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Is There a Link Between Maternal Infection and Juvenile Idiopathic Arthritis?

Previous attempts to make associations between JIA and prenatal maternal infection is difficult due to the rarity of JIA diagnosis and recall bias.

The developmental origins of disease have been previously associated with fetal environment resulting in immune function-related health outcomes including asthma, type 1 diabetes, and celiac disease. However, according to a study published in Pediatric Rheumatology,1 an increased risk of juvenile idiopathic arthritis (JIA) in children exposed to maternal infection was not observed.

“Prospectively studying associations of JIA and prenatal maternal infection is difficult due to rarity of JIA diagnosis and recall bias as JIA is often diagnosed several years later in early or late childhood,” investigators stated. “Hence, we used existing linked medical records and Washington State birth records to evaluate the association between JIA and maternal infection.”

Using an established database, a case-control study included 1290 patients with JIA and 6072 randomly selected controls, matched for age. Information on maternal infection, both viral and bacterial, was attained through Washington State birth records. Diagnosis of JIA, as well as subcategories, were determined through a chart review. Logistic regression was utilized to calculate both adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs).

Eligible patients with JIA were < 20 years old, identified by ICD-9 codes, and were treated between 1997-2010 at a tertiary care hospital in Washington state. Among patients with JIA, according to the International League of Associations for Rheumatology (ILAR) JIA classification, persistent oligoarticular (n = 402), rheumatoid factor (RF) negative polyarticular (n = 275), enthesitis-related (n = 263), systemic (n = 75), extended oligoarticular (n = 74), psoriatic (n = 71), polyarticular (n = 63), and undifferentiated arthritis (n = 39) were reported.

Patients with JIA were more likely to be female (68%) and mothers of cases were more likely to be White, more educated, receive prenatal care earlier in pregnancy, and were privately insured. Ultimately, JIA was not linked to maternal infection, either during pregnancy or in labor and delivery (OR = 1.02, 95%CI: 0.78–1.34). Additionally, there was no association with persistent oligoarticular (OR = 1.05, 95%CI: 0.70 to 1.59), rheumatoid factor (RF) negative polyarticular (OR = 1.17, 95%CI: 0.71 to 1.92), or enthesitis-related (OR = 0.79, 95%CI: 0.40 to 1.56) JIA and maternal infection. No significant associations were found in the larger “polygo” category, which combined persistent and extended oligoarticular, RF-negative polyarticular arthritis (OR = 1.09, 95%CI: 0.80 to 1.51).

According to sex-stratified analysis, evidence suggested an increased association between maternal infection and JIA in female patients (OR = 1.12, 95%CI: 0.79 to 1.57) when compared with males (OR = 0.85, 95%CI: 0.53 to 1.37). However, results were not statistically significant. Children diagnosed at < 5 years were 1.27 times as likely to have been exposed to maternal infection when compared with those diagnosed at ≥ 5 years.

The study was strengthened by the large database of patients with JIA linked to state birth records, which were not hindered by recall bias. Further, investigators were able to analyze maternal infections on a broad scale due to multiple infection variables that were included in birth certificate records. Misclassification was reduced by utilizing ICD-9 codes; however, patients with mild JIA may have been treated by a primary care physician instead of a pediatric rheumatologist. The retrospective nature of the study design limited the detail of data collected regarding maternal infection and category-specific analysis was restricted due to the small number of patients. Additionally, infections that occurred earlier in pregnancy may have been underreported and cases of JIA may have been missed in those with limited access to care.

“While childhood infection has been closely examined as a risk factor for JIA, maternal infection has not,” investigators concluded. “This study is an initial exploration of fetal response to infection as a mechanism for JIA. While we did not find an overall association between JIA and maternal infection, our results suggest that future studies focused on the individual categories of JIA and gender related differences should be considered.”

Reference:

Sutton A, Quraishi SM, Shenoi S. Association of juvenile idiopathic arthritis with maternal infection: a case control study. Pediatr Rheumatol Online J. 2022;20(1):45. Published 2022 Jun 23. doi:10.1186/s12969-022-00703-9