Researchers say success is possible, but the risks remain high, with one in four pregnancies facing pre-eclampsia, preterm birth or severe postpartum haemorrhage.
A new French prospective study provides crucial insights into pregnancy outcomes in women with systemic sclerosis and those with a very early diagnosis of systemic sclerosis.
Results of the analysis were published this week in The Lancet Rheumatology, and highlight both maternal and foetal risks in this rare autoimmune disease.
“This study provides novel insights into pregnancy outcomes in women with systemic sclerosis, including those with Very Early Diagnosis of Systemic Sclerosis (VEDOSS),” the researchers wrote.
“Despite the small sample size, it is the first prospective study to offer detailed, longitudinal data on maternal and obstetrical outcomes in this population.
“Serious complications were infrequent in women without previous systemic sclerosis-related organ involvement. However, the results of this study support that women with systemic sclerosis remain at increased risk for pre-eclampsia, preterm birth and severe postpartum haemorrhage.
“Particular attention should be paid to cutaneous vascular manifestations in the postpartum period. Altogether, these findings support the importance of multidisciplinary care and individualised risk assessment in managing pregnancies in women with systemic sclerosis.”
The researchers noted that pregnancy had for a long time been considered contraindicated in women with systemic sclerosis, largely due to the prevailing hypothesis that obstetric complications were driven by the disease’s underlying vasculopathy.
“Vasculopathy, a hallmark feature of systemic sclerosis, always presenting with Raynaud’s phenomenon, can lead to complications such as digital ulcers, telangiectasia, pulmonary arterial hypertension, and scleroderma renal crisis,” they wrote.
“Because systemic sclerosis is a rare disease that predominantly affects women beyond childbearing age, research on pregnancy outcomes in this population is scarce and often based on retrospective or outdated data.”
A 2020 systematic literature review and meta-analysis of 16 retrospective studies, involving 307 pregnancies, found that women with systemic sclerosis had a higher prevalence of miscarriages, foetal growth restriction (FGR), preterm births, maternal hypertensive disorders and newborns with low birthweight, although there was no significant increase in small-for-gestational-age (SGA) infants compared with healthy controls.
However, this meta-analysis was limited by the inclusion of mainly retrospective studies with high heterogeneity and absence of data on factors associated with adverse pregnancy outcomes, the authors of the new paper said.
As part of their study, pregnant women with systemic sclerosis (American College of Rheumatology–European League Against Rheumatism 2013 classification) or with VEDOSS criteria were included in the GR2 French prospective study.
Frequency of composite adverse pregnancy outcomes (preterm birth at 34 weeks or less, placental insufficiency complications, small for gestational age or foetal or neonatal death) and maternal disease course were the primary objectives.
The secondary objectives were to assess other complications related to pregnancy (including delivery outcomes and postpartum complications) and compare these results with outcomes for age-matched controls from the French perinatal survey (ENP) 2016 (i.e., general population), and to identify predictive factors associated with composite adverse pregnancy outcomes and maternal disease course using univariate analysis.
The research followed 58 pregnancies in 52 women from 2014 to 2020. Among these pregnancies, 53 (91.4%) resulted in livebirths, demonstrating that successful outcomes are achievable, yet the study revealed that maternal and foetal risks remain significant compared with the general population.
Of the 53 pregnancies continuing beyond 22 weeks, 14 (26.4%) experienced composite adverse outcomes, which included preterm birth at or before 34 weeks, placental insufficiency complications such as pre-eclampsia or foetal growth restriction and small-for-gestational-age infants. Pre-eclampsia occurred in seven women (13.2%), and severe postpartum haemorrhage was reported in six cases (11.3%).
Compared with data from the 2016 French perinatal survey, women with systemic sclerosis had significantly higher rates of pre-eclampsia, preterm birth before 37 weeks, low birthweight infants and severe postpartum haemorrhage.
The researchers noted that no specific clinical or serologic factors were identified as predictors of these composite adverse pregnancy outcomes, underscoring the complexity of risk stratification in this population.
Maternal disease progression occurred in 23 (39.7%) of 58 pregnancies, primarily during the postpartum period. Worsening typically involved vascular cutaneous manifestations, including Raynaud’s phenomenon, digital ulcers and telangiectasias.
Diffuse cutaneous systemic sclerosis and prior cutaneous vascular involvement were associated with increased risk of disease progression, while the presence of anticentromere antibodies appeared protective.
Severe complications were uncommon but included one case of scleroderma renal crisis at 33 weeks gestation leading to preterm delivery and two cases of worsening interstitial lung disease postpartum.
None of the women with VEDOSS progressed to systemic sclerosis during the study period, although four of eight pregnancies in this group were complicated by adverse outcomes, including two losses and two cases of pre-eclampsia or foetal growth restriction, the researchers noted.
They also acknowledged several limitations of the study, including the fact that the median inclusion term was 11 weeks’ gestation. This study focused on livebirth after 22 weeks of gestation to compare the rates of adverse pregnancy outcome with those in the French general population.
“This approach limits the ability to draw conclusions about first-trimester complications such as miscarriage or early foetal deaths,” they wrote.
“Additionally, data on certain obstetrical outcomes (such as HELLP syndrome or exact birthweight) were not available in the ENP 2016 study, which limited the ability to compare these specific adverse pregnancy outcomes.”
The cohort also did not include women with previous pulmonary arterial hypertension, scleroderma renal crisis or severe organ damage, as pregnancy was generally discouraged in these women with these high-risk conditions. Data on antiphospholipid antibodies were not collected for all pregnancies, although their presence was a known predictor of adverse pregnancy outcomes and is not uncommon in women with systemic sclerosis.
The authors also used caution when highlighting associations between pregnancy and obstetric complications, as these conditions might be interdependent; and noted the study’s relatively small size limited the power of some analyses, although it was “the largest prospective study of pregnancy in women with systemic sclerosis to date”.
“This first prospective study of pregnancies in women with systemic sclerosis and VEDOSS demonstrates an overall favourable outcome, with a 91·4% livebirth rate and few severe events,” they concluded.
“However, 26.4% of ongoing pregnancies at 22 weeks of gestation were complicated by adverse pregnancy outcomes, primarily pre-eclampsia and preterm birth, as well as severe postpartum haemorrhage, which were more frequent than in general population.
“Additionally, disease worsening occurred in one third of women, mostly vascular cutaneous lesions, during the third trimester or postpartum, particularly in women with diffuse cutaneous systemic sclerosis and previous cutaneous vascular involvement.”
