Background: It has been suggested that reproductive factors may be involved in the etiology of multiple sclerosis (MS). We studied associations of reproductive history with MS risk in a population-based setting.
Methods: Using national databases, we established a cohort comprising 4.4 million Danish men and women born between 1935 and 1989 and alive in 1968 or later. We obtained information about their live-born children, pregnancy losses, pregnancy complications, and infertility diagnoses. MS cases in the cohort were identified through 2004 in the Danish Register of Multiple Sclerosis. Associations between reproductive factors and MS risk were evaluated using rate ratios (RRs) obtained in log-linear Poisson regression analysis.
Results: MS was diagnosed in 6332 women and 3426 men. In both sexes, parents had a lower risk of MS compared with childless persons (in women, RR = 0.76 [95% confidence interval = 0.71–0.82]; in men, 0.89 [0.80–0.98]). RRs were inversely associated with number of children, age at first childbirth, and proximity in time since most recent birth. Among women, MS risk was unrelated to histories of pregnancy loss, pregnancy complications, or infertility. A supplementary analysis in which the date of MS diagnosis was backdated by 5 years to address the possibility of reverse causality did not confirm a protective effect of parenthood (in women, 0.95 [0.88–1.03]; in men, 1.08 [0.98–1.20]).
Conclusions: Similar findings in women and men argue against a biologic role of pregnancy in the etiology of MS. Moreover, the observed differences in childbearing patterns were restricted to the 5 years before MS diagnosis, suggesting that reverse causality (ie, reduced reproductive activity in persons with yet-undiagnosed MS) might explain the observed associations.
From the aDepartment of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark; bThe Danish Multiple Sclerosis Registry, Rigshospitalet, Copenhagen, Denmark; cNational Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark; dInstitute of Regional Research Services, University of Southern Denmark, Odense, Denmark; eDepartment of Neurology, MS Clinic of Southern Jutland (Sønderborg, Vejle, Esbjerg), Sønderborg, Denmark; fThe Danish Cancer Society, Institute of Cancer Epidemiology, Copenhagen, Denmark; and gGynecologic Clinic, The Juliane Marie Center, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark.
Submitted 14 July 2010; accepted 20 January 2011; posted 22 April 2011.
Supported by the Augustinus Foundation, the A.P. Møller's Foundation, and the Aase og Ejnar Danielsen's Foundation. The Danish Register of Multiple Sclerosis is supported financially by the Danish Society of Multiple Sclerosis.
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Correspondence: Nete Munk Nielsen, Department of Epidemiology Research, Statents Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark. E-mail: NMN@ssi.dk.