Abstract
BackgroundExisting data on associations between maternal and early childhood exposures and juvenile idiopathic arthritis (JIA) risk is scant and inconsistent with previous studies showing potential role for prematurity, number of siblings and infections. We explored JIA and International League of Associations for Rheumatology (ILAR) JIA categories in relation to selected infant (birthweight, size-for-gestational-age, gestational age), and maternal (parity, delivery type, prior fetal loss) characteristics that may be markers for exposures related to two pathways (hygiene hypothesis, microchimerism) potentially associated with autoimmune disorder occurrence.MethodsA case–control analysis with 1,234 JIA cases and 5,993 birth year-matched controls was conducted. Exposure information was obtained from WA state birth certificates. Multivariable logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for associations with maternal and early life exposures for JIA and JIA categories.ResultsGreater maternal parity was associated with a decreased OR for JIA (most marked for persistent oligoarticular JIA, OR 0.32, 95% CI 0.15; 0.71, p for trend = 0.0001). Prior fetal loss (except for oligoarticular JIA) was associated with an increased OR for JIA. Prematurity was associated with increased risk of enthesitis related arthritis (OR 1.9, 95% CI: 1.3–2.9) and rheumatoid factor positive polyarticular JIA (OR 2.2, 95% CI: 1.0–4.8).ConclusionsWe observed associations of selected maternal factors with JIA, some of which varied across JIA categories. The findings of decreased ORs for JIA in relation to greater maternal parity may be consistent with the hygiene and microchimerism hypotheses. Future studies with biomarkers relevant to these hypotheses will help elucidate any associations.
Highlights
Existing data on associations between maternal and early childhood exposures and juvenile idiopathic arthritis (JIA) risk is scant and inconsistent with previous studies showing potential role for prematurity, number of siblings and infections
Lacking direct indicators of early prior infection relevant to the hygiene hypothesis, or of the presence of microchimerism, we explored associations of JIA and its individual categories in relation to selected maternal reproductive and infant characteristics as proxies for these, as assessed by birth certificate data among children with, and without JIA
After examining the odds ratios (OR) for JIA in relation to plurality status, all remaining analyses were restricted to singleton infants only (1,234 cases; 5,993 controls) because characteristics of infants and pregnancies differ for singleton and multiple gestation pregnancies
Summary
Existing data on associations between maternal and early childhood exposures and juvenile idiopathic arthritis (JIA) risk is scant and inconsistent with previous studies showing potential role for prematurity, number of siblings and infections. Evidence suggests that adult rheumatoid arthritis (RA) [4], JIA [5, 6], and other autoimmune diseases such as multiple sclerosis [7, 8] may be associated with maternal or early childhood exposures such as maternal parity, birthweight, or gestational age. The “Hygiene hypothesis” suggests that early exposure to infection results in decreased risk of childhood autoimmune disease [9] due to modulation of the developing immune system. Proxy measures often used to assess this include maternal parity
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