Biomarker Predicts Poor Pregnancy Outcomes in Lupus, APL

Alice Goodman

October 29, 2013

SAN DIEGO — Early imbalances in angiogenic factors predict poor pregnancy outcomes in women with systemic lupus erythematosus or antiphospholipid syndrome (APL), new research shows.

These findings could lead to a test to predict poor pregnancy outcomes as early as 16 weeks of gestation.

In lupus, "pregnancy can place the mother and fetus at high risk, but we can't predict which patients will develop pre-eclampsia, unexplained fetal or neonatal death, and other poor outcomes," said lead author Jane Salmon, MD, from the Hospital for Special Surgery in New York City. "The fact that angiogenic imbalance is associated with a spectrum of poor pregnancy outcomes suggests a common pathogenesis. Our findings reveal novel targets for treatment."

Dr. Salmon presented the findings during a plenary session here at the American College of Rheumatology (ACR) 2013 Annual Meeting.

Pre-eclampsia is clinically silent in the early stages, but leads to placental hypoperfusion. The maternal response — hypertension, proteinuria, and other end-organ manifestations — is mediated by angiogenic factors in the placenta. The ensuing angiogenic imbalance leads to endothelial cell damage, which has been associated with an overexpression of sFlt1 in pregnant animal models, she explained.

Dr. Salmon and her team sought to identify angiogenic biomarkers that predict poor pregnancy outcome. They used the patient population from the PROMISSE trial, which enrolled 503 pregnant women who met at least 4 ACR criteria for lupus or APL and 204 healthy pregnant control subjects.

 
Our findings reveal novel targets for treatment.
 

The women were classified as being positive for both lupus and APL antibodies, negative for both, or positive for one and negative for the other. The composite end point for poor outcomes was fetal death, neonatal death, an infant small for gestational age, and preterm delivery before 36 weeks because of hypertension, pre-eclampsia, or placental insufficiency.

Poor outcomes were reported in 85 patients. Of these, 42 had pre-eclampsia at some point during their pregnancy and 33 developed pre-eclampsia before 34 weeks of gestation. Outcomes were not poor in 336 patients with lupus or APL and 168 healthy control subjects.

Elevated sFlt1 preceded poor outcome, and an elevated sFLT1/PlGF ratio was associated with poor outcome. When the sFlt1/PlGF ratio was used as a screening test with a cutoff of more than 3.45 at 16 to 19 weeks, the positive predictive value was 41% and the negative predictive value was 97%.

Dr. Salmon concluded that "low sFlt1/PlGF ratios, as well as low sFlt1 levels or high PlGF levels, can reassure physicians and patients that preterm pre-eclampsia is unlikely. The ratio can be used at 16 to 19 weeks to stratify risk in future trials pregnant women with lupus and/or APL."

"This study might provide new information that would allow us to follow pregnant patients with lupus or APL in a hypervigilant way to prevent the ultimate possibility of pregnancy loss and serious sequelae for the mother," said session moderator and ACR president Audrey Uknis, MD, from Temple University School of Medicine in Philadelphia.

Dr. Salmon reports financial relationships with Roche Pharmaceuticals, Alexion Pharmaceuticals, and Novartis. Dr. Uknis reports receiving research grants and consulting fees from ABIM, Biogen-Idec, and Roche.

ACR 2013 Annual Meeting: Abstract 765. Presented October 27, 2013.

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