Systemic lupus erythematosus, also called SLE or lupus, is a chronic inflammatory disease that can affect the skin, joints, kidneys, lungs, nervous system, and/or other organs of the body. The most common symptoms include skin rashes and arthritis, often accompanied by fatigue and fever. Lupus occurs mostly in women, typically developing in individuals in their twenties and thirties - prime child-bearing age.
Lupus has been known to cause complications for pregnant women. Researchers recently set out to determine the frequency, predictors, and potential causes of these complications to help physicians better counsel women with lupus who are considering pregnancy.
In a project that is part of the PROMISSE (Predictors of pRegnancy Outcome: bioMarkers In antiphospholipid antibody Syndrome and Systemic lupusErythematosus) Study (funded by the National Institute of Arthritis, Musculoskeletal and Skin Diseases of NIH to identify biomarkers that would predict poor pregnancy outcomes in lupus patients), Jill P. Buyon, MD; Professor of Medicine; New York University School of Medicine; New York, Jane E. Salmon, MD; Collette Kean Research Chair; Hospital for Special Surgery, New York and their team identified a few predictors of pregnancy complications, but also discovered that that the majority of women with stable lupus had successful pregnancies.
The researchers evaluated 333 women from their first trimester until three months postpartum (after delivery). At entry into the study, none of the women were pregnant with more than one child, taking more than 20mg/d of prednisone, had abnormally high excretion of protein as evidenced by more than one gram of protein in their urine per 24 hours, and/or had currently impaired kidney function. Nearly half of the women were ethnicities other than Caucasian, and 31 percent had a history of previous lupus affecting their kidneys. When enrolled in the study, 60 percent were taking hydroxychloroquine, 41 percent were taking prednisone, and 18 percent were taking azathioprine. On average, the participants' lupus was relatively inactive.
The researchers followed each participant to determine if any of the following serious complications occurred during their pregnancies: death of the baby or fetus, birth before 36 weeks of pregnancy due to a lack of oxygen or nutrients to the placenta, high blood pressure, preeclampsia (which is a combination of high blood pressure and protein in the urine), and birth of a baby of very small size relative to the gestational age (less than 5th percentile).
Two categories of pregnancy complications were evaluated. One related to the child and the other to the mother. In terms of the child, the outcomes chosen for study were those that represented the worst outcome - death - or situations in which the well being of the child would require extended hospitalization in a critical care setting. In terms of the mother, the outcomes focused on the development of mild, moderate, or severe increases of lupus activity (called flares).
Poor outcomes occurred in 63 of the participants. Of these, 19 experienced death of the baby and 30 delivered before 36 weeks or had newborns of small gestational size. "This death rate is still not acceptable, but is actually much lower than most physicians have assumed," explains Drs. Buyon and Salmon. "While confirming a lower death rate than expected is a step in the right direction, more research needs to be done to help ensure more successful pregnancies and healthy babies and mothers."
In addition, 10 percent of the mothers developed preeclampsia, 10 percent experienced mild or moderate flares at 20 weeks and eight percent experienced them at 32 weeks. Severe flares occurred very rarely (under three percent of women at 20 weeks and at 32 weeks).
Overall, 80 percent of the women in the study had successful pregnancies, and Drs. Buyon and Salmon note that these findings support advising lupus patients who wish to become pregnant that the best time is when the lupus is stable and they are not experiencing a flare of the disease. "Although it is acknowledged that health care delivery and monitoring of pregnancy has improved in the last decade, the observation that lupus patients with stable or inactive disease (even with preexisting kidney disease) can have a healthy baby is very reassuring," they explain.
Of the 20 percent of women who experienced pregnancy complications, the researchers noted those who entered the study with specific characteristics were more likely to have a pregnancy complication. These characteristics include: higher levels of lupus activity, highantibodies that may put a person at risk for a blood clot. Additionally, women who experienced increased lupus activity at 20 or 32 weeks and a worsened physician's global assessment of their health had a tendency toward complications in their pregnancies.
"This very large study including racial and ethnic minorities, provided evidence that women who conceived while their disease was stable or only mildly active had relatively infrequent flares during their pregnancies and delivered healthy babies," says Drs. Buyon and Salmon. "This held true regardless of past disease severity or past kidney disease (a frequent consequence of lupus). These findings inform women with lupus on how to best plan when to conceive to assure the most favorable outcome for themselves and their babies."
The American College of Rheumatology is an international professional medical society that represents more than 8,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Scientific Meeting is the premier meeting in rheumatology. For more information about the meeting, visit www.rheumatology.org/education. Follow the meeting on Twitter by using the official hashtag: #ACR2011.
Editor's Notes: Jill P. Buyon, MD will present this research during the ACR Annual Scientific Meeting at McCormick Place Convention Center at 4:30 pm on Monday, November 7 in Room W183a. Drs. Buyon and Salmon will be available for media questions and briefing at 8:30 am on Tuesday, November 8 in the on-site press conference room, W 175C.
Learn more about living well with rheumatic disease as well as rheumatologistsand the role they play in health care. Also, discover the ACR's Simple Taskscampaign, which highlights how rheumatic diseases strike women disproportionately and in the prime of their lives.
Presentation Number: 1707
Favorable Prognosis in a Large, Prospective Multicenter Study of Lupus Pregnancies
Jill P. Buyon (New York University School of Medicine, New York, NY)
Lamya Garabet (Hospital for Special Surgery, New York, NY)
Mimi Kim (Albert Einstein College of Medicine, Bronx, NY)
Emily R. Reeves (Hospital for Special Surgery, New York, NY)
Marta M. Guerra (Hospital for Special Surgery, New York, NY)
Michael D. Lockshin (Barbara Volcker Center for Women and Rheumatic Diseases: Hospital for Special Surgery, New York, NY)
Carl A. Laskin (University of Toronto and LifeQuest Centre for Reproductive Medicine, Toronto, ON)
Ware Branch (Univ of Utah, Salt Lake City, UT)
Lisa R. Sammaritano (Hospital for Special Surgery, New York, NY)
Michelle Petri (Johns Hopkins University School of Medicine, Baltimore, MD)
Joan T. Merrill (Oklahoma Medical Research Foundation, Oklahoma City, OK)
Allen D. Sawitzke (University of Utah Medical Ctr, Salt Lake City, UT)
Jane E. Salmon (Hospital for Special Surgery, Weill Cornell Medical College, New York, NY)
Background/Purpose: Accurate prediction of fetal and maternal outcomes of pregnancies complicated by lupus is required to plan treatment. The frequency of adverse outcomes and associated clinical and laboratory variables were evaluated in a large, prospective multicenter, multiethnic study.
Method: The PROMISSE Study (Predictors of pRegnancy Outcome: BioMarkers In antiphospholipid antibody Syndrome and Systemic Lupus Erythematosus) evaluated 333 pregnant women each month with ≥4 ACR SLE criteria enrolled in the first trimester. Exclusion criteria were multi-fetal pregnancy, prednisone >20mg/d, proteinuria >1gm/24hr, and/or creatinine >1.2 mg/dL. An adverse pregnancy outcome was at least one of the following: fetal/neonatal death, birth <36 weeks due to placental insufficiency, hypertension, or preeclampsia, and small for gestational age <5th percentile (SGA). Mild/moderate and severe flares were defined by SLEPDAI Index (SLE Pregnancy Disease Activity Index), which excludes physiologic changes of pregnancy but incorporates the components of the SELENA-SLEDAI score as well as changes in clinical parameters and medications, and physician's global assessment (PGA). Subjects were: 56.8% Caucasian, 19.8% Black, 10.2% Asian, 13.2% mixed or other races; overall 16.0% Hispanic by ethnicity. Thirty-one percent had previous renal disease. At enrollment 38% were anti-dsDNA positive; 60% took HCQ, 41% prednisone, and 18% azathioprine. Mean SLEPDAI was 2.6 ± 2.8.
Result: Adverse pregnancy outcome occurred in 63 (19%) patients: 19 had fetal/neonatal death and 30 each had birth <36 weeks or SGA infants. The following baseline variables associated with poor outcome: SLEPDAI ≥4 (p=.02), high titer aPL (LAC + or IgG aCL > 40, p<.0001), higher median uric acid levels (3.4±1.4 vs. 3.0±2.2 mg/dL, p=.01), as was an increase over baseline in SLEPDAI ≥3 at 20 or 32 wks (p =.03) and an increase in PGA ≥0.3. None of the following influenced pregnancy outcomes: Hispanic ethnicity, prior renal disease or use of cylophosphamide, or at entry, proteinuria ≥2+ or 500-1000mg/d, positive anti-dsDNA, initial C3 or C4 level, HCQ, prednisone, or azathioprine. Ten percent of patients developed preeclampsia. Mild/moderate flares occurred in 10.2% at 20 wks and 7.8% at 32 weeks. Severe flares occurred in 2.1% at 20 wks and 2.4% at 32 weeks. Of the 15 patients with severe flares: 4 were renal, 5 pleuritis, 1 thrombocytopenia, 1 CNS, 2 arthritis, 1 myositis and 1 pericarditis. Neither the initial mean C3 or C4 nor presence of anti-dsDNA associated with flare.
Conclusion: Eighty percent of patients have a favorable pregnancy outcome. Adverse outcome was associated with an increase in lupus activity during pregnancy, high titer aPL antibody, and higher levels of uric acid at baseline. Mild/moderate and severe flares were infrequent in patients clinically stable at baseline despite anti-dsDNA antibodies or past history of renal disease. This large, prospective study provides reassurances for patients with stable lupus contemplating pregnancy and suggests parameters that merit caution for the minority at risk of adverse outcome.
Disclosure: J. P. Buyon, None; L. Garabet, None; M. Kim, None; E. R. Reeves, None;M. M. Guerra, None; M. D. Lockshin, None; C. A. Laskin, None; W. Branch, None; L. R. Sammaritano, None; M. Petri, None; J. T. Merrill, None; A. D. Sawitzke, None; J. E. Salmon, None.