Original Research4 August 2015
A Cohort Study
    Author, Article and Disclosure Information

    Because systemic lupus erythematosus (SLE) affects women of reproductive age, pregnancy is a major concern.


    To identify predictors of adverse pregnancy outcomes (APOs) in patients with inactive or stable active SLE.


    Prospective cohort.




    385 patients (49% non-Hispanic white; 31% with prior nephritis) with SLE in the PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus) study. Exclusion criteria were urinary protein–creatinine ratio greater than 1000 mg/g, creatinine level greater than 1.2 mg/dL, prednisone use greater than 20 mg/d, and multifetal pregnancy.


    APOs included fetal or neonatal death; birth before 36 weeks due to placental insufficiency, hypertension, or preeclampsia; and small-for-gestational-age (SGA) neonate (birthweight below the fifth percentile). Disease activity was assessed with the Systemic Lupus Erythematosus Pregnancy Disease Activity Index and the Physician's Global Assessment (PGA).


    APOs occurred in 19.0% (95% CI, 15.2% to 23.2%) of pregnancies; fetal death occurred in 4%, neonatal death occurred in 1%, preterm delivery occurred in 9%, and SGA neonate occurred in 10%. Severe flares in the second and third trimesters occurred in 2.5% and 3.0%, respectively. Baseline predictors of APOs included presence of lupus anticoagulant (LAC) (odds ratio [OR], 8.32 [CI, 3.59 to 19.26]), antihypertensive use (OR, 7.05 [CI, 3.05 to 16.31]), PGA score greater than 1 (OR, 4.02 [CI, 1.84 to 8.82]), and low platelet count (OR, 1.33 [CI, 1.09 to 1.63] per decrease of 50 × 109 cells/L). Non-Hispanic white race was protective (OR, 0.45 [CI, 0.24 to 0.84]). Maternal flares, higher disease activity, and smaller increases in C3 level later in pregnancy also predicted APOs. Among women without baseline risk factors, the APO rate was 7.8%. For those who either were LAC-positive or were LAC-negative but nonwhite or Hispanic and using antihypertensives, the APO rate was 58.0% and fetal or neonatal mortality was 22.0%.


    Patients with high disease activity were excluded.


    In pregnant patients with inactive or stable mild/moderate SLE, severe flares are infrequent and, absent specific risk factors, outcomes are favorable.

    Primary Funding Source:

    National Institutes of Health.


    • 1. Silva CA Leal MM Leone C Simone VP Takiuti AD Saito MI et alGonadal function in adolescents and young women with juvenile systemic lupus erythematosus. Lupus2002;11:419-25. [PMID: 12195782] CrossrefMedlineGoogle Scholar
    • 2. Østensen M New insights into sexual functioning and fertility in rheumatic diseases. Best Pract Res Clin Rheumatol2004;18:219-32. [PMID: 15121041] CrossrefMedlineGoogle Scholar
    • 3. Petri M Allbritton J Fetal outcome of lupus pregnancy: a retrospective case-control study of the Hopkins Lupus Cohort. J Rheumatol1993;20:650-6. [PMID: 8496859] MedlineGoogle Scholar
    • 4. Georgiou PE Politi EN Katsimbri P Sakka V Drosos AA Outcome of lupus pregnancy: a controlled study. Rheumatology (Oxford)2000;39:1014-9. [PMID: 10986308] CrossrefMedlineGoogle Scholar
    • 5. Clowse ME Jamison M Myers E James AH A national study of the complications of lupus in pregnancy. Am J Obstet Gynecol2008;199:127. [PMID: 18456233] doi:10.1016/j.ajog.2008.03.012 CrossrefMedlineGoogle Scholar
    • 6. Al Arfaj AS Khalil N Pregnancy outcome in 396 pregnancies in patients with SLE in Saudi Arabia. Lupus2010;19:1665-73. [PMID: 20947541] doi:10.1177/0961203310378669 CrossrefMedlineGoogle Scholar
    • 7. Ko HS Ahn HY Jang DG Choi SK Park YG Park IY et alPregnancy outcomes and appropriate timing of pregnancy in 183 pregnancies in Korean patients with SLE. Int J Med Sci2011;8:577-83. [PMID: 22022210] CrossrefMedlineGoogle Scholar
    • 8. Liu J Zhao Y Song Y Zhang W Bian X Yang J et alPregnancy in women with systemic lupus erythematosus: a retrospective study of 111 pregnancies in Chinese women. J Matern Fetal Neonatal Med2012;25:261-6. [PMID: 21504337] doi:10.3109/14767058.2011.572310 CrossrefMedlineGoogle Scholar
    • 9. Shand AW Algert CS March L Roberts CL Second pregnancy outcomes for women with systemic lupus erythematosus. Ann Rheum Dis2013;72:547-51. [PMID: 22753385] doi:10.1136/annrheumdis-2011-201210 CrossrefMedlineGoogle Scholar
    • 10. Smyth A Oliveira GH Lahr BD Bailey KR Norby SM Garovic VD A systematic review and meta-analysis of pregnancy outcomes in patients with systemic lupus erythematosus and lupus nephritis. Clin J Am Soc Nephrol2010;5:2060-8. [PMID: 20688887] doi:10.2215/CJN.00240110 CrossrefMedlineGoogle Scholar
    • 11. Clowse ME Magder LS Petri M The clinical utility of measuring complement and anti-dsDNA antibodies during pregnancy in patients with systemic lupus erythematosus. J Rheumatol2011;38:1012-6. [PMID: 21406496] doi:10.3899/jrheum.100746 CrossrefMedlineGoogle Scholar
    • 12. Bramham K Hunt BJ Bewley S Germain S Calatayud I Khamashta MA et alPregnancy outcomes in systemic lupus erythematosus with and without previous nephritis. J Rheumatol2011;38:1906-13. [PMID: 21632681] doi:10.3899/jrheum.100997 CrossrefMedlineGoogle Scholar
    • 13. Lynch A Marlar R Murphy J Davila G Santos M Rutledge J et alAntiphospholipid antibodies in predicting adverse pregnancy outcome. A prospective study. Ann Intern Med1994;120:470-5. [PMID: 8093135] doi:10.7326/0003-4819-120-6-199403150-00004 LinkGoogle Scholar
    • 14. Petri M Howard D Repke J Frequency of lupus flare in pregnancy. The Hopkins Lupus Pregnancy Center experience. Arthritis Rheum1991;34:1538-45. [PMID: 1670196] CrossrefMedlineGoogle Scholar
    • 15. Ruiz-Irastorza G Lima F Alves J Khamashta MA Simpson J Hughes GR et alIncreased rate of lupus flare during pregnancy and the puerperium: a prospective study of 78 pregnancies. Br J Rheumatol1996;35:133-8. [PMID: 8612024] CrossrefMedlineGoogle Scholar
    • 16. Wong KL Chan FY Lee CP Outcome of pregnancy in patients with systemic lupus erythematosus. A prospective study. Arch Intern Med1991;151:269-73. [PMID: 1992954] CrossrefMedlineGoogle Scholar
    • 17. Lockshin MD Pregnancy does not cause systemic lupus erythematosus to worsen. Arthritis Rheum1989;32:665-70. [PMID: 2638570] CrossrefMedlineGoogle Scholar
    • 18. Urowitz MB Gladman DD Farewell VT Stewart J McDonald J Lupus and pregnancy studies. Arthritis Rheum1993;36:1392-7. [PMID: 8216399] CrossrefMedlineGoogle Scholar
    • 19. Clowse ME Wallace DJ Weisman M James A Criscione-Schreiber LG Pisetsky DS Predictors of preterm birth in patients with mild systemic lupus erythematosus. Ann Rheum Dis2013;72:1536-9. [PMID: 23361085] doi:10.1136/annrheumdis-2012-202449 CrossrefMedlineGoogle Scholar
    • 20. Hochberg MC Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus [Letter]. Arthritis Rheum1997;40:1725. [PMID: 9324032] CrossrefMedlineGoogle Scholar
    • 21. Lockshin MD Kim M Laskin CA Guerra M Branch DW Merrill J et alPrediction of adverse pregnancy outcome by the presence of lupus anticoagulant, but not anticardiolipin antibody, in patients with antiphospholipid antibodies. Arthritis Rheum2012;64:2311-8. [PMID: 22275304] doi:10.1002/art.34402 CrossrefMedlineGoogle Scholar
    • 22. Buyon JP Kalunian KC Ramsey-Goldman R Petri MA Lockshin MD Ruiz-Irastorza G et alAssessing disease activity in SLE patients during pregnancy. Lupus1999;8:677-84. [PMID: 10568906] CrossrefMedlineGoogle Scholar
    • 23. Levy RA Vilela VS Cataldo MJ Ramos RC Duarte JL Tura BR et alHydroxychloroquine (HCQ) in lupus pregnancy: double-blind and placebo-controlled study. Lupus2001;10:401-4. [PMID: 11434574] CrossrefMedlineGoogle Scholar
    • 24. Petri M Kim MY Kalunian KC Grossman J Hahn BH Sammaritano LR et alOC-SELENA TrialCombined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med2005;353:2550-8. [PMID: 16354891] CrossrefMedlineGoogle Scholar
    • 25. Miyakis S Lockshin MD Atsumi T Branch DW Brey RL Cervera R et alInternational consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost2006;4:295-306. [PMID: 16420554] CrossrefMedlineGoogle Scholar
    • 26. James G Witten D Hastie T Tibshirani R An Introduction to Statistical Learning—With Applications in R. New York: Springer; 2013. Google Scholar
    • 27. Roberts JM Myatt L Spong CY Thom EA Hauth JC Leveno KJ et alEunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units NetworkVitamins C and E to prevent complications of pregnancy-associated hypertension. N Engl J Med2010;362:1282-91. [PMID: 20375405] doi:10.1056/NEJMoa0908056 CrossrefMedlineGoogle Scholar
    • 28. MacDorman MF Kirmeyer SE Wilson EC Fetal and perinatal mortality, United States, 2006. Natl Vital Stat Rep2012;60:1-22. [PMID: 24979970] MedlineGoogle Scholar
    • 29. Brucato A Frassi M Franceschini F Cimaz R Faden D Pisoni MP et alRisk of congenital complete heart block in newborns of mothers with anti-Ro/SSA antibodies detected by counterimmunoelectrophoresis: a prospective study of 100 women. Arthritis Rheum2001;44:1832-5. [PMID: 11508435] CrossrefMedlineGoogle Scholar
    • 30. Friedman DM Kim MY Copel JA Davis C Phoon CK Glickstein JS et alPRIDE InvestigatorsUtility of cardiac monitoring in fetuses at risk for congenital heart block: the PR Interval and Dexamethasone Evaluation (PRIDE) prospective study. Circulation2008;117:485-93. [PMID: 18195175] doi:10.1161/CIRCULATIONAHA.107.707661 CrossrefMedlineGoogle Scholar
    • 31. Izmirly PM Kim MY Llanos C Le PU Guerra MM Askanase AD et alEvaluation of the risk of anti-SSA/Ro-SSB/La antibody-associated cardiac manifestations of neonatal lupus in fetuses of mothers with systemic lupus erythematosus exposed to hydroxychloroquine. Ann Rheum Dis2010;69:1827-30. [PMID: 20447951] doi:10.1136/ard.2009.119263 CrossrefMedlineGoogle Scholar
    • 32. Izmirly PM Costedoat-Chalumeau N Pisoni CN Khamashta MA Kim MY Saxena A et alMaternal use of hydroxychloroquine is associated with a reduced risk of recurrent anti-SSA/Ro-antibody-associated cardiac manifestations of neonatal lupus. Circulation2012;126:76-82. [PMID: 22626746] doi:10.1161/CIRCULATIONAHA.111.089268 CrossrefMedlineGoogle Scholar
    • 33. Abramson SB Buyon JP Activation of the complement pathway: comparison of normal pregnancy, preeclampsia, and systemic lupus erythematosus during pregnancy. Am J Reprod Immunol1992;28:183-7. [PMID: 1285875] CrossrefMedlineGoogle Scholar
    • 34. Girardi G Yarilin D Thurman JM Holers VM Salmon JE Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction. J Exp Med2006;203:2165-75. [PMID: 16923853] CrossrefMedlineGoogle Scholar
    • 35. Saavedra MA Cruz-Reyes C Vera-Lastra O Romero GT Cruz-Cruz P Arias-Flores R et alImpact of previous lupus nephritis on maternal and fetal outcomes during pregnancy. Clin Rheumatol2012;31:813-9. [PMID: 22278163] doi:10.1007/s10067-012-1941-4 CrossrefMedlineGoogle Scholar
    • 36. Fischer-Betz R Specker C Brinks R Aringer M Schneider M Low risk of renal flares and negative outcomes in women with lupus nephritis conceiving after switching from mycophenolate mofetil to azathioprine. Rheumatology (Oxford)2013;52:1070-6. [PMID: 23382355] doi:10.1093/rheumatology/kes425 CrossrefMedlineGoogle Scholar
    • 37. Smyth A Radovic M Garovic VD Women, kidney disease, and pregnancy. Adv Chronic Kidney Dis2013;20:402-10. [PMID: 23978545] doi:10.1053/j.ackd.2013.06.004 CrossrefMedlineGoogle Scholar