Skip to main content

Advertisement

SpringerLink
Log in

Pregnancy outcomes in partners of male ankylosing spondylitis patients treated with anti-tumour necrosis factor-α biologics: real-life results from a single-centre cross-sectional study

  • Observational Research
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

Most patients with inflammatory arthritis are at their reproductive ages. Use of anti-tumour necrosis factor alpha (anti-TNF-α) agents, one of the important treatment options for inflammatory arthritis, can cause foetal morbidity and mortality. While most studies on the effects of anti-TNF-α agents on pregnancy outcomes are about maternal exposure, the number of studies on the risks related to paternal exposure is insufficient. This study aimed to assess pregnancy periods and outcomes of the partners of male ankylosing spondylitis (AS) patients receiving anti-TNF-α treatment during the preconception period. Totally, 163 male AS patients using anti-TNF-α agents were identified from the Hacettepe University Biological Registry. Of these patients, 45 (27.6%) who declared that their partners got pregnant after initiation on anti-TNF-α agents were included. Data regarding demographics and drug exposure and pregnancy and infant outcomes were evaluated. Of 45 pregnancies, 39 (86.7%) resulted in healthy live births, 3 (6.7%) resulted in spontaneous abortion, and 3 (6.7%) were terminated with curettage. Of 39 live births, 34 (87.2%) were term and 5 (12.8%) were preterm, 30 (76.9%) had normal birth weight, 6 (15.4%) had low birth weight, and 3 (7.7%) had fetal macrosomia. No congenital malformations related to paternal exposure were observed. This study is valuable as being one of the studies providing pregnancy outcomes of partners of male AS patients receiving anti-TNF-α agents with its relatively high number of patients. The results suggested that paternal exposure to anti-TNF-α agents during preconception period could be safe on 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

Fig. 1

Similar content being viewed by others

References

  1. Meadows M (2001) Pregnancy and the drug dilemma. FDA Consum Mag 35(3):16–20. https://doi.org/10.1037/e542682006-004

    Article  CAS  Google Scholar 

  2. Carter JD, Ladhani A, Ricca LR, Valeriano J, Vasey FB (2009) A safety assessment of tumor necrosis factor antagonists during pregnancy: a review of the Food and Drug Administration database. J Rheumatol 36(3):635–641

    Article  Google Scholar 

  3. Komaki F, Komaki Y, Micic D, Ido A, Sakuraba A (2017) Outcome of pregnancy and neonatal complications with anti-tumor necrosis factor-α use in females with immune mediated diseases; a systematic review and meta-analysis. J Autoimmun 76:38–52. https://doi.org/10.1016/j.jaut.2016.11.004

    Article  PubMed  Google Scholar 

  4. Mao EJ, Mahadevan U (2018) The debate is over: continue anti-tumor necrosis factor therapy throughout pregnancy. Am J Gastroenterol. https://doi.org/10.1038/s41395-018-0254-x

    Article  PubMed  Google Scholar 

  5. Micu MC, Micu R, Surd S, Gîrlovanu M, Bolboacă SD, Ostensen M (2014) TNF-α inhibitors do not impair sperm quality in males with ankylosing spondylitis after short-term or long-term treatment. Rheumatology 53(7):1250–1255. https://doi.org/10.1093/rheumatology/keu007

    Article  CAS  PubMed  Google Scholar 

  6. Wallenius M, Lie E, Daltveit AK, Salvesen KÅ, Skomsvoll JF, Kalstad S et al (2015) Brief report: no excess risks in offspring with paternal preconception exposure to disease-modifying antirheumatic drugs. Arthritis Rheumatol 67(1):296–301. https://doi.org/10.1002/art.38919

    Article  CAS  PubMed  Google Scholar 

  7. Micu MC, Ostensen M, Bojincă V, Șerban O, Mihai M, Suța C et al (2019) Pregnancy outcome in couples with males exposed to long term anti-TNF alpha blocker therapies: a prospective study. J Rheumatol. https://doi.org/10.3899/jrheum.180588

    Article  PubMed  Google Scholar 

  8. Puchner R, Danninger K, Puchner A, Pieringer H (2012) Impact of TNF-blocking agents on male sperm characteristics and pregnancy outcomes in fathers exposed to TNF-blocking agents at time of conception. Clin Exp Rheumatol 30(5):765–767

    PubMed  Google Scholar 

  9. Alijotas-Reig J, Esteve-Valverde E, Ferrer-Oliveras R, Llurba E, Gris JM (2017) Tumor necrosis factor-alpha and pregnancy: focus on biologics. An updated and comprehensive review. Clin Rev Allergy Immunol 53(1):40–53. https://doi.org/10.1007/s12016-016-8596-x

    Article  CAS  PubMed  Google Scholar 

  10. Larsen MD, Friedman S, Magnussen B, Nørgård BM (2016) Birth outcomes in children fathered by men treated with anti-TNF-α agents before conception. Am J Gastroenterol 111(11):1608. https://doi.org/10.1038/ajg.2016.405

    Article  CAS  PubMed  Google Scholar 

  11. Katz JA, Antoni C, Keenan GF, Smith DE, Jacobs SJ, Lichtenstein GR (2004) Outcome of pregnancy in women receiving infliximab for the treatment of Crohn’s disease and rheumatoid arthritis. Am J Gastroenterol 99(12):2385. https://doi.org/10.1111/j.1572-0241.2004.30186.x

    Article  PubMed  Google Scholar 

  12. Wang X, Chen C, Wang L, Chen D, Guang W, French J, Reproductive Health Study Group (2003) Conception, early pregnancy loss, and time to clinical pregnancy: a population-based prospective study. Fertil Steril 79(3):577–584. https://doi.org/10.1016/s0015-0282(02)04694-0

    Article  PubMed  Google Scholar 

  13. Blencowe H, Cousens S, Chou D, Oestergaard M, Say L, Moller AB et al (2013) Born too soon: the global epidemiology of 15 million preterm births. Reprod Health 10(1):S2. https://doi.org/10.1186/1742-4755-10-s1-s2

    Article  PubMed  PubMed Central  Google Scholar 

  14. Diav-Citrin O, Otcheretianski-Volodarsky A, Shechtman S, Ornoy A (2014) Pregnancy outcome following gestational exposure to TNF-alpha-inhibitors: a prospective, comparative, observational study. Reprod Toxicol 43:78–84. https://doi.org/10.1016/j.reprotox.2013.11.004

    Article  CAS  PubMed  Google Scholar 

  15. Verstappen SM, King Y, Watson KD, Symmons DP, Hyrich KL, BSRBR Control Centre Consortium, BSR Biologics Register (2011) Anti-TNF therapies and pregnancy: outcome of 130 pregnancies in the British Society for Rheumatology Biologics Register. Ann Rheum Dis 70(5):823–826. https://doi.org/10.1136/ard.2010.140822

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Mahadevan U, Martin CF, Dubinsky M, Kane SV, Sands BE, Sandborn W (2014) 960 exposure to anti-TNFα therapy in the third trimester of pregnancy is not associated with increased adverse outcomes: results from the PIANO registry. Gastroenterology 146(5):S-170. https://doi.org/10.1016/s0016-5085(14)60602-8

    Article  Google Scholar 

  17. Winter RW, Larsen MD, Magnussen B, Friedman S, Kammerlander H, Nørgård BM (2017) Birth outcomes after preconception paternal exposure to methotrexate: a nationwide cohort study. Reprod Toxicol 74:219–223. https://doi.org/10.1016/j.reprotox.2017.10.004

    Article  CAS  PubMed  Google Scholar 

  18. Garritsen FM, van den Broek MPH, van Zuilen AD, Fidder HH, de Bruin-Weller MS, Spuls PI (2017) Pregnancy and fetal outcomes after paternal exposure to azathioprine, methotrexate or mycophenolic acid: a critically appraised topic. Br J Dermatol. https://doi.org/10.1111/bjd.15320

    Article  PubMed  Google Scholar 

  19. Lysiak JJ (2004) The role of tumor necrosis factor-alpha and interleukin-1 in the mammalian testis and their involvement in testicular torsion and autoimmune orchitis. Reprod Biol Endocrinol 2(1):9. https://doi.org/10.1186/1477-7827-2-9

    Article  PubMed  PubMed Central  Google Scholar 

  20. Perdichizzi A, Nicoletti F, La Vignera S, Barone N, D’Agata R, Vicari E, Calogero AE (2007) Effects of tumour necrosis factor-α on human sperm motility and apoptosis. J Clin Immunol 27(2):152–162. https://doi.org/10.1007/s10875-007-9071-5

    Article  CAS  PubMed  Google Scholar 

  21. Wildi LM, Haraoui B (2012) Reversible male infertility under treatment with an anti-TNFα agent: a case report. Ann Rheum Dis 71(3):473–474. https://doi.org/10.1136/annrheumdis-2011-200299

    Article  CAS  PubMed  Google Scholar 

  22. La Montagna G, Malesci D, Buono R, Valentini G (2005) Asthenoazoospermia in patients receiving anti-tumour necrosis factor α agents. Ann Rheum Dis 64(11):1667–1667. https://doi.org/10.1136/ard.2005.038620

    Article  PubMed  PubMed Central  Google Scholar 

  23. Mahadevan U, Terdiman JP, Aron J, Jacobsohn S, Turek P (2005) Infliximab and semen quality in men with inflammatory bowel disease. Inflamm Bowel Dis 11(4):395–399. https://doi.org/10.1097/01.MIB.0000164023.10848.c4

    Article  PubMed  Google Scholar 

  24. Villiger PM, Caliezi G, Cottin V, Förger F, Senn A, Østensen M (2010) Effects of TNF antagonists on sperm characteristics in patients with spondyloarthritis. Ann Rheum Dis 69(10):1842–1844. https://doi.org/10.1136/ard.2009.127423

    Article  CAS  PubMed  Google Scholar 

  25. Lichtenstein GR, Feagan BG, Mahadevan U, Salzberg BA, Langholff W, Morgan GJ et al (2018) Pregnancy outcomes reported during the 13-year TREAT registry: a descriptive report. Am J Gastroenterol 113(11):1678. https://doi.org/10.1038/s41395-018-0202-9

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We wish to thank Emre Bilgin (Hacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology), Mahire BAYKAL and Sadile AK (HUR-BIO) for their valuable contributions in performing this study. There isn’t any external editing support by any agents and agencies.

Funding

None of the authors received a financial support and/or specific funding for this work. None of the authors has relationships with pharmaceutical agencies.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Sihhiye, 06100, Ankara, Turkey

    Oguz Abdullah Uyaroglu & Emrah Seyhoglu

  2. Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey

    Abdulsamet Erden, Levent Kilic, Omer Karadag, Ali Akdogan, Sule Apras Bilgen, Ali Ihsan Ertenli, Sedat Kiraz & Umut Kalyoncu

Authors
  1. Oguz Abdullah Uyaroglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emrah Seyhoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abdulsamet Erden
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Levent Kilic
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Omer Karadag
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ali Akdogan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sule Apras Bilgen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ali Ihsan Ertenli
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Sedat Kiraz
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Umut Kalyoncu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All co-authors satisfy all four criteria (participated in study design, data collection, analysis, interpretation and writing equally), and take full responsibility for the integrity of the study and the final manuscript.

Corresponding author

Correspondence to Oguz Abdullah Uyaroglu.

Ethics declarations

Conflict of interest

The authors declare no potential conflicts of interest.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Uyaroglu, O.A., Seyhoglu, E., Erden, A. et al. Pregnancy outcomes in partners of male ankylosing spondylitis patients treated with anti-tumour necrosis factor-α biologics: real-life results from a single-centre cross-sectional study. Rheumatol Int 40, 1501–1507 (2020). https://doi.org/10.1007/s00296-020-04518-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-020-04518-3

Keywords

Search

Navigation