Biomarker linked to poor outcomes in pregnant lupus patients

The study, titled "Angiogenic Factor Dysregulation and Risk of Adverse Pregnancy Outcome In Lupus Pregnancies" will be presented at the American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting on October 27 in San Diego.

Investigators found that an imbalance of angiogenic factors, proteins required for the development of the placenta and the health of blood vessels, is associated with poor pregnancy outcomes. Increased levels of an anti-angiogenic protein called sFlt1 in pregnant lupus patients placed them at increased risk of placental insufficiency and preeclampsia, a potentially life-threatening complication. Scientists determined that higher levels of sFlt1 reduce the activity of other angiogenic proteins (placental growth factor, PIGF; vascular endothelial growth factor, VEGF) that are necessary for growth of the placenta and the mother's blood vessels.

"Pregnant women with lupus or antiphospholipid syndrome are at increased risk for adverse outcomes, particularly preeclampsia, yet identification of those destined for complications has been elusive," said Jane Salmon, MD, director of the Lupus and APS Center of Excellence at Hospital for Special Surgery and lead author of the study. "We prospectively studied patients to see if we could find a biomarker early in pregnancy that would predict a poor outcome."

The study is part of an ongoing, multi-center research initiative led by Dr. Salmon known as PROMISSE (Predictors of pRegnancy Outcome: bioMarkers In antiphospholipid antibody Syndrome and Systemic lupus Erythematosus) funded by the National Institutes of Health to identify factors that predict pregnancy complications in women with lupus and antiphospholipid syndrome.

Lupus is a chronic inflammatory disease in which the body's own immune system attacks tissues of the body and can cause complications during pregnancy. Preeclampsia, which is characterized by the onset of high blood pressure and impaired kidney function, is life-threatening to both mother and baby.

Scientists enrolled 384 pregnant women with lupus and 153 healthy pregnant controls.

Subjects were evaluated and blood was drawn monthly beginning 12 weeks into their pregnancy. Poor pregnancy outcomes were defined as preeclampsia, fetal death, neonatal death, preterm delivery before 36 weeks because of placental insufficiency, or intrauterine growth restriction (IUGR), which refers to a poor growth rate of the baby while in the womb. Levels of sFlt1 and other angiogenic proteins were measured and compared in women with lupus versus controls.

In the study, 20 percent of pregnant lupus patients developed preeclampsia or another poor outcome. Levels of sFlt1 protein, an anti-angiogenic factor, were significantly higher in patients destined for complications compared to lupus patients whose pregnancies were uncomplicated. In contrast, levels of PlGF, an angiogenic factor, were lower. Alteration in the balance of angiogenic factors was evident as early as 12 to 15 weeks into the pregnancy and persisted throughout pregnancy in women who experienced preeclampsia or another complication.

"Measurement of sFlt1 and PlGF provide a powerful tool to identify pregnant lupus patients at high risk for poor pregnancy outcomes sufficiently early to intervene," Dr. Salmon said. "Hopefully, this will facilitate trials of novel treatments to prevent these devastating complications."