Pregnancy Outcomes in Women with Systemic Sclerosis: A Systematic Review and Meta-Analysis

Abstract

Systemic sclerosis (SSc) is a rare chronic autoimmune disease of the body's connective tissue. It affects women who are of childbearing age. Although there has been only one prior systematic review and meta-analysis (in 2020) addressing this issue, many additional controlled studies have recently appeared. The present analysis followed the PRISMA 2020 Guidelines for a systematic review and meta-analysis. A comprehensive literature search was conducted on all databases from the start date through 15 June 2026 without regard to language. Eligible studies were comparative observational studies that provided raw event counts regarding pregnant women with SSc compared to women without SSc. Pooled risk ratios (RR) along with 95% confidence intervals (CI) were generated using a random-effects Mantel-Haenszel method (DerSimonian-Laird). Outcomes that were reported by fewer than 3 of the included studies were summarized narratively. Heterogeneity among studies was estimated using the I² statistic. Thirteen controlled studies (one case-control study and twelve cohort studies; nine countries; years 1999 – 2026) qualified for inclusion. Of those thirteen, eight studies contributed to the quantitative synthesis. Pregnancies in women with SSc had significantly greater risks of developing preeclampsia (RR = 4.84 [3.05 – 7.67]; I² = 0%) and giving birth before term (RR = 3.39 [2.59 – 4.44]; I² = 39.5%) when compared to women without SSc. There was also a significantly increased risk of preterm premature rupture of membranes (RR = 3.32 [1.17 – 9.41]; I² = 83%), intrauterine/ fetal growth restriction (RR = 3.25 [1.65 – 6.39]; I² = 0%), C-sections (RR = 1.91 [1.49 – 2.46]; I² = 69%), and low birth-weight babies (RR = 1.48 [1.08 – 2.04]; I² = 33%). Studies that could not be included in the quantitative analysis due to an insufficient number of events reported similar results concerning direction. There appears to be a significant association between pregnancy in women with SSc and an elevated risk for hypertension, preterm birth, and issues related to growth and development in newborns. This finding provides further support for providing education on preconception counseling.