Growth of unruptured aneurysms: A meta-analysis of natural history and endovascular studies

•Incidence of growth after endovascular therapy was higher than expected natural history.•The difference remained statistically significant after confounder adjustment.•The risk of bias of the studies and the risk of ecological bias should incur caution.•The effect seems present nevertheless.•Research on potential causes is warranted.•Inflammation of the aneurysm wall might play a role in aneurysm growth after treatment. The growth of unruptured intracranial aneurysms (UIAs) is a strong predictor of rupture. Clinical observations suggest that some UIAs might grow faster after endovascular treatment than untreated UIAs. There are no head-to-head comparisons of incidence rates of UIAs thus far. We searched PubMed, Embase and Google Scholar for relevant articles from the inception of the databases to March 2020. We pooled and compared the incidence rates for the growth of aneurysms from natural history studies and endovascular treatment studies. Generalized linear models were used for confounder adjustment for the prespecified confounders age, size and location. Twenty-five studies (10 describing growth in natural history and 15 reporting growth after endovascular therapy) considering 6325 aneurysms were included in the meta-analysis. The median size of aneurysms was 3.7 mm in the natural history studies and 6.4 mm in endovascular treatment studies (p = 0.001). The pooled incidence rate (IR) of growth was significantly higher in endovascular treatment studies (IR 52 per 1000 person-years, with a 95% confidence interval (CI) 36–79) compared to natural history studies (IR 28 per 1000 person-years, 95% CI 17 – 46, p-value