Increased incidence of pregnancy complications in women who later develop scleroderma: a case control study

Abstract

IntroductionStudies have shown that fetal progenitor cells persist in maternal blood or bone marrow for more than 30 years after delivery. Increased trafficking of fetal cells occurs during pregnancy complications, such as hypertension, preeclampsia, miscarriage and intra-uterine growth restriction (IUGR). Women with these pregnancy complications are significantly more often HLA-class II compatible with their spouses. Women who later develop scleroderma also give birth to an HLA-class II child more often. From these prior studies we hypothesized that preeclampsia and other pregnancy complications could be associated with increased levels of fetal cell trafficking, and later be involved in the development of scleroderma.MethodsThis study was a retrospective multi-centre matched case-control study. One-hundred-and-three women with systemic sclerosis (SSc) and 103 women with no history of SSc or other autoimmune disease were given a questionnaire regarding complications during pregnancy, such as hypertension, intra-uterine growth restriction (IUGR) and miscarriage. Conditional logistic regression analysis was used to assess associations.ResultsWe found a statistically significantly increased incidence of having had a pregnancy history of hypertension or a fetus with IUGR in women who subsequently developed SSc compared to healthy controls. We found an odds ratio of 2.6 (95% confidence interval (CI): 1.1 to 4.6) for hypertensive complications during pregnancy and an odds ratio of 3.9 (95% CI: 1.2 to 12.3) for intra-uterine growth restriction for women with SSc compared to healthy controls.ConclusionsThis is the first study to show an association between hypertensive complications during pregnancy or IUGR and the development of SSc at a later age. We speculate that the pregnancy abnormalities may have resulted in increased fetomaternal trafficking, which may have played a role in the increased incidence of SSc. Further studies are indicated to examine this putative relationship.

Preeclampsia and scleroderma: a prospective nationwide analysis

“…Our observations confirm and extend an earlier retrospectively designed study (4). We found a significantly 69% increased risk of later scleroderma among women with preeclampsia.…”

“…This study reported higher numbers of fetal origin microchimerism in women with scleroderma compared with healthy women (18). The study by van Wyk et al (4), and now also the present brief report, indirectly support the notion that fetal origin cells increase the risk of scleroderma, documented by an increased risk of scleroderma after preeclampsia. Both the quantity and type of cells acquired during pregnancy as well as other factors may have an impact on later maternal health (18).…”

“…The frequency of scleroderma is low, and risk factors are poorly described (3). Interestingly, in a preliminary case-control study, van Wyk et al (4) report a significant association between preeclampsia and scleroderma (4). In their retrospective study, women who later developed scleroderma reportedly had twice the odds of having had a pregnancy complicated by a hypertensive disorder compared with healthy women.…”

Early, Incomplete, or Preclinical Autoimmune Systemic Rheumatic Diseases and Pregnancy Outcome

“…Previous epidemiologic investigations into the relationship between obstetric antecedents of subsequent rheumatic disease were based mainly on retrospective evaluations of obstetric history before the development of a definite rheumatic disease (26,27). Van Wyk et al have shown that, compared with healthy controls, the reproductive history of women who later developed SSc was characterized by increased rates of FGR and preeclampsia (28). Other retrospective studies of obstetric history before and after a diagnosis of SLE (29) suggested that preclinical SLE was associated with increased rates of FGR and pregnancy complications.…”

Undifferentiated connective tissue diseases and adverse pregnancy outcomes. An undervalued association?

“…Many epidemiological studies have suggested that increased rates of adverse pregnancy outcomes can precede a definite diagnosis of ARD by years, suggesting that autoimmune diseases in early, undifferentiated, or incomplete states can negatively affect the reproductive outcome . A nationwide Danish cohort study on 1.9 million infants showed a reduction in birthweight and placental weight for infants born to women with preclinical AR, in addition to a 30% increased risk of preterm birth .…”