Background/Purpose: Rheumatoid arthritis (RA) is more common among women than among men and the gender difference in incidence seems to be most striking before menopause (1). The importance of hormonal/reproductive factors has been hypothesized to explain this difference, but the literature is scarce and contradictory. Parity has been suggested to decrease the risk of RA and postpone the disease onset but, on the contrary, a higher risk of RA in the post-partum period has been described (2). The aim of this work was to study the association between parity, post-partum period and age at first birth and the risk of developing RA in pre-menopausal women, by stratifying the cases according to presence/absence of antibodies to citrullinated peptides (ACPA).

Methods: Data from the Swedish population-based EIRA (Epidemiological Investigation of RA) case-control study comprising 603 incident cases aged 18-44 years old women and 906 controls (matched by age and residential area) was analyzed. Parity, post-partum period before the onset of symptoms and age at first birth were assessed by means of an identical questionnaire answered by the participants. In all analyses, nulliparous women were used as the reference group. Unconditional logistic regression analyses to obtain odds ratios (ORs) with 95% confidence intervals (CI) were performed.

Results: An increased risk of developing ACPA-negative RA in parous women compared with nulliparous women (OR 2.1 (95% CI 1.4-3.2)) was found. Women whose most recent delivery occurred the same year as the disease onset showed an increased risk of developing ACPA-negative RA (OR 2.6 (95% CI 1.4-4.7)). This risk decreased after 1 year (OR 1.8 (95% CI 0.9-3.6)) and reached the null value after 2 years (p-value for trend 0.0147). Women who delivered their first child at a younger age had an increased risk of developing ACPA-negative RA (p-value for trend 0.0158). No association between parity, post-partum period or age at first birth and the risk of ACPA-positive RA was observed.

Conclusion: Our results indicate that parity increases the risk of ACPA-negative RA in pre-menopausal women, but has no association with ACPA-positive RA. The increased risk seemed to be more pronounced in the post-partum period within 1 year after child delivery and among women who had their first child at young age. As previously described, a postponed onset of RA, comparable with the amelioration of the pre-established disease in pregnant women followed by a post-partum flare-up might explain these results in regards to the post-partum period. Further research is needed in order to explore the biological mechanisms behind our findings but the effect of hormonal/reproductive factors such as parity might partly explain the higher incidence of RA in pre-menopausal women.

References

1. Doran, M.F., et al., Trends in incidence and mortality in rheumatoid arthritis in Rochester, Minnesota, over a forty-year period. Arthritis Rheum, 2002. 46(3): p. 625-31.

2. Wallenius, M., et al., Postpartum onset of rheumatoid arthritis and other chronic arthritides: results from a patient register linked to a medical birth registry. Ann Rheum Dis, 2010. 69(2): p. 332-6.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/parity-and-the-risk-of-developing-rheumatoid-arthritis-results-from-the-swedish-epidemiological-investigation-of-rheumatoid-arthritis-study/