Reproductive factors and the risk of scleroderma: an Italian case-control study

To investigate the association between scleroderma (systemic sclerosis; SSc) and reproductive factors in a hospital-based case-control study conducted at the University Hospital of Verona in Northeastern Italy.

Forty-six confirmed cases of SSc in women (42 with diffuse SSc and 4 with limited SSc) and 153 female control subjects with orthopedic disorders were recruited at the University Hospital. For each subject, information on age at first pregnancy, number of children and abortions, and use of oral contraceptives was obtained by means of a structured questionnaire, and information on the subject's occupational history and lifestyle factors was also sought.

Parous women had a reduced risk of SSc (age-adjusted odds ratio [OR] 0.3, 95% confidence interval [95% CI] 0.1-0.8) compared with nulliparous women. The risk decreased with an increasing number of children: the age-adjusted OR was 0.6 (95% CI 0.2-1.7) for those women who had had 1 child, 0.3 (95% CI 0.1-0.7) for those having had 2 children, and 0.3 (95% CI 0.1-0.8) for those having had 3 or more children. Abortive pregnancies were inversely related to SSc risk: for women who had an abortion, the OR was 0.5 (95% CI 0.2-1.5) compared with women with no history of abortion. The overall history of any pregnancy (abortive or age-adjusted complete) was associated with a reduced risk of SSc (age-adjusted OR 0.3, 95% CI 0.1-0.7).

Since the incidence of SSc is higher in women and has its peak after childbearing age, it has been hypothesized that immunobiologic modifications during pregnancy may be associated with SSc development. Our findings showing a reduced risk of SSc among parous women seem to exclude the possibility of pregnancy itself as a risk factor for SSc. The role of HLA compatibility between the mother and the fetus, however, should be evaluated in further research.