An Update on the Connection Between Acetaminophen and Autism: Expanding Evidence and Misinterpreted Sibling Control Studies

More than 30 lines of discrete, independent evidence implicate the exposure of susceptible babies and children to acetaminophen with the etiology of autism spectrum disorder (ASD). The most abundant source of evidence is from the fields of pharmacology and toxicology, with clinical and epidemiological observations, numerous miscellaneous observations, and studies in laboratory animal models providing conclusive support. This narrative review summarizes that evidence, and discusses recent work with sibling control analysis that has been unfortunately misinterpreted as a result of incorrect assignment of interacting variables as confounding factors. Susceptibility to acetaminophen-induced injury is imposed by a range of genetic, epigenetic, and environmental factors associated with oxidative stress, and is apparently the greatest immediately after birth. Susceptibility then decreases until about six years of age, which is outside of the developmental window in which regression into ASD typically occurs. Although associations between heavy use of acetaminophen during pregnancy and ASD suggest some risk may be present during pregnancy, insufficient evidence is available to know if sporadic use of acetaminophen during pregnancy poses any risks. Given continued use of acetaminophen during labor and delivery, and routine use during early childhood including for indications including circumcision, vaccination, and some chronic medical conditions, a course correction in clinical practice is much needed.