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Pregnancy in patients affected by axial-spondyloarthritis: a narrative review of disease activity and obstetric outcomes

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Received: 5 January 2024
Published: 11 September 2024
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Objective. This review aims to summarize the most recent and updated data on pregnancy in patients with axial spondyloarthritis (axSpA), focusing on the recurrence of pregnancy-related complications, the disease activity throughout gestation and the postpartum, and the latest indications for the treatments of future mothers.

Methods. We have conducted a narrative review with an online literature search on Medline and PubMed. We selected only studies written in English published until January 2024, including observational and retrospective studies, meta-analyses, and systematic reviews.

Results. Proper preconception counseling and maternal-fetal monitoring are necessary to ensure the best outcome for both the mother and her baby. Despite the limited and conflicting evidence about the prevalence of adverse pregnancy outcomes in women with axSpA compared to healthy controls, primary findings demonstrate an increased risk of preterm delivery (PTD), low birth weight (LBW), and elective cesarean section (CS). Concerning disease activity, data suggests that 25-80% of women with ankylosing spondylitis experience disease flares during pregnancy, particularly around 20 weeks of gestation. On the contrary, the data on the postpartum disease flare are heterogeneous. The use of biological drugs in pregnancy is safe and effective in controlling disease activity.

Conclusions. Data on pregnancy outcomes in patients with axSpA are scarce and discordant. Probably the difference in maternal disease classification, the evolution of treatment indications, and the differences emerging from study designs can account for these discrepancies. The main evidence shows an increased risk of PTD, LBW, and elective CS (although the latter may reflect cultural influences rather than medical needs due to axSpA itself). The majority of drugs used to treat axSpA, including TNFi, are safe in pregnancy without harming mothers or fetuses. Further data is needed to clarify many controversial aspects in this area.

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Ward MM, Deodhar A, Akl EA, Lui A, Ermann J, Gensler LS, et al. American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Rheumatol 2016; 68: 282-98. DOI: https://doi.org/10.1002/art.39298

Sammaritano LR. Pregnancy in rheumatic disease patients. J Clin Rheumatol 2013; 19: 259-66. DOI: https://doi.org/10.1097/RHU.0b013e31829ce35f

Lee W, Reveille JD, Weisman MH, et al. Women with ankylosing spondylitis: a review. Arthritis Rheum 2008; 59: 449-54. DOI: https://doi.org/10.1002/art.23321

Ostensen M, Ostensen H. Ankylosing spondylitis--the female aspect. J Rheumatol 1998; 25: 120-4.

Sieper J, Poddubnyy D. Axial spondyloarthritis. Lancet 2017; 390: 73-84. DOI: https://doi.org/10.1016/S0140-6736(16)31591-4

Maguire S, Wilson F, Gallagher P, Ms Mohamed M, Maher S, O’Shea F. What to expect when women with axial spondyloarthritis are expecting: prevalence of complications of pregnancies in women with axial spondyloarthritis. Semin Arthritis Rheum 2022; 54: 151993. DOI: https://doi.org/10.1016/j.semarthrit.2022.151993

Zbinden A, van den Brandt S, Østensen M, Villiger PM, Förger F. Risk for adverse pregnancy outcome in axial spondyloarthritis and rheumatoid arthritis: disease activity matters. Rheumatology 2018; 57: 1235-42. DOI: https://doi.org/10.1093/rheumatology/key053

Lui NL, Haroon N, Carty A, Shen H, Cook RJ, Shanmugarajah S, et al. Effect of pregnancy on ankylosing spondylitis: a case-control study. J Rheumatol 2011; 38: 2442-4. DOI: https://doi.org/10.3899/jrheum.101174

Ostensen M, Husby G. Pregnancy and rheumatic disease. A review of recent studies in rheumatoid arthritis and ankylosing spondylitis. Klin Wochenschr 1984; 62: 891-5. DOI: https://doi.org/10.1007/BF01727437

Giles I, Yee CS, Gordon C. Stratifying management of rheumatic disease for pregnancy and breastfeeding. Nat Rev Rheumatol 2019; 15: 391-402. DOI: https://doi.org/10.1038/s41584-019-0240-8

Smith CJFF, Bandoli G, Kavanaugh A, Chambers CD. Birth outcomes and disease activity during pregnancy in a prospective cohort of women with psoriatic arthritis and ankylosing spondylitis. Arthritis Care Res 2020; 72: 1029-37. DOI: https://doi.org/10.1002/acr.23924

Morin M, Frisell T, Stephansson O, Hellgren K. Temporal trends in adverse pregnancy outcomes in axial spondyloarthritis in Sweden: a cohort study. Lancet Rheumatol 2023; 5: e121-9. DOI: https://doi.org/10.1016/S2665-9913(23)00001-2

Ostensen M, Husby G. A prospective clinical study of the effect of pregnancy on rheumatoid arthritis and ankylosing spondylitis. Arthritis Rheum 1983; 26: 1155-9. DOI: https://doi.org/10.1002/art.1780260915

Ostensen M, Romberg O, Husby G. Ankylosing spondylitis and motherhood. Arthritis Rheum 1982; 25: 140-3. DOI: https://doi.org/10.1002/art.1780250204

Timur H, Tokmak A, Türkmen GG, İnal HA, Uygur D, Danışman N. Pregnancy outcome in patients with ankylosing spondylitis. J Matern Fetal Neonatal Med 2016; 29: 2470-4. DOI: https://doi.org/10.3109/14767058.2015.1089432

Ursin K, Lydersen S, Skomsvoll JF, Wallenius M. Disease activity during and after pregnancy in women with axial spondyloarthritis: a prospective multicentre study. Rheumatology 2018; 57: 1064-71. DOI: https://doi.org/10.1093/rheumatology/key047

Jakobsson GL, Stephansson O, Askling J, Jacobsson LTH. Pregnancy outcomes in patients with ankylosing spondylitis: a nationwide register study. Ann Rheum Dis 2016; 75: 1838-42. DOI: https://doi.org/10.1136/annrheumdis-2015-207992

Maguire S, O’Dwyer T, Mockler D, O’Shea F, Wilson F. Pregnancy in axial spondyloarthropathy: a systematic review & meta-analysis. Semin Arthritis Rheum 2020; 50; 1269-79. DOI: https://doi.org/10.1016/j.semarthrit.2020.08.011

Zhou Q, Bian X, Liu J. Management of pregnancy with ankylosing spondylitis. Chin Med Sci J 2012; 27: 46-9. DOI: https://doi.org/10.1016/S1001-9294(12)60022-4

Förger F, Ostensen M, Schumacher A, Villiger P. Impact of pregnancy on health related quality of life evaluated prospectively in pregnant women with rheumatic diseases by the SF-36 health survey. Ann Rheum Dis 2005; 64: 1494-9. DOI: https://doi.org/10.1136/ard.2004.033019

Förger F, Villiger PM, Ostensen M. Pregnancy in patients with ankylosing spondylitis: do regulatory T cells play a role?. Arthritis Rheum 2009; 61: 279-83. DOI: https://doi.org/10.1002/art.24161

Boerma T, Ronsmans C, Melesse DY, Barros AJD, Barros FC, Juan L, et al. Global epidemiology of use of and disparities in caesarean sections. Lancet 2018; 392: 1341-8. DOI: https://doi.org/10.1016/S0140-6736(18)31928-7

Rito AI, Buoncristiano M, Spinelli A, Salanave B, Kunešová M, Hejgaard T, et al, Association between characteristics at birth, breastfeeding and obesity in 22 countries: the WHO European Childhood Obesity Surveillance Initiative - COSI 2015/2017. Obes Facts 2019; 12: 226-43. DOI: https://doi.org/10.1159/000500425

Ibanez G, Martin N, Denantes M, Saurel-Cubizolles MJ, Ringa V, Magnier AM. Prevalence of breastfeeding in industrialized countries. Rev Epidemiol Sante Publique 2012; 60: 305-20. DOI: https://doi.org/10.1016/j.respe.2012.02.008

Østensen M, Andreoli L, Brucato A, Cetin I, Chambers C, Clowse MEB, et al. State of the art: Reproduction and pregnancy in rheumatic diseases. Autoimmun Rev 2015; 14: 376-86. DOI: https://doi.org/10.1016/j.autrev.2014.12.011

Clowse MEB, Chakravarty E, Costenbader KH, Chambers C, Michaud K. Effects of infertility, pregnancy loss, and patient concerns on family size of women with rheumatoid arthritis and systemic lupus erythematosus. Arthritis Care Res 2012; 64: 668-74. DOI: https://doi.org/10.1002/acr.21593

Mokbel A, Lawson DO, Farrokhyar F. Pregnancy outcomes in women with ankylosing spondylitis: a scoping literature and methodological review. Clin Rheumatol 2021; 40: 3465-80. DOI: https://doi.org/10.1007/s10067-021-05588-9

Keeling SO, Oswald AE. Pregnancy and rheumatic disease: “by the book” or “by the doc”. Clin Rheumatol 2009; 28: 1-9. DOI: https://doi.org/10.1007/s10067-008-1031-9

Helland Y, Dagfinrud H, Kvien TK. Perceived influence of health status on sexual activity in RA patients: associations with demographic and disease-related variables. Scand J Rheumatol 2008; 37: 194-9. DOI: https://doi.org/10.1080/03009740701867349

Khnaba D, Rostom S, Lahlou R, Bahiri R, Abouqal R, Hajjaj-Hassouni N. Sexual dysfunction and its determinants in Moroccan women with rheumatoid arthritis. Pan Afr Med J 2016; 24: 16. DOI: https://doi.org/10.11604/pamj.2016.24.16.9081

Hansen KR, Knowlton NS, Thyer AC, Charleston JS, Soules MR, Klein NA. A new model of reproductive aging: the decline in ovarian non-growing follicle number from birth to menopause. Hum Reprod 2008; 23: 699-708. DOI: https://doi.org/10.1093/humrep/dem408

Østensen M. Sexual and reproductive health in rheumatic disease. Nat Rev Rheumatol 2017; 13: 485-93. DOI: https://doi.org/10.1038/nrrheum.2017.102

Eudy AM, Siega-Riz AM, Engel SM, Franceschini N, Green Howard A, Clowse MED, et al. Effect of pregnancy on disease flares in patients with systemic lupus erythematosus. Ann Rheum Dis 2018; 77: 855-60. DOI: https://doi.org/10.1136/annrheumdis-2017-212535

Mørk S, Voss A, Möller S, Bliddal M. Spondyloarthritis and outcomes in pregnancy and labor: a nationwide register-based cohort study. Arthritis Care Res 2021; 73: 282-8. DOI: https://doi.org/10.1002/acr.24111

Redeker I, Strangfeld A, Callhoff J, Marschall U, Zink A, Baraliakos X. Maternal and infant outcomes in pregnancies of women with axial spondyloarthritis compared with matched controls: results from nationwide health insurance data. RMD Open 2022; 8: e002146. DOI: https://doi.org/10.1136/rmdopen-2021-002146

Hamroun S, Hamroun A, Bigna JJ, Allado E, Förger F, Molto A. Fertility and pregnancy outcomes in women with spondyloarthritis: a systematic review and meta-analysis. Rheumatology 2022; 61: 1314-27. DOI: https://doi.org/10.1093/rheumatology/keab589

Bernardy C, Baillet A, Gaudin P, Romand X. Comment on the article by Maguire et al. pregnancy in axial spondyloarthropathy: a systematic review & meta-analysis. Semin Arthritis Rheum 2022; 52: 151845. DOI: https://doi.org/10.1016/j.semarthrit.2021.05.005

Unal C, Fadiloglu E, Tanacan A, Zaim OC, Beksac MS. Retrospective evaluation of pregnancies with ankylosing spondylitis in a tertiary center in Turkey. Int J Rheum Dis 2020; 23: 101-5. DOI: https://doi.org/10.1111/1756-185X.13746

Meissner Y, Strangfeld A, Molto A, Forger F, Wallenius M, Costedoat-Chalumeau N, et al. Pregnancy and neonatal outcomes in women with axial spondyloarthritis: pooled data analysis from the European Network of Pregnancy Registries in Rheumatology (EuNeP). Ann Rheum Dis 2022; 81: 1524-33. DOI: https://doi.org/10.1136/ard-2022-222641

Fuchs F, Monet B, Ducruet T, Chaillet N, Audibert F. Effect of maternal age on the risk of preterm birth: a large cohort study. PloS One 2018; 13: e0191002. DOI: https://doi.org/10.1371/journal.pone.0191002

Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet 2008; 371: 75-84. DOI: https://doi.org/10.1016/S0140-6736(08)60074-4

Vogel JP, Chawanpaiboon S, Moller AB, Watananirun K, Bonet M, Lumbiganon P. The global epidemiology of preterm birth. Best Pract Res Clin Obstet Gynaecol 2018; 52: 3-12. DOI: https://doi.org/10.1016/j.bpobgyn.2018.04.003

BrownMA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, et al. Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice. Hypertension 2018; 72: 24-43. DOI: https://doi.org/10.1161/HYPERTENSIONAHA.117.10803

Mol BWJ, Roberts CT, Thangaratinam S, Magee LA, de Groot CJM, Hofmeyr GJ. Pre-eclampsia. Lancet 2016; 387: 999-1011. DOI: https://doi.org/10.1016/S0140-6736(15)00070-7

Redman CWG, Sargent IL. Immunology of pre-eclampsia. Am J Reprod Immunol 2010; 63: 534-43. DOI: https://doi.org/10.1111/j.1600-0897.2010.00831.x

Wadström H, Eriksson JK, Neovius M, Askling J. How good is the coverage and how accurate are exposure data in the Swedish Biologics Register (ARTIS)?. Scand J Rheumatol 2015; 44: 22-8. DOI: https://doi.org/10.3109/03009742.2014.927918

Ibfelt EH, Jensen DV, Hetland ML. The Danish nationwide clinical register for patients with rheumatoid arthritis: DANBIO. Clin Epidemiol 2016; 8: 737-42. DOI: https://doi.org/10.2147/CLEP.S99490

Pape Secher AE, Granath F, Glintborg B, Rom A, Hetland ML, Hellgren K. Risk of pre-eclampsia and impact of disease activity and antirheumatic treatment in women with rheumatoid arthritis, axial spondylarthritis and psoriatic arthritis: a collaborative matched cohort study from Sweden and Denmark. RMD Open 2022; 8: e002445. DOI: https://doi.org/10.1136/rmdopen-2022-002445

Andreoli L, Bertsias GK, Agmon-Levin N, Brown S, Cervera R, Costedoat-Chalumeau N, et al. 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 2017; 76: 476-85. DOI: https://doi.org/10.1136/annrheumdis-2016-209770

Onno Teng YK, Bredewold EOW, Rabelink TJ, HuizingaTWJ, Jeroen Eikenboom HC, Limper M. An evidence-based approach to pre-pregnancy counselling for patients with systemic lupus erythematosus. Rheumatology 2018; 57: 1707-20. DOI: https://doi.org/10.1093/rheumatology/kex374

Espinoza J, Kusanovic JP, Bahado-Singh R, Gervasi MT, Romero R, Lee W, et al. Should bilateral uterine artery notching be used in the risk assessment for preeclampsia, small-for-gestational-age, and gestational hypertension?. J Ultrasound Med 2010; 29: 1103-15. DOI: https://doi.org/10.7863/jum.2010.29.7.1103

Park EH, Lee JS, Kim Y, Lee SM, Jun JK, Lee EB, et al. Pregnancy outcomes in Korean women with ankylosing spondylitis. Korean J Intern Med 2021; 36: 721-30. DOI: https://doi.org/10.3904/kjim.2019.144

Skomsvoll JF, Ostensen M, Baste V, Irgens LM. Number of births, interpregnancy interval, and subsequent pregnancy rate after a diagnosis of inflammatory rheumatic disease in Norwegian women. J Rheumatol 2001; 28: 2310-4.

van den Brandt S, Zbinden A, Baeten D, Villiger PM, Østensen M, Förger F. Risk factors for flare and treatment of disease flares during pregnancy in rheumatoid arthritis and axial spondyloarthritis patients. Arthritis Res Ther 2017; 19: 64. DOI: https://doi.org/10.1186/s13075-017-1269-1

Declercq E, Menacker F, MacDorman M. Maternal risk profiles and the primary cesarean rate in the United States, 1991-2002. Am J Public Health 2006; 96: 867-72. DOI: https://doi.org/10.2105/AJPH.2004.052381

Thuillier C, Roy S, Peyronnet V, Quibel T, Nlandu A, Rozenberg P. Impact of recommended changes in labor management for prevention of the primary cesarean delivery. Am J Obstet Gynecol 2018; 218: 341.e1-e9. DOI: https://doi.org/10.1016/j.ajog.2017.12.228

Tsao NW, Rebic N, Lynd LD, De Vera MA. Maternal and neonatal outcomes associated with biologic exposure before and during pregnancy in women with inflammatory systemic diseases: a systematic review and meta-analysis of observational studies. Rheumatology 2020; 59: 1808-17. DOI: https://doi.org/10.1093/rheumatology/keaa064

Bröms G, Kieler H, Ekbom A, Gissler M, Hellgren K, Leinonen MK. Paediatric infections in the first 3 years of life after maternal anti-TNF treatment during pregnancy. Aliment Pharmacol Ther 2020; 52: 843-54. DOI: https://doi.org/10.1111/apt.15971

Jethwa H, Lam S, Smith C, Giles I. Does rheumatoid arthritis really improve during pregnancy? A systematic review and metaanalysis. J Rheumatol 2019; 46: 245-50. DOI: https://doi.org/10.3899/jrheum.180226

Ursin K, Lydersen S, Skomsvoll JF, Wallenius M. Psoriatic arthritis disease activity during and after pregnancy: a prospective multicenter study. Arthritis Care Res 2019; 71: 1092-100. DOI: https://doi.org/10.1002/acr.23747

Østensen M, Fuhrer L, Mathieu R, Seitz M, Villiger PM. A prospective study of pregnant patients with rheumatoid arthritis and ankylosing spondylitis using validated clinical instruments. Ann Rheum Dis 2004; 63: 1212-7. DOI: https://doi.org/10.1136/ard.2003.016881

Tham M, Schlör GR, Yerly D, Mueller C, Surbek D, Villiger PM, et al. Reduced pro-inflammatory profile of γδT cells in pregnant patients with rheumatoid arthritis. Arthritis Res Ther 2016; 18: 26. DOI: https://doi.org/10.1186/s13075-016-0925-1

de Man YA, Dolhain RJEM, van de Geijn FE, Willemsen SP, Hazes JMW. Disease activity of rheumatoid arthritis during pregnancy: results from a nationwide prospective study. Arthritis Rheum 2008; 59: 1241-8. DOI: https://doi.org/10.1002/art.24003

Lockshin MD, Reinitz E, Druzin ML, Murrman M, Estes D. Lupus pregnancy. Case-control prospective study demonstrating absence of lupus exacerbation during or after pregnancy. Am J Med 1984; 77: 893-8. DOI: https://doi.org/10.1016/0002-9343(84)90538-2

Ostensen M. The effect of pregnancy on ankylosing spondylitis, psoriatic arthritis, and juvenile rheumatoid arthritis. Am J Reprod Immunol 1992; 28: 235-7. DOI: https://doi.org/10.1111/j.1600-0897.1992.tb00801.x

Østensen M, Förger F, Nelson JL, Schuhmacher A, Hebisch G, Villiger PM. Pregnancy in patients with rheumatic disease: anti-inflammatory cytokines increase in pregnancy and decrease post partum. Ann Rheum Dis 2005; 64: 839-44. DOI: https://doi.org/10.1136/ard.2004.029538

Ostensen M. The influence of pregnancy on blood parameters in patients with rheumatic disease. Scand J Rheumatol 1984; 13: 203-8. DOI: https://doi.org/10.3109/03009748409100388

Nalli C, Manfredi L, Fredi M, Crisafulli F, Bertocchi S, amilya Khizroeva J, et al. Managing puerperium in patients with systemic autoimmune diseases: an update. Expert Rev Clin Immunol 2022; 18; 391-9. DOI: https://doi.org/10.1080/1744666X.2022.2050216

Hainline B. Low-back pain in pregnancy. Adv Neurol 1994; 64: 65-76.

Andreoli L, Gerardi MC, Fernandes M, Bortoluzzi A, Bellando-Randone S, Brucato A, et al. Disease activity assessment of rheumatic diseases during pregnancy: a comprehensive review of indices used in clinical studies. Autoimmun Rev 2019; 18: 164-76. DOI: https://doi.org/10.1016/j.autrev.2018.08.008

Russell MD, Dey M, Flint J, Davie P, Allen A, Crossley A, et al. British Society for Rheumatology guideline on prescribing drugs in pregnancy and breastfeeding: immunomodulatory anti-rheumatic drugs and corticosteroids. Rheumatology 2023; 62: e48-88. DOI: https://doi.org/10.1093/rheumatology/keac686

Schreiber K, Frishman M, Russell MD, Dey M, Flint J, Allen A, et al. British Society for Rheumatology guideline on prescribing drugs in pregnancy and breastfeeding: comorbidity medications used in rheumatology practice. Rheumatology 2023; 62: e89-104. DOI: https://doi.org/10.1093/rheumatology/keac700

Sammaritano LR, Bermas BL, Chakravarty EE, Chambers C, Clowse MEB, D Lockshin MD, et al. 2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Rheumatol 2020; 72: 529-56. DOI: https://doi.org/10.1002/art.41191

Skorpen CG, Hoeltzenbein M, Tincani A, Fischer-Betz R, Elefant E, Chambers C, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis 2016; 75: 795-810. DOI: https://doi.org/10.1136/annrheumdis-2015-208840

SIR. Recommendations of the Italian Society of Rheumatology on the reproductive health of patients with rheumatological diseases, available on the website of the Italian National Institute of Health. Available from: https://www.reumatologia.it/obj/files/lineeguida/LG_C006_SIR_SRMR.pd. [Material in Italian].

Ramiro S, Nikiphorou E, Sepriano A, Ortolan A, Webers C, Baraliakos X, et al. ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update. Ann Rheum Dis 2023; 82: 19-34. DOI: https://doi.org/10.1136/ard-2022-223296

Lindström U, Olofsson T, Wedrén S, Qirjazo I, Askling J. Biological treatment of ankylosing spondylitis: a nationwide study of treatment trajectories on a patient level in clinical practice», Arthritis Res. Ther., vol. 21, fasc. 1, p. 128, mag. 2019, doi: 10.1186/s13075-019-1908-9. DOI: https://doi.org/10.1186/s13075-019-1908-9

Komaki F, Komaki Y, Micic D, Ido A, Sakuraba A. 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 2017; 76: 38-52. DOI: https://doi.org/10.1016/j.jaut.2016.11.004

Binns C, Lee M, Low WY. The long-term public health benefits of breastfeeding. Asia Pac J Public Health 2016; 28: 7-14. DOI: https://doi.org/10.1177/1010539515624964

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1.
Pregnancy in patients affected by axial-spondyloarthritis: a narrative review of disease activity and obstetric outcomes. Reumatismo [Internet]. 2024 Sep. 11 [cited 2026 Aug. 23];76(3). Available from: https://www.reumatismo.org/reuma/article/view/1697