Perinatal characteristics, maternal reproductive history and juvenile idiopathic arthritis: A case-control study

Abstract

Background: Juvenile Idiopathic Arthritis (JIA) is a heterogeneous group of chronic inflammatory arthritis conditions in children with onset before 16 years of age, and is the leading cause of acquired short and long-term disability in childhood. The etiology of JIA is largely unknown, however there is increasing evidence that autoimmune diseases, including JIA, may be associated with maternal reproductive or early childhood exposures. Methods: We conducted a case-control study of JIA cases identified at a regional children's hospital in the Seattle-Puget Sound area, using linked birth certificate data from 1987 - 2009. Potential cases included all children <20 years with relevant ICD codes who had received inpatient or outpatient care. Their records were linked to Washington State birth records for 1980-2009 to identify those with a Washington State birth certificate (N=1,518). For comparison, control children were randomly selected in a ratio of 4:1 from the remaining birth records, frequency matched on year of birth (N=6,072). Review of medical records further refined case ascertainment based on specific clinical criteria (N=1,254) and allowed categorization of cases into JIA subtypes. Multivariable logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for the associations of JIA/JIA subtypes with maternal and early life exposures as measured in the birth certificates. Results: Decreased ORs were observed for JIA in relation to greater maternal parity (2 prior live births, OR 0.70, 95% CI 0.58, 0.85; 4+ prior live births, OR 0.68, 95% CI 0.48, 0.97), a finding also observed for the persistent oligoarticular JIA subtype. Fewer cases (11.4%) than controls (13.3%) had a birth weight >4000 g (OR 0.81, 95% CI 0.67, 0.98). Mothers of cases (5.2%) were slightly more likely than those of controls (4.1%) to have had preeclampsia during their pregnancy (OR 1.29, 95% CI 0.96, 1.73). Discussion: To our knowledge, no studies to date in the United States have examined these exposures in relation to JIA. Greater maternal parity, specifically having 2 or more prior live births, was significantly associated with a decreased OR for JIA, a finding consistent with both the hygiene and microchimerism hypotheses.