention deficit/hyperactivity disorder are prevalent in U.S. children.  Search hard enough, and you might find some association. 

Causation is different.  We won’t overly rehash what we wrote before, but the court concluded that it was not reliable to draw a causal inference from a mere association.  The vast majority of the published analyses did not find any increased risk of autism or ADHD, and many studies that did find increased risks suffered from problematic data collection and other methodological limitations.  The FDA conducted multiple reviews, and it concluded in 2022 and 2023 that study results did not support a determination of causality. 

The plaintiff’s expert employed a “transdiagnostic evaluation” that applied the Bradford Hill criteria to multiple associations at once.  But that approach only obscured the limitations in the scientific literature, and by blending multiple associations together, it resulted in analysis of questionable relevance.  Even worse, the court found that the plaintiffs expert engaged in classic cherry picking, under which his treatment of a study depended on whether it supported his opinions.  Overall, the court was not impressed: 

In sum, Dr. Baccarelli failed to sufficiently explain the appropriateness of conducting a single Bradford Hill analysis for NDDs [neurodevelopmental disabilities] which included ASD and ADHD, selectively analyzed the consistency of the literature and the issue of genetic confounding, repeatedly pressed conclusions that study authors were not willing to make, and disregarded studies that do not support his opinion due to limitations that he did not view as disqualifying in studies that did support his opinion. Together, these deficiencies demonstrate that his opinion does not “reflect[ ] a reliable application of the principles and methods to the facts of the case.” Fed. R. Evid. 702.

Id. at 356 (quoting Fed. R. Evid. 702).  Having excluded the plaintiffs’ general causation experts, the court granted summary judgment a few months later. 

We are revisiting these developments because the issue was recently headline news.  Moreover, the MDL judge’s order excluding the plaintiffs’ experts is currently on appeal, and the plaintiffs filed a Rule 28(j) letter in the Second Circuit submitting an HHS press release, the FDA’s statements, a transcript of the press conference, and an unsworn statement from their expert as supplemental authority. 

The Second Circuit will not be impressed either.  As we stated at the start of this post, the FDA’s position (“to be clear”) is that a causal relationship between prenatal acetaminophen exposure and autism or ADHD has not been established, and the information that the plaintiffs submitted to the Second Circuit reflects exactly that.  Even worse, the plaintiffs’ 28(j) letter quotes the FDA Commissioner, who himself purported to quote the plaintiffs’ expert Dr. Baccarelli as stating that “there is a causal relationship.”  That is wrong.  In his written statement, Dr. Baccarelli actually reported “the possibility of a causal relationship” and that further research is required “to determine causality.” 

Think about that.  The plaintiffs submitted supplemental “authority” to a United States Court of Appeals prominently citing a misquote of an unsworn statement from an expert who has written time and again that causation has not been established.  Sheesh. 

As far as we can tell, nothing has changed in the science since the MDL judge excluded the plaintiff’s expert’s unreliable causation opinions.  Earlier this year, Dr. Baccarelli and co-authors published a review of studies on acetaminophen and neurodevelopmental disorders, but they found nothing new.  They reported an association between prenatal acetaminophen use and neurodevelopmental disorders, but admitted—as they had to—that “observational limitations preclude definitive causation.” 

The FDA’s statements and the President’s remarks will likely generate more wasteful litigation, which we will be watching.  Also imagine the women who may now be scared away from the standard-of-care treatment for pain and fever during pregnancy, which themselves pose significant risks to fetal health.  This is not the promotion of public health.  We are disappointed.