Association of childhood infections and perinatal factors with ankylosing spondylitis: a Swedish nationwide case–control and sibling study

OBJECTIVES: To identify perinatal and early-life risk factors for ankylosing spondylitis (AS), controlling for family-shared confounding with a sibling comparison design. METHODS: In this nationwide, register-based case–control study, we identified 5612 AS cases from the Swedish National Patient Register, and matched them with 22 042 individuals without inflammatory arthritis from the general population. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of AS in relation to childhood infections and a broad range of perinatal factors including fetal growth. Significant associations were further tested in a sibling comparison analysis, including 3965 patients with AS and their 6070 siblings without a diagnosis of spondyloarthritis. RESULTS: We found no statistically significant associations between any studied fetal growth-related factor or other perinatal factors and the risk of developing AS. In contrast, having older siblings (adjusted OR 1.12; 95% CI 1.04 to 1.22 for one vs no older sibling) and history of a childhood tonsillectomy (adjusted OR 1.30; 95% CI 1.13 to 1.49) were associated with AS in the case–control analysis, results that also held in the sibling comparison. Serious childhood infection and multiple birth were significantly associated with AS in the case–control sample, but estimates were attenuated in the sibling comparison. CONCLUSIONS: Having older siblings and a history of tonsillectomy in childhood were independently associated with development of AS, even after adjustment for family-shared factors in a sibling comparison analysis. This strengthens the hypothesis that childhood infections play a role in the aetiology of AS.