Repeated Diagnosis of Illnesses Involving Fever or Pain During Early Childhood is Very Strongly Associated with Autism Spectrum Disorder

A large body of evidence implicates the exposure of susceptible individuals to acetaminophen in the etiology of ASD. We undertook this study to probe the association between ASD and a wide range of childhood diagnoses that would typically warrant acetaminophen use for treatment of pain, fever, or both. The Florida Medicaid database was utilized as the source of medical records. Associations between “acetaminophen exposure surrogates” and ASD were unexpectedly large, with odds ratios of 2.629 (2.343 to 2.949), p-value < 0.0001, for children with at least four diagnoses considered surrogates for acetaminophen use. When fever alone was inspected girls had a statistically different and greater odds ratio 3.663 (3.264 to 4.109), p-value < 0.0001, compared to boys with an odds ratio of 2.844 (2.664 to 3.036), p-value < 0.0001. The greater odds ratios for girls compared to boys appeared to be a consequence of fewer girls without ASD having acetaminophen exposure surrogates. The presence of less than four exposure surrogates was less well associated with ASD, suggesting that multiple exposure surrogates may carry the greatest relative risk of ASD, especially for girls.