Cerebral edema (CE) refers to excess accumulation of fluid in the brain parenchyma, which can result from trauma, stroke, infections, or metabolic insults. Despite its clinical importance, national trends and disparities in CE-related mortality remain understudied. We analyzed mortality data from 1999 to 2023 using the CDC WONDER database. Deaths listing CE, defined by the International Classification of Diseases, 10th Revision, as a contributing cause were included. The trends were stratified by age, sex, race/ethnicity, region, and urbanization level. We calculated crude and age-adjusted mortality rates (AAMRs) and assessed trends using the Joinpoint Regression Program with results considered statistically significant if the two-sided t-test yielded p-values < 0.05. A total of 77,278 CE-related deaths occurred from 1999 to 2023. National AAMRs rose from 0.94 per 100,000 population in 1999 to 1.3 per 100,000 population in 2023, with a significant overall increase (AAPC: +1.41 %, 95 % CI: 1.2–1.6; p < 0.001). Adults aged 25–44 exhibited the sharpest rise (AAPC: 1.56 %; 95 % CI: 1.33 to 1.81). Black individuals experienced the highest mortality (peak AAMR: 0.43, AAPC: +2.08 %, 95 % CI: 1.67–2.51). The South showed the highest regional burden (AAMR: 0.32, AAPC: +1.59 %, 95 % CI: 1.38–1.79), while non-metropolitan areas reported disproportionately high mortality rates (AAPC: +2.4 %, 95 % CI: 1.5–3.2; p < 0.001). CE-related mortality has increased significantly in the U.S., with marked disparities by age, race, and geography. These findings highlight the need for targeted prevention, early detection, and equity-focused intervention strategies.
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