To Örebro University

Background and Purpose: Ischemic stroke is a common cause of death in adults, however, mortality after pediatric ischemic stroke is not well explored. We investigate long-term and cause-specific mortality in children with ischemic stroke and their first-degree relatives.

Methods: Through nationwide Swedish registers, we identified 1606 individuals <18 years old with ischemic stroke between 1969 and 2016 and their first-degree relatives (n=5714). Each individual with ischemic stroke was compared with 10 reference individuals (controls) matched for age, sex, and county of residence. Our main analysis examined 1327 children with ischemic stroke still alive 1 week after the event. First-degree relatives to children with ischemic stroke were compared with first-degree relatives to the reference individuals. Using a Cox proportional hazard regression model, the risk of overall and cause-specific mortality was computed in individuals with pediatric ischemic stroke and their first-degree relatives.

Results: The mortality rate in the first 6 months was 40.1 (95% CI, 24.7-55.6) per 1000 person-years compared with 1.1/1000 in controls (95% CI, 0.3-1.9). The overall mortality risk was hazard ratio (HR)=10.8 (95% CI, 8.1-14.3) and remained elevated beyond 20 years (HR=3.9 [95% CI, 2.1-7.1]). Children with ischemic stroke were at increased risk of death from neurological diseases (HR=29.9 [95% CI, 12.7-70.3]), cardiovascular diseases (HR=6.2 [95% CI, 1.8-22.2]), cancers (HR=6.5 [95% CI, 2.6-15.9]) and endocrine, nutritional and metabolic diseases (HR=49.2 [95% CI, 5.7-420.8]). First-degree relatives to children with ischemic stroke had an increased mortality risk (HR=1.21 [95% CI, 1.05-1.39]), with the highest risk among siblings (HR=1.52 [95% CI, 1.09-2.11]) and relatives to individuals with ischemic stroke >28 days of age (HR=1.23 [95% CI, 1.06-1.42]) compared with the relatives of the controls.

Conclusions: Long-term mortality increased after pediatric ischemic stroke, even 20 years later, with neurological diseases as the most frequent cause of death.