In the not so distant past, women with systemic lupus erythematosus (SLE), an autoimmune disease, were advised not to have children, and if they became pregnant, to have therapeutic abortions to prevent severe flares of their lupus. Research by rheumatologists at Hospital for Special Surgery in New York, in patients with lupus who have had successful pregnancies is yielding insights that support a reversal of that thinking.
The research effort, a multi-center research initiative lead by Jane Salmon, M.D., attending physician at Hospital for Special Surgery, is known as the PROMISSE (Predictors of pRegnancy Outcome: bioMarkers In antiphospholipid antibody Syndrome and Systemic lupus Erythematosus) Study.
Two research projects will be presented at this year's American College of Rheumatology meeting in San Francisco on October 24-29 by Dr. Salmon, based on data gathered from the PROMISSE Study. She and her collaborators identified factors that help a woman and her doctor plan for a healthy pregnancy.
Patients with lupus can live free of symptoms for long periods of time and then experience a disease "flare," when symptoms such as a red rash across the nose and cheeks, painful or swollen joints, swollen legs or extreme fatigue suddenly appear. The first presentation will examine whether problems during pregnancy can be correlated to the severity, frequency and timing of disease flares. Dr. Salmon and her colleagues followed 198 pregnant patients with lupus. The investigators found that women who conceived while their disease was stable or only mildly active had relatively infrequent flares during their pregnancies and delivered healthy babies. This held true regardless of past disease severity or past kidney disease (a frequent consequence of lupus). The findings inform women with lupus on how to plan when to conceive to have a low risk pregnancy.
Lupus patients, as well as other patients with the antiphospholipid syndrome, produce special types of proteins called antiphospholipid antibodies that can attack their own tissues and cause pregnancy complications. The second study to be presented by Dr. Salmon showed that the presence of a specific subset of these autoantibodies is highly associated with poor pregnancy outcomes. Specifically, the researchers found that women who tested positive for an autoantibody called lupus anticoagulant were more likely to have complications such as miscarriage or preeclampsia during pregnancy.
These results can help doctors identify patients at high risk for complications by obtaining a blood test to determine if they are positive or negative for the lupus anticoagulant autoantibody. While women with lupus or the antiphospholipid syndrome who are positive for this protein can still have successful pregnancies, their doctors should monitor them more closely for early signs of pregnancy complications.
"Based on our new data, we believe we are in a position to help doctors counsel and care for their patients," says Dr. Salmon, Collette Kean Research Chair and co-director, Mary Kirkland Center for Lupus Research at HSS. "In the past, women were discouraged from becoming pregnant because of a very high risk to the mother and the baby. Our findings from the PROMISSE study show that women with lupus can have normal pregnancies when they work together with their doctors, beginning with the decision of when it is safe to conceive and continuing with close follow-up to anticipate potential problems."
The PROMISSE study was funded by the National Institute of Arthritis, Musculoskeletal and Skin Diseases of the National Institutes of Health in 2003 to identify biomarkers that would predict poor pregnancy outcomes in lupus patients. To date, Dr. Salmon and the PROMISSE investigative team have enrolled 457 volunteers who are monitored with monthly checkups and research laboratory studies looking at genes and circulating proteins that may predict the course of pregnancy. After a review of the progress of and findings from the PROMISSE study, the NIH extended the funding for an additional five years, beginning with $1.4 million for the first year of renewal, which starts in October 2008. The continued support will allow Dr. Salmon and her co-investigators from 11 academic centers to increase the number of volunteers to 700 and expand the study to examine a broader range of genes and molecular pathways that can affect pregnancy in patients with lupus, and, very probably, cause miscarriage and preeclampsia in healthy women.
The PROMISSE Study is coordinated by Dr. Salmon, Michael Lockshin, M.D., and Lisa Sammaritano, M.D., at Hospital for Special Surgery; Jill Buyon, M.D., at New York University School of Medicine; Ware Branch, M.D., at University of Utah Health Sciences Center; Carl Laskin, M.D., at Mt. Sinai Hospital in Toronto, Canada; Joan Merrill, M.D., at the Oklahoma Medical Research Foundation; Michelle Petri, M.D., MPH, at Johns Hopkins University School of Medicine; Mimi Kim, D.Sc., at Albert Einstein College of Medicine; and Mary Stephenson, M.D., at the University of Chicago.
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