A role for antibiotic usage, particularly in the first two years of life, but up to the date of diagnosis with JIA, was also observed in a Finnish national registry case-control study based on antibiotic prescription reimbursement records. The study also found a higher risk of JIA was associated with more courses of antibiotic use and with certain antibiotics, including lincosamides and cephalosporins.18 An altered fecal microbiome, including a reduction in Firmicutes and increase in Bacteroides species, was reported at diagnosis in the stool samples of children with JIA compared with healthy control children.19
A recent study of children with JIA and anti-CCP autoantibodies found they were more likely to have tender/bleeding gums on oral health history and higher antibody titers to Porphyromonas (P.) gingivalis and P. intermedia, suggesting a role for periodontitis and the oral microbiome in a subgroup of patients with JIA.20
A large case-control Swedish registry found an association between a higher risk for JIA and the number of hospitalizations for infection in the first year of life, including for respiratory, gastrointestinal or skin/soft-tissue infections21 (see Table 2). However, a smaller U.S. playmate-matched case-control questionnaire study did not find this association with hospitalization for infection in the first year of life, nor with attendance at daycare for those younger than 6 years of age.22
Several analyses of demographic factors suggest smaller (vs. larger) family size and urban environments are modifiers of JIA risk, but the data are mixed. A higher risk of JIA was associated with being a single child in a family and with higher parental income in a national Danish case-control study of incident JIA cases, which used socioeconomic registry data to extract demographic and socioeconomic factors (see Table 2, Demographics).5
Having any siblings, particularly three or more siblings, was protective for JIA risk in an Australian case-hospital control questionnaire study.23 No effect of sibling number was reported in the Swedish case-control registry study or birth order in the Seattle case-control study.21,22 These first two studies are consistent with the hygiene hypothesis, but the latter two are not.
The Danish national registry case-control study found a higher risk of JIA with urban dwelling compared with living on a farm (see Table 2, Demographics).5 However, the Seattle case-control study did not find an association with rural residence or with the frequency or type of household pets.22
A German case-hospital control questionnaire study saw no effect of living in an urban vs. rural area, living on a farm in the first year of life or exposure to farm animals or pets during infancy on development of oligoarticular JIA.25
