Abstract
Pregnancy is an important condition that can affect and be affected by rheumatic disease. Overall, pregnancy is viewed as a Th2-predominant state, but several Th1-related cytokines are vital to early pregnancy. In rheumatoid arthritis for example, the majority of women improve by the beginning of the second trimester, but the majority (90%) will flare in the first 3 to 4 months postpartum. In contrast, systemic lupus erythematosus has an unpredictable course in pregnancy, leaving most rheumatologists to recommend a disease-quiescent state prior to conception. Other diseases such as scleroderma are less clear because the disease less commonly presents in the childbearing period. Many immunosuppressive medications for the rheumatic diseases are contraindicated in pregnancy because of their mechanisms of action leaving only a select few “safe” medications. Significant heterogeneity between the Food and Drug Administration (FDA) category for a medication and what a rheumatologist does in clinic leads to confusion on how a patient should be treated for active rheumatic disease both peripartum and postpartum, particularly if the patient is breastfeeding. We review the general state of pregnancy and how it is affected by prototypical rheumatic diseases including rheumatoid arthritis and systemic lupus erythematosus. In addition, we present the most commonly used disease-modifying antirheumatic drugs and immunosuppressants and explain the difference between the FDA category and clinical practice among rheumatologists. Finally, we provide some general recommendations on how to manage a rheumatic disease during pregnancy including: (a) preconception planning to ensure no teratogenic medications on board, (b) early disclosure of pregnancy to all caregivers including the rheumatologist, family physician, obstetrician, and maternal–fetal medicine specialist, and (c) planning of safe medication use for acute flare-ups and disease suppression peripartum and postpartum.
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References
Lockshin MD (2006) Treating rheumatic diseases in pregnancy: dos and don’ts. Ann Rheum Dis 65(Suppl III):iii58–iii60
Ostensen M, Villiger PM (2007) The remission of rheumatoid arthritis during pregnancy. Semin Immunopathol 29:185–191
Wegmann TG, Lin H, Guilbert L et al (1993) Bidirectional cytokine interactions in the maternal–fetal relationship: is successful pregnancy a Th2 phenomenon? Immunol Today 14:353–356
Ostensen M, Forger F, Villiger P (2006) Cytokines and pregnancy in rheumatic disease. Ann N Y Acad Sci 1069:353–363
Chaouat G, Ledee-Bataille N, Dubanchet S et al (2004) Th1/Th2 paradigm in pregnancy: paradigm lost? Int Arch Allergy Immunol 139:93–119
Ashkar AA, Di Santo JP, Croy BA (2000) Interferon gamma contributes to initiation of uterine vascular modification, decidual integrity, and uterine natural killer cell maturation during normal murine pregnancy. J Exp Med 192:25970
Fukushima K, Miyamoto S, Tsukimori K et al (2005) Tumor necrosis factor and vascular endothelial growth factor induce endothelial integrin repertories, regulating endovascular differentiation and apoptosis in a human extravillous trophoblast cell line. Biol Reprod 73:172–179
Kupferminc M, Peaceman A, Aderka D (1995) Soluble tumor necrosis factor receptors in maternal plasma and second-trimester amniotic fluid. Am J Obstet Gynecol 173:900–905
Ellis J, Wennerholm UB, Bengtsson A et al (2000) Levels of dimethylarginines and cytokines in mild and severe preeclampsia. Hum Reprod 80:602–608
Bahar A, Ghalib H, Moosa R et al (2003) Maternal serum interleukin-6, interleukin-8, tumor necrosis factor-α and interferon-γ in preterm labor. Acta Obstet Gynecol Scand 82:543–549
Gerli R, Lunardi C, Vinante F et al (2001) Role of CD30+ T cells in rheumatoid arthritis: a counter-regulatory paradigm for Th1-driven diseases. Trends Immunol 2:72–77
Correale J, Arias M, Gilmore W (1998) Steroid hormone regulation of cytokine secretion by proteolipid protein-specific CD4+ T cells clone isolated from multiple sclerosis patients and normal control subjects. J Immunol 161:3365–3374
Chrousos G, Torpy D, Gold P (1998) Interactions between the hypothalamic–pituitary–adrenal axis and the female reproductive system: clinical implications. Ann Intern Med 129:229–240
Barrett J, Brennan P, Fiddler M et al (2000) Breastfeeding and postpartum relapse in women with rheumatoid and inflammatory arthritis. Arthritis Rheum 43:1010–1015
Somerset D, Zheng Y, Kilby M et al (2004) Normal human pregnancy is associated with an elevation in the immune suppressive CD4+CD25+ regulatory T cell subset. Immunology 112:38–43
Brennan P (1997) HLA sharing and history of miscarriage among women with rheumatoid arthritis. Am J Hum Genet 60:738–739
Hunt JS (2006) Stranger in a strange land. Immunol Rev 213:36–37
Crocker I, Baker P, Fletcher J (2000) Neutrophil function in pregnancy and rheumatoid arthritis. Ann Rheum Dis 59:555–564
Ostensen M (2004) New insights into sexual functioning and fertility in rheumatic diseases. Best Pract Res Clin Rheumatol 18(2):219–232
Perselin R (1977) The effect of pregnancy on rheumatoid arthritis. Bull Rheum Dis 27:922
Silman A, Kay A, Brennan P (1992) Timing of pregnancy in relation to the onset of rheumatoid arthritis. Arthritis Rheum 35:152
Ostensen M, Husby G, Romberg O (1982) Ankylosing spondylitis and motherhood. Arthritis Rheum 25:140–143
Skomsvoll J, Ostensen M, Schei B (2000) Reproduction in women reporting chronic musculoskeletal disorders. Scand J Rheumatol 29:103–107
Ostensen M, Ostensen H (1998) Ankylosing spondylitis—the female aspect. J Rheumatol 25:120–124
Khamashta M, Hughes G (1996) Pregnancy in systemic lupus erythematosus. Curr Opin Rheumatol 8:424–442
Hardy C, Palmer BP, Morton S et al (1999) Pregnancy outcome and family size in systemic lupus erythematosus: a case-control study. Rheumatology 38:559–563
Clowse M, Madger L, Witter F et al (2006) Early risk factor for pregnancy loss in lupus. Obstet Gynecol 107:293–299
Ruiz-Irastorza G, Lima F, Alves J et al (1996) Increased rate of lupus flare during pregnancy and the puerperium; a prospective study of 78 pregnancies. Br J Rheumatol 35:133
Kong N (2006) Pregnancy of a lupus patient—a challenge to the nephrologist. Nephrol Dial Transplant 21:268
Lockshin M (1989) Pregnancy does not cause SLE to worsen. Arthritis Rheum 32:665
McNeil H, Chesterman C, Krilis S (1991) Immunology and clinical importance of antiphospholipid antibodies. Adv Immunol 49:193
Gordon P, Khamasthta M, Rosenthal E et al (2004) Anti-52 kDa Ro, anti-60 kDa Ro and anti-La antibody profiles in neonatal lupus. J Rheumatol 31:2480–2487
Tsakonas E, Esdaile J, Choquette D et al (1998) A long-term study on hydroxychloroquine withdrawal on exacerbations of systemic lupus erythematosus. The Canadian Hydroxychloroquine Study Group. Lupus 7(2):80–85
Steen V, Conte C, Day N et al (1989) Pregnancy in women with systemic sclerosis. Arthritis Rheum 32:151–157
Black C, Stevens W (1989) Scleroderma. Rheum Dis Clin North Am 15:193
Scialli A, Buelke-Sam J, Chambers C et al (2004) Communicating risks during pregnancy: a workshop on the use of data from animal developmental toxicity studies in pregnancy labels for drugs. Birth Defects Res A Clin Mol Teratol 70:7–12
Park-Wyllie L, Mazzotta P, Pastuszak A et al (2000) Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies. Teratology 62:385–392
Blanford A, Murphy B (1977) In vitro metabolism of prednisolone, dexamethasone, betamethasone, and cortisol by the human placenta. Am J Obstet Gynecol 127:264–267
Temprano K, Bandlamudi R, Moore T (2005) Antirheumatic drugs in pregnancy and lactation. Semin Arthritis Rheum 35:112–121
Ostensen M (2001) Rheumatological disorders. Best Pract Res Clin Obstet Gynaecol 15(6):953–969
Motta M, Tincani A (2002) Antimalarial agents in pregnancy. Lancet 359:524–525
Canadian Rheumatology Association (2000) Canadian Consensus Conference on Hydroxychloroquine. J Rheumatol 27:2919–2920
Costedoat-Chalumeau N, Amoura Z, Dunaut P et al (2003) Safety of hydroxychloroquine in pregnant patients with connective tissue disease. Arthritis Rheum 48:3207–3214
Chambers C, Tutuncu Z, Johnson D et al (2006) Human pregnancy safety for agents used to treat rheumatoid arthritis: adequacy of available information and strategies for developing post-marketing data. Arthritis Res Ther 8:215
Jarnerot G, Into-Malmberg M (1979) Sulphasalazine treatment during breastfeeding. Scand J Gastroentrol 14:869–871
Committee on Drugs (1994) American academy of pediatrics: the transfer of drugs and other chemicals into human milk. Pediatrics 93:137–150
Armenti V, Ahlswede K, Ahlswede B et al (1994) National transplantation pregnancy registry-outcome of 154 pregnancies in cyclosporine-treated female kidney transplant recipients. Transplantation 57:502
Armenti V, Radomski J, Moritz M et al (2001) Report from the National Transplantation Pregnancy Registry (NTPR): outcomes of pregnancy after transplantation. In: Terasaki P, Cecka JM (eds) Clinical transplants. UCLA Immunogenetics Center, Los Angeles, pp 97–105
Katz J, Keenan G, Snith D (2003) Outcome of pregnancy in patients receiving infliximab for the treatment of Crohn’s disease and rheumatoid arthritis. Digestive Disease Week May 17–22, 2004 Orlando, FL
Ostensen M, Eigenmann G (2004) Etanercept in breast milk. J Rheumatol 31:1017–1018
Kimby E, Sverrisdottir A, Elinder G (2004) Safety of rituximab therapy during the first trimester of pregnancy: a case history. Eur J Haematol 72:292–295
Herold M, Schnohr S, Bittrich H (2001) Efficacy and safety of a combined rituximab chemotherapy during pregnancy. J Clin Oncol 19:3439
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Presented as Medical Grand Rounds at the University of Alberta.
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Keeling, S.O., Oswald, A.E. Pregnancy and rheumatic disease: “by the book” or “by the doc”. Clin Rheumatol 28, 1–9 (2009). https://doi.org/10.1007/s10067-008-1031-9
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DOI: https://doi.org/10.1007/s10067-008-1031-9