From 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.
Neurology. 2022 May 10;98(19):e1953-e1963. doi: 10.1212/WNL.0000000000200253. Epub 2022 Mar 21.
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.
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.
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.
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.
缺血性中风会增加神经发育障碍的风险；然而，自闭症的风险尚未得到充分探讨。我们的目的是评估儿童缺血性中风及其一级亲属患自闭症的风险和自闭症的相关因素。
在这项队列研究中，我们在瑞典国家登记处确定了 1969 年至 2016 年间年龄<18 岁、中风后 1 周存活且无自闭症既往史的缺血性中风患者。为每位索引个体匹配了 10 名对照，以及索引个体和对照的所有一级亲属。采用条件 Cox 回归计算自闭症的风险。采用非条件 logistic 回归分析性别、胎龄、中风诊断年龄、合并不良运动结局、合并癫痫以及自闭症同胞作为缺血性中风患儿自闭症的相关因素。
在 1322 名索引个体中，46 名（3.5%）被诊断为自闭症，而 161 名（1.2%）对照（调整后的危险比[aHR]3.02，95%CI 2.15-4.25）。根据中风年龄，自闭症的风险无显著差异：围产期（aHR 2.69，95%CI 1.44-5.03）和儿童期中风（aHR 3.18，95%CI 2.12-4.78）。排除早产儿或小于胎龄儿（aHR 3.78，95%CI 2.55-5.60）和仅分析 1997 年至 2014 年诊断为中风的儿童（aHR 2.91，95%CI=1.95-4.35）后，风险仍增加。与对照组相比，伴有癫痫合并不良运动结局的缺血性中风个体（aHR 7.05，95%CI 3.74-13.30）和单纯不良运动结局（aHR 4.28，95%CI 2.44-7.51）的自闭症风险增加。当排除不良运动结局和癫痫的个体后，自闭症的风险仍然增加（aHR 2.37，95%CI 1.45-3.85）。性别、胎龄和自闭症同胞与儿童缺血性中风患者的自闭症无关。
在儿童缺血性中风后，自闭症的风险增加，特别是在合并癫痫的个体中，且不能用早产或小于胎龄来解释。在无癫痫和不良运动结局的个体中，风险也增加了，这意味着如果怀疑患有自闭症，所有缺血性中风患儿都应进行自闭症筛查。
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