Pregnancy in women with systemic lupus erythematosus
- Bonnie L Bermas, MD
Bonnie L Bermas, MD
- Associate Professor of Medicine
- Harvard Medical School
- Nicole A Smith, MD, MPH
Nicole A Smith, MD, MPH
- Assistant Professor of Obstetrics, Gynecology, and Reproductive Biology
- Harvard Medical School
- Section Editors
- David S Pisetsky, MD, PhD
David S Pisetsky, MD, PhD
- Section Editor — Lupus
- Professor of Medicine and Immunology
- Duke University Medical Center
- Charles J Lockwood, MD, MHCM
Charles J Lockwood, MD, MHCM
- Section Editor — Obstetrics
- Senior Vice President, USF Health
- Dean, Morsani College of Medicine
- Professor, Obstetrics and Gynecology
- University of South Florida
Systemic lupus erythematosus (SLE) predominantly affects women of childbearing age. Fertility in SLE patients does not appear to be altered by disease itself; however, a decrease in ovarian reserve can occur in women exposed to cyclophosphamide.
Pregnancy in women with SLE carries a higher maternal and fetal risk compared with pregnancy in healthy women. The prognosis for both mother and child is best when SLE has been quiescent for at least six months prior to the pregnancy. Disease flares during SLE pregnancy pose challenges with respect to distinguishing physiologic changes related to pregnancy from disease-related manifestations. Thus, a multidisciplinary approach with close medical, obstetric, and neonatal monitoring is necessary to optimize both maternal and fetal outcomes.
This topic review will discuss the major risks associated with pregnancy in SLE patients, as well as management recommendations. Issues related to menstrual function, menopause, estrogen replacement therapy, and the use of oral contraceptives in women with systemic lupus erythematosus are presented separately (see "Menstrual function, menopause, and hormone replacement therapy in women with systemic lupus erythematosus" and "Approach to contraception in women with systemic lupus erythematosus"). Issues related to pregnancy in patients with impaired renal function or with antiphospholipid syndrome (APS) are also presented elsewhere. (See "Pregnancy in women with underlying renal disease" and "Pregnancy in women with antiphospholipid syndrome" and "Neonatal lupus: Epidemiology, pathogenesis, clinical manifestations, and diagnosis".)
Ideally, disease should be quiescent for six months prior to systemic lupus erythematosus (SLE) patients attempting conception. Active SLE at the time of conception is a strong predictor of adverse maternal and obstetrical outcomes [1-3]. In spite of this risk, the majority of such pregnancies still result in live births. The following studies are illustrative:
●The largest observational study, including 385 pregnant lupus patients with inactive or mild or moderate disease at conception, found 81 percent of subjects had uncomplicated pregnancies . After controlling for baseline risk factors such as lupus anticoagulant, treatment for hypertension, thrombocytopenia, disease flare, or moderate disease activity at baseline, non-Hispanic white patients had an 8 percent rate of adverse pregnancy outcomes. However, the study population was limited as it excluded women with high disease activity, active lupus nephritis, uncontrolled hypertension, and diabetes.
- Clowse ME, Magder LS, Witter F, Petri M. The impact of increased lupus activity on obstetric outcomes. Arthritis Rheum 2005; 52:514.
- Yang H, Liu H, Xu D, et al. Pregnancy-related systemic lupus erythematosus: clinical features, outcome and risk factors of disease flares--a case control study. PLoS One 2014; 9:e104375.
- Kwok LW, Tam LS, Zhu T, et al. Predictors of maternal and fetal outcomes in pregnancies of patients with systemic lupus erythematosus. Lupus 2011; 20:829.
- Buyon JP, Kim MY, Guerra MM, et al. Predictors of Pregnancy Outcomes in Patients With Lupus: A Cohort Study. Ann Intern Med 2015; 163:153.
- Andreoli L, Bertsias GK, Agmon-Levin N, et al. EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome. Ann Rheum Dis 2017; 76:476.
- Ruiz-Irastorza G, Khamashta MA. Lupus and pregnancy: ten questions and some answers. Lupus 2008; 17:416.
- Lateef A, Petri M. Managing lupus patients during pregnancy. Best Pract Res Clin Rheumatol 2013; 27:435.
- Henderson JT, Whitlock EP, O'Conner E, et al. Low-Dose Aspirin for the Prevention of Morbidity and Mortality From Preeclampsia: A Systematic Evidence Review for the U.S. Preventive Services Task Force [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US) 2014.
- Clowse ME, Magder L, Witter F, Petri M. Hydroxychloroquine in lupus pregnancy. Arthritis Rheum 2006; 54:3640.
- Al-Herz A, Schulzer M, Esdaile JM. Survey of antimalarial use in lupus pregnancy and lactation. J Rheumatol 2002; 29:700.
- Parke AL, Rothfield NF. Antimalarial drugs in pregnancy--the North American experience. Lupus 1996; 5 Suppl 1:S67.
- Klinger G, Morad Y, Westall CA, et al. Ocular toxicity and antenatal exposure to chloroquine or hydroxychloroquine for rheumatic diseases. Lancet 2001; 358:813.
- Costedoat-Chalumeau N, Amoura Z, Duhaut P, et al. Safety of hydroxychloroquine in pregnant patients with connective tissue diseases: a study of one hundred thirty-three cases compared with a control group. Arthritis Rheum 2003; 48:3207.
- Levy RA, Vilela VS, Cataldo MJ, et al. Hydroxychloroquine (HCQ) in lupus pregnancy: double-blind and placebo-controlled study. Lupus 2001; 10:401.
- Sperber K, Hom C, Chao CP, et al. Systematic review of hydroxychloroquine use in pregnant patients with autoimmune diseases. Pediatr Rheumatol Online J 2009; 7:9.
- Mekinian A, Lazzaroni MG, Kuzenko A, et al. The efficacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid syndrome: Data from a European multicenter retrospective study. Autoimmun Rev 2015; 14:498.
- Webster P, Wardle A, Bramham K, et al. Tacrolimus is an effective treatment for lupus nephritis in pregnancy. Lupus 2014; 23:1192.
- Smyth A, Oliveira GH, Lahr BD, et al. A systematic review and meta-analysis of pregnancy outcomes in patients with systemic lupus erythematosus and lupus nephritis. Clin J Am Soc Nephrol 2010; 5:2060.
- Petri M. Prospective study of systemic lupus erythematosus pregnancies. Lupus 2004; 13:688.
- Gladman DD, Tandon A, Ibañez D, Urowitz MB. The effect of lupus nephritis on pregnancy outcome and fetal and maternal complications. J Rheumatol 2010; 37:754.
- Saavedra MA, Cruz-Reyes C, Vera-Lastra O, et al. Impact of previous lupus nephritis on maternal and fetal outcomes during pregnancy. Clin Rheumatol 2012; 31:813.
- Saavedra MA, Sánchez A, Morales S, et al. Primigravida is associated with flare in women with systemic lupus erythematosus. Lupus 2015; 24:180.
- Clowse ME, Jamison M, Myers E, James AH. A national study of the complications of lupus in pregnancy. Am J Obstet Gynecol 2008; 199:127.e1.
- Yasmeen S, Wilkins EE, Field NT, et al. Pregnancy outcomes in women with systemic lupus erythematosus. J Matern Fetal Med 2001; 10:91.
- Borella E, Lojacono A, Gatto M, et al. Predictors of maternal and fetal complications in SLE patients: a prospective study. Immunol Res 2014; 60:170.
- Chakravarty EF, Colón I, Langen ES, et al. Factors that predict prematurity and preeclampsia in pregnancies that are complicated by systemic lupus erythematosus. Am J Obstet Gynecol 2005; 192:1897.
- Bramham K, Hunt BJ, Bewley S, et al. Pregnancy outcomes in systemic lupus erythematosus with and without previous nephritis. J Rheumatol 2011; 38:1906.
- Abalos E, Cuesta C, Grosso AL, et al. Global and regional estimates of preeclampsia and eclampsia: a systematic review. Eur J Obstet Gynecol Reprod Biol 2013; 170:1.
- Gibbins KJ, Ware Branch D. Pre-eclampsia as a manifestation of antiphospholipid syndrome: assessing the current status. Lupus 2014; 23:1229.
- Wagner SJ, Craici I, Reed D, et al. Maternal and foetal outcomes in pregnant patients with active lupus nephritis. Lupus 2009; 18:342.
- Carvalheiras G, Vita P, Marta S, et al. Pregnancy and systemic lupus erythematosus: review of clinical features and outcome of 51 pregnancies at a single institution. Clin Rev Allergy Immunol 2010; 38:302.
- Clowse ME. Lupus activity in pregnancy. Rheum Dis Clin North Am 2007; 33:237.
- Brucato A, Frassi M, Franceschini F, et al. Risk of congenital complete heart block in newborns of mothers with anti-Ro/SSA antibodies detected by counterimmunoelectrophoresis: a prospective study of 100 women. Arthritis Rheum 2001; 44:1832.
- Buyon JP, Hiebert R, Copel J, et al. Autoimmune-associated congenital heart block: demographics, mortality, morbidity and recurrence rates obtained from a national neonatal lupus registry. J Am Coll Cardiol 1998; 31:1658.
- Izmirly PM, Llanos C, Lee LA, et al. Cutaneous manifestations of neonatal lupus and risk of subsequent congenital heart block. Arthritis Rheum 2010; 62:1153.
- Llanos C, Izmirly PM, Katholi M, et al. Recurrence rates of cardiac manifestations associated with neonatal lupus and maternal/fetal risk factors. Arthritis Rheum 2009; 60:3091.
- Ambrosi A, Wahren-Herlenius M. Congenital heart block: evidence for a pathogenic role of maternal autoantibodies. Arthritis Res Ther 2012; 14:208.
- Barnabe C, Faris PD, Quan H. Canadian pregnancy outcomes in rheumatoid arthritis and systemic lupus erythematosus. Int J Rheumatol 2011; 2011:345727.
- Nalli C, Iodice A, Andreoli L, et al. Children born to SLE and APS mothers. Lupus 2014; 23:1246.
- Ross G, Sammaritano L, Nass R, Lockshin M. Effects of mothers' autoimmune disease during pregnancy on learning disabilities and hand preference in their children. Arch Pediatr Adolesc Med 2003; 157:397.
- Vinet É, Pineau CA, Clarke AE, et al. Neurodevelopmental disorders in children born to mothers with systemic lupus erythematosus. Lupus 2014; 23:1099.
- McGrory CH, McCloskey LJ, DeHoratius RJ, et al. Pregnancy outcomes in female renal recipients: a comparison of systemic lupus erythematosus with other diagnoses. Am J Transplant 2003; 3:35.
- Chighizola CB, Andreoli L, de Jesus GR, et al. The association between antiphospholipid antibodies and pregnancy morbidity, stroke, myocardial infarction, and deep vein thrombosis: a critical review of the literature. Lupus 2015; 24:980.
- Izmirly PM, Kim MY, Llanos C, et al. Evaluation 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 Dis 2010; 69:1827.
- Izmirly PM, Costedoat-Chalumeau N, Pisoni CN, et al. Maternal use of hydroxychloroquine is associated with a reduced risk of recurrent anti-SSA/Ro-antibody-associated cardiac manifestations of neonatal lupus. Circulation 2012; 126:76.
- Askanase AD, Miranda-Carus ME, Tang X, et al. The presence of IgG antibodies reactive with components of the SSA/Ro-SSB/La complex in human breast milk: implications in neonatal lupus. Arthritis Rheum 2002; 46:269.
- Lockshin MD, Sammaritano LR. Lupus pregnancy. Autoimmunity 2003; 36:33.
- Andrade RM, McGwin G Jr, Alarcón GS, et al. Predictors of post-partum damage accrual in systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (XXXVIII). Rheumatology (Oxford) 2006; 45:1380.
- Buyon JP, Cronstein BN, Morris M, et al. Serum complement values (C3 and C4) to differentiate between systemic lupus activity and pre-eclampsia. Am J Med 1986; 81:194.
- Buyon JP, Tamerius J, Ordorica S, et al. Activation of the alternative complement pathway accompanies disease flares in systemic lupus erythematosus during pregnancy. Arthritis Rheum 1992; 35:55.
- Boumpas DT, Fessler BJ, Austin HA 3rd, et al. Systemic lupus erythematosus: emerging concepts. Part 2: Dermatologic and joint disease, the antiphospholipid antibody syndrome, pregnancy and hormonal therapy, morbidity and mortality, and pathogenesis. Ann Intern Med 1995; 123:42.
- Lockshin MD, Harpel PC, Druzin ML, et al. Lupus pregnancy. II. Unusual pattern of hypocomplementemia and thrombocytopenia in the pregnant patient. Arthritis Rheum 1985; 28:58.
- Drugs and lactation database (LactMed) of the United States National Library of Medicine http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT (Accessed on March 15, 2012).
- PREGNANCY PLANNING
- Preconception evaluation
- - Risk assessment
- - Specific laboratory testing
- - Medications
- Selective use allowed during pregnancy
- Selective use with caution in pregnancy
- Contraindicated in pregnancy
- SPECIFIC CONSIDERATIONS DURING PREGNANCY
- Exacerbation of SLE
- Impact of lupus on pregnancy
- Preterm birth
- Fetal complications
- Special considerations
- - Lupus nephritis
- - Presence of antiphospholipid antibodies
- - Presence of anti-Ro and anti-La antibodies
- MANAGEMENT DURING PREGNANCY
- Monitoring SLE activity
- - Initial evaluation
- - Laboratory testing
- - Postpartum laboratory testing
- Maternal-fetal monitoring
- - Preeclampsia versus lupus nephritis
- Treating active SLE
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS