Biomarkers Measured in Maternal Blood Can Identify Pregnant Women with Lupus at Low Risk for Developing Adverse Outcomes

Ability to identify and stratify low vs high risk patients early in pregnancy would significantly impact prenatal care and allocation of healthcare resources, according to a new study in the American Journal of Obstetrics & Gynecology

Philadelphia, PA, September 29, 2015

Pregnant women with systemic lupus erythematosus (SLE), are at higher risk for adverse pregnancy outcomes, including preeclampsia, placental insufficiency, fetal death, miscarriages, and other complications. In a study published in the American Journal of Obstetrics & Gynecology, a consortium of top researchers funded by NIH/NIAMS report that monitoring specific angiogenic biomarkers in maternal blood during early pregnancy can successfully predict patients who will likely have normal pregnancies and those at high risk for adverse outcomes. This will enable physicians to identify, counsel, and manage high risk patients at an early stage of pregnancy.

SLE is a multisystem autoimmune disease that predominantly affects women and presents during their childbearing years. In SLE the immune system that normally protects against infection turns against the woman and can cause damage to multiple organs. Another condition, antiphospholipid antibodies (APL), which can occur in patients with or without SLE, can damage the placenta and cause arterial and venous thromboses. Both of these conditions, whether occurring separately or together, can lead to fetal death, miscarriages, preeclampsia, and/or growth restricted babies.  

“Given that over 20% of pregnant women with lupus APL experience adverse pregnancy outcomes, the ability to identify patients early in pregnancy, who are destined for poor outcomes, would significantly impact care of this high risk population,” explained lead investigator Jane E. Salmon, MD, of the Division of Rheumatology, Hospital for Special Surgery, and Weill Cornell Medical College, New York, NY.

Using data and samples from the PROMISSE Study (Predictors of pRegnancy Outcome: bioMarker In antiphospholipid antibody Syndrome and Systemic lupus Erythematosus) investigators found that biomarkers, specifically circulating angiogenic factors that regulate development of the placenta and influence the health of blood vessels in the mother, can be assessed early in pregnancy. As early as 12-15 weeks into pregnancies, changes in these biomarkers can signal an increased risk for severe complications, including preeclampsia before 34 weeks gestation, fetal or neonatal death, or preterm delivery before 30 weeks, because of placental insufficiency.

The researchers also found that measuring these biomarkers had a high negative predictive value, meaning that severe complications could actually be ruled out in most patients, leading to more appropriate prenatal care and less anxious patients. “Timely risk stratification of patients is important for effective clinical care and optimal allocation of healthcare resources,” commented Dr. Salmon.

The PROMISSE Study is the largest multicenter, multiethnic and multiracial study to prospectively assess the frequency of adverse pregnancy outcomes. In this research, 497 pregnant patients with SLE and/or APL were enrolled at <12 weeks gestation between September 2003 and August 2013 at seven sites, along with 207 matched healthy controls, and were followed every month of pregnancy.

Without good predictive monitors for complications, most SLE and APL patients undergo extensive antenatal evaluation, including serial obstetrical ultrasound exams and multiple visits to rheumatologists and obstetricians. The majority of lupus and/or APL women would be identified as being at low risk for severe adverse outcomes and in this group the number of medical visits could be substantially reduced.  Patients at low risk can be reassured and healthcare costs for their pregnancies decreased, whereas those at high risk can be managed by specialists with close monitoring and delivery for severe maternal and/or fetal disease.

“Pregnancies in patients with SLE and/or APL can result in poor outcomes, even when disease activity is low, and baseline clinical features and laboratory tests have only modest ability to identify patients at highest risk for adverse pregnancy outcomes,” noted Dr. Salmon. “Our study is the first to demonstrate, in a prospective cohort, the usefulness of angiogenic biomarkers measured as early as the 12th week of pregnancy, in combination with clinical criteria, to identify patients with SLE and/or APL at risk of severe adverse pregnancy outcomes.”

"A fundamental question of pregnant mothers with lupus or antiphospholipid antibody syndrome is whether their pregnancy will turn out fine or they will develop complications of pregnancy. This important study indicates that if the concentration of biomarkers measured in maternal blood in early pregnancy is normal, over 95% of the pregnancies will not develop preeclampsia, fetal growth restriction, or death. Therefore, the simple measurement of these biomarkers can be highly reassuring to mothers, families, and physicians," said Roberto Romero, MD, DMedSci, Editor-in-Chief for Obstetrics of the American Journal of Obstetrics & Gynecology and Chief of the Perinatology Research Branch of NICHD/NIH.

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Notes for Editors
“Angiogenic Factor Imbalance Early in Pregnancy Predicts Adverse Outcomes in Patients with Lupus and Antiphospholipid Antibodies: Results of the PROMISSE Study,” by Mimi Y. Kim, ScD, Jill P. Buyon, MD, Marta M. Guerra, MS, Sarosh Rana, MD, Dongsheng Zhang, PhD, Carl A. Laskin, MD, Michelle Petri, MD, MPH, Michael D. Lockshin, MD, Lisa R. Sammaritano, MD, D. Ware Branch, MD, T. Flint Porter, MD, MPH, Joan T. Merrill, MD, Mary D. Stephenson, MD, MSc, Qi Gao, PhD, S. Ananth Karumanchi, MD, and Jane E. Salmon, MD (DOI: http://dx.doi.org/10.1016/j.ajog.2015.09.066). Published online in advance of Volume 214, Issue 1 (January 2016) of the American Journal of Obstetrics & Gynecology, published by Elsevier.

Research reported in this press release was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award number R01AR049772 and RO1AR43727 and by the Mary Kirkland Center for Lupus Research.

Full text of this article is available to credentialed journalists upon request. Contact Eileen Leahy at +1 732 238 3628 or ajogmedia@elsevier.com to obtain copies. Journalists wishing to interview the authors should contact Tracy Hickenbottom, Assistant Director, Public Relations, Hospital for Special Surgery, at +1 212 606 1197 or hickenbottomt@hss.edu. Dr. Roberto Romero may be reached for comment at rr.ajoged@gmail.com.

About the American Journal of Obstetrics & Gynecology
The American Journal of Obstetrics & Gynecology, known as “The Gray Journal,” presents coverage of the entire spectrum of the field, from the newest diagnostic procedures to leading-edge research. The Journal provides comprehensive coverage of the specialty, including maternal-fetal medicine, reproductive endocrinology/infertility, and gynecologic oncology. It also publishes the annual meeting papers of several of its eight sponsoring societies, including the Society for Maternal-Fetal Medicine and the Society of Gynecologic Surgeons.

The American Journal of Obstetrics & Gynecology's 2014 Impact Factor is 4.704. The journal ranks third in Eigenfactor score, continues to be first in total citations, and is the number 3 journal in the Obstetrics & Gynecology category according to the 2014 Journal Citation Reports®, published by Thomson Reuters, 2015. The journal has also been recognized as one of the 100 most influential journals in Biology & Medicine over the last 100 years, as determined by the BioMedical & Life Sciences Division of the Special Libraries Association (2009).

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Elsevier
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