Background Rheumatoid arthritis (RA) is more common among women than among men and the gender difference in incidence seems to be highest before menopause (1). The importance of hormonal/reproductive factors has been hypothesized to explain this difference, but the literature is contradictory and still under discussion. 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).
Objectives The aim of this work was to study the association between parity, post-partum period, age at first birth and the risk of RA in women, by stratifying the cases according to antibodies to citrullinated peptides (ACPA) and age.
Methods Data from the Swedish population-based EIRA (Epidemiological Investigation of RA) case-control study comprising 2035 incident female cases, aged 18-70, and 2911 controls (matched by age and residential area) between 1996 and 2009 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) with adjustment for matching factors were performed.
Results An increased risk of ACPA-negative RA in parous compared with nulliparous women (OR 2.1, 95% CI 1.4-3.2) was found in women aged 18-44, but no in older women. Women whose most recent delivery occurred during the year of disease onset showed an increased risk of developing ACPA-negative RA (OR 2.6, 95% CI 1.4-4.7). This odds ratio after one year was 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 younger ages 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.
Conclusions Our results indicate that parity increases the risk of ACPA-negative RA in women aged 18-44, but has no association with ACPA-positive RA. The increased risk seemed to be more pronounced in the post-partum period within one year after child delivery and among women who had their first child at younger ages. 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 studies are 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.
Doran MF, et al. Trends in incidence and mortality in rheumatoid arthritis in Rochester, Minnesota, over a forty-year period. Arthritis Rheum 2002.46(3):625-31.
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):332-6.
Acknowledgements This study was supported by grants from the Swedish Medical Research Council, the Swedish Council for Working Life and Social Research, King Gustav V’s 80-year foundation, the Swedish Rheumatic Foundation, Stockholm County Council, and the insurance company AFA.
Disclosure of Interest None Declared