Supplementary Material for: Early-life Factors and Risk of Brain Arteriovenous Malformations: A Prospective Cohort Study

Abstract
Objective: 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.
Methods: This prospective cohort study included 329,121 participants aged 40 to 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, and birth weight) and subsequent diagnosis of bAVMs.
Results: A total of 141 patients had diagnosed 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 internal [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.
Conclusions: 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.