Etiology of intracerebral hemorrhage in children: cohort study, systematic review, and meta-analysis

OBJECTIVE Understanding the etiological spectrum of nontraumatic pediatric intracerebral hemorrhage (pICH) is key to the diagnostic workup and care pathway. The authors aimed to evaluate the etiological spectrum of diseases underlying pICH. METHODS Children treated at the authors' institution for a pICH were included in an inception cohort initiated in 2008 and retrospectively inclusive to 2000, which was analyzed in October 2019. They then conducted a systematic review of relevant articles in PubMed published between 1990 and 2019, identifying cohorts with pICH. Identified populations and patients from the authors' cohort were pooled in a multicategory meta-analysis. RESULTS A total of 243 children with pICH were analyzed in the cohort study. The final primary diagnosis was an intracranial vascular lesion in 190 patients (78.2%), a complication of a cardiac disease in 17 (7.0%), and a coagulation disorder in 14 (5.8%). Hematological and cardiological etiologies were disproportionately more frequent in children younger than 2 years (p < 0.001). The systematic review identified 1309 children in 23 relevant records pooled in the meta-analysis. Overall, there was significant heterogeneity. The dominant etiology was vascular lesion, with an aggregate prevalence of 0.59 (95% CI 0.45-0.64; p < 0.001, Q = 302.8, I-2 = 92%). In 18 studies reporting a detailed etiological spectrum, arteriovenous malformation was the dominant etiology (68.3% [95% CI 64.2%-70.9%] of all vascular causes), followed by cavernoma (15.7% [95% CI 13.0%-18.2%]). CONCLUSIONS The most frequent etiology of pICH is brain arteriovenous malformation. The probability of an underlying vascular etiology increases with age, and, conversely, hematological and cardiac causes are dominant causes in children younger than 2 years.