Long-term Mortality Increased After Pediatric Ischemic Stroke

Heléne E.K. Sundelin, MD, PhD

A recent study found that long-term mortality increased after pediatric ischemic stroke, with investigators further concluding that this excess risk continued for 20 years after incident of stroke. The most frequent cause of death was neurological diseases. 

A total of 1606 participants under the age of 18 years with ischemic stroke and 5714 of their first-degree relatives were originally identified through nationwide Swedish registers. Those with ischemic stroke were diagnosed between 1969 and 2016, with each participant compared with 10 reference individuals matched for age, sex, and country of residence. First-degree relatives of children with ischemic stroke were also compared with first-degree relatives to reference individuals. 

After excluding 279 children (17%)—24 with perinatal and 255 with childhood ischemic stroke—that died 1 week after stroke, a total of 1327 index individuals and their controls were used in analyses. In the first 6 months, the mortality rate was 40.1 per 1000 person–years (95% CI, 24.7-55.6), when compared with 1.1 per 1000 person–years in the controls (95% CI, 0.3-1.9). Overall mortality, as evaluated when follow-up started 1 week after stroke, was increased for those with ischemic stroke (HR, 10.8; 95% CI, 8.1-14.3). Beyond 1 year, the mortality risk was 7.7-fold (95% CI, 5.6-10.7) higher, with the increased risk persisting beyond 20 years (HR, 3.9; 95% CI, 2.1-7.1). 

Investigators, led by Heléne E.K. Sundelin, MD, PhD, postdoctoral researcher, Department of Women’s and Children’s Health, Karolinska Institutet, in Stockholm, Sweden, observed a statistically significant difference between mortality in girls (HR, 16.7; 95% CI, 10.2-27.4) and boys (HR, 8.5; 95% CI, 6.0-12.1; P = .03). Children with ischemic stroke also had an 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). 

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“This nationwide register-based study of children with ischemic stroke showed an 11-fold increased mortality risk beyond the first week after stroke, an 8-fold risk beyond 1 year, and a 4-fold risk even 20 years later,” Sundelin et al wrote. “To our knowledge, there are no studies of mortality risk with such an extensive follow-up after ischemic stroke in children.”

First-degree relatives also had an increased mortality (HR, 1.21; 95% CI, 1.05-1.39), and the highest risk was among siblings (HR, 1.52; 95% CI, 1.09-2.11), and relatives of those who had stroke occur in childhood after 28 days of age (HR, 1.23; 95% CI, 1.06-1.42), compared with relatives of the controls. When estimating cause-specific mortality in first-degree relatives, there was also an increased mortality due to accidents, neurological, and endocrine/nutritional/metabolic diseases. 

Investigators utilized prospectively collected data from the National Patient Register, the Medical Birth Register, the Cause of Death Register, and the Total Population Register. Follow-up began at the date of stroke, ending in December 2016 of with death. Causes of death were defined according to the International Classification of Diseases (ICD) codes.

“The main strength of our study is the nationwide and population-based cohort with matched reference individuals and first-degree relatives,” Sundelin et al wrote. “We have not been able to identify any earlier mortality studies in children with ischemic stroke in which reference individuals or first-degree relatives have been used as comparators.”

Limitations were noted as a lack of socioeconomic data, as well as the definition of ischemic stroke, which was based on ICD codes, including both arterial ischemic stroke and cerebral venous thrombosis, which could not be reliably distinguished. According to investigators, these study findings highlight the need for long-term follow-up in this patient population.

REFERENCE
Sundelin HEK, Walås A, Söderling J, Band P, Ludvigsson JF. Long-term mortality in children with ischemic stroke: A nationwide register-based study cohort. Stroke. Published online December 8, 2021. doi:10.1161/STROKEAHA.121.034797