Abstract A063: Family History in an International Cohort of Children with Arterial Ischemic Stroke

Background: AHA guidelines recommend obtaining a family history of stroke as a means of identifying adult patients with increased stroke risk. Risk factors for childhood arterial ischemic stroke (AIS) differ from those in adults, with a mix of genetic and environmental factors. We aimed to determine the relevance of family history in predicting the risk of arterial ischemic stroke (AIS) in childhood. Methods: The Vascular effects of Infection in Pediatric Stroke (VIPS) studies prospectively enrolled and centrally confirmed 560 children (29 days to 18 years) with acute AIS at centers in North and South America, Europe, Asia and Australia, 1/2010-3/2014 (VIPS I) and 12/2016-1/2022 (VIPS II). Study neuroradiologist (M.W.) and pediatric vascular neurologist (H.J.F.) independently reviewed all baseline and follow-up brain and vascular imaging and clinical data to classify the AIS etiological sub-type using published definitions. Sites also enrolled 501 stroke-free control children. To measure family history of stroke, myocardial infarction (MI), systemic thrombosis (blood clots in the legs or lungs), and other vascular disease, sites performed standardized interviews of caregivers (parents or legal guardians) of both cases and controls. Results: Cases of childhood AIS and stroke-free controls had similar demographics (Table 1). We observed no significant difference in caregiver-reported family history, despite the potential for acquisition bias (i.e., caregivers of cases seeking out family history more than those of controls). Children with cardioembolic stroke were more likely to have a first degree relative with a systemic thrombosis than children with other stroke-subtypes: 8% of cases with cardioembolic stroke, 2% with definite arteriopathy, 4% possible arteriopathy, and none with idiopathic stroke (p=0.006, chi-square test across groups; Table 2). We observed no other significant difference in family history across the stroke subtypes. Conclusions: Unlike in adults, family history of stroke does not appear to predict risk of AIS in childhood. However, a family history of systemic thrombosis was relevant in children with cardioembolic stroke, consistent with prior literature suggesting that genetic thrombophilia contributes to stroke risk in children with congenital heart disease.