Pregnancy in the Rheumatic Diseases

  • Megan E. B. Clowse
  • Rosalind Ramsey-Goldman


Few conditions in rheumatology are fraught with greater concern and more unknowns than those of fertility and pregnancy. Patients with rheumatologic disease are not at higher risk for infertility than the general population, unless they have received cyclophosphamide. In general, the inflammation from active rheumato-logic disease is more dangerous to a pregnancy than immunosuppressant medications. Medications to continue if needed to control disease: hydroxychloroquine, azathioprine, sulfasalazine, and prednisone. Medications to discontinue prior to pregnancy: metho-trexate, leflunamide, mycophenolate mofetil, cyclophos-phamide. Normal pregnancy can alter laboratory findings. In particular, the creatinine should fall and proteinuria may increase mildly. The sedimentation rate and complement may increase. Flares in lupus during pregnancy tend to be mild. Patients at highest risk for a severe flare have active lupus at the time of conception. Even treated with low molecular weight heparin and aspirin 81mg a day, up to 25% of pregnancies in women with antiphospholipid syndrome will result in a pregnancy loss. Maternal SSA/Ro and SSB/La antibodies put a baby at risk for neonatal lupus. Up to 50% of these mothers do not fit criteria for a rheumatologic disease. Rheumatoid arthritis will improve in many women during pregnancy, but often flares post-partum. Medications may be tapered during pregnancy but should be restarted following delivery to avoid a severe flare.


Systemic Lupus Erythematosus Pulmonary Hypertension Lupus Nephritis Assisted Reproductive Technology Connective Tissue Disorder 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Armenti VT, Radomski JS, et al Report from the National Transplantation Pregnancy Registry (NTPR): outcomes of pregnancy after transplantation. Clin Transpl 2004;103–114Google Scholar
  2. Baethge, B. A. and R. E. Wolf (1989). “Successful pregnancy with scle-roderma renal disease and pulmonary hypertension in a patient using angiotensin converting enzyme inhibitors.” Ann Rheum Dis 48(9): 776–8PubMedCrossRefGoogle Scholar
  3. Barr, M., Jr. (1994). “Teratogen update: angiotensin-converting enzyme inhibitors.“ Teratology 50(6): 399–409PubMedCrossRefGoogle Scholar
  4. Barrett JH, Brennan P, et al Does rheumatoid arthritis remit during pregnancy and relapse postpartum? Results from a nationwide study in the United Kingdom performed prospectively from late pregnancy. Arthritis Rheum 1999; 42:1219–1227Google Scholar
  5. Brun JG, Nilssen S, Kvale G. Breast feeding, other reproductive factors and rheumatoid arthritis: A prospective study. Br J Rheumatol 1995; 34:542–546Google Scholar
  6. Chakravarty EF, Sanchez-Yamamoto D, Bush TM. The use of disease modifying antirheumatic drugs in women with rheumatoid arthritis of childbearing age: A survey of practice patterns and pregnancy outcomes. J Rheumatol 2003; 30:241–246PubMedGoogle Scholar
  7. Chakravarty, E. F., D. Khanna, et al (2008). “Pregnancy outcomes in systemic sclerosis, primary pulmonary hypertension, and sickle cell disease.” Obstet Gynecol 111(4): 927–34PubMedCrossRefGoogle Scholar
  8. Cooper W. O., S. Hernandez-Diaz, et al (2006). “Major congenital malformations after first-trimester exposure to ACE inhibitors.” N Engl J Med 354(23): 2443–51PubMedCrossRefGoogle Scholar
  9. Clowse M. Lupus activity in pregnancy. Rheum Dis Clin N Amer 2007; 33:237–252CrossRefGoogle Scholar
  10. Clowse MEB, Witter F, et al Complement and anti-double stranded DNA antibodies predict pregnancy outcomes in lupus patients. Arthritis Rheum 2004; 50(suppl):S689CrossRefGoogle Scholar
  11. Clowse ME, Magder LS, et al The impact of increased lupus activity on obstetric outcomes. Arthritis Rheum 2005; 52:514–521PubMedCrossRefGoogle Scholar
  12. Clowse ME, Magder L, et al Hydroxychloroquine in lupus pregnancy. Arthritis Rheum 2006a; 54:3640–3647CrossRefGoogle Scholar
  13. Clowse ME, Magder LS, et al Early risk factors for pregnancy loss in lupus. Obstet Gynecol 2006b; 107(2 Pt 1):293–299CrossRefGoogle Scholar
  14. Clowse ME, Jamison M, et al A national study of the complications of lupus in pregnancy. Am J Obstet Gynecol 2008; 199:127.e1–e6CrossRefGoogle Scholar
  15. Costa M, Colia D. Treating infertility in autoimmune patients. Rheumatology (Oxford) 2008; 47(Suppl 3):38–41Google Scholar
  16. Costedoat-Chalumeau N, Amoura Z, Duhaut P, et al Safety of dyroxy-chlroroquine in pregnant patients with connective tissue diseases: A study of one hundred thirty-three cases compared with a control group. Arthritis Rheum 2003; 48:3207–3211PubMedCrossRefGoogle Scholar
  17. Costenbader KH, Feskanich D, Stampfer MJ, Karlson EW. Reproductive and menopausal factors and risk of systemic lupus erythematosus in women. Arthritis Rheum 2007; 56:1251–1262PubMedCrossRefGoogle Scholar
  18. Duley L, Henderson-Smart DJ, et al Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev 2007; (2):CD004659Google Scholar
  19. Empson M, Lassere M, et al Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant. Cochrane Database Syst Rev 2005; (2):CD002859Google Scholar
  20. FDA, 2007. Scholar
  21. Gayed, M. and C. Gordon (2007). “Pregnancy and rheumatic diseases.” Rheumatology (Oxford) 46(11): 1634–40CrossRefGoogle Scholar
  22. Gordon PA. Congenital heart block: Clinical features and therapeutic options. Lupus 2007; 16:642–646PubMedCrossRefGoogle Scholar
  23. Izmirly PM, Rivera TL, Buyon JP. Neonatal lupus syndromes. Rheum Dis Clin N Amer 2007; 33:267–285CrossRefGoogle Scholar
  24. Karlson EW, Mandl LA, Hankinson SE, Grodstein F. Do breast-feeding and other reproductive factors influence future risk of rheumatoid arthritis. Arthritis Rheum 2004; 50:3458–3467PubMedCrossRefGoogle Scholar
  25. Katz PP. Childbearing decisions and family size among women with rheumatoid arthritis. Arthritis Rheum 2006; 55:217–223PubMedCrossRefGoogle Scholar
  26. Kikuchi K, Shibahara H, et al Antinuclear antibody reduces the pregnancy rate in the first IVF-ET treatment cycle but not the cumulative pregnancy rate without specific medication. Am J Reprod Immunol 2003; 50:363–367PubMedCrossRefGoogle Scholar
  27. Levy M, Buskila D, Gladman DD, Urowitz MB, Koren G. Prengnancy outcome following first trimester exposure to chloroquine. Am J Perinatol 1991; 8:174–178PubMedCrossRefGoogle Scholar
  28. Lin P, Bonaminio P, Ramsey-Goldman R. Pregnancy & rheumatic diseases. In: Imboden J, Hellmann D, Stone J (eds) Current diagnosis & treatment. Rheumatology (2nd edn). New York, McGraw-Hill, 2007, pp. 146–159Google Scholar
  29. Lockshin MD. Autoimmunity, infertility and assisted reproductive technologies. Lupus 2004; 13(9):669–672PubMedCrossRefGoogle Scholar
  30. Martin V, Lee LA, Askanase AD, Katholi M, Buyon JP. Long-term fol-lowup of children with neonatal lupus and their unaffected siblings. Arthritis Rheum 2002; 46:2377–2383PubMedCrossRefGoogle Scholar
  31. McKay DB, Josephson MA, et al Reproduction and transplantation: Report on the AST Consensus Conference on reproductive issues and transplantation. Am J Transplant 2005; 5:1592–1599PubMedCrossRefGoogle Scholar
  32. Meads CA, Cnossen, et al Methods of prediction and prevention of pre-eclampsia: Systematic reviews of accuracy and effectiveness literature with economic modelling. Health Technol Assess 2008; 12(6):iii–iv, 1–270Google Scholar
  33. Merlino LA, Cerhan JR, Criswell LA, Mikuls TR, Saag KG. Estrogen and other female reproductive risk factors are not strongly associated with the development of rheumatoid arthritis in elderly women. Semin Arthritis Rheum 2003; 33:72–82PubMedCrossRefGoogle Scholar
  34. Milunsky A, Graef JW, Gaynor MF. Methotrexate-induced congenital malformations. Med J Aust 1968; 2:1076–1077Google Scholar
  35. Miniati, I., S. Guiducci, et al (2008). “Pregnancy in systemic sclerosis.” Rheumatology (Oxford) 47 Suppl 3: iii16–8CrossRefGoogle Scholar
  36. Moak JP, Barron KS, Hougen TJ, et al Congenital heart block: Development of late-onset cardiomyopathy, a previously underappreciated sequela. J Am Coll Cardiol 2001; 37:238–242PubMedCrossRefGoogle Scholar
  37. Neville CE, McNally J. Maternal exposure to leflunomide associated with blindness and cerebral palsy (letter). Rheumatol 2007; 46:1506CrossRefGoogle Scholar
  38. Østensen M, Khmashta M, Lockshin M, et al. Anti-inflammatory and immunosuppressive drugs in reproduction. Arthritis Res Ther 2006; 8:1–19CrossRefGoogle Scholar
  39. Østensen M, Lockshin M, Doria A, et al Update on safety during pregnancy of biological agents and some immunosuppressive anti-rheumatic drugs. Rheumatol 2008; 47:iii28–iii31CrossRefGoogle Scholar
  40. Parke AL, West B. Hydroxychloroquine in pregnant patients with systemic lupus erythematosus. J Rheumatol 1996; 23:1715–1718PubMedGoogle Scholar
  41. Paufique L, Magnard P. Retinal degeneration in 2 children following preventive anitmalarail treatment of the mother during pregnancy. Bull Soc Ophtalmol Fr 1969; 69:466–467PubMedGoogle Scholar
  42. Petri M, Allbritton J. Fetal outcome of lupus pregnancy: A retrospective case-control study of the Hopkins Lupus Cohort. J Rheumatol 1993; 20:650–656PubMedGoogle Scholar
  43. Petri M, Kim MY, et al Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med 2005; 353(24): 2550–2558PubMedCrossRefGoogle Scholar
  44. Pikwer M, Bergströom U, Nilsson J-Å, Jacobsson L, Berglund G, Turesson C. Breast feeding, but not use of oral contraceptives, is associated with a reduced risk of rheumatoid arthritis. Ann Rheum Dis online May 14, 2008 as 10.1136/aard.2007.084707Google Scholar
  45. Ramsey-Goldman R, Schilling E. Optimum use of disease-modifying and immunosuppressive antirheumatic agents during pregnancy and lactation. Clin Immunother 1996; 5:40–58CrossRefGoogle Scholar
  46. Ramsey-Goldman R, Mientus JM, Kutzer JE, Mulvihill JJ, Medsger TA Jr. Pregnancy outcome in women with systemic lupus erythemato-sus (SLE) treated with immunosuppressive drugs (ISD). J Rheumatol 1993; 20:1152–1157PubMedGoogle Scholar
  47. Raptopoulou A, Sidiropoulos P, Boumpas D. Ovarian failure and strategies for fertility preservation in patients with systemic lupus erythematosus. Lupus 2004; 13(12):887–890PubMedCrossRefGoogle Scholar
  48. Schwarz, E. B. and S. Manzi (2008). “Risk of unintended pregnancy among women with systemic lupus erythematosus.” Arthritis Rheum 59(6): 863–6PubMedCrossRefGoogle Scholar
  49. Simaard JF, Karlson EW, Costenbader KH, Hernán MA, Stampfer MJ, Liang MH, Mittlemen MA. Perinatal factors and adult-onset lupus. Arthritis Rheum (Arthritis Care Res) 2008; 59: 1155–1161CrossRefGoogle Scholar
  50. Soares PMF, Borba EF, Bonfa E, Hallak J, Corrêa AL, Silva CAA. Gondal evalution in male systemic lupus erythematosus. Arthritis Rheum 2007; 56:2352–2361PubMedCrossRefGoogle Scholar
  51. Somers EC, Marder W, Christman GM, et al Use of a gonadotro-pin-releasing hormone analog for protection against premature ovarian failure failure during cyclophosphamide therapy in women with severe lupus. Arthritis Rheum 2005; 52(9): 2761–2767PubMedCrossRefGoogle Scholar
  52. Steen, V. D. (1999). “Pregnancy in women with systemic sclerosis.” Obstet Gynecol 94(1): 15–20PubMedCrossRefGoogle Scholar
  53. Steen, V. D., C. Conte, et al (1989). “Pregnancy in women with systemic sclerosis.” Arthritis Rheum 32(2): 151–7PubMedCrossRefGoogle Scholar
  54. Taguchi N, Rubin ET, Hosokawa A, et al Prenatal exposure to HMG-CoA reductase inhibitors: Effects on fetal and neonatal outcomes. Reproductive Toxicology 2008 [Epub]Google Scholar
  55. Wilson JG, Scott WJ, Ritter EJ, Fradkin R. Comparative distribution and embryo toxicity of methotrexate in pregnant rats and rhesus monkeys. Teratology 1979; 19:71–98PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Megan E. B. Clowse
    • 1
  • Rosalind Ramsey-Goldman
    • 2
  1. 1.Medicine, Division of Rheumatology and ImmunologyDuke UniversityDurhamUSA
  2. 2.Northwestern UniversityDivision of Rheumatology FSM-300 240ChicagoUSA

Personalised recommendations