title: Parity influences the severity of ACPA-negative early rheumatoid arthritis: a cohort study based on the Swedish EIRA material.
abstract: BACKGROUND
  In women with rheumatoid arthritis (RA) it has been observed that during pregnancy a majority of patients experience amelioration, but after delivery a relapse of the disease is common. However, there are few studies, with diverging results, addressing the effect of parity on the severity of RA over time. Our aim was to explore the impact of parity, with stratification for anti-citrullinated protein antibody (ACPA) status as well as for onset during reproductive age or not.
  
  
  METHODS
  Female RA cases aged 18-70 years were recruited for the Epidemiological Investigation of Rheumatoid Arthritis (EIRA). Information on disease severity (the health assessment questionnaire (HAQ) and the disease activity score 28 (DAS28)) was retrieved from the Swedish Rheumatology Quality Register at inclusion and 3, 6, 12 and 24 months after diagnosis. Mixed models were used to compare mean DAS28 and HAQ scores over time in parous and nulliparous women. Mean differences at individual follow-up visits were compared using analysis of covariance. The odds of having DAS28 or HAQ above the median in parous verus nulliparous women were estimated in logistic regression models.
  
  
  RESULTS
  A total of 1237 female cases (mean age 51 years, 65 % ACPA-positive) were included. ACPA-negative parous women, aged 18-44 years, had on average 1.17 units higher DAS28 (p < 0.001) and 0.43 units higher HAQ score (p < 0.001) compared to nulliparous women during the follow-up time, adjusted for age. In this subgroup, the average DAS28 and HAQ scores were significantly higher in parous women at all follow-up time points. Younger parous ACPA-negative women were significantly more likely to have DAS28 and HAQ values above the median compared to nulliparous women at all follow-up visits. No association between parity and severity of ACPA-positive disease was observed.
  
  
  CONCLUSIONS
  Parity was a predictor of a more severe RA among ACPA-negative younger women, which might indicate that immunomodulatory changes during and after pregnancy affect RA severity, in particular for the ACPA-negative RA phenotype.
authors.affiliation: Rheumatology Unit, Mälarsjukhuset Hospital, Eskilstuna, Sweden. mitra.pikwer@med.lu.se.|Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. mitra.pikwer@med.lu.se.|Centre for Clinical Research Sörmland, Uppsala University, Eskilstuna, Sweden. mitra.pikwer@med.lu.se.|Rheumatology, Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden. mitra.pikwer@med.lu.se.
authors.forename: Mitra
authors.initials: M
authors.lastname: Pikwer
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. cecilia.orellana@ki.se.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Orellana
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. henrik.kallberg@ki.se.
authors.forename: Henrik
authors.initials: H
authors.lastname: Källberg
authors.affiliation: Centre for Clinical Research Sörmland, Uppsala University, Eskilstuna, Sweden. andreas.pikwer@med.lu.se.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pikwer
authors.affiliation: Rheumatology, Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden. carl.turesson@med.lu.se.
authors.forename: Carl
authors.initials: C
authors.lastname: Turesson
authors.affiliation: Rheumatology Unit, Department of Medicine, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden. lars.klareskog@ki.se.
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. lars.alfredsson@ki.se.|Centre of Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden. lars.alfredsson@ki.se.
authors.forename: Lars
authors.initials: L
authors.lastname: Alfredsson
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. saedis.saevarsdottir@ki.se.|Rheumatology Unit, Department of Medicine, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden. saedis.saevarsdottir@ki.se.
authors.forename: Saedis
authors.initials: S
authors.lastname: Saevarsdottir
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. camilla.bengtsson@ki.se.
authors.forename: Camilla
authors.initials: C
authors.lastname: Bengtsson
mesh_terms: D000293:Adolescent; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology*; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D016022:Case-Control Studies; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D010298:Parity / Q000276:immunology*; D013548:Sweden; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D001324:Autoantigens