title: National cohort study of reproductive risk factors for rheumatoid arthritis in Denmark: a role for hyperemesis, gestational hypertension and pre-eclampsia?
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. ktj@ssi.dk
authors.forename: K T
authors.initials: KT
authors.lastname: Jørgensen
authors.forename: B V
authors.initials: BV
authors.lastname: Pedersen
authors.forename: S
authors.initials: S
authors.lastname: Jacobsen
authors.forename: R J
authors.initials: RJ
authors.lastname: Biggar
authors.forename: M
authors.initials: M
authors.lastname: Frisch
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000453:epidemiology* / Q000209:etiology*; D003718:Denmark; D004812:Epidemiologic Methods; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D006939:Hyperemesis Gravidarum / Q000453:epidemiology; D046110:Hypertension, Pregnancy-Induced / Q000453:epidemiology; D008297:Male; D008423:Maternal Age; D008875:Middle Aged; D011225:Pre-Eclampsia / Q000453:epidemiology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology*; D017584:Reproductive History; D017678:Sex Distribution; D055815:Young Adult