Does pregnancy provide vaccine‐like protection against rheumatoid arthritis?

OBJECTIVE: Previous studies have evaluated the correlation between rheumatoid arthritis (RA) risk and pregnancy history, with conflicting results. Fetal cells acquired during pregnancy provide a potential explanation for modulation of RA risk by pregnancy. The present study was undertaken to examine the effect of parity on RA risk. METHODS: We examined parity and RA risk using results from a population-based prospective study in Seattle, Washington and the surrounding area and compared women who were recently diagnosed as having RA (n = 310) with controls (n = 1,418). We also evaluated the distribution of parity in cases according to HLA genotype. RESULTS: We found a significant reduction of RA risk associated with parity (relative risk [RR] 0.61 [95% confidence interval 0.43-0.86], P = 0.005). RA risk reduction in parous women was strongest among those who were younger. Most striking was that RA risk reduction correlated with the time that had elapsed since the last time a woman had given birth. RA risk was lowest among women whose last birth occurred 1-5 years previously (RR 0.29), with risk reduction lessening progressively as the time since the last birth increased (for those 5-15 years since last birth, RR 0.51; for those >15 years, RR 0.76), compared with nulliparous women (P for trend = 0.007). No correlation was observed between RA risk and either age at the time a woman first gave birth or a woman's total number of births. Among cases with the highest genetic risk of RA (i.e., those with 2 copies of RA-associated HLA alleles), a significant underrepresentation of parous women versus nulliparous women was observed (P = 0.02). CONCLUSION: In the present study, there was a significantly lower risk of RA in parous women that was strongly correlated with the time elapsed since a woman had last given birth. While the explanation for our findings is not known, HLA-disparate fetal microchimerism can persist many years after a birth and could confer temporary protection against RA.