Systemic sclerosis linked to increased risk for pregnancy adverse events

medwireNews: A study of pregnant women with systemic sclerosis or Very Early Diagnosis of Systemic Sclerosis (VEDOSS) shows an “overall favourable outcome,” researchers say, despite a significantly increased risk for preterm birth, pre-eclampsia, and severe postpartum hemorrhage compared with the general population.

The results, published in The Lancet Rheumatology, also indicate a risk for disease worsening during the postpartum period, particularly among women with diffuse cutaneous systemic sclerosis, previous cutaneous vascular involvement, and antibodies other than anticentromere.

Successful pregnancies, but risks persist

The investigators identified 52 patients from the prospective French GR2 national study on pregnancy and rare diseases. The women were aged a median of 34 years and had conceived prior to the end of 2020. Forty-six women had systemic sclerosis (16 had diffuse cutaneous systemic sclerosis and 30 limited cutaneous systemic sclerosis), while six women met VEDOSS criteria. All the participants were followed up for 12 months after delivery.

Benjamin Chaigne (Assistance Publique–Hôpitaux de Paris, France) and colleagues report that of 58 pregnancies (five women had more than one pregnancy) studied, 91.4% continued beyond 22 weeks of gestation and resulted in livebirths.

However, 26.4% of pregnancies met the composite adverse pregnancy outcome, including preterm deliveries at 34 weeks of gestation or less (3.8%), placental insufficiency complications such as pre-eclampsia or fetal growth restriction (22.6%), and small for gestational age infants (11.3%).  There were also severe postpartum hemorrhage events in 11.3% of pregnancies.

Adverse outcome risks increased compared with general population

Chaigne and team compared rates of the adverse pregnancy outcomes with those of women from the French perinatal survey 2016, who had healthy ongoing pregnancies to at least 22 weeks and were matched for age and parity.

Women with systemic sclerosis were significantly more likely than the general population to have preterm births before 37 weeks (13.2 vs 5.8%), pre-eclampsia (13.2 vs 3.0%), infants weighing less than 2500 g (21.1 vs 4.3%), and severe postpartum hemorrhage (11.3 vs 1.4%).

Additionally, systemic sclerosis was associated with higher rates of fetal growth restriction (9.4 vs 3.8%), induced labor (32.6 vs 20.6%) and cesarean section (30.0 vs 20.6%), although the differences were not statistically significant. 

Univariate analysis found that factors such as maternal age, systemic sclerosis disease subtype, antibody status, prior disease duration, prior vascular/organ involvement, or VEDOSS, were not significantly associated with the likelihood of composite adverse pregnancy outcomes.

Maternal disease progression affected

Maternal disease progression worsened in 39.7% of pregnancies, mainly during the postpartum period, and was significantly predicted by diffuse cutaneous systemic sclerosis diagnosis and prior cutaneous vascular involvement (odds ratio [OR]=3.7 for both). Conversely, anticentromere antibody positive status, found in 32.7% of women, was associated with a reduced likelihood of disease worsening (OR=0.2).

The authors of an accompanying comment, Megha Singh and Francesca Crowe, both from the University of Birmingham in the UK, say that the pregnancy findings “are consistent with previous retrospective studies suggesting an increased risk of placental dysfunction in pregnancies with systemic sclerosis, likely driven by underlying vascular pathology.”

They point out that the “absence of data on medication exposure during pregnancy and postpartum period is a marked limitation” of the study. Nevertheless, they say that the researchers “offer timely and valuable evidence in an area where prospective data are scarce.”

They note that “[c]linical care for women with systemic sclerosis remains fragmented,” and advise that “multidisciplinary care, including phenotype-based risk assessment, antenatal monitoring, and postpartum rheumatology review, especially for those with diffuse cutaneous systemic sclerosis or vascular involvement needs to be standard practice.”

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Lancet Rheumatol 2025; doi:10.1016/S2665-9913(25)00185-7
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