Early-Life Factors and Risk of Brain Arteriovenous Malformations: A Prospective Cohort Study

The pathophysiological basis of brain arteriovenous malformations (bAVMs) remains incompletely understood. Early-life factors are hypothesized to influence cerebrovascular development; however, their potential associations with bAVMs have not been systematically evaluated. This study aimed to investigate the associations between eight early-life factors and the risk of bAVMs.

This prospective cohort study included 329,121 participants aged 40-69 years from the UK Biobank with complete covariate data at baseline. Multiple-adjusted logistic regression models were used to explore the associations between eight self-reported early-life factors (breastfed as a baby, part of a multiple birth, maternal smoking around birth, comparative body size at age 10, handedness, childhood sunburn occasions, number of older siblings, birth weight) and subsequent diagnosis of bAVMs.

A total of 141 patients were diagnosed with bAVMs. After multivariable adjustment, three early-life factors were associated with an increased risk of bAVMs: very low birth weight (<1.5 kg vs. 2.5-4.0 kg; odds ratio [OR], 3.27; 95% confidence interval [CI], 1.04-10.67), having one or more older siblings (≥1 person vs. none; OR, 1.83; 95% CI, 1.03-3.24), and frequent childhood sunburn (>10 episodes vs. none; OR, 2.83; 95% CI, 1.13-7.08). No statistically significant associations were observed in other early-life factors. Sensitivity analyses confirmed the robustness of these findings.

In this large prospective cohort, very low birth weight, the presence of older siblings, and repeated childhood sunburn were associated with a higher risk of bAVMs. These findings warrant validation and further investigation into the underlying biological mechanisms.