Timing and number of minor infections as risk factors for childhood arterial ischemic stroke

Abstract

Objective: In a population-based case-control study, we examined whether the timing and number of minor infections increased risk of childhood arterial ischemic stroke (AIS).

Methods: Among 102 children with AIS and 306 age-matched controls identified from a cohort of 2.5 million children in a large integrated health care plan (1993-2007), we abstracted data on all medical visits for minor infection within the 2 years prior to AIS or index date for pairwise age-matched controls. We excluded cases of AIS with severe infection (e.g., sepsis, meningitis). Using conditional logistic regression, we examined the effect of timing and total number of minor infections on stroke risk.

Results: After adjusting for known pediatric stroke risk factors, the strongest association between infection and AIS was observed for infectious visits ≤3 days prior to stroke (odds ratio [OR] 12.1, 95% confidence interval [CI] 2.5, 57, p = 0.002). Respiratory infections represented 80% of case infections in that time period. Cases had more infectious visits, but not significantly so, for all time periods ≥4 days prior to the stroke. A greater cumulative number of infectious visits over 2 years did not increase risk of AIS.

Conclusions: Minor infections appear to have a strong but short-lived effect on pediatric stroke risk, while cumulative burden of infection had no effect. Proposed mechanisms for the link between minor infection and stroke in adults include an inflammatory-mediated prothrombotic state and chronic endothelial injury. The transient effect of infection in children may suggest a greater role for a prothrombotic mechanism.

Figure 1. Identification of study cases and controls

Flow diagram demonstrates how study cases and controls were identified within the cohort of 2.5 million children enrolled in Kaiser Permanente Northern California from 1993 through 2007. AIS = arterial ischemic stroke.

Figure 2. Minor infections preceding childhood arterial ischemic stroke

(A) Recent minor infection by age at stroke. Proportion of childhood arterial ischemic stroke cases (n = 102) with a visit for minor infection within 3 days prior to stroke, stratified by age group. (B) Number of infection visits in prior 2 years. Cumulative number of visits for minor infection in the 2-year period prior to stroke/index date in cases of childhood arterial ischemic stroke (n = 83) and age-matched controls (n = 249). Repeat visits within 1 week were considered part of the same infection, and therefore counted as a single visit.