Three-decade Review Clarifies Pregnancy Risk in Lupus

Three-decade Review Clarifies Pregnancy Risk in Lupus
Researchers find higher risks of adverse events, underutilized options for mitigation.

Women with systemic lupus erythematosus (SLE) and their babies have a much higher incidence of adverse events from pregnancy than women and babies in cases where the mother lacks an autoimmune disease.

These adverse events may include maternal mortality, stillbirth, miscarriage, preeclampsia, preterm birth, and Caesarian section delivery, as well as heightened risks of disease flare both during and following delivery.

Small sample sizes have limited the scope of research on treatment and outcomes in women with lupus, but at Vanderbilt University Medical Center, rheumatologist April Barnado, M.D., and her team are working to change that.

They have developed algorithms for identifying large cohorts of women with SLE using a database of more than three million, enabling them to track outcomes and trends of 174 pregnant women with lupus. Monitoring these women’s pregnancies and comparing them with controls over three decades is giving the researchers a novel lens for analyzing the adverse pregnancy outcomes mothers and their babies face.

“What is unique about our work is its longitudinal nature and the granularity of the data we were able to examine,” she said. “We also looked at pregnancy outcomes six months out from delivery, as well as prenatal complications, medication use, and demographic data across a larger swath of well-defined lupus patients than have been examined to date.”

Their findings also support the American College of Rheumatology’s recommendations for patients to use of hydroxychloroquine and aspirin in pregnancy to avoid flares and reduce corticosteroids, as well as using aspirin to prevent preeclampsia. The team found a low and basically unchanged use of aspirin over time, even though low-dose aspirin lowers the risk of preeclampsia in high-risk pregnant women.

“I hope work like this will reinforce and encourage safe use of these drugs and that this will help move the needle on what have been virtually unchanged outcomes for decades.”

Delivery Outcomes Unchanged Across Three Decades

In 2020, Barnado and colleagues published their algorithms for isolating a clean patient database of lupus deliveries. They validated these algorithms with databases at Duke University Medical Center and the Medical University of South Carolina.

“What is unique about our work is its longitudinal nature and the granularity of the data we were able to examine.”

In a new, unpublished study, the algorithms were used to extract data from a de-identified EHR database of over 3.2 million patients from 1989 to present. This yielded outcome data on 255 pregnancies in 174 mothers with lupus, which they compared to 604 pregnancies in 224 mothers without known autoimmune diseases.

From this, Barnado and colleagues observed that trends in medication use among pregnant women with lupus remained relatively stable, despite increasing evidence supporting use of hydroxychloroquine, proven safe for pregnant women with lupus.

Barnado says the disparity between recommended medication use and clinical practice is concerning. Her team’s preliminary findings indicate that rates of preterm delivery and preeclampsia for women with lupus have not improved over the past 30 years, with women with lupus being 6.7 times more likely to have a preterm delivery and 3.2 times more likely to have preeclampsia.

Postpartum Precautions

In another analysis of hospital and postpartum outcomes, the researchers found that women with SLE have higher rates of blood transfusion (16 versus 2 percent) and postpartum infection (25 versus 4 percent), as well as longer length of stay (4.7 versus 2.9 days), compared to mothers without autoimmune disease.

Barnado is now working to characterize disease activity and flares during the postpartum period. Preliminary data shows that 38 percent of women with SLE experience postpartum flares, and these were significantly more common when the patient was not on an antimalarial.

“This is a particularly tough time for flares because they’re healing from childbirth, they are taking care of a newborn,” Barnado said. “It’s a really vulnerable time where having symptom control is important.”

“I hope work like this will reinforce and encourage safe use of these drugs and that this will help move the needle on what have been virtually unchanged outcomes for decades,” Barnado said.