National cohort study of reproductive risk factors for rheumatoid arthritis in Denmark: a role for hyperemesis, gestational hypertension and pre-eclampsia?

TY - JOUR

T1 - National cohort study of reproductive risk factors for rheumatoid arthritis in Denmark: a role for hyperemesis, gestational hypertension and pre-eclampsia?

AU - Jørgensen, K T

AU - Pedersen, B V

AU - Jacobsen, S

AU - Biggar, R J

AU - Frisch, M

PY - 2010/2/1

Y1 - 2010/2/1

N2 - 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.

AB - 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.

U2 - 10.1136/ard.2008.099945

DO - 10.1136/ard.2008.099945

M3 - Journal article

SN - 0003-4967

VL - 69

SP - 358

EP - 363

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

IS - 2

ER -