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Systemic Lupus Erythematosus and Pregnancy: a Portuguese Case–Control Study

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Abstract

Pregnancy in systemic lupus erythematosus (SLE) patients is associated with an increased risk of adverse outcomes. During pregnancy, SLE patients have a higher rate of miscarriage, stillbirth, preterm delivery, fetal growth restriction, or hypertensive disorders of pregnancy. To date, only a few case–control studies were published with the purpose to evaluate the magnitude of risk associated with pregnancy in lupus patients. The aim of our study was to evaluate the maternal and fetal outcomes in a cohort of Portuguese SLE patients and to compare it with a group of healthy pregnant women. We conducted a retrospective case–control study that included all pregnant women with SLE managed at a Portuguese tertiary center, between 2010 and 2019. Pregnancy outcomes were compared between SLE patients and a group of matched healthy pregnant women. Baseline maternal data was collected, and maternal–fetal and neonatal outcomes were evaluated. One hundred twenty-four SLE pregnancies were included. Of the patients, 95.2% were in remission at conception. In 13.7% of cases, a lupus flare was diagnosed during gestation and in 17.9% in the postpartum period. The live birth rate was 84.6%, and the incidence of adverse outcomes was 40.3% (OR 2.64, 95% CI 1.67–4.18). Considering only patients in remission at conception, the presence of adverse outcomes remained significantly higher (36.8% vs. 20.3%, P < 0.01). Miscarriage rate was 15.3% (OR 5.85, 95% CI 2.57–13.34) and preterm delivery occurred in 12.4% of the patients (OR 1.72, 95% CI 0.83–3.57). Preeclampsia prevalence was higher in SLE patients (OR 3.92, 95% CI 1.32–11.57). In the SLE group, the newborn admission to an intensive care unit rate was increased (OR 4.99, 95% CI 1.47–16.90). No neonatal or maternal deaths were reported. In our study, pregnancy with SLE was associated with an increased incidence of adverse outcomes, even in a population of SLE patients with well-controlled disease.

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References

  1. Oktem O, Yagmur H, Bengisu H, Urman B (2016) Reproductive aspects of systemic lupus erythematosus [Internet]. J Reprod Immunol 117:57–65. Elsevier Ireland Ltd; [cited 2020 Feb 24].  Available from: http://www.ncbi.nlm.nih.gov/pubmed/27474801

  2. Oktem O, Guzel Y, Aksoy S, Aydin E, Urman B (2015) Ovarian function and reproductive outcomes of female patients with systemic lupus erythematosus and the strategies to preserve their fertility [Internet]. Obstet Gynecol Surv 70:196-210. Lippincott Williams and Wilkins; [cited 2020 Feb 25]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25769434

  3. McMurray RW, May W (2003) Sex hormones and systemic lupus erythematosus: Review and meta-analysis. Arthritis Rheum [Internet]. 48(8):2100–2110. [cited 2020 Apr 6]. Available from: http://doi.wiley.com/10.1002/art.11105

  4. Østensen M, Andreoli L, Brucato A, Cetin I, Chambers C, Clowse MEB et al (2015) State of the art: Reproduction and pregnancy in rheumatic diseases [Internet]. Autoimmun Rev 14(5):376–86. Available from: https://doi.org/10.1016/j.autrev.2014.12.011

  5. Cortes-Hernandez J (2002) Clinical predictors of fetal and maternal outcome in systemic lupus erythematosus: a prospective study of 103 pregnancies. Rheumatology 41(6):643–650

    Article  CAS  Google Scholar 

  6. Ostensen M, Clowse M (2013) Pathogenesis of pregnancy complications in systemic lupus erythematosus. Curr Opin Rheumatol 25(5):591–596

    Article  CAS  Google Scholar 

  7. Bundhun PK, Soogund MZS, Huang F (2017) Impact of systemic lupus erythematosus on maternal and fetal outcomes following pregnancy: a meta-analysis of studies published between years 2001–2016 [Internet]. J Autoimmun 79:17–27. [cited 2019 Oct 12]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28256367

  8. Arkema EV, Palmsten K, Sjöwall C, Svenungsson E, Salmon JE, Simard JF (2016) What to expect when expecting with systemic lupus erythematosus (SLE): a population-based study of maternal and fetal outcomes in SLE and pre-SLE. Arthritis Care Res 68(7):988–994

    Article  Google Scholar 

  9. Canti V, Castiglioni MT, Rosa S, Franchini S, Sabbadini MG, Manfredi AA et al (2012) Pregnancy outcomes in patients with systemic autoimmunity. Autoimmunity 45(2):169–175

    Article  Google Scholar 

  10. Phansenee S, Sekararithi R, Jatavan P, Tongsong T (2018) Pregnancy outcomes among women with systemic lupus erythematosus: a retrospective cohort study from Thailand [Internet]. Lupus 27(1):158–64. [cited 2019 Oct 12]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28705036

  11. Zhan Z, Yang Y, Zhan Y, Chen D, Liang L, Yang X (2017) Fetal outcomes and associated factors of adverse outcomes of pregnancy in southern Chinese women with systemic lupus erythematosus. PLoS One 12(4)

  12. Kroese SJ, Abheiden CNH, Blomjous BS, van Laar JM, Derksen RWHM, Bultink IEM et al (2017) Maternal and perinatal outcome in women with systemic lupus erythematosus: a retrospective bicenter cohort study. J Immunol Res 28(2017):1–9

    Google Scholar 

  13. Rezk M, Ellakwa H, Al-Halaby A, Shaheen A, Zahran A, Badr H (2017) Predictors of poor obstetric outcome in women with systemic lupus erythematosus: a 10-year experience of a university hospital. J Matern Neonatal Med 30(17):2031–2035

    Article  Google Scholar 

  14. Feld J, Kibari A, Rozenbaum M, Riskin-Mashiah S, Eder L, Laor A et al (2015) The fetal outcomes of pregnancies of systemic lupus erythematosus patients in northern Israel. J Matern Neonatal Med 28(5):564–567

    Article  CAS  Google Scholar 

  15. Pastore DEA, Costa ML, Surita FG (2019) Systemic lupus erythematosus and pregnancy: the challenge of improving antenatal care and outcomes. Lupus 28(12):1417–1426

    Article  CAS  Google Scholar 

  16. Naseri EP, Surita FG, Borovac-Pinheiro A, Santos M, Appenzeller S, Costallat LTL (2018) Systemic lupus erythematosus and pregnancy: a single-center observational study of 69 pregnancies [Internet]. Rev Bras Ginecol e Obstet 40(10):587–92. [cited 2020 Feb 8]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30352455

  17. Aggarwal N, Raveendran A, Suri V, Chopra S, Sikka P, Sharma A (2011) Pregnancy outcome in systemic lupus erythematosus: Asia’s largest single centre study. Arch Gynecol Obstet 284(2):281–285

    Article  Google Scholar 

  18. Clowse MEB, Jamison M, Myers E, James AH (2008) A national study of the complications of lupus in pregnancy. Am J Obstet Gynecol 199(2):127.e1-127.e6

    Article  Google Scholar 

  19. Buyon JP, Kim MY, Guerra MM, Laskin CA, Petri M, Lockshin MD et al (2015) Predictors of pregnancy outcomes in patients with lupus [Internet]. Ann Intern Med 163(3):153.[cited 2017 Oct 15]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26098843

  20. Bundhun PK, Soogund MZS, Huang F (2017) Impact of systemic lupus erythematosus on maternal and fetal outcomes following pregnancy: a meta-analysis of studies published between years 2001–2016. J Autoimmun 79:17–27. Academic Press

  21. Khan A, Thomas M, P K SD (2018) Pregnancy complicated by systemic lupus erythematosus and its outcome over 10 years [Internet]. J Obstet Gynaecol 38(4):476–81. [cited 2019 Oct 6]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29433371

  22. Wu J, Ma J, Bao C, Di W, Zhang WH (2018) Pregnancy outcomes among Chinese women with and without systemic lupus erythematosus: a retrospective cohort study [Internet]. BMJ Open 8(4):e020909. [cited 2020 Feb 22]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29654043

  23. Eudy AM, Siega-Riz AM, Engel SM, Franceschini N, Howard AG, Clowse MEB et al (2018) Effect of pregnancy on disease flares in patients with systemic lupus erythematosus [Internet]. Ann Rheum Dis 77(6):855–60. [cited 2020 Feb 22]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29463519

  24. Sammaritano LR, Bermas BL, Chakravarty EE, Chambers C, Clowse MEB, Lockshin MD et al (2020) 2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Rheumatol 72(4):529–556

    Article  Google Scholar 

  25. Andreoli L, Bertsias GK, Agmon-Levin N, Brown S, Cervera R, Costedoat-Chalumeau N et al (2017) 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 76(3):476–485

    Article  CAS  Google Scholar 

  26. Knight CL, Nelson-Piercy C ( 2017) Management of systemic lupus erythematosus during pregnancy: Challenges and solutions. Vol. 9, Open Access Rheumatology: Research and Reviews

  27. Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey-Goldman R et al (2019) 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis 78(9):1151–1159

    Article  Google Scholar 

  28. Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey-Goldman R et al (2019) 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Arthritis Rheumatol 71(9):1400–1412

    Article  Google Scholar 

  29. Fanouriakis A, Kostopoulou M, Alunno A, Aringer M, Bajema I, Boletis JN et al (2019) 2019 Update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis 78(6):736–745

    Article  CAS  Google Scholar 

  30. Gladman DD, Ibañez D, Urowitz MB (2013) Systemic Lupus Erythematosus Disease Activity Index 2000 Responder Index-50 Website. J Rheumatol 40(5):733

    Article  Google Scholar 

  31. Buyon JP, Kalunian KC, Ramsey-Goldman R, Petri MA, Lockshin MD, Ruiz-Irastorza G et al (1999) Assessing disease activity in SLE patients during pregnancy. Lupus 8(8):677–684

    Article  CAS  Google Scholar 

  32. Direção-Geral da Saúde (2015) Programa Nacional para Vigilância da Gravidez de Baixo Risco [Internet]. Direção-Geral da Saúde 112. Available from: www.dgs.pt

  33. Sousa-Santos RF, Miguelote RF, Cruz-Correia RJ, Santos CC, Bernardes JFMAL (2016) Development of a birthweight standard and comparison with currently used standards. What is a 10th centile? Eur J Obstet Gynecol Reprod Biol [Internet] 206:184–93. https://doi.org/10.1016/j.ejogrb.2016.09.028

    Article  Google Scholar 

  34. ACOG (2020) Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222. Obstet Gynecol. 135(6):e237–60

  35. Catarina A, Endocrinologia M, Garcia H (2017) Consenso Diabetes Gestacional. Rev Port Diabetes 12(1):24–38

    Google Scholar 

  36. Shang M, Lin L (2014) IADPSG criteria for diagnosing gestational diabetes mellitus and predicting adverse pregnancy outcomes [Internet]. J Perinatol 34(2):100–4. Available from: https://doi.org/10.1038/jp.2013.143

  37. Barnado A, Wheless L, Meyer AK, Gilkeson GS, Kamen DL (2014) Pregnancy outcomes among African-American patients with systemic lupus erythematosus compared with controls. Lupus Sci Med 1(1):1–8

    Article  Google Scholar 

  38. McGrory CH, McCloskey LJ, DeHoratius RJ, Dunn SR, Moritz MJ, Armenti VT (2003) Pregnancy outcomes in female renal recipients: A comparison of systemic lupus erythematosus with other diagnoses. Am J Transplant 3(1):35–42

    Article  Google Scholar 

  39. Molokhia M, Maconochie N, Patrick AL, Doyle P (2007) Cross-sectional analysis of adverse outcomes in 1,029 pregnancies of Afro-Caribbean women in Trinidad with and without systemic lupus erythematosus. Arthritis Res Ther 9(6):5–9

    Article  Google Scholar 

  40. Yuen SY, Krizova A, Ouimet JM, Pope JE (2009) Pregnancy outcome in systemic lupus erythematosus (SLE) is improving: results from a case control study and literature review. Open Rheumatol J 2(1):89–98

    Article  Google Scholar 

  41. Hamijoyo L, Martha JW, Hidayat S, Akbar MR, Tantono H, Sakasasmita S et al (2019) Risk factors for poor pregnancy outcome in systemic lupus erythematosus patients. Acta Med Indones 51(2):102–109

    PubMed  Google Scholar 

  42. Naseri EP, Surita FG, Borovac-Pinheiro A, Santos M, Appenzeller S, Costallat LTL (2018) Systemic lupus erythematosus and pregnancy: a single-center observational study of 69 pregnancies. Rev Bras Ginecol e Obstet 40(10):587–592

    Article  Google Scholar 

  43. Sugawara E, Kato M, Fujieda Y, Oku K, Bohgaki T, Yasuda S et al (2019) Pregnancy outcomes in women with rheumatic diseases: a real-world observational study in Japan. Lupus 28(12):1407–1416

    Article  CAS  Google Scholar 

  44. Barnabe C, Faris PD, Quan H (2011) Canadian pregnancy outcomes in rheumatoid arthritis and systemic lupus erythematosus. Int J Rheumatol

  45. Jakobsen IM, Helmig RB, Stengaard-Pedersen K (2015) Maternal and foetal outcomes in pregnant systemic lupus erythematosus patients: an incident cohort from a stable referral population followed during 1990–2010. Scand J Rheumatol 44(5):377–384

    Article  CAS  Google Scholar 

  46. Wallenius M, Salvesen K, Daltveit AK, Skomsvoll JF (2014) Systemic lupus erythematosus and outcomes in first and subsequent births based on data from a national birth registry. Arthritis Care Res 66(11):1718–1724

    Article  Google Scholar 

  47. Ruiz-Irastorza G, Khamashta MA, Hughes GR (2000) Systemic lupus erythematosus and antiphospholipid syndrome during pregnancy: maternal and fetal complications and their management [Internet]. Isr Med Assoc J 2(6):462–9. [cited 2020 Mar 22]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10897239

  48. Danza Á, Ruiz-Irastorza G, Khamashta M (2016) El embarazo en las enfermedades autoinmunes sistémicas: mitos, certezas y dudas [Internet]. Medicina Clinica. Ediciones Doyma SL 147:306–12. [cited 2020 Feb 24]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27143525

  49. Rezk M, Ellakwa H, Al-Halaby A, Shaheen A, Zahran A, Badr H (2017) Predictors of poor obstetric outcome in women with systemic lupus erythematosus: a 10-year experience of a university hospital. [Internet]. J Matern Neonatal Med 30(17):2031–50. [cited 2020 Feb 24]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27628505

  50. Kwok LW, Tam LS, Zhu TY, Leung YY, Li EK (2011) Predictors of maternal and fetal outcomes in pregnancies of patients with systemic lupus erythematosus. Lupus 20(8):829–836

    Article  Google Scholar 

  51. Chen S, Sun X, Wu B, Lian X (2015) Pregnancy in women with systemic lupus erythematosus: a retrospective study of 83 pregnancies at a single centre. Int J Environ Res Public Health 12(8):9876–9888

    Article  CAS  Google Scholar 

  52. Nili F, McLeod L, O’Connell C, Sutton E, McMillan D (2013) Maternal and neonatal outcomes in pregnancies complicated by systemic lupus erythematosus: a population-based study. [Internet]. J Obstet Gynaecol Canada 35(4):323–8. Available from: https://doi.org/10.1016/S1701-2163(15)30959-2

  53. Duan J, Ma D, Wen X, Guo Q, Gao J, Zhang G et al (2021) Hydroxychloroquine prophylaxis for preeclampsia, hypertension and prematurity in pregnant patients with systemic lupus erythematosus: A meta-analysis [Internet]. Lupus 096120332110071. [cited 2021 May 12]. Available from: http://journals.sagepub.com/10.1177/09612033211007199

  54. Clowse MEB, Eudy AM, Kiernan E, Williams MR, Bermas B, Chakravarty E et al (2018) The prevention, screening and treatment of congenital heart block from neonatal lupus: A survey of provider practices [Internet]. Rheumatology (United Kingdom). Oxford University Press; [cited 2020 Feb 9]. 57:9–17. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30137589

  55. Barsalou J, Jaeggi E, Laskin CA, Brown P, Tian SY, Hamilton RM et al (2017) Prenatal exposure to antimalarials decreases the risk of cardiac but not non-cardiac neonatal lupus: a single-centre cohort study. Rheumatol (United Kingdom) 56(9):1552–1559

    CAS  Google Scholar 

  56. Imbasciati E, Tincani A, Gregorini G, Doria A, Moroni G, Cabiddu G et al (2009) Pregnancy in women with pre-existing lupus nephritis: Predictors of fetal and maternal outcome. Nephrol Dial Transplant 24(2):519–525

    Article  Google Scholar 

  57. Khan A, Thomas M, Syamala Devi PK (2018) Pregnancy complicated by systemic lupus erythematosus and its outcome over 10 years. J Obstet Gynaecol (Lahore) 38(4):476–481

    Article  Google Scholar 

  58. Ruiz-Irastorza G, Khamashta MA (2011) Lupus and pregnancy: integrating clues from the bench and bedside. Eur J Clin Invest 41(6):672–678

    Article  Google Scholar 

  59. Ruiz-Irastorza G, Lima F, Alves J, Khamashta MA, Simpson J, Hughes GRV et al (1996) Increased rate of lupus flare during pregnancy and the puerperium: a prospective study of 78 pregnancies. Br J Rheumatol 35(2):133–138

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  61. Teh CL, Wan SA, Cheong YK, Ling GR (2017) Systemic lupus erythematosus pregnancies: ten-year data from a single centre in Malaysia. Lupus 26(2):218–223

    Article  CAS  Google Scholar 

  62. Ku M, Guo S, Shang W, Li Q, Zeng R, Han M et al (2016) Pregnancy outcomes in Chinese patients with systemic lupus erythematosus (SLE): a retrospective study of 109 pregnancies [Internet]. PLoS One 11(7):e0159364. [cited 2020 Feb 24]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27442513

  63. Abdwani R, Al Shaqsi L, Al-Zakwani I (2018) Neonatal and obstetrical outcomes of pregnancies in systemic lupus erythematosus. Oman Med J 33(1)

  64. Chen D, Lao M, Zhang J, Zhan Y, Li W, Cai X et al (2018) Fetal and maternal outcomes of planned pregnancy in patients with systemic lupus erythematosus: a retrospective multicenter study [Internet]. J Immunol Res 2413637. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30255104

  65. Andreoli L, Bertsias GK, Agmon-Levin N, Brown S, Cervera R, Costedoat-Chalumeau N et al (2017) 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. 76(3)

  66. Clowse MEB, Magder L, Witter F, Petri M (2006) Hydroxychloroquine in lupus pregnancy. Arthritis Rheum 54(11):3640–3647

    Article  Google Scholar 

  67. Clowse MEB (2007) Lupus activity in pregnancy. Rheum Dis Clin North Am 33(2):237–252

    Article  Google Scholar 

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Authors and Affiliations

  1. Maternal Fetal Unit, Centro Materno Infantil Do Norte, Centro Hospitalar Universitário Do Porto, Oporto, Portugal

    António Braga, Tânia Barros & Jorge Braga

  2. Instituto Ciências Biomédicas Abel Salazar, Universidade do Porto, Oporto, Portugal

    António Braga, Raquel Faria, António Marinho, Guilherme Rocha, Fátima Farinha, Esmeralda Neves, Carlos Vasconcelos & Jorge Braga

  3. Clinical Immunology Unit, Centro Hospitalar Universitário Do Porto, Oporto, Portugal

    Raquel Faria, António Marinho, Guilherme Rocha, Fátima Farinha, Esmeralda Neves, Carlos Vasconcelos & Jorge Braga

  4. Nephrology Department, Centro Hospitalar Universitário Do Porto, Oporto, Portugal

    Guilherme Rocha

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Contributions

AB, CV, and JB conceived and designed the study. AB and TB collected the patient data. AB, RF, CV, and JB contributed to the analysis and interpretation of data. All authors drafted the manuscript, revised it critically, and approved the final version for submission.

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Correspondence to António Braga.

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Braga, A., Barros, T., Faria, R. et al. Systemic Lupus Erythematosus and Pregnancy: a Portuguese Case–Control Study. Clinic Rev Allerg Immunol 62, 324–332 (2022). https://doi.org/10.1007/s12016-021-08893-y

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