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National cohort study of reproductive risk factors for rheumatoid arthritis in Denmark: a role for hyperemesis, gestational hypertension and pre-eclampsia?
  1. K T Jørgensen1,
  2. B V Pedersen1,
  3. S Jacobsen2,
  4. R J Biggar1,
  5. M Frisch1
  1. 1
    Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
  2. 2
    Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  1. Correspondence to Mr K T Jørgensen, Department of Epidemiology Research, Statens Serum Institut, 5 Artillerivej, DK-2300 Copenhagen S, Denmark; ktj{at}


Objectives: While reproductive factors might plausibly be involved in the aetiology of rheumatoid arthritis (RA), the female predominance remains unexplained. A study was undertaken to address the possible impact of live births, pregnancy losses and pregnancy complications on the subsequent risk of RA in a nationwide cohort study.

Methods: National register data were used to link reproductive histories and later RA hospitalisations in a cohort of 4.4 million Danes. As a measure of relative risk associated with different reproductive histories, ratios of first inpatient RA hospitalisation rates (RRs) were used with 95% confidence intervals (CIs) obtained by Poisson regression analysis.

Results: Overall, 7017 women and 3041 men were admitted to hospital with RA in 1977–2004 (88.8 million person-years). The risk of RA was inversely associated with age at birth of first child in both women and men (p for trend <0.001). Overall, nulliparity and a history of pregnancy loss were not associated with RA risk but, compared with one-child mothers, women with two (RR 0.84; 95% CI 0.78 to 0.90) or three (RR 0.83; 95% CI 0.77 to 0.91) children were at reduced risk. The risk of RA was increased in women with a history of hyperemesis (RR 1.70; 95% CI 1.06 to 2.54), gestational hypertension (RR 1.49; 95% CI 1.06 to 2.02) or pre-eclampsia (RR 1.42; 95% CI 1.08 to 1.84).

Conclusions: One-child mothers and young parents are at increased risk of RA later in life, possibly due to socioeconomic factors. The novel finding of a significantly increased risk of RA in women whose pregnancies were complicated by hyperemesis, gestational hypertension or pre-eclampsia might reflect reduced immune adaptability to pregnancy in women disposed to RA or a role of fetal microchimerism in the aetiology of RA.

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  • Funding The study was supported by unrestricted research grants from the Danish Ministry of Interior and Health, Danish Graduate School in Public Health Science, The Lundbeck Foundation, The Danish Rheumatism Association, Aase and Ejnar Danielsen’s Foundation, Max Fodgaard’s Foundation, Aage and Johanne Louis-Hansen’s Foundation, Novo Nordisk Foundation and The A P Møller and Wife Chastine Mc-Kinney Møller’s Foundation.

  • Competing interests None.

  • Ethics approval The study was approved by the Danish Data Protection Agency (approval no. 2008-41-2374).

  • Provenance and Peer review Not commissioned; externally peer reviewed.