Rheumatoid arthritis and pregnancy
- Bonnie L Bermas, MD
Bonnie L Bermas, MD
- Professor of Medicine
- UT Southwestern Medical Center
- Section Editors
- James R O'Dell, MD
James R O'Dell, MD
- Section Editor — Rheumatoid Arthritis
- Bruce Professor and Vice Chairman Internal Medicine
- University of Nebraska Medical Center
- Charles J Lockwood, MD, MHCM
Charles J Lockwood, MD, MHCM
- Section Editor — Obstetrics
- Senior Vice President, USF Health
- Dean, Morsani College of Medicine
- Professor, Obstetrics and Gynecology
- University of South Florida
Rheumatoid arthritis (RA) affects about 1 percent of adults, but the frequency varies depending upon the population studied. There is a female predominance in RA, and many female patients are of childbearing age . Thus, the management of RA during conception and pregnancy is a common challenge for rheumatologists. In many patients with RA, disease activity improves substantially in the gravid state. However, modification of treatment so as to minimize the potential for fetal toxicity while maintaining adequate disease control can be difficult in patients whose RA flares or remains active.
The influence of RA upon fertility and pregnancy, the influence of pregnancy upon the disease, and the management of RA during conception, pregnancy and lactation will be reviewed here. The use of antiinflammatory and immunosuppressive drugs in patients with rheumatic diseases during pregnancy and lactation is discussed in detail separately. (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation".)
EFFECT OF RA ON FERTILITY
Smaller family size has been observed in women with rheumatoid arthritis (RA). The reasons for this appear multifactorial, including patient choice, medication use during the usual period of family planning, and subfertility related to disease activity [2,3]. The relative importance of each potential factor has been difficult to determine [2-7]. As examples:
●In one structured telephone survey of 411 women with RA, 8 percent reported having been advised by medical professionals to limit family size, and 20 percent reported that having RA affected their decision to have children; concerns for carrying the child, caring for the child, and passing on RA to biologic offspring were cited as contributing reasons . In this same group, receiving the diagnosis of RA prior to the birth of the first child or receiving the diagnosis prior to age 18 were associated with fewer pregnancies and children; by contrast, women who were diagnosed with RA after age 30 did not report smaller family sizes compared with the reference population. Similarly, in a registry-based study from Norway, women with RA who did not have children prior to diagnosis were less likely to become pregnant than controls at the end of the observation period .
●In another survey involving 578 women with RA, patients were asked about the number of pregnancies, live births, miscarriages, and pregnancy terminations they had had . Over half (55 percent) of the patients had fewer pregnancies than intended; of these women, 42 percent cited infertility as a reason and the remainder limited the number of pregnancies because of arthritis-related concerns, which included the ability to care for children, the concern that the disease activity would be impacted, and concerns about passing on the susceptibility to RA to their offspring.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Dugowson CE, Koepsell TD, Voigt LF, et al. Rheumatoid arthritis in women. Incidence rates in group health cooperative, Seattle, Washington, 1987-1989. Arthritis Rheum 1991; 34:1502.
- Brouwer J, Laven JS, Hazes JM, et al. Levels of serum anti-Müllerian hormone, a marker for ovarian reserve, in women with rheumatoid arthritis. Arthritis Care Res (Hoboken) 2013; 65:1534.
- Brouwer J, Hazes JM, Laven JS, Dolhain RJ. Fertility in women with rheumatoid arthritis: influence of disease activity and medication. Ann Rheum Dis 2015; 74:1836.
- Katz PP. Childbearing decisions and family size among women with rheumatoid arthritis. Arthritis Rheum 2006; 55:217.
- Clowse ME, Chakravarty E, Costenbader KH, et al. Effects of infertility, pregnancy loss, and patient concerns on family size of women with rheumatoid arthritis and systemic lupus erythematosus. Arthritis Care Res (Hoboken) 2012; 64:668.
- Wallenius M, Skomsvoll JF, Irgens LM, et al. Parity in patients with chronic inflammatory arthritides childless at time of diagnosis. Scand J Rheumatol 2012; 41:202.
- KAY A, BACH F. SUBFERTILITY BEFORE AND AFTER THE DEVELOPMENT OF RHEUMATOID ARTHRITIS IN WOMEN. Ann Rheum Dis 1965; 24:169.
- Henes M, Froeschlin J, Taran FA, et al. Ovarian reserve alterations in premenopausal women with chronic inflammatory rheumatic diseases: impact of rheumatoid arthritis, Behçet's disease and spondyloarthritis on anti-Müllerian hormone levels. Rheumatology (Oxford) 2015; 54:1709.
- Jawaheer D, Zhu JL, Nohr EA, Olsen J. Time to pregnancy among women with rheumatoid arthritis. Arthritis Rheum 2011; 63:1517.
- Tham M, et al. Reduced pro-inflammatory profile of yDT cells in pregnant patients with rheumatoid arthritis. Arthritis Res Ther 2016; 18.
- Förger F, Zbinden A, Villiger PM. Certolizumab treatment during late pregnancy in patients with rheumatic diseases: Low drug levels in cord blood but possible risk for maternal infections. A case series of 13 patients. Joint Bone Spine 2016; 83:341.
- Heikkinen J, Möttönen M, Alanen A, Lassila O. Phenotypic characterization of regulatory T cells in the human decidua. Clin Exp Immunol 2004; 136:373.
- Dekel N, Gnainsky Y, Granot I, Mor G. Inflammation and implantation. Am J Reprod Immunol 2010; 63:17.
- Veenstra van Nieuwenhoven AL, Heineman MJ, Faas MM. The immunology of successful pregnancy. Hum Reprod Update 2003; 9:347.
- Wegmann TG, Lin H, Guilbert L, Mosmann TR. Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? Immunol Today 1993; 14:353.
- Tham M, Schlör GR, Yerly D, et al. Reduced pro-inflammatory profile of γδT cells in pregnant patients with rheumatoid arthritis. Arthritis Res Ther 2016; 18:26.
- Hench PS. The ameliorating effect of pregnancy on chronic atrophic (infectious rheumatoid) arthritis, fibrosis and intermittent hydrarthrosis. Mayo Clin Proc 1938; 13:161.
- Persellin RH. The effect of pregnancy on rheumatoid arthritis. Bull Rheum Dis 1976-1977; 27:922.
- Silman A, Kay A, Brennan P. Timing of pregnancy in relation to the onset of rheumatoid arthritis. Arthritis Rheum 1992; 35:152.
- Ostensen M. The influence of pregnancy on blood parameters in patients with rheumatic disease. Scand J Rheumatol 1984; 13:203.
- Nelson JL, Ostensen M. Pregnancy and rheumatoid arthritis. Rheum Dis Clin North Am 1997; 23:195.
- de Man YA, Bakker-Jonges LE, Goorbergh CM, et al. Women with rheumatoid arthritis negative for anti-cyclic citrullinated peptide and rheumatoid factor are more likely to improve during pregnancy, whereas in autoantibody-positive women autoantibody levels are not influenced by pregnancy. Ann Rheum Dis 2010; 69:420.
- Zrour SH, Boumiza R, Sakly N, et al. The impact of pregnancy on rheumatoid arthritis outcome: the role of maternofetal HLA class II disparity. Joint Bone Spine 2010; 77:36.
- Nelson JL, Hughes KA, Smith AG, et al. Remission of rheumatoid arthritis during pregnancy and maternal-fetal class II alloantigen disparity. Am J Reprod Immunol 1992; 28:226.
- Barrett JH, Brennan P, Fiddler M, Silman AJ. Does rheumatoid arthritis remit during pregnancy and relapse postpartum? Results from a nationwide study in the United Kingdom performed prospectively from late pregnancy. Arthritis Rheum 1999; 42:1219.
- de Man YA, Hazes JM, van de Geijn FE, et al. Measuring disease activity and functionality during pregnancy in patients with rheumatoid arthritis. Arthritis Rheum 2007; 57:716.
- Soscia PN, Zurier RB. Drug therapy of rheumatic diseases during pregnancy. Bull Rheum Dis 1992; 41:1.
- Guidelines for monitoring drug therapy in rheumatoid arthritis. American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Arthritis Rheum 1996; 39:723.
- Bermas BL, Hill JA. Effects of immunosuppressive drugs during pregnancy. Arthritis Rheum 1995; 38:1722.
- Roubenoff R, Hoyt J, Petri M, et al. Effects of antiinflammatory and immunosuppressive drugs on pregnancy and fertility. Semin Arthritis Rheum 1988; 18:88.
- de Man YA, Hazes JM, van der Heide H, et al. Association of higher rheumatoid arthritis disease activity during pregnancy with lower birth weight: results of a national prospective study. Arthritis Rheum 2009; 60:3196.
- Bowden AP, Barrett JH, Fallow W, Silman AJ. Women with inflammatory polyarthritis have babies of lower birth weight. J Rheumatol 2001; 28:355.
- KAPLAN D, DIAMOND H. RHEUMATOID ARTHRITIS AND PREGNANCY. Clin Obstet Gynecol 1965; 17:286.
- Morris WI. Pregnancy in rheumatoid arthritis and systemic lupus erythematosus. Aust N Z J Obstet Gynaecol 1969; 9:136.
- Ostensen M, Husby G. A prospective clinical study of the effect of pregnancy on rheumatoid arthritis and ankylosing spondylitis. Arthritis Rheum 1983; 26:1155.
- Rom AL, Wu CS, Olsen J, et al. Fetal growth and preterm birth in children exposed to maternal or paternal rheumatoid arthritis: a nationwide cohort study. Arthritis Rheumatol 2014; 66:3265.
- EFFECT OF RA ON FERTILITY
- Immunology of pregnancy
- EFFECTS OF PREGNANCY ON DISEASE ACTIVITY
- Disease activity during pregnancy
- Postpartum flare
- MANAGEMENT OF RA DURING PREGNANCY AND LACTATION
- Medication use during pregnancy
- - Moderate to high risk of fetal harm
- - Selective use allowed during pregnancy
- - Minimal fetal and maternal risk
- Treatment approach
- - Prior to pregnancy
- - Routine management during pregnancy
- - Persistent or flaring disease activity
- Medication use during breastfeeding
- PREGNANCY OUTCOME
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS