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As genetics only play a small role in the risk of developing juvenile idiopathic arthritis, environmental factors, such as infections and antibiotic usage, are believed to be the main cause of the disease.
While dose-dependent, there is an association between early exposure to antibiotics and later onset juvenile idiopathic arthritis, according to a study published in Pediatric Rheumatology.1
“Genetic components make up only a small part (10–25%) of the cause, and unknown environmental factors are believed to be the main cause of the disease,” investigators stated. “Environmental factors such as viral infections have been suggested, but other studies have not been able to confirm these results.”
Parents of children born between October 1, 1997, and October 1, 1999, were sent a survey from the All Babies in Southeast Sweden (ABIS) designed to collect data on infections and antibiotic use during pregnancy and early childhood. A total of 17,055 (78.6%) families agreed to participate in the population-based prospective study, of which 102 children were diagnosed with JIA according to an International Classification of Diseases (ICD) code during the 19-year follow-up period.
In addition to blood samples taken at birth and at 1, 3, 5, and 8 years, parents were periodically asked about nutrition, drug use, vaccinations, and infections. Logistic regression analyses adjusted for any confounding factors.
The majority of JIA cases were female (68%) and median age at diagnosis was 12 years. Most JIA was categorized as either oligoarthritis and polyarthritis.
Results indicated that exposure to antibiotics from 1-12 months, 1-3 years, and 5-8 years was linked to an increased risk of developing JIA. Further, JIA was 3 times more prevalent in patients who were exposed to antibiotics during the first 3 years of life when compared with controls (aOR 3.17; 95% CI 1.11–9.03, p = 0.031) and twice as high for those who received antibiotics during the first 5 years of life (aOR 2.18; 95% CI 1.36–3.50, p = 0.001). The odds of developing JIA were 78% higher for patients who were given antibiotics during the first 8 years of life when compared with controls (aOR 1.78; 95% CI 1.15–2.73, p = 0.009).
The number of courses of antibiotics was significantly higher in patients who were later diagnosed with JIA (p < 0.001).
Infection during the first year of life was seen in more patients with JIA when compared with controls (39% vs 26%, respectively). However, after adjustment, the association was no longer significant.
Antibiotic use during pregnancy was linked to systemic-onset juvenile idiopathic arthritis (sJIA) and oligoarticular JIA was seen more often in patients who had a higher number of doses of penicillin from ages 5 to 8.
The prospective nature of the study limits recall and selection bias and distributes any bias equally among both patients with JIA and controls. Additionally, all JIA diagnoses were validated via both medical records and the Swedish Pediatric Rheumatology Registry and the ABIS cohort is generally representative of the Swedish population. However, the small amount of JIA patients and a significant percentage of patients lost to follow-up limits the study.
“The findings suggest a causal relationship between use of antibiotics specifically and the development of JIA,” investigators concluded. “Irrespective of mediating mechanisms, these results suggest that restrictive antibiotic policies during the first years of life should be advisable.”
Kindgren E, Ludvigsson J. Infections and antibiotics during fetal life and childhood and their relationship to juvenile idiopathic arthritis: a prospective cohort study. Pediatr Rheumatol Online J. 2021;19(1):145. Published 2021 Sep 16. doi:10.1186/s12969-021-00611-4