Between January 1985 and May 1986, following completion of a pilot study, a main study concerning the possible association between
Reye's syndrome and
salicylates was conducted. Twenty-seven patients with stage II or deeper
Reye's syndrome whose diagnoses were confirmed by an expert panel and who had appropriate antecedent illnesses (
chickenpox, respiratory illness, or gastrointestinal illness) prior to the onset of
Reye's syndrome were compared with 140 controls matched for age, race (black or not black), and type and timing of onset of antecedent illness. Controls were selected from the same hospital, emergency room, or school as case-patients or were identified by random-digit telephone dialing. As in the pilot study, a strong statistical association with ingestion of
salicylates during the antecedent illness and prior to the onset of
Reye's syndrome was observed (odds ratio, 40; lower 95% confidence limit, 5.8). Analysis of the independent risk of
aspirin and nonaspirin
salicylates revealed a significant association with
aspirin (odds ratio, 26; lower 95% confidence limit, 6.4); the independent risk of nonaspirin
salicylates could not be assessed because only two cases were not exposed to
aspirin. Assessment of epidemiologic issues of concern, including case-control differences in the severity of the antecedent illness, did not explain the high odds ratios that were observed. The high percentage of patients with
Reye's syndrome exposed to
salicylates (greater than or equal to 90%) in this and prior studies suggests that, though the reported incidence of
Reye's syndrome has declined in recent years, concomitant with a decline in
salicylate use among children, a majority of
Reye's syndrome cases may be attributable to
salicylate use.