Editorial: The acetaminophen scare: association vs causation.

With high twin concordance and sibling recurrence risk, the influence of genetic factors in the etiology of autism is not disputed. The contribution of environmental risk to the etiology of autism is less well established. While the prevalence increase observed worldwide has fueled beliefs of an epidemic driven by environmental changes, the evidence for such interpretations of the secular change in prevalence is lacking (Fombonne, 2025). In epidemiological surveys, no clustering in time or space has been reported that could point to candidate exposures. Thus, observational (cohort and case-control) studies have been wide-ranging and exploratory rather than hypothesis-driven. In light of growing evidence of atypical development occurring in the first months of life (Dawson et al., 2023, Lancet Neurology, 22, 244), environmental risk research in autism has focused on prenatal or periconceptional exposures. In the last 20 years, a myriad of associations have been reported between autism risk and prenatal exposure to: pesticides, phthalates, air pollutants, maternal fever or infection during pregnancy, inter-pregnancy interval, lack of folic acid supplementation, vitamin D deficiency, maternal diet, advancing parental age, exposure to heavy metals, prenatal exposure to antidepressants, valproic acid, benzodiazepines, acetaminophen, maternal smoking, cannabis or alcohol use during pregnancy, maternal obesity and excessive gestational weight gain, prematurity, low birth weight, maternal immune activation, C-section, use of oxytocin, assisted reproductive technologies, and countless others. With few exceptions (advanced parental age, prenatal exposure to valproic acid), associations have not been replicated, or when they have, their causal nature has not been established.