ABSTRACT Objective: To identify risk factors for intracranial hemorrhage in the natural history course of brain arteriovenous malformations (AVMs) using individual patient data meta-analysis of 4 existing cohorts. Methods: We harmonized data from Kaiser Permanente of Northern California (n 5 856), University of California San Francisco (n 5 787), Columbia University (n 5 672), and the Scottish Intracranial Vascular Malformation Study (n 5 210). We censored patients at first treatment, death, last visit, or 10-year follow-up, and performed stratified Cox regression analysis of timeto-hemorrhage after evaluating hemorrhagic presentation, sex, age at diagnosis, deep venous drainage, and AVM size as predictors. Multiple imputation was performed to assess impact of missing data. Results: A total of 141 hemorrhage events occurred during 6,074 patient-years of follow-up (annual rate of 2.3%, 95% confidence interval [CI] 2.0%-2.7%), higher for ruptured (4.8%, 3.9%-5.9%) than unruptured (1.3%, 1.0%-1.7%) AVMs at presentation. Hemorrhagic presentation (hazard ratio 3.86, 95% CI 2.42-6.14) and increasing age (1.34 per decade, 1.17-1.53) independently predicted hemorrhage and remained significant predictors in the imputed dataset. Female sex (1.49, 95% CI 0.96-2.30) and exclusively deep venous drainage (1.60, 0.95-2.68, p 5 0.02 in imputed dataset) may be additional predictors. AVM size was not associated with intracerebral hemorrhage in multivariable models (p . 0.5). Conclusion: This large, individual patient data meta-analysis identified hemorrhagic presentation and increasing age as independent predictors of hemorrhage during follow-up. Additional AVM cohort data may further improve precision of estimates, identify new risk factors, and allow validation of prediction models. Brain arteriovenous malformations (BAVMs) are the most common cause of intracranial hemorrhage in younger people, who are at risk of long-term morbidity and mortality. The most common presentation is hemorrhage (approximately 50%), followed by seizures and neurologic deficits. Understanding hemorrhage risk in the natural history course of BAVM is crucial when making treatment decisions. However, obtaining accurate estimates is challenging because of short follow-up times from censoring by treatment, low event rates, and low prevalence of disease, which are major limitations of all BAVM longitudinal studies. Current BAVM annual hemorrhage rates range from 2%-4% overall 1-9 to 1%-3% among unruptured patients, 1,4,6,9 but vary †Deceased
