Reye's syndrome in the United States from 1981 through 1997.
Level 4 - case-series / case-control
National epidemiological analysis of a voluntary passive surveillance registry (case series without comparison group).
PubMed 10228187 · doi:10.1056/NEJM199905063401801
What was done
Researchers analyzed United States national surveillance data collected between December 1980 and November 1997 (surveillance years 1981 through 1997) using standardized case-report forms to track epidemiology, clinical characteristics, and risk factors for mortality in patients under 18 years of age with Reye's syndrome.
What was found
A total of 1207 pediatric cases were reported across the surveillance period. Following warnings regarding salicylate use during viral illness, reported cases dropped from a peak of 555 in 1980 to no more than 36 cases per year after 1987. Among cases with demographic data, 93% were white and 52% were female. Antecedent illness was documented in 93% and detectable blood salicylate levels in 82%. The overall case-fatality rate was 31%. Mortality risk was significantly higher in children under 5 years of age (relative risk 1.8, 95% CI 1.5–2.1) and in patients with serum ammonia levels above 45 µg/dL (26 µmol/L) (relative risk 3.4, 95% CI 1.9–6.2).
Why it matters
This study documents the dramatic national decline in Reye's syndrome following public health warnings against aspirin use in children with viral infections, establishing that the condition is now exceptionally rare and highlighting high ammonia and age under 5 as markers of fatal outcomes.
Limits
The surveillance system relies on voluntary passive reporting, creating potential for underreporting or reporting bias. Inborn errors of metabolism that mimic Reye's syndrome may have been misclassified in historical cases before widespread metabolic testing became standard.
Cited by
- supports Aspirin warnings in children are due to the risk of Reye's syndrome rather than hearing loss.