Infection, vaccination, and childhood arterial ischemic stroke: Results of the VIPS study

Abstract

Objectives: Minor infection can trigger adult arterial ischemic stroke (AIS) and is common in childhood. We tested the hypotheses that infection transiently increases risk of AIS in children, regardless of stroke subtype, while vaccination against infection is protective.

Methods: The Vascular Effects of Infection in Pediatric Stroke study is an international case-control study that prospectively enrolled 355 centrally confirmed cases of AIS (29 days-18 years old) and 354 stroke-free controls. To determine prior exposure to infections and vaccines, we conducted parental interviews and chart review.

Results: Median (interquartile range) age was 7.6 years for cases and 9.3 for controls (p = 0.44). Infection in the week prior to stroke, or interview date for controls, was reported in 18% of cases, vs 3% of controls, conferring a 6.3-fold increased risk of AIS (p < 0.0001); upper respiratory infections were most common. Prevalence of preceding infection was similar across stroke subtypes: arteriopathic, cardioembolic, and idiopathic. Use of vasoactive cold medications was similarly low in both groups. Children with some/few/no routine vaccinations were at higher stroke risk than those receiving all or most (odds ratio [OR] 7.3, p = 0.0002). In an age-adjusted multivariate logistic regression model, independent risk factors for AIS included infection in the prior week (OR 6.3, p < 0.0001), undervaccination (OR 8.2, p = 0.0004), black race (compared to white; OR 1.9, p = 0.009), and rural residence (compared to urban; OR 3.0, p = 0.0003).

Conclusions: Infection may act as a trigger for childhood AIS, while routine vaccinations appear protective. Hence, efforts to reduce the spread of common infections might help prevent stroke in children.

Figure. Age and seasonal distributions of childhood arterial ischemic stroke cases and controls

Histograms demonstrate (A) age distribution of cases of childhood arterial ischemic stroke (n = 355), routine visit controls (n = 234), and trauma visit controls (n = 120); (B) seasonal distribution of arterial ischemic strokes in northern hemisphere children, stratified by those with (n = 63) vs without (n = 262) infection in the prior week; and (C) seasonal distribution of enrollment of routine visit controls (n = 234) and trauma visit controls (n = 120). (All controls were enrolled in the northern hemisphere.)