Early life exposures association with later diagnosis of spondyloarthritis: A population-based case-control study

Abstract

Objective To assess whether early-life antibiotics are associated with spondyloarthritis (SpA) diagnosed by age 21. Methods In this population-based, matched case–control study, we used Danish live births (1997-2023) restricted to those reaching minimum relevant ages by December 31, 2024: 1–21 years for psoriatic arthritis (PsA), 6–21 years for peripheral/axial SpA and inflammatory bowel disease-associated arthritis (IBD-AA). Cases (n=560) had physician-recorded SpA (peripheral/axial SpA, PsA, or IBD-AA). Controls were matched 1:50 by birth year, sex, and calendar year of diagnosis. Primary exposure was systemic antibiotic use the first year of life; secondary exposures included antibiotic class, number of courses, delivery mode, early upper respiratory tract infection (URTI), and systemic nonbacterial antimicrobials. Conditional logistic regression estimated adjusted odds ratios (aORs); dose-response was tested with the Wald test. Results Among cases (median age 16.8 years; 59% peripheral/axial SpA, 28% PsA, 13% IBDAA), 50% received antibiotics, versus 42% of controls. First-year antibiotic exposure was associated with higher odds of SpA (aOR 1.35, 95% CI: 1.14–1.59). Broad-spectrum penicillins had the strongest class-specific association (aOR 1.42, 95% CI 1.19-1.70). Early URTI was independently associated with SpA (aOR 1.88, 95% CI 1.32-2.67); delivery mode and systemic nonbacterial antimicrobials were not. In SpA subgroup analysis, the association with first-year antibiotics was significant only for PsA (aOR 1.75, 95% CI: 1.27-2.41). Conclusion Antibiotic exposure in the first year of life, particularly broad-spectrum penicillins, was associated with increased odds of SpA by age 21, supporting the hypothesis that early-life microbiome disruption may increase later SpA risk.