Skip to main content
SpringerLink
Log in

Pregnancy and the Autoimmune Patient

  • Review
  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

This article will review the current understanding of the immunologic changes that occur during pregnancy. It will discuss the impact of pregnancy on the disease activity of autoimmune or inflammatory rheumatic diseases (AIRD). Lastly, it will highlight the most recent data on pre-conception and pregnancy management practices that can improve pregnancy outcomes in autoimmune patients.

Recent Findings

Pregnancy is an immunologically complex and dynamic state that may affect the activity of AIRDs, with more patients having active disease during pregnancy than previously thought. Uncontrolled inflammatory diseases are associated with poor pregnancy outcomes such as preeclampsia, small for gestational age infants, and prematurity. Pre-conception counseling and early pregnancy planning discussions can help ensure optimal disease control and medication management prior to attempting conception.

Summary

Adequate control of AIRDs on pregnancy-compatible medications during the pre-conception, pregnancy, and postpartum periods is required for optimal pregnancy outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Wegmann TG, Lin H, Guilbert L, Mosmann TR. Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? Immunol Today. 1993;14(7):353–6.

    Article  CAS  PubMed  Google Scholar 

  2. Förger F, Villiger PM. Immunological adaptations in pregnancy that modulate rheumatoid arthritis disease activity. Nat Rev Rheumatol. 2020;16(2):113–22.

    Article  PubMed  Google Scholar 

  3. Weiss G, Goldsmith LT, Taylor RN, Bellet D, Taylor HS. Inflammation in reproductive disorders. Reprod Sci. 2009;16(2):216–29.

    Article  CAS  PubMed  Google Scholar 

  4. Ander SE, Diamond MS, Coyne CB (2019) Immune responses at the maternal-fetal interface. Sci Immunol 4(31). PMID: 30635356.

  5. Miko E, Meggyes M, Doba K, Barakonyi A, Szereday L. Immune checkpoint molecules in reproductive immunology. Front Immunol. 2019;10:846.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Deshmukh H, Way SS. Immunological Basis for Recurrent Fetal Loss and Pregnancy Complications. Annu Rev Pathol. 2019;14:185–210.

    Article  CAS  PubMed  Google Scholar 

  7. McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007;7(6):429–42.

    Article  CAS  PubMed  Google Scholar 

  8. Jethwa H, Lam S, Smith C, Giles I. Does rheumatoid arthritis really improve during pregnancy? A systematic review and metaanalysis. J Rheumatol. 2019;46(3):245–50.

    Article  PubMed  Google Scholar 

  9. Sammaritano LR, Bermas BL, editors. Contraception and pregnancy in patients with rheumatic disease. Springer-Verlag New York; 2014. p. 313. ASIN : B00S15F60U. https://doi.org/10.1007/978-1-4939-0673-4_1.

  10. Yan Z, Aydelotte T, Gadi VK, Guthrie KA, Nelson JL. Acquisition of the rheumatoid arthritis HLA shared epitope through microchimerism. Arthritis Rheum. 2011;63(3):640–4.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Kwok L-W, Tam L-S, Zhu T, Leung Y-Y, Li E. Predictors of maternal and fetal outcomes in pregnancies of patients with systemic lupus erythematosus. Lupus. 2011;20(8):829–36.

    Article  PubMed  Google Scholar 

  12. Andrade D, Kim M, Blanco LP, Karumanchi SA, Koo GC, Redecha P, et al. Interferon-α and angiogenic dysregulation in pregnant lupus patients who develop preeclampsia. Arthritis Rheumatol (Hoboken, NJ). 2015;67(4):977–87.

    Article  CAS  Google Scholar 

  13. Oktem O, Yagmur H, Bengisu H, Urman B. Reproductive aspects of systemic lupus erythematosus. J Reprod Immunol. 2016;117:57–65.

    Article  PubMed  Google Scholar 

  14. Teirilä L, Heikkinen-Eloranta J, Kotimaa J, Meri S, Lokki AI. Regulation of the complement system and immunological tolerance in pregnancy. Semin Immunol. 2019;45: 101337.

    Article  PubMed  Google Scholar 

  15. Chakravarty EF, Nelson L, Krishnan E. Obstetric hospitalizations in the United States for women with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum. 2006;54(3):899–907.

    Article  PubMed  Google Scholar 

  16. Clowse MEB, Jamison M, Myers E, James AH. A national study of the complications of lupus in pregnancy. Am J Obstet Gynecol. 2008;199(2):127.e1-6.

    Article  PubMed  Google Scholar 

  17. Chen Y-J, Chang J-C, Lai E-L, Liao T-L, Chen H-H, Hung W-T, et al. Maternal and perinatal outcomes of pregnancies in systemic lupus erythematosus: a nationwide population-based study. Semin Arthritis Rheum. 2020;50(3):451–7.

    Article  PubMed  Google Scholar 

  18. Yang H, Liu H, Xu D, Zhao L, Wang Q, Leng X, et al. Pregnancy-related systemic lupus erythematosus: clinical features, outcome and risk factors of disease flares–a case control study. PLoS ONE. 2014;9(8): e104375.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Wagner SJ, Craici I, Reed D, Norby S, Bailey K, Wiste HJ, et al. Maternal and foetal outcomes in pregnant patients with active lupus nephritis. Lupus. 2009;18(4):342–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Skorpen CG, Lydersen S, Gilboe I-M, Skomsvoll JF, Salvesen KÅ, Palm Ø, et al. Influence of disease activity and medications on offspring birth weight, pre-eclampsia and preterm birth in systemic lupus erythematosus: a population-based study. Ann Rheum Dis. 2018;77(2):264–9.

    Article  CAS  PubMed  Google Scholar 

  21. Buyon JP, Kim MY, Guerra MM, Laskin CA, Petri M, Lockshin MD, et al. Predictors of pregnancy outcomes in patients with lupus: a cohort study. Ann Intern Med. 2015;163(3):153–63.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Sammaritano LR, Bermas BL, Chakravarty EE, Chambers C, Clowse MEB, Lockshin MD, et al. 2020 American College of Rheumatology Guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Care Res (Hoboken). 2020;72(4):461–88.

    Article  PubMed  Google Scholar 

  23. D’Ippolito S, Ticconi C, Tersigni C, Garofalo S, Martino C, Lanzone A, et al. The pathogenic role of autoantibodies in recurrent pregnancy loss. Am J Reprod Immunol. 2020;83(1): e13200.

    Article  PubMed  Google Scholar 

  24. Garcia D, Erkan D. Diagnosis and Management of the Antiphospholipid Syndrome. N Engl J Med. 2018;378(21):2010–21.

    Article  CAS  PubMed  Google Scholar 

  25. Abrahams VM, Chamley LW, Salmon JE. Emerging treatment models in rheumatology: antiphospholipid syndrome and pregnancy: pathogenesis to translation. Arthritis Rheumatol (Hoboken, NJ). 2017;69(9):1710–21.

    Article  Google Scholar 

  26. Marder W, Knight JS, Kaplan MJ, Somers EC, Zhang X, O’Dell AA, et al. Placental histology and neutrophil extracellular traps in lupus and pre-eclampsia pregnancies. Lupus Sci Med. 2016;3(1): e000134.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Sammaritano LR. Antiphospholipid syndrome. Best Pract Res Clin Rheumatol [Internet]. 2020;34(1):101463. Accessed 10 Nov 2023. http://www.sciencedirect.com/science/article/pii/S1521694219301597

  28. Duley L, Meher S, Hunter KE, Seidler AL, Askie LM. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane database Syst Rev. 2019;2019(10). PMID: 31684684.

  29. LeFevre ML. Low-dose aspirin use for the prevention of morbidity and mortality from preeclampsia: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;161(11):819–26.

    Article  PubMed  Google Scholar 

  30. Miranda-Carús ME, Askanase AD, Clancy RM, Di Donato F, Chou TM, Libera MR, et al. Anti-SSA/Ro and anti-SSB/La autoantibodies bind the surface of apoptotic fetal cardiocytes and promote secretion of TNF-alpha by macrophages. J Immunol. 2000;165(9):5345–51.

    Article  PubMed  Google Scholar 

  31. Brucato A, Frassi M, Franceschini F, Cimaz R, Faden D, Pisoni MP, 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(8):1832–5.

    Article  CAS  PubMed  Google Scholar 

  32. Llanos C, Izmirly PM, Katholi M, Clancy RM, Friedman DM, Kim MY, et al. Recurrence rates of cardiac manifestations associated with neonatal lupus and maternal/fetal risk factors. Arthritis Rheum. 2009;60(10):3091–7.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Izmirly PM, Saxena A, Sahl SK, Shah U, Friedman DM, Kim MY, et al. Assessment of fluorinated steroids to avert progression and mortality in anti-SSA/Ro-associated cardiac injury limited to the fetal conduction system. Ann Rheum Dis. 2016;75(6):1161–5.

    Article  CAS  PubMed  Google Scholar 

  34. Barsalou J, Costedoat-Chalumeau N, Berhanu A, Fors-Nieves C, Shah U, Brown P, et al. Effect of in utero hydroxychloroquine exposure on the development of cutaneous neonatal lupus erythematosus. Ann Rheum Dis. 2018;77(12):1742–9.

    Article  CAS  PubMed  Google Scholar 

  35. Erkan D, Harrison MJ, Levy R, Peterson M, Petri M, Sammaritano L, et al. Aspirin for primary thrombosis prevention in the antiphospholipid syndrome: a randomized, double-blind, placebo-controlled trial in asymptomatic antiphospholipid antibody-positive individuals. Arthritis Rheum. 2007;56(7):2382–91.

    Article  CAS  PubMed  Google Scholar 

  36. •• Barbhaiya M, Zuily S, Naden R, Hendry A, Manneville F, Amigo M-C, et al. 2023 ACR/EULAR antiphospholipid syndrome classification criteria. Ann Rheum Dis. 2023;82(10):1258–70. The updated antiphospholipid antibody syndrome classification criteria have a higher specificity for diagnosis than the previous 2006 revised Sapporo classification criteria

    Article  CAS  PubMed  Google Scholar 

  37. Mak A, Cheung MWL, Cheak AA, Ho RCM. Combination of heparin and aspirin is superior to aspirin alone in enhancing live births in patients with recurrent pregnancy loss and positive anti-phospholipid antibodies: a meta-analysis of randomized controlled trials and meta-regression. Rheumatology (Oxford). 2010;49(2):281–8.

    Article  CAS  PubMed  Google Scholar 

  38. Sciascia S, Hunt BJ, Talavera-Garcia E, Lliso G, Khamashta MA, Cuadrado MJ. The impact of hydroxychloroquine treatment on pregnancy outcome in women with antiphospholipid antibodies. Am J Obstet Gynecol [Internet]. 2016;214(2):273.e1–273.e8. Accessed 10 Nov 2023. https://www.sciencedirect.com/science/article/pii/S0002937815011928

  39. Mekinian A, Lazzaroni MG, Kuzenko A, Alijotas-Reig J, Ruffatti A, Levy P, et al. The efficacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid syndrome: Data from a European multicenter retrospective study. Autoimmun Rev. 2015;14(6):498–502.

    Article  CAS  PubMed  Google Scholar 

  40. Arslan E, Fellow V, Medicine M, Branch DW, James R, Endowed JS. Best Practice & Research clinical obstetrics and gynaecology antiphospholipid syndrome: diagnosis and management in the obstetric patient. Best Pract Res Clin Obstet Gynaecol. 2020;64:31–40. https://doi.org/10.1016/j.bpobgyn.2019.10.001.

    Article  PubMed  Google Scholar 

  41. Cowchock FS, Reece EA, Balaban D, Branch DW, Plouffe L. Repeated fetal losses associated with antiphospholipid antibodies: a collaborative randomized trial comparing prednisone with low-dose heparin treatment. Am J Obstet Gynecol. 1992;166(5):1318–23.

    Article  CAS  PubMed  Google Scholar 

  42. Finer LB, Zolna MR. Declines in unintended pregnancy in the United States, 2008–2011. N Engl J Med. 2016;374(9):843–52. https://doi.org/10.1056/NEJMsa1506575.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. • Stransky OM, Wolgemuth T, Kazmerski T, Chodoff A, Borrero S, Birru TM. Contraception decision-making and care among reproductive-aged women with autoimmune diseases. Contraception. 2021;103(2):86–91. Findings from this study highlight common patient misconceptions with regards to the use of contraception in the setting of their systemic rheumatic disease and reveal why contraception rates may be lower than desired in this patient population.

    Article  PubMed  Google Scholar 

  44. Raine TR, Harper CC, Rocca CH, Fischer R, Padian N, Klausner JD, et al. Direct access to emergency contraception through pharmacies and effect on unintended pregnancy and STIs: a randomized controlled trial. JAMA. 2005;293(1):54–62.

    Article  CAS  PubMed  Google Scholar 

  45. Turok DK, Gero A, Simmons RG, Kaiser JE, Stoddard GJ, Sexsmith CD, et al. Levonorgestrel vs copper intrauterine devices for emergency contraception. N Engl J Med. 2021;384(4):335–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Leung VWY, Levine M, Soon JA. Mechanisms of action of hormonal emergency contraceptives. Pharmacotherapy. 2010;30(2):158–68.

    Article  CAS  PubMed  Google Scholar 

  47. • Wolgemuth T, Stransky OM, Chodoff A, Kazmerski TM, Clowse MEB, Birru TM. Exploring the preferences of women regarding sexual and reproductive health care in the context of rheumatology: a qualitative study. Arthritis Care Res (Hoboken). 2021;73(8):1194–200. Findings from this qualitative study highlight that women with rheumatic diseases want their providers, specifically their rheumatologists, to initiate conversations regarding sexual and reproductive health and revisit the conversation periodically.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Texas Southwestern Medical Center, 2001 Inwood Road, Dallas, TX, 75390, USA

    Brooke S. Mills & Bonnie L. Bermas

Authors
  1. Brooke S. Mills
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bonnie L. Bermas
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

B.M. and B.B. wrote and edited the main manuscript text and B.M. prepared tables 1-2. All authors reviewed the manuscript.

Corresponding author

Correspondence to Bonnie L. Bermas.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mills, B., Bermas, B.L. Pregnancy and the Autoimmune Patient. Curr Allergy Asthma Rep (2024). https://doi.org/10.1007/s11882-024-01143-z

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11882-024-01143-z

Keywords

Search

Navigation