CHICAGO – Women with low-activity systemic lupus erythematosus can have healthy pregnancies with few complications, even those with a history of renal disease.
"The good news was that the overall pregnancy adverse outcome was 19%, so 81% of the women [with low-activity disease] had a very favorable outcome," lead author Dr. Jill Buyon said when she announced the results of the largest such study to date at the annual meeting of the American College of Rheumatology.
The findings are very good news for women with systemic lupus erythematosus (SLE) who want to become pregnant. "Previous data suggested that women with lupus would have difficulty with regard to their own health and the health of their fetus and subsequent baby, [so] many rheumatologists have discouraged these women from childbearing," said Dr. Buyon, a professor of medicine and associate director of the division of rheumatology at New York University.
The findings suggest that rheumatologists should advise patients with very active disease to hold off on pregnancy until the disease is under better control, she said.
This study is part of a larger project, the PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus) study. "We also felt that this would be a huge opportunity to evaluate patients, whom we [rheumatologists] would normally advise to get pregnant," she said.
This study comprises four groups: women who only have antiphospholipid antibodies (group 1); women with lupus and antiphospholipid antibodies (group 2); women with lupus but no antiphospholipid antibodies (group 3); and a very selective group of healthy women, who already had a previously healthy child and no major pregnancy losses (group 4).
A total of 10 sites participated in the study, which included both rheumatologists and obstetricians. The study was initiated in 2003. At the time that the abstract was written, 700 women had been recruited to this study; at the time of abstract submission, 599 pregnancies had been completed.
Patients were all enrolled prior to 12 weeks’ gestation and were seen by a rheumatologist every trimester. Women were excluded from the study if they had a multifetal pregnancy; were on more than 20 mg/day of prednisone; had a proteinuria level greater than 1 g/day; and/or had a creatinine level greater than 1.2 mg/dL.
An adverse pregnancy outcome was strictly defined as at least one of the following: fetal/neonatal death; birth indicated at less than 36 weeks due to placental insufficiency, hypertension, or preeclampsia; and small for gestational age (less than fifth percentile).
In addition, mild/moderate and severe flares were defined by the SLEPDAI (SLE Pregnancy Disease Activity Index) score, which excludes physiologic changes of pregnancy but incorporates the components of the SELENA (Safety of Estrogen in Lupus Erythematosus National Assessment), as well as changes in clinical parameters and medications, and physician’s global assessment.
The researchers evaluated 333 women from their first trimester until 3 months post partum. Nearly half of the women were ethnicities other than white, an important characteristic given that women from minority groups can have an increased risk of SLE.
Also importantly, 31% had a history of previous lupus affecting their kidneys. "This is really important because when we see a young woman who develops lupus nephritis – and that’s a fairly serious manifestation of the disease – they always ask, ‘Even if I get better from this, does that mean that I can never have a child?’ " said Dr. Buyon.
Half of the women with a prior history of lupus nephritis had anti-DNA antibodies, "which many of us worry quite a bit about and suggests perhaps a more serious disease." However, their baseline characteristics were good in terms of low disease activity and disease stability.
When enrolled in the study, 60% of the women were taking hydroxychloroquine, 41% were taking prednisone, and 18% were taking azathioprine. On average, the participants’ lupus was relatively inactive
Fetal death occurred in 4.5%. "But if you look at the national population, this is about 2%," Dr. Buyon said.
Neonatal death in this cohort was very similar to that for neonatal death nationally: 1.2%, compared with 1% nationally.
Indicated preterm delivery or small for gestational age occurred in 9.1% of SLE pregnancies. In addition, 10% of the mothers developed preeclampsia; the national level is closer to 4%.
Greater levels of lupus activity and greater levels of antiphospholipid antibodies – particularly the lupus anticoagulant – were associated with poorer outcomes.
The researchers also performed a multivariate analysis to identify independent predictors of these poor outcomes. They found that a history of renal disease predicted a poor pregnancy outcome.