INTRODUCTION
Two weeks ago, the Second Circuit reversed the summary judgment entered by Judge Denise Cote, in the acetaminophen autism litigation. Judge Cote had excluded the plaintiffs’ expert witnesses on causation, under Rule 702, in a lengthy, careful opinion that found numerous deviations from the standard of scientific care by the challenged witnesses.[1] Rule 702 of the Federal Rules of Evidence cried out for application, especially subparts (b), (c), and (d):
(b) the testimony is based on sufficient facts or data;
(c) the testimony is the product of reliable principles and methods; and
(d) the expert’s opinion reflects a reliable application of the principles and methods to the facts of the case.
The Second Circuit, in an opinion by Judge Guido Calebresi, held that Judge Cote abused her discretion with respect to the most important of the plaintiffs’ witnesses.[2] Judge Calebresi’s opinion in turn failed to engage meaningfully with the science of causation, and abused both the facts and the law to reach its conclusions. Judge Calebresi cited opinions discredited by the 2023 amendment to Rule 702, and he failed to engage with the legal requirements of that amendment and controlling decisions of the Supreme Court.
The errors in Judge Calebresi’s opinion are symptomatic of a deep confusion between causation and precautionary policy. This confusion is prevalent in litigation and regulation, and it even infects what purport to be purely scientific determinations, such as the carcinogenicity determinations of the International Agency for Research on Cancer.[3] To appreciate the depth and extent of Judge Calebresi’s errors requires exploring the scientific record and an analysis of the appellate opinion’s errors and omissions.
BACKGROUND
Acetaminophen is a generic medication available for treating pain (analgesic) and fever (antipyretic), without a prescription in the United Sates. The chemical compound, N-acetyl-para-aminophenol (or APAP) was first prepared in 1878, and it was initially used in clinical practice in 1893. Acetaminophen did not become commercially available in the United States until the 1950s. Starting in 1960, acetaminophen became available to consumers as an over-the-counter medication.[4]
The 1970s marked the discovery of potential harms to both pregnant women and fetuses from mothers’ use of aspirin as an analgesic or antipyretic medication. In the 1980s, scientists suspected that aspirin may cause Reyes syndrome in children. Because untreated fevers in pregnant women can harm fetuses, including miscarriage and birth defects, fever presents a difficult clinical problem for women and their physicians.[5] Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with miscarriage and birth defects, and opioid pain medications are associated with birth defects and maternal and neonatal addiction.[6] Clinicians have thus considered acetaminophen the preferred analgesic and antipyretic medication for pregnant women because of its consistently reassuring safety profile, and the absence of alternatives.
In December 2021, a group of advocacy scientists published a self-proclaimed consensus that precautionary action should be taken to restrict the use of acetaminophen by pregnant women.[7] The authors included advocacy scientist Shanna Swan, who was a protagonist on behalf of plaintiffs in notorious litigations involving silicone gel implants[8] and bendectin, and David Kriebel, a zealous proponent of the precautionary principle.[9] Swan and co-authors manifestly did not conclude that the available scientific evidence supported a causal inference between maternal acetaminophen use and their children’s autism. Instead, the authors asserted a precautionary policy approach that acetaminophen “be used by pregnant women cautiously at the lowest effective dose for the shortest possible time.”[10] Although the authors appropriately stopped short of causal conclusions, they incoherently argued that they had a “professional and social responsibility” to argue for precaution “even in the face of uncertainty, in light of the serious consequences of inaction.”[11] Given that they were addressing an uncertain and undetermined causal nexus, the authors had no warrant for suggesting that there would be any benefits from their recommendations or any untoward consequences from their having taken no action at all.
The pretense of the self-proclaimed consensus was dispelled by spirited dissent in response to the Call for Precautionary Action. One letter to the editor chided the precautionists for their misleading analysis.[12] Another letter highly critical of the faux consensus, was submitted by 50 or so signatories, including members of the Organization of Teratology Information Specialists, the Society of Birth Defects Research and Prevention, and Anthony R. Scialli, a past president of the Teratology Society, and founder and editor-in-chief of the journal Reproductive Toxicology.[13]
The American College of Obstetricians and Gynecologists (ACOG) issued a strongly worded rebuttal statement to highlight that the precautionists had not cited any clear evidence to show that acetaminophen use during any trimester causes fetal developmental issues.[14] ACOG reiterated its identification of acetaminophen as the only safe analgesic and antipyretic medication for pregnant women. ACOG further pointed out that despite the fear-mongering language of the Call for Precautionary Action, ACOG’s clinical guidance has long emphasized that medications in pregnancy should be used only when needed, in moderation, and in consultation with physicians. Indeed, the Food & Drug Administration already required that all over-the-counter medications intended for systemic absorption, including acetaminophen, be labeled: “If pregnant or breast-feeding, ask a health professional before use.”[15] At best, the precautionists had not managed to say anything important; at worst, they had stoked serious and unnecessary anxiety and concern among families and their physicians.
The precautionists also stoked the lawsuit industry. True to form, that industry was unfazed by the lack of certainty and the inability to infer causation even by the advocacy scientists who called for precautionary action. Within a few months of the 2021 opinion piece, the lawsuit industry started to file complaints, and the mass of litigation quickly led to consolidation and transfer to the Southern District of New York, for coordinated pre-trial procedures as a multi-district litigation (MDL).[16] A mass tort was born without scientific support for actual causation between the product and the harm, autism and other neurocognitive impairments.
Unsurprisingly, given the fragile and indeterminate scientific record on causation, the defense moved to exclude the plaintiffs’ causation expert witnesses, pursuant to Rule 702, at the close of discovery. Finding that the plaintiffs’ expert witnesses’ testimony failed to evidence a reliable application of epidemiologic method to reach the proffered conclusions, the district court excluded the challenged testimony,[17] and in August 2024, the district court dismissed over 500 cases in the MDL.[18]
(to be continued)
[1] In re Acetaminophen ASD-ADHD Prods. Liab. Litig., 707 F. Supp. 3d 309 (S.D.N.Y. 2023). Judge Cote addressed the admissibility of an additional expert witness in a subsequent opinion. In re Acetaminophen – ASD-ADHD Prods. Liab. Litig., 2024 WL 6 3874183 (S.D.N.Y. Aug. 20, 2024).
[2] Rutledge v. Walgreen Co., Nos. 24-916-cv(L), 24-1121(Con), 24-2360(Con); 24-2594-cv, Slip Op. (2nd Cir. July 13, 2026), available at https://scholar.google.com/scholar_case?case=13067399726798054350&q=rutledge+v.+walgreen&hl=en&as_sdt=2006.
[3] See Nathan Schachtman, IARC’s Precautionary Science: How the WHO Cancer Research Agency Misinforms Regulation and Litigation, Wash. Legal Found. Monograph (2026), available at https://www.wlf.org/wp-content/uploads/2026/04/WLF-Precautionary-Science-monograph.pdf
[4] Laurie F. Prescott. Paracetamol: past, present, and future, 7 AM. J. THERAPEUTICS 143 (2000).
[5] See, e.g., Stephanie Antoun, Pierre Ellul, Hugo Peyre, Michelle Rosenzwajg, Pierre Gressens, David Klatzmann & Richard Delorme, Fever during pregnancy as a risk factor for neurodevelopmental disorders: results from a systematic review and meta-analysis, 12 MOLECULAR AUTISM 60 (2021).
[6] Rachela Smith & Jonathan S. Zipursky, Safety of acetaminophen use in pregnancy: review of existing evidence, 8 AM. J. OBSTET. & GYN. 101925 (2025).
[7] Ann Z. Bauer, Shanna H. Swan, David Kriebel, Zeyan Liew, Hugh S. Taylor, Carl- Gustaf Bornehag, Anderson M. Andrade, Jørn Olsen, Rigmor H. Jensen, Rod T. Mitchell, Niels E. Skakkebaek, Bernard Jégou & David M. Kristensen, Paracetamol use during pregnancy — a call for precautionary action, 17 NATURE REV. ENDOCRINOL. 757 (2021). [Call for Precautionary Action]
[8] See Judge Jack B. Weinstein, Preliminary Reflections on Administration of Complex Litigation, 2009 CARDOZO L. REV. de novo 1, 14 (2009) (describing plaintiffs’ expert witnesses in silicone litigation as “charlatans”; “[t]he breast implant litigation was largely based on a litigation fraud. … Claims—supported by medical charlatans—that enormous damages to women’s systems resulted could not be supported.”).
[9] See, e.g., David Kriebel, Joel Tickner, Paul Epstein, John Lemons, Richard Levins, Edward L. Loechler, Margaret Quinn, Ruthann Rudel, Ted Schettler & Michael Stoto, The Precautionary Principle in Environmental Science, 109 ENVT’L HEALTH PERSP. 871 (2001).
[10] Call for Precautionary Action at 764.
[11] Call for Precautionary Action at 763 (emphasis added).
[12] Joseph O’Sullivan, Alexandra E. Cairns, Elena Plesca, Rebecca S. Black, Charlotte Frise, Manu Vatish and Ana Sofia Cerdeira, Paracetamol use in pregnancy — neglecting context promotes misinterpretation, 18 NATURE REV. ENDOCRINOL. 385 (2022) (noting that the Swan review, in the absence of conclusive evidence, was propagating a scare that acetaminophen use in pregnancy was unsafe and should be unduly restricted).
[13] Sura Alwan, Elizabeth A. Conover, Lorrie Harris-Sagaribay, Steven H. Lamm, Sharon V. Lavigne, Shari I. Lusskin, Sarah G. Obican, Alfred N. Romeo, Anthony R. Scialli & Katherine L. Wisner, Paracetamol Use in Pregnancy—Caution Over Causal Inference from Available Data, 18 NATURE REV. ENDOCRINOL. 190 (2022).
[14] American College of Obstetricians and Gynecologists, Response to Consensus Statement on Paracetamol Use During Pregnancy (Sept. 29, 2021), available at https://www.acog.org/news/news-articles/2021/09/response-to-consensus-statement-on-paracetamol-use-during-pregnancy.
[15] 21 C.F.R. § 201.63(a). See also Pregnant or Nursing Women, 47 Fed. Reg. at 54,751.
[16] 28 U.S.C. § 1407
[17] In re Acetaminophen – ASD-ADHD Prods. Liab. Litig., 707 F. Supp. 3d 309 (S.D.N.Y. 2023) (Cote, J.). Additional plaintiffs designated one other expert witness, who succumbed to a later Rule 702 challenge. In re Acetaminophen – ASD-ADHD Prods. Liab. Litig., No. 22md3043 (DLC), 2024 WL 3357608 (S.D.N.Y. Jul. 10, 2024).
[18] In re Acetaminophen – ASD-ADHD Prods. Liab. Litig., No. 22md3043 (DLC), Order & Opinion (Aug. 20, 2024).
