Adverse Pregnancy Outcomes Remain Significant in Women with Systemic Sclerosis

Fetal deaths have been on the decline among US women with systemic sclerosis in the last 2 decades, according to new findings from a database assessment of adverse pregnancy outcomes in patients with the rheumatic disease.

Data presented at the American College of Rheumatology (ACR) 2021 Convergence this week showed risk of adverse pregnancy outcomes is still higher in deliveries involving women with systemic sclerosis, but deaths were nonetheless significantly decreasing.

Led by Yumeko Kawano, MD, Clinical Research Fellow in Rheumatology at Brigham & Women’s Hospital, investigators sought to determine the occurrence of adverse pregnancy outcomes among women with and without systemic sclerosis relative to the past 18 years of such outcomes. As Kawano and colleagues noted, autoimmune connective tissue diseases frequently driven burdens in childbearing women.

“Systemic sclerosis is associated with increased risk of adverse pregnancy outcomes,” they wrote. “However, changes in obstetric practices may have improved systemic sclerosis pregnancy outcomes in recent years, as seen for systemic lupus erythematosus (SLE).”

Their analysis included 2000-2017 entries from the National Inpatient Sample (NIS) database, which derived estimated annual delivery-associated hospitalizations in the US. Investigators used Internal Classification of Diseases (ICD) codes to identify systemic sclerosis patient-associated deliveries; for the assessment, they excluded patients with concurrent SLE or rheumatoid arthritis.

Each systemic sclerosis delivery hospitalization from the NIS was matched 1:100 to a control delivery hospitalization based on age, delivery year, and patient race. Kawano and colluges included the follow adverse pregnancy outcomes:

• Fetal death
• Cesarean delivery
• Hospital length of stay
• Preterm birth
• Intrauterine growth restriction
• Hypertensive pregnancy disorders

The team used maternal age, race, presence of diabetes mellitus and preexisting hypertension as covariates for the adjusted odds ratio generated for each adverse pregnancy outcomes in the observed trial period. They pooled data into 6-year intervals and applied logistic/linear regression to compare the differences in temporal trends in pregnancy outcomes between maternal patients with and without systemic sclerosis.

Investigators observed 3740 estimated delivery-associated hospitalizations for women with systemic sclerosis between 2000 and 2017. Mean maternal patient age was 30 years at delivery.

Pre-existing hypertension, renal disease, and pulmonary hypertension were among the significantly differing comorbidities between hospitalized maternal patients with and without systemic sclerosis; patients with the rheumatic disease were more likely to have each.

Every observed adverse pregnancy outcome was significantly more likely to occur in patients with systemic sclerosis than in those without. Maternal patients with systemic sclerosis were 4 times as likely to experience a fetal death per 100,000 admissions than control (OR, 4.00; 95% CI, 2.55 – 6.27). They were additionally 66% more likely to experience a Cesarean section procedure (OR, 1.66; 95% CI, 1.44 – 1.92), and were at even greater risk of preterm birth (OR, 2.65; 95% CI, 2.23 – 3.14) or hypertensive disorders (OR, 1.97; 95% CI, 1.61 – 2.41).

Fetal deaths, however, declined in the first and last observed 6-year time periods: from 4896 per 100,000 in 2000-2005, to 1619 per 100,000 in 2012-2017.

“In this large nationwide sample, the risk of fetal death among women with systemic sclerosis markedly improved over the past 18 years,” investigators concluded. “We focused on delivery-associated hospitalizations rather than all obstetric hospitalizations; therefore, fetal death represents stillbirth, and captures neither miscarriages earlier in pregnancy nor neonatal death. The risk of other adverse pregnancy outcomes remained high in systemic sclerosis deliveries, and further studies are needed to determine what factors or therapeutics can improve these outcomes.”

The study, “Trends in Adverse Pregnancy Outcomes Among Women with Systemic Sclerosis in the United States,” was presented at ACR 2021.