There was a time when women diagnosed with lupus were cautioned against getting pregnant; the combination of lupus and pregnancy was thought to be too dangerous for mother and child. However, research by Jane Salmon, MD, a rheumatologist at the Hospital for Special Surgery (HSS) in New York City, is now helping change this belief. By carefully risk-stratifying patients on the basis of clinical and biological markers, it seems that the vast majority of pregnant patients with lupus can be assured that their pregnancies will be uncomplicated. Medscape recently spoke to Dr Salmon about her work.
Medscape: Tell us a little about how you began studying pregnancy and lupus.
Dr Salmon: Patients with lupus tend to be young women in their reproductive years. Lupus generally presents between age 20 and 40 years, and 90% of the patients are women. Some of the first questions they often ask when they receive their diagnosis are, "Can I have children?" "Will my pregnancy be safe?" and "Will my children have lupus?"
In the 1980s, when I was training in rheumatology, the feeling was that pregnancy in lupus was dangerous. This wasn't based on strong evidence, but on the rational concept that because lupus tends to be a disease of women, hormones may play a role in disease pathogenesis, and pregnancy is a state with high levels of female hormones (ie, estrogens, progesterone). Thus, it was anticipated that patients with lupus who become pregnant would have severe flares. And in fact, patients who become pregnant when their disease is active and not well-controlled often develop even more severe organ dysfunction. So there was clinical basis for the anxiety among the physicians, but perhaps it was applied too broadly.
Medscape: How has your research helped changed this way of thinking?
Dr Salmon: Patients asked for and deserve data around such an important question. They wanted the evidence that, in fact, this was true. And we wanted to identify the predictors of poor pregnancy outcomes and the mechanisms that caused damage to the placenta and the developing baby.
My team and I spent about 15 years addressing these questions in mouse models. We adapted a model of lupus pregnancy, in which placental and fetal injury was triggered by antiphospholipid antibodies derived from patients. About 25% of patients with lupus have antiphospholipid antibodies, and the presence of these antibodies has traditionally been associated with pregnancy complications. We performed studies in mice treated with antiphospholipid antibodies to understand what triggers poor placental development, poor growth of the fetus, and miscarriages.
We found that inflammation, not thrombosis, was the major causative factor—inflammation driven by activation of complement. While we were engaged in these mouse studies, we recognized that once we had identified a pathway of injury, we would want to consider an interventional trial in patients to block this pathway. For such a trial, we would have to understand which patients are at the highest risk for adverse outcomes.
We were fortunate to be funded by the National Institutes of Health to perform a large, multicenter, multiethnic observational study in North America to identify predictors of pregnancy outcome in patients with lupus and/or antiphospholipid antibodies. In 11 years, we enrolled over 700 patients—500 with lupus and 200 controls—whom we followed for every month of their pregnancies.
I must point out that our patients with systemic lupus erythematosus were required to have stable disease and well-controlled blood pressure, and were not taking high doses of prednisone. Our study focused on pregnancy outcomes in well-controlled lupus.
We defined a panel of clinical risk factors that affected outcome. We measured laboratory tests monthly and potential biomarkers that are not yet clinically available.
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Cite this: A Rosy Outlook for Pregnancy and Lupus - Medscape - Apr 20, 2017.