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.