The Dangers of Acetaminophen for Neurodevelopment Outweigh Scant Evidence for Long-Term Benefits

Abstract

Based on available data that include approximately 20 lines of evidence from studies in laboratory animal models, observations in humans, correlations in time, and pharmacological/toxicological considerations, it has been concluded without reasonable doubt and with no evidence to the contrary that exposure of susceptible babies and children to acetaminophen (paracetamol) induces many, if not most, cases of autism spectrum disorder (ASD). However, the relative number of cases of ASD that might be induced by acetaminophen has not yet been estimated. Here, we examine a variety of evidence, including the acetaminophen-induced reduction of social awareness in adults, the prevalence of ASD through time, and crude estimates of the relative number of ASD cases induced by acetaminophen during various periods of neurodevelopment. We conclude that the very early postpartum period poses the greatest risk for acetaminophen-induced ASD, and that nearly ubiquitous use of acetaminophen during early development could conceivably be responsible for the induction in the vast majority, perhaps 90% or more, of all cases of ASD. Despite over a decade of accumulating evidence that acetaminophen is harmful for neurodevelopment, numerous studies demonstrate that acetaminophen is frequently administered to children in excess of currently approved amounts and under conditions in which it provides no benefit. Further, studies have failed to demonstrate long-term benefits of acetaminophen for the pediatric population, leaving no valid rationale for continued use of the drug in that population given its risks to neurodevelopment.

Evaluating the Role of Susceptibility Inducing Cofactors and of Acetaminophen in the Etiology of Autism

“…That evidence will be summarized in this Introduction. While no one association or other line of evidence is sufficient to reach any firm conclusion, we view the weight of evidence, when taken together, as overwhelming [1][2][3].…”

“…The drug fits the description of the factor sought by Matsuishi in 1987, and by Coury and Nash in 2003. Further, since drugs that are metabolized into acetaminophen by the human body have been commercially available for over a century (discussed by our group in Parker et al [3]), it is plausible that acetaminophen was the root cause of at least some cases of ASD when, in the 1940s, Kanner tragically and wrongly attributed ASD to aloof parenting [39].…”

“…The role of acetaminophen in the pathogenesis of ASD is illuminated by numerous lines of evidence, diverse in nature, taken together as a whole. Twenty-two lines of evidence, most listed above, were tallied in our most recent review of that evidence [3]. The apparently low prevalence of ASD in countries with chronic shortages of even the most basic medicines, which likely includes acetaminophen, is described above, and adds a 23 rd line of evidence.…”

“…Numerous similarities, described above, between ASD and fetal alcohol syndrome, a known effect of pathologic drug metabolism, adds a 24 th line of evidence. Among the evidence lies over a dozen associations that remain unexplained if acetaminophen is not considered in the etiology of ASD [3]. Examples of observations that lack any reasonable explanation other than the involvement of acetaminophen in the pathogenesis of ASD include the association of cord blood acetaminophen with ASD (OR = 3.62; CI = 1.62-8.60 for the third compared to the first tertile) [7], the association of circumcision with more than double the incidence of infantile ASD (HR = 2.06; CI = 1.36-3.13) [8], and a case-controlled study showing that regression into ASD is associated with acetaminophen use between 12 and 18 months of age (OR = 20.9; CI = 1.33-32.9) [4].…”

“…Evidence regarding a causal relationship between early life exposure to acetaminophen and ASD has been reviewed recently by our group [1][2][3]. Twenty-two distinct lines of evidence have been described (see Table 1 in Parker et al [3]), allowing us to conclude with no reasonable doubt that factors leading to susceptibility combined with acetaminophen exposure cause many if not most cases of ASD. That evidence will be summarized in this Introduction.…”