Report Outlines New Risk Factors for Adverse Pregnancy Outcomes in SLE

The report suggests remission and disease activity state alone are not the most important risk factors in pregnant women with well-controlled systemic lupus erythematosus.

A new report of more than 200 women with systemic lupus erythematosus (SLE) suggested that lupus anticoagulant and chronic irreversible damage in the first trimester are associated with adverse outcomes in pregnancy.

The findings were reported in the journal Rheumatology.

Investigators, including corresponding author Nathalie Costedoat-Chalumeau, MD, PhD, of the Public Assistance Hospital of Paris and the University of Paris, explained that because SLE affects women of child-bearing age, pregnancies among patients with the disease require vigilance from patients and physicians alike.

They noted the current guidelines call for women to be prescribed hydroxychloroquine during pregnancy and for patients to attempt to time their pregnancies to correspond with remission or lupus low disease activity state (LLDAS). Despite the guidelines, Costedoat-Chalumeau and colleagues explained it is not clear exactly how much these factors impact pregnancy risk, due to a lack of robust evidence. In addition, they said LLDAS does not have a universally accepted definition, nor has it been defined in pregnant women specifically.

To better understand the issue and assess risk, the investigators turned to the GR2 Study, a prospective study launched in 2014 to track women with rare diseases, including SLE, and their outcomes in pregnancy.

The study included 238 women with SLE, of whom 230 had live births. The women had singleton pregnancies, a mean age of 31.6 and had sought care at one of 34 health care centers. The vast majority of patients (98.3%) were on hydroxychloroquine during their pregnancy, in line with guidelines.

Half were taking prednisone, and many were also taking immunosuppressive drugs (23.5%) and low-dose aspirin (69.3%). Five women were taking antihypertensive drugs. Sixty-seven women had reported lupus nephritis, and the diagnosis was confirmed by biopsy in 62 of those patients.

The cohort’s median score according to the SLE Pregnancy Activity Index 2000 was 2, and the majority of patients achieved remission, with rates varying by the specific index used.

The investigators said 30 women reported irreversible chronic damage, all of whom had been treated with prednisone. Seven of those women also had antiphospholipid syndrome and 16 had a history of renal involvement.

Of the 238 women in the study, 35 reported having at least one flare during their second or third trimester. Adverse outcomes were defined in the study as fetal or neonatal death, placental insufficiency with preterm delivery, and a birth weight that was small for the newborn’s gestational age. Thirty-four women said they had at least one adverse pregnancy outcome. The most common adverse outcome (22 patients) was placental insufficiency with preterm delivery, the investigators said.

The authors next compared first-trimester disease features among the women with rates of maternal flares and adverse outcomes. They found just one risk factor for maternal flares: hypocomplementemia. However, several disease features emerged as risk factors for adverse pregnancy outcomes. A logistic regression analysis found 2 features had statistically significant correlations with adverse outcomes: chronic irreversible damage (based on Systemic Lupus International Collaborating Clinics scores) and lupus anticoagulant.

In addition to these findings, the authors also highlighted what they did not find. The data did not suggest a link between remission or LLDAS and adverse outcomes, although the authors noted the women in the study were all stable, with well-controlled SLE.

“This finding suggests that damage should be considered in preconception counseling and in early pregnancy,” Costedoat-Chalumeau and colleagues concluded. “It also reinforces the importance of achieving remission/LLDAS to prevent the accrual of additional damage.”

Reference:

Larosa M, Le Guern V, Guettrot-Imbert G, et al. Evaluation of lupus anticoagulant, damage, and remission as predictors of pregnancy complications in lupus women: the French GR2 study Rheumatology (Oxford). Published online January 7, 2022. doi:10.1093/rheumatology/keab943