Reye's syndrome and aspirin. Evidence for a dose-response effect

Data collected from the Public Health Service Main Study of Reye's Syndrome and Medications were analyzed to assess the relationship between the development of Reye's syndrome and the dose of aspirin received during the antecedent respiratory or chickenpox illness. Among those exposed to aspirin, case-patients were found to have received greater average daily and maximum daily doses of aspirin and greater doses of aspirin on the first four days of the antecedent illness (median, 25.1 mg/kg; 33.0 mg/kg; and 65.4 mg/kg; respectively) than did controls (median, 14.5 mg/kg; 19.0 mg/kg; and 27.0 mg/kg; respectively). The excess risk associated with increasing aspirin doses was due primarily to intermediate levels of dose (eg, 15 to 27 mg/kg per day) rather than higher levels (greater than 27 mg/kg per day). The dose difference between exposed case-patients and controls was greatest on days 3 and 4 of the antecedent illness.