OBJECTIVE: To examine reproductive history and rheumatoid arthritis (RA) risk in 
a highly predisposed population of North American Natives (NAN) with unique 
fertility characteristics.
METHODS: The effect of pregnancy on the risk of RA was examined by comparing 
women enrolled in 2 studies: a study of RA in NAN patients and their unaffected 
relatives; and NAN patients with RA and unrelated healthy NAN controls enrolled 
in a study of autoimmunity. All participants completed questionnaires detailing 
their reproductive history.
RESULTS: Patients with RA (n = 168) and controls (n = 400) were similar overall 
in age, education, shared epitope frequency, number of pregnancies, age at first 
pregnancy, smoking, and breastfeeding history. In multivariate analysis, for 
women who had ≥ 6 births the OR for developing RA was 0.43 (95% CI 0.21-0.87) 
compared with women who had 1-2 births (p = 0.046); for women who gave birth for 
the first time after age 20 the OR for developing RA was 0.33 (95% CI 0.16-0.66) 
compared with women whose first birth occurred at age ≤ 17 (p = 0.001). The 
highest risk of developing RA was in the first postpartum year (OR 3.8; 95% CI 
1.45-9.93) compared with subsequent years (p = 0.004).
CONCLUSION: In this unique population, greater parity significantly reduced the 
odds of RA; an early age at first birth increased the odds, and the postpartum 
period was confirmed as high risk for RA onset. The protective effect of 
repeated exposure to the ameliorating hormonal and immunological changes of 
pregnancy may counterbalance the effect of early exposure to the postpartum 
reversal of these changes.