Risk of Autism After Pediatric Ischemic Stroke: A Nationwide Cohort Study

BACKGROUND AND OBJECTIVES: Ischemic stroke increases the risk of neurodevelopmental disorders; however, the risk of autism is not thoroughly explored. Our aim was to evaluate risk of autism and risk factors for autism in children with pediatric ischemic stroke and in their first-degree relatives. METHODS: In this cohort study, individuals with ischemic stroke from 1969 to 2016, <18 years of age, alive 1 week after stroke, and without prior autism were identified in Swedish national registers. Ten matched controls per index individual and all first-degree relatives of index individuals and controls were identified. Conditional Cox regression was used to calculate the risk of autism. Unconditional logistic regression was performed to analyze sex, gestational age, age at stroke diagnoses, comorbid adverse motor outcome, comorbid epilepsy, and a sibling with autism as risk factors for autism in children with ischemic stroke. RESULTS: Of the 1,322 index individuals, 46 (3.5%) were diagnosed with autism compared to 161 (1.2%) controls (adjusted hazard ratio [aHR] 3.02, 95% CI 2.15–4.25). There was no significant difference in risk of autism according to age at stroke: perinatal (aHR 2.69, 95% CI 1.44–5.03) and childhood stroke (aHR 3.18, 95% CI 2.12–4.78). The increased risk remained after exclusion of children born preterm or small for gestational age (aHR 3.78, 95% CI 2.55–5.60) and when children with stroke diagnosed from 1997 to 2014 were analyzed (aHR 2.91, 95% CI = 1.95–4.35). Compared to controls, the risk of autism was increased in individuals with ischemic stroke and comorbid epilepsy (aHR 7.05, 95% CI 3.74–13.30), as well as adverse motor outcome (aHR 4.28, 95% CI 2.44–7.51). When individuals with adverse motor outcome and epilepsy were censored, the risk of autism was still increased (aHR 2.37, 95% CI 1.45–3.85). Sex, gestational age, and having a sibling with autism were not associated with autism in individuals with pediatric ischemic stroke. DISCUSSION: An increased risk of autism was seen after pediatric ischemic stroke, particularly in individuals with comorbid epilepsy, and could not be explained by being born preterm or small for gestational age. The risk was increased also in individuals free from epilepsy and adverse motor outcome, implying that all children with ischemic stroke should be readily screened for autism if the disorder is suspected.