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Low aspirin use and high prevalence of pre-eclampsia risk factors among pregnant women in a multinational SLE inception cohort
  1. Arielle Mendel1,
  2. Sasha B Bernatsky1,2,
  3. John G Hanly3,
  4. Murray B Urowitz4,
  5. Ann Elaine Clarke5,
  6. Juanita Romero-Diaz6,
  7. Caroline Gordon7,8,
  8. Sang-Cheol Bae9,
  9. Daniel J Wallace10,
  10. Joan T Merrill11,
  11. Jill P Buyon12,
  12. David A Isenberg13,
  13. Anisur Rahman13,
  14. Ellen M Ginzler14,
  15. Michelle Petri15,
  16. Mary Anne Dooley16,
  17. Paul R Fortin17,
  18. Dafna D Gladman4,
  19. Kristján Steinsson18,
  20. Rosalind Ramsey-Goldman19,
  21. Munther A Khamashta20,
  22. Cynthia Aranow21,
  23. Meggan Mackay21,
  24. Graciela S Alarcón22,
  25. Susan Manzi23,
  26. Ola Nived24,
  27. Andreas Jönsen24,
  28. Asad A Zoma25,
  29. Ronald F van Vollenhoven26,
  30. Manuel Ramos-Casals27,
  31. Guillermo Ruiz-Irastorza28,
  32. Sam Lim29,
  33. Ken C Kalunian30,
  34. Murat Inanc31,
  35. Diane L Kamen32,
  36. Christine A Peschken33,
  37. Søren Jacobsen34,
  38. Anca Askanase35,
  39. Jorge Sanchez-Guerrero36,
  40. Ian N Bruce37,38,
  41. Nathalie Costedoat-Chalumeau39,
  42. Évelyne Vinet1,2
  1. 1 Division of Rheumatology, McGill University Health Centre, Montreal, Quebec, Canada
  2. 2 Division of Clinical Epidemiology, Research Institute of the McGill University Health Center, Montreal, Quebec, Canada
  3. 3 Division of Rheumatology, Department of Medicine and Department of Pathology, Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia, Canada
  4. 4 Lupus Program, Centre for Prognosis Studies in the Rheumatic Disease and Krembil Research Institute, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada
  5. 5 Division of Rheumatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
  6. 6 Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición, Tlalpan, Mexico
  7. 7 Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
  8. 8 Rheumatology Department, City Hospital, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK
  9. 9 Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea
  10. 10 Cedars-Sinai Medical Centre, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
  11. 11 Department of Clinical Pharmacology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
  12. 12 Division of Rheumatology, Department of Medicine, New York School of Medicine, New York City, New York, USA
  13. 13 Department of Medicine, Centre for Rheumatology, University College London, London, UK
  14. 14 Department of Medicine, SUNY Downstate Medical Center, Brooklyn, New York, USA
  15. 15 Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  16. 16 Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, North Carolina, USA
  17. 17 Division of Rheumatology, Centre Hospitalier Universitaire de Québec et Université Laval, Québec City, Quebec, Canada
  18. 18 Center for Rheumatology Research, Landspitali University Hospital, Reykjavik, Iceland
  19. 19 Division of Rheumatology, Feinberg School of Medicine, Northwestern University Chicago, Chicago, Illinois, USA
  20. 20 Lupus Research Unit, The Rayne Institute, St Thomas' Hospital, King's College London School of Medicine, London, UK
  21. 21 Lupus Center of Excellence, Feinstein Institute for Medical Research, Manhasset, New York, USA
  22. 22 Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
  23. 23 Lupus Center of Excellence, Allegheny Health Network, Pittsburgh, Pennsylvania, USA
  24. 24 Department of Clinical Sciences and Rheumatology, Lund University, Lund, Sweden
  25. 25 Lanarkshire Centre for Rheumatology, Hairmyres Hospital, East Kilbride, UK
  26. 26 Unit for Clinical Therapy Research (CliTRID), Karolinska Institute, Stockholm, Sweden
  27. 27 Josep Font Autoimmune Diseases Laboratory, IDIBAPS, Department of Autoimmune Diseases, Hospital Clínic, Barcelona, Spain
  28. 28 Autoimmune Diseases Research Unit, Department of Internal Medicine, BioCruces Health Research Institute, Hospital Universitario Cruces, University of the Basque Country, Barakaldo, Spain
  29. 29 Division of Rheumatology, Emory University School of Medicine, Atlanta, Georgia, USA
  30. 30 University of California San Diego School of Medicine, La Jolla, California, USA
  31. 31 Division of Rheumatology, Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
  32. 32 Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
  33. 33 Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
  34. 34 Copenhagen Lupus and Vasculitis Clinic, Section 4242, Center for Rheumatology and Spine Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  35. 35 Hospital for Joint Diseases, Seligman Centre for Advanced Therapeutics, New York University, New York City, New York, USA
  36. 36 Department of Rheumatology, Mount Sinai Hospital and University Health Network, University of Toronto, Toronto, Ontario, Canada
  37. 37 NIHR Manchester Biomedical Research Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
  38. 38 Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, School of Biological Sciences, The University of Manchester, Manchester, UK
  39. 39 Centre de Reference Maladies Auto-immunes et Systemiques Rares, Service de Medecine Interne, Hospital Cochin, Paris, France
  1. Correspondence to Dr Évelyne Vinet, Research Institute of the McGill University Health Centre, Montréal, QC H4A 3S5, Canada; evelyne.vinet{at}mcgill.ca

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Women with systemic lupus erythematosus (SLE) carry a substantially higher risk for pre-eclampsia compared with the general population.1 Aspirin reduces the risk of pre-eclampsia in high-risk pregnancies by more than half2 and thus is recommended in SLE.3–5 The European League Against Rheumatism recommends aspirin in SLE pregnancies, particularly in those with nephritis or positive antiphospholipid antibodies (aPL).5 Despite this, little is known about current practice. Therefore, we assessed the prevalence of aspirin use in SLE pregnancies within the Systemic Lupus International Collaborating Clinics inception cohort, which has been described elsewhere.6

SLE women aged 18–45 with a pregnancy documented at one or more annual study visits (spanning 2000–2017) were included. For each pregnant visit, aspirin use, traditional pre-eclampsia risk factors (hypertension, chronic kidney disease, diabetes, nulliparity, body mass index ≥35, age >40), aPL and active lupus nephritis were assessed (see variable definitions in online supplementary material). Aspirin use was compared among those with and without each/any risk factor, and over time.

We identified 475 pregnancies among 300 women. Mean SLE duration at the time of pregnancy was 5.6 years (SD 3.1). Half (51%) of pregnancies had ≥1 traditional pre-eclampsia risk factor, 34/104 (33%) had positive aPL and 53/475 (11%) had nephritis (table 1). Aspirin was used in 121 (25%) pregnancies. While a third of pregnancies in Caucasians (71/209, 34%, 95% CI 28% to 41%) and Hispanics (20/62, 32%, 95% CI 22% to 45%) were aspirin exposed, only 9/88 (10%, 95% CI 5% to 18%) and 7/66 (11%, 95% CI 5% to 20%) of pregnancies in Black and Asian subjects were respectively aspirin exposed. Aspirin use did not differ among pregnancies with or without ≥1 traditional risk factor (58/234, 25% (95% CI 20% to 31%) vs 63/241, 26% (95% CI 21% to 32%)), any traditional risk factor individually, or nephritis (see online supplementary table 1). There was a potential trend for increased aspirin use among pregnancies with positive aPL (13/34, 38%, 95% CI 24% to 55%) compared with those without aPL (16/70, 23%, 95% CI 15% to 34%), although CI overlapped. Sensitivity analyses excluding multiple pregnancies within the same women yielded similar results. Aspirin use did not increase from 2000 to 2017 (χ2 test for trend in proportions, p=0.13).

Table 1

Characteristics of SLE pregnancies overall and according to aspirin use

Our study is the first to assess aspirin use in SLE pregnancies according to the presence of pre-eclampsia risk factors. Among the 475 SLE pregnancies in this prospective, multinational inception cohort, additional pre-eclampsia risk factors were present in half, while aspirin was taken in only one-quarter and did not differ from background aspirin use among the same women at non-pregnant visits (see online supplementary material). Even without considering SLE itself as a major risk factor, aspirin use was no more prevalent among those with other traditional indications for aspirin in pregnancy, and the majority of those with aPL and nephritis were not taking aspirin. The low aspirin use among Black SLE subjects is noteworthy given the worse reproductive outcomes observed in this population.7

Study limitations include lack of data on gestational age and pregnancy outcomes. In addition, aspirin could have been introduced at/or following the study visit when the pregnancy was documented, highlighting the importance of the rheumatologist in reviewing aspirin use and initiating it, if not already done, in pregnant SLE women. However, assuming either a somewhat normal or a left-skewed distribution of gestational ages at the pregnant visits, a substantial proportion of visits would have taken place after 12–16 weeks’ gestation, by which time aspirin should have been initiated.2 3

In conclusion, we have potentially identified an important gap between practices and current recommendations for the care of pregnant SLE women, and call for further studies of factors contributing to aspirin use in lupus pregnancies.

References

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Footnotes

  • Handling editor Josef S Smolen

  • Contributors EV had full access to all the data in this study and takes full responsibility as a guarantor for the integrity of the data and the accuracy of the data analysis. EV, AM, SBB, JGH, MBU, AEC, JRD, CG, SCB, DJW, JTM, JPB, DAI, AR, EMG, MP, MAD, PRF, DDG, KS, RRG, MAK, CA, MM, GSA, SM, ON, AJ, AAZ, RFV, MRC, GRI, SL, KCK, MI, DLK, CAP, SJ, AA, JSG, INB and NCC conceived and designed the study. EV, AM, SBB, JGH, MBU, AEC, JRD, CG, SCB, DJW, JTM, JPB, DAI, AR, EMG, MP, MAD, PRF, DDG, KS, RRG, MAK, CA, MM, GSA, SM, ON, AJ, AAZ, RFV, MRC, GRI, SL, KCK, MI, DLK, CAP, SJ, AA, JSG, INB and NCC analysed the data. EV, AM, SBB, JGH, MBU, AEC, JRD, CG, SCB, DJW, JTM, JPB, DAI, AR, EMG, MP, MAD, PRF, DDG, KS, RRG, MAK, CA, MM, GSA, SM, ON, AJ, AAZ, RFV, MRC, GRI, SL, KCK, MI, DLK, CAP, SJ, AA, JSG, INB and NCC interpreted the data and drafted the manuscript.

  • Funding This study was funded through a McGill University Health Centre Research Award. EV receives a salary support from a Fonds de Recherche Québec Santé Clinical Research Scholar-Junior 1 Award. SCB is supported by the Bio & Medical Technology Development Program of the National Research Foundation funded by the Ministry of Science and ICT (NRF-2017M3A9B4050335). SJ is supported by The Danish Rheumatism Association (A-3865). AEC is supported by an Arthritis Society Chair in Rheumatic Diseases. The Hopkins Lupus Cohort is supported by a National Institutes of Health grant (R01 AR069572) awarded to MP. The Birmingham SLICC cohort was funded by a Lupus UK grant awarded to CG.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval McGill University Health Centre.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional data available.

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