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Risk of Autism After Pediatric Ischemic Stroke: A Nationwide Cohort Study
Heléne Sundelin1, Jonas Söderling1, Peter Bang1
1From the Department of Women's and Children's Health (H.S.), Neuropediatric Unit, Karolinska University Hospital; Department of Medicine Solna (J.S., J.B.), Clinical Epidemiology Division, Karolinska Institutet, Stockholm; Department of Biomedical and Clinical Sciences (H.S., P.B.), Division of Children's and Women's Health, Linköping University; Department of Clinical Science and Education Södersjukhuset (J.B.); and Sachs' Children and Youth Hospital (J.B.), Stockholm, Sweden.
Insights
Pediatric ischemic stroke significantly increases autism risk, especially with epilepsy or motor issues. This risk persists even without these comorbidities, highlighting the need for autism screening in all children with stroke.
Area of Science:
- Neurology
- Developmental Pediatrics
- Autism Spectrum Disorders
Background:
- Ischemic stroke in children is a known risk factor for neurodevelopmental disorders.
- The specific association between pediatric ischemic stroke and autism spectrum disorder (ASD) requires further investigation.
- Understanding risk factors for ASD in this population is crucial for early intervention.
Purpose of the Study:
- To evaluate the risk of autism in children who have experienced an ischemic stroke.
- To identify specific risk factors for autism in pediatric ischemic stroke survivors and their relatives.
- To inform clinical screening and management strategies for children with a history of ischemic stroke.
Main Methods:
- A Swedish cohort study identified individuals with ischemic stroke (1969-2016) under 18 years old.
- Conditional Cox regression analyzed autism risk, with 10 matched controls per index case.
- Unconditional logistic regression examined risk factors including sex, gestational age, stroke timing, and comorbidities.
Main Results:
- Individuals with pediatric ischemic stroke had a significantly higher risk of autism (aHR 3.02).
- Comorbid epilepsy (aHR 7.05) and adverse motor outcome (aHR 4.28) further increased autism risk.
- The elevated risk was independent of gestational age or being small for gestational age.
Conclusions:
- Pediatric ischemic stroke is associated with an increased risk of autism.
- Comorbidities like epilepsy and motor deficits are significant risk factors, but the risk is present even without them.
- Routine autism screening is recommended for all children with a history of ischemic stroke.
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.
