Skip to main content

Erkenntnisse zu Schwangerschaft und Stillzeit bei entzündlich rheumatischen Erkrankungen durch Beobachtungsdaten

Insights into pregnancy and breastfeeding in inflammatory rheumatic diseases through observational data

Zusammenfassung

Informationen zu Schwangerschaft und Stillzeit bei Frauen mit chronischen entzündlich rheumatischen Erkrankungen sind sowohl für eine erfolgreiche Schwangerschaft als auch für die mütterliche und kindliche Gesundheit relevant. Da Schwangere und Stillende von randomisierten klinischen Studien meist ausgeschlossen sind, muss die Evidenz für die klinische Betreuung und Beratung aus Beobachtungsstudien generiert werden. In den vergangenen Jahrzehnten wurden hierfür neben den bestehenden Spontanmeldesystemen der Arzneimittelbehörden verschiedene Datensammlungen aufgebaut, mit dem Ziel das teratogene Risiko eines Arzneimittels zu überwachen. Zunehmend werden für die Erforschung schwangerschaftsassoziierter Ereignisse auch Versichertendaten, elektronische Krankenakten und skandinavische Register eingesetzt. Allen diesen Datenquellen fehlt aber die Einbeziehung der mütterlichen Erkrankung, besonders hinsichtlich ihrer inflammatorischen Komponente. Etablierte Kohortenstudien, Biologika- und Krankheitsregister erheben zwar die Krankheitsaktivität, sind aber nicht für schwangerschaftsspezifische Fragestellungen konzipiert. Schwangerschaftsregister und -studien in der Rheumatologie schließen diese Lücke. Um die Möglichkeiten und Limitationen vorhandener Datenquellen zu Schwangerschaft und Stillzeit besser einschätzen zu können, werden sie in der folgenden Übersichtsarbeit mit ihren jeweiligen Vor- und Nachteilen als auch Beispielen aus der Rheumatologie ausführlich vorgestellt. Zudem werden bestehende Kooperationen sowie Studien zur Untersuchung des Einflusses einer väterlichen rheumatischen Erkrankung beleuchtet.

Abstract

Information on pregnancy and breastfeeding in women with chronic inflammatory rheumatic diseases is relevant for a successful pregnancy and also for maternal and child health. In general, pregnant and breastfeeding women are excluded from randomized clinical trials and therefore evidence for clinical care and counselling has to be generated from observational studies. In the past decades, various data collections have been established for this purpose in addition to the existing spontaneous reporting systems initiated by drug authorities, with the aim of monitoring the teratogenic risk of a drug. Health insurance claims data, electronic health records and Scandinavian registers are also increasingly being used for research on pregnancy-associated events; however, all these data sources lack the inclusion of the maternal disease, especially with respect to its inflammatory component. Established cohort studies, biologics and disease registries record disease activity but are not designed for pregnancy-specific questions. Pregnancy registries and studies in rheumatology close this gap. In order to be able to make a better assessment of the possibilities and limitations of existing data sources on pregnancy and lactation, they are presented in detail in the following review including their respective advantages and disadvantages and examples from rheumatology are given. In addition, existing collaborations as well as studies for investigating the influence of paternal rheumatic disease are highlighted.

This is a preview of subscription content, access via your institution.

Abb. 1
Abb. 2

Literatur

  1. 1.

    RKI (2012) Daten und Fakten: Ergebnisse der Studie „Gesundheit in Deutschland aktuell 2010“. In: GBE-Hefte, S 1–188

    Google Scholar 

  2. 2.

    Kersten I, Lange AE, Haas JP et al (2014) Chronic diseases in pregnant women: prevalence and birth outcomes based on the SNiP-study. BMC Pregnancy Childbirth 14:75

    Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Lange U, Schnepp W, Zu Sayn-Wittgenstein F (2015) The experiences of chronically ill women in the time of pregnancy, birth and postnatal period—a review of qualitative studies. Z Geburtshilfe Neonatol 219(4):161–169

    CAS  Article  Google Scholar 

  4. 4.

    HMA (2019) Guideline on good pharmacovigilance practices (GVP). EMA/653036/2019:1–27. Draft for Public Consultation

  5. 5.

    Levy RA, Vilela VS, Cataldo MJ et al (2001) Hydroxychloroquine (HCQ) in lupus pregnancy: double-blind and placebo-controlled study. Lupus 10(6):401–404

    CAS  Article  Google Scholar 

  6. 6.

    Hamulyak EN, Scheres LJJ, Goddijn M et al (2021) Antithrombotic therapy to prevent recurrent pregnancy loss in antiphospholipid syndrome-what is the evidence? J Thromb Haemost 19(5):1174–1185

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Weber-Schoendorfer C (2019) Sicherheit von Antirheumatika in der Schwangerschaft: Empfehlungen von Embryotox. Arthritis Rheuma 39(04):226–233

    Article  Google Scholar 

  8. 8.

    Langhoff-Roos J, Krebs L, Klungsoyr K et al (2014) The Nordic medical birth registers—a potential goldmine for clinical research. Acta Obstet Gynecol Scand 93(2):132–137

    Article  Google Scholar 

  9. 9.

    Wallenius M, Skomsvoll JF, Irgens LM et al (2012) Parity in patients with chronic inflammatory arthritides childless at time of diagnosis. Scand J Rheumatol 41(3):202–207

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Harris N, Eudy A, Clowse M (2019) Patient-reported disease activity and adverse pregnancy outcomes in systemic lupus erythematosus and rheumatoid arthritis. Arthritis Care Res 71(3):390–397

    Article  Google Scholar 

  11. 11.

    Zbinden A, van den Brandt S, Ostensen M et al (2018) Risk for adverse pregnancy outcome in axial spondyloarthritis and rheumatoid arthritis: disease activity matters. Rheumatology 57(7):1235–1242

    Article  Google Scholar 

  12. 12.

    Murray K, Moore L, McAuliffe F et al (2019) Reproductive health outcomes in women with psoriatic arthritis. Ann Rheum Dis 78(6):850–852

    Article  Google Scholar 

  13. 13.

    de Man YA, Hazes JM, van de Geijn FE et al (2007) Measuring disease activity and functionality during pregnancy in patients with rheumatoid arthritis. Arthritis Rheum 57(5):716–722

    Article  Google Scholar 

  14. 14.

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

    Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Meissner Y, Strangfeld A, Costedoat-Chalumeau N et al (2019) European Network of Pregnancy Registers in Rheumatology (EuNeP)-an overview of procedures and data collection. Arthritis Res Ther 21(1):241

    Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Chambers CD, Johnson DL, Xu R et al (2019) Birth outcomes in women who have taken adalimumab in pregnancy: a prospective cohort study. PLoS ONE 14(10):e223603

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Cassina M, Johnson DL, Robinson LK et al (2012) Pregnancy outcome in women exposed to leflunomide before or during pregnancy. Arthritis Rheum 64(7):2085–2094

    CAS  Article  Google Scholar 

  18. 18.

    Smith CJF, Bandoli G, Kavanaugh A et al (2020) Birth outcomes and disease activity during pregnancy in a prospective cohort of women with psoriatic arthritis and ankylosing spondylitis. Arthritis Care Res 72(7):1029–1037

    CAS  Article  Google Scholar 

  19. 19.

    Forger F, Bandoli G, Luo Y et al (2019) No association of discontinuing tumor necrosis factor inhibitors before gestational week twenty in well-controlled rheumatoid arthritis and juvenile idiopathic arthritis with a disease worsening in late pregnancy. Arthritis Rheumatol 71(6):901–907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Clowse ME, Wolf DC, Forger F et al (2015) Pregnancy outcomes in subjects exposed to certolizumab pegol. J Rheumatol 42(12):2270–2278

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Warren RB, Reich K, Langley RG et al (2018) Secukinumab in pregnancy: outcomes in psoriasis, psoriatic arthritis and ankylosing spondylitis from the global safety database. Br J Dermatol 179(5):1205–1207

    CAS  Article  Google Scholar 

  22. 22.

    Weber-Schoendorfer C, Oppermann M, Wacker E et al (2015) Pregnancy outcome after TNF-alpha inhibitor therapy during the first trimester: a prospective multicentre cohort study. Br J Clin Pharmacol 80(4):727–739

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Weber-Schoendorfer C, Chambers C, Wacker E et al (2014) Pregnancy outcome after methotrexate treatment for rheumatic disease prior to or during early pregnancy: a prospective multicenter cohort study. Arthritis Rheumatol 66(5):1101–1110

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Clowse ME, Feldman SR, Isaacs JD et al (2016) Pregnancy outcomes in the tofacitinib safety databases for rheumatoid arthritis and psoriasis. Drug Saf 39(8):755–762

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Hoeltzenbein M, Beck E, Rajwanshi R et al (2016) Tocilizumab use in pregnancy: analysis of a global safety database including data from clinical trials and post-marketing data. Semin Arthritis Rheum 46(2):238–245

    CAS  Article  Google Scholar 

  26. 26.

    Petri M, Daly RP, Pushparajah DS (2015) Healthcare costs of pregnancy in systemic lupus erythematosus: retrospective observational analysis from a US health claims database. J Med Econ 18(11):967–973

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Joo YB, Kim KJ, Park KS et al (2020) Pregnancy rates and perinatal outcomes in women with systemic lupus erythematosus: data from the Korean national health claims database. Clin Rheumatol 40(6):2243–2250

    Article  PubMed  Google Scholar 

  28. 28.

    Kishore S, Mittal V, Majithia V (2019) Obstetric outcomes in women with rheumatoid arthritis: results from Nationwide Inpatient Sample Database 2003–2011(). Semin Arthritis Rheum 49(2):236–240

    Article  PubMed  Google Scholar 

  29. 29.

    Wallenius M, Salvesen KA, Daltveit AK et al (2014) Rheumatoid arthritis and outcomes in first and subsequent births based on data from a national birth registry. Acta Obstet Gynecol Scand 93(3):302–307

    Article  PubMed  Google Scholar 

  30. 30.

    Mork S, Voss A, Moller S et al (2021) Spondyloarthritis and outcomes in pregnancy and labor: a nationwide register-based cohort study. Arthritis Care Res 73(2):282–288

    Article  Google Scholar 

  31. 31.

    Drechsel P, Studemann K, Niewerth M et al (2020) Pregnancy outcomes in DMARD-exposed patients with juvenile idiopathic arthritis-results from a JIA biologic registry. Rheumatology 59(3):603–612

    Google Scholar 

  32. 32.

    Pons M, Dougados M, Costedoat-Chalumeau N et al (2021) Pregnancy rates and outcomes in early axial spondyloarthritis: an analysis of the DESIR cohort. Joint Bone Spine 88(2):105075

    Article  Google Scholar 

  33. 33.

    Ursin K, Lydersen S, Skomsvoll JF et al (2020) Factors associated with time to pregnancy in women with axial spondyloarthritis: A registry-based multicenter study. Arthritis Care Res (Hoboken) 73(8):1201–1209

    Article  Google Scholar 

  34. 34.

    Gotestam Skorpen C, Hoeltzenbein M, Tincani A et al (2016) The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis 75(5):795–810

    Article  CAS  Google Scholar 

  35. 35.

    Meissner Y, Fischer-Betz R, Andreoli L et al (2021) EULAR recommendations for a core data set for pregnancy registries in rheumatology. Ann Rheum Dis 80(1):49–56

    Article  Google Scholar 

  36. 36.

    Broms G, Haerskjold A, Granath F et al (2018) Effect of maternal psoriasis on pregnancy and birth outcomes: a population-based cohort study from Denmark and Sweden. Acta Derm Venereol 98(8):728–734

    Article  Google Scholar 

  37. 37.

    Broms G, Kieler H, Ekbom A et al (2020) Anti-TNF treatment during pregnancy and birth outcomes: a population-based study from Denmark, Finland, and Sweden. Pharmacoepidemiol Drug Saf 29(3):316–327

    Article  CAS  Google Scholar 

  38. 38.

    Tucker FD, Morris JK, Committee JRCM et al (2018) EUROCAT: an update on its functions and activities. J Community Genet 9(4):407–410

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Plauborg AV, Hansen AV, Garne E (2016) Use of azathioprine and corticosteroids during pregnancy and birth outcome in women diagnosed with inflammatory bowel disease. Birth Defects Res Part A Clin Mol Teratol 106(6):494–499

    CAS  Article  Google Scholar 

  40. 40.

    Palmsten K, Bandoli G, Watkins J et al (2021) Oral corticosteroids and risk of preterm birth in the california medicaid program. J Allergy Clin Immunol Pract 9(1):375–384e5

    Article  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Strouse J, Donovan BM, Fatima M et al (2019) Impact of autoimmune rheumatic diseases on birth outcomes: a population-based study. RMD Open 5(1):e878

    Article  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Berard A, Sheehy O, Girard S et al (2018) Risk of preterm birth following late pregnancy exposure to NSAIDs or COX‑2 inhibitors. Pain 159(5):948–955

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Sammaritano LR, Bermas BL, Chakravarty EE 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  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Flint J, Panchal S, Hurrell A et al (2016) BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatology 55(9):1693–1697

    CAS  Article  Google Scholar 

  45. 45.

    Flint J, Panchal S, Hurrell A et al (2016) BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part II: analgesics and other drugs used in rheumatology practice. Rheumatology 55(9):1698–1702

    Article  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Perez-Garcia LF, Te Winkel B, Carrizales JP et al (2020) Sexual function and reproduction can be impaired in men with rheumatic diseases: A systematic review. Semin Arthritis Rheum 50(3):557–573

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Weber-Schoendorfer C, Hoeltzenbein M, Wacker E et al (2014) No evidence for an increased risk of adverse pregnancy outcome after paternal low-dose methotrexate: an observational cohort study. Rheumatology 53(4):757–763

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Wallenius M, Lie E, Daltveit AK et al (2015) No excess risks in offspring with paternal preconception exposure to disease-modifying antirheumatic drugs. Arthritis Rheumatol 67(1):296–301

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Viktil KK, Engeland A, Furu K (2012) Outcomes after anti-rheumatic drug use before and during pregnancy: a cohort study among 150,000 pregnant women and expectant fathers. Scand J Rheumatol 41(3):196–201

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Espinosa G, Galindo-Izquierdo M, Marcos Puig B et al (2021) Pregnancy control in patients with systemic lupus erythematosus and antiphospholipid syndrome. Part 1: infertility, ovarian preservation and preconception assessment. Consensus document of the Spanish society of Gynaecology and obstetrics (SEGO), the Spanish society of internal medicine (SEMI) and the Spanish society of rheumatology (SER). Reumatol Clin 17(2):61–66

    Article  PubMed  Google Scholar 

  51. 51.

    Rodriguez Almaraz E, Saez-Comet L, Casellas M et al (2021) Pregnancy control in patients with systemic lupus erythematosus/antiphospholipid syndrome. Part 2: Pregnancy follow-up. Reumatol Clin 17(3):125–131

    Article  PubMed  Google Scholar 

  52. 52.

    Delgado P, Robles A, Martinez Lopez JA et al (2021) Pregnancy control in patients with systemic lupus erythematosus/Antiphospholipid syndrome. Part 3: childbirth. Puerperium. Breastfeeding contraception. Newborn. Reumatol Clin 17(4):183–186

    Article  PubMed  Google Scholar 

  53. 53.

    Tektonidou MG, Andreoli L, Limper M et al (2019) EULAR recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis 78(10):1296–1304

    CAS  Article  PubMed  Google Scholar 

  54. 54.

    Andreoli L, Bertsias GK, Agmon-Levin 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

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    Jethwa H, Lam S, Smith C et al (2019) Does rheumatoid arthritis really improve during pregnancy? A systematic review and metaanalysis. J Rheumatol 46(3):245–250

    Article  PubMed  Google Scholar 

  56. 56.

    Blagojevic J, AlOdhaibi KA, Aly AM et al (2020) Pregnancy in systemic sclerosis: results of a systematic review and metaanalysis. J Rheumatol 47(6):881–887

    Article  PubMed  Google Scholar 

  57. 57.

    Maguire S, O’Dwyer T, Mockler D et al (2020) Pregnancy in axial spondyloarthropathy: a systematic review & meta-analysis. Semin Arthritis Rheum 50(6):1269–1279

    Article  Google Scholar 

  58. 58.

    Andreoli L, Gerardi MC, Fernandes M et al (2019) Disease activity assessment of rheumatic diseases during pregnancy: a comprehensive review of indices used in clinical studies. Autoimmun Rev 18(2):164–176

    Article  Google Scholar 

Download references

Danksagung

Unser herzlicher Dank gilt Angela Zink für das kritische Lesen des Manuskripts.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Yvette Meißner.

Ethics declarations

Interessenkonflikt

Y. Meißner: Vortragshonorar von Pfizer. A. Strangfeld: Honorare für Vorträge oder Beratungen von AbbVie, Bristol-Myers Squibb, Celltrion, MSD, Pfizer und Roche.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

Additional information

figureqr

QR-Code scannen & Beitrag online lesen

Redaktion

Rebecca Fischer-Betz, Düsseldorf

Frauke Förger, Bern

Anja Strangfeld, Berlin

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Meißner, Y., Strangfeld, A. Erkenntnisse zu Schwangerschaft und Stillzeit bei entzündlich rheumatischen Erkrankungen durch Beobachtungsdaten. Z Rheumatol 80, 733–742 (2021). https://doi.org/10.1007/s00393-021-01082-4

Download citation

Schlüsselwörter

  • Arzneimitteltherapiesicherheit
  • Teratogenität
  • Pharmakovigilanz
  • Kohortenstudien
  • Register

Keywords

  • Drug treatment safety
  • Teratogenicity
  • Pharmacovigilance
  • Cohort studies
  • Register