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Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation

Bonnie L Bermas, MD
Section Editors
Daniel E Furst, MD
Charles J Lockwood, MD, MHCM
Deputy Editor
Paul L Romain, MD


Inflammatory disorders such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and inflammatory bowel disease (IBD) often occur in women of childbearing age. When considering treatment options, a major tenet of treating women during pregnancy is to minimize or avoid medications that may increase maternal or fetal risk. However, the relative benefits and risks to the mother and fetus of using a particular medication to maintain disease control or to treat active disease during pregnancy depend upon the specific clinical context and may be influenced by the stage of the pregnancy and other factors.

For practical purposes, we divide the antiinflammatory and immunosuppressive medications used to treat inflammatory disorders into four categories, recognizing that there are differences in risks between medications in any category and that some drugs may fall into more than one category depending upon various factors. These categories are:

Minimal fetal or maternal risk

Selective use allowed during pregnancy

Moderate to high risk of fetal harm


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Literature review current through: Sep 2016. | This topic last updated: Sep 9, 2016.
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  1. Parke A, West B. Hydroxychloroquine in pregnant patients with systemic lupus erythematosus. J Rheumatol 1996; 23:1715.
  2. Clowse ME, Magder L, Witter F, Petri M. Hydroxychloroquine in lupus pregnancy. Arthritis Rheum 2006; 54:3640.
  3. Buchanan NM, Toubi E, Khamashta MA, et al. Hydroxychloroquine and lupus pregnancy: review of a series of 36 cases. Ann Rheum Dis 1996; 55:486.
  4. Costedoat-Chalumeau N, Amoura Z, Duhaut P, et al. Safety of hydroxychloroquine in pregnant patients with connective tissue diseases: a study of one hundred thirty-three cases compared with a control group. Arthritis Rheum 2003; 48:3207.
  5. Canadian rheumatology association. Canadian Consensus Conference on hydroxychloroquine. J Rheumatol 2000; 27:2919.
  6. Järnerot G, Into-Malmberg MB, Esbjörner E. Placental transfer of sulphasalazine and sulphapyridine and some of its metabolites. Scand J Gastroenterol 1981; 16:693.
  7. Järnerot G, Andersen S, Esbjörner E, et al. Albumin reserve for binding of bilirubin in maternal and cord serum under treatment with sulphasalazine. Scand J Gastroenterol 1981; 16:1049.
  8. Hoo JJ, Hadro TA, Von Behren P. Possible teratogenicity of sulfasalazine. N Engl J Med 1988; 318:1128.
  9. Craxi A, Pagliarello F. Possible embryotoxicity of sulfasalazine. Arch Intern Med 1980; 140:1674.
  10. Hernández-Díaz S, Werler MM, Walker AM, Mitchell AA. Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med 2000; 343:1608.
  11. Mogadam M, Dobbins WO 3rd, Korelitz BI, Ahmed SW. Pregnancy in inflammatory bowel disease: effect of sulfasalazine and corticosteroids on fetal outcome. Gastroenterology 1981; 80:72.
  12. Levy N, Roisman I, Teodor I. Ulcerative colitis in pregnancy in Israel. Dis Colon Rectum 1981; 24:351.
  13. Esbjörner E, Järnerot G, Wranne L. Sulphasalazine and sulphapyridine serum levels in children to mothers treated with sulphasalazine during pregnancy and lactation. Acta Paediatr Scand 1987; 76:137.
  14. Järnerot G, Into-Malmberg MB. Sulphasalazine treatment during breast feeding. Scand J Gastroenterol 1979; 14:869.
  15. Branski D, Kerem E, Gross-Kieselstein E, et al. Bloody diarrhea--a possible complication of sulfasalazine transferred through human breast milk. J Pediatr Gastroenterol Nutr 1986; 5:316.
  16. Østensen M, Khamashta M, Lockshin M, et al. Anti-inflammatory and immunosuppressive drugs and reproduction. Arthritis Res Ther 2006; 8:209.
  17. Kozer E, Nikfar S, Costei A, et al. Aspirin consumption during the first trimester of pregnancy and congenital anomalies: a meta-analysis. Am J Obstet Gynecol 2002; 187:1623.
  18. Daniel S, Matok I, Gorodischer R, et al. Major malformations following exposure to nonsteroidal antiinflammatory drugs during the first trimester of pregnancy. J Rheumatol 2012; 39:2163.
  19. Nezvalová-Henriksen K, Spigset O, Nordeng H. Effects of ibuprofen, diclofenac, naproxen, and piroxicam on the course of pregnancy and pregnancy outcome: a prospective cohort study. BJOG 2013; 120:948.
  20. Askie LM, Duley L, Henderson-Smart DJ, et al. Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data. Lancet 2007; 369:1791.
  21. Koren G, Florescu A, Costei AM, et al. Nonsteroidal antiinflammatory drugs during third trimester and the risk of premature closure of the ductus arteriosus: a meta-analysis. Ann Pharmacother 2006; 40:824.
  22. Heymann MA, Rudolph AM, Silverman NH. Closure of the ductus arteriosus in premature infants by inhibition of prostaglandin synthesis. N Engl J Med 1976; 295:530.
  23. Heymann MA. Non-narcotic analgesics. Use in pregnancy and fetal and perinatal effects. Drugs 1986; 32 Suppl 4:164.
  24. Drug Facts and Comparisons. In: Facts and Comparison, 50th, Wolters Kluwer, St. Louis 1996.
  25. Ostensen M, Ramsey-Goldman R. Treatment of inflammatory rheumatic disorders in pregnancy: what are the safest treatment options? Drug Saf 1998; 19:389.
  26. Mendonça LL, Khamashta MA, Nelson-Piercy C, et al. Non-steroidal anti-inflammatory drugs as a possible cause for reversible infertility. Rheumatology (Oxford) 2000; 39:880.
  27. Uhler ML, Hsu JW, Fisher SG, Zinaman MJ. The effect of nonsteroidal anti-inflammatory drugs on ovulation: a prospective, randomized clinical trial. Fertil Steril 2001; 76:957.
  28. Pall M, Fridén BE, Brännström M. Induction of delayed follicular rupture in the human by the selective COX-2 inhibitor rofecoxib: a randomized double-blind study. Hum Reprod 2001; 16:1323.
  29. Nakhai-Pour HR, Broy P, Sheehy O, Bérard A. Use of nonaspirin nonsteroidal anti-inflammatory drugs during pregnancy and the risk of spontaneous abortion. CMAJ 2011; 183:1713.
  30. Nielsen GL, Sørensen HT, Larsen H, Pedersen L. Risk of adverse birth outcome and miscarriage in pregnant users of non-steroidal anti-inflammatory drugs: population based observational study and case-control study. BMJ 2001; 322:266.
  31. Li DK, Liu L, Odouli R. Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study. BMJ 2003; 327:368.
  32. Edwards DR, Aldridge T, Baird DD, et al. Periconceptional over-the-counter nonsteroidal anti-inflammatory drug exposure and risk for spontaneous abortion. Obstet Gynecol 2012; 120:113.
  33. Daniel S, Koren G, Lunenfeld E, et al. Fetal exposure to nonsteroidal anti-inflammatory drugs and spontaneous abortions. CMAJ 2014; 186:E177.
  34. Beitins IZ, Bayard F, Ances IG, et al. The transplacental passage of prednisone and prednisolone in pregnancy near term. J Pediatr 1972; 81:936.
  36. Mossey PA, Little J, Munger RG, et al. Cleft lip and palate. Lancet 2009; 374:1773.
  37. Carmichael SL, Shaw GM. Maternal corticosteroid use and risk of selected congenital anomalies. Am J Med Genet 1999; 86:242.
  38. Park-Wyllie L, Mazzotta P, Pastuszak A, et al. Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies. Teratology 2000; 62:385.
  39. Hviid A, Mølgaard-Nielsen D. Corticosteroid use during pregnancy and risk of orofacial clefts. CMAJ 2011; 183:796.
  40. Guller S, Kong L, Wozniak R, Lockwood CJ. Reduction of extracellular matrix protein expression in human amnion epithelial cells by glucocorticoids: a potential role in preterm rupture of the fetal membranes. J Clin Endocrinol Metab 1995; 80:2244.
  41. Lockwood CJ, Radunovic N, Nastic D, et al. Corticotropin-releasing hormone and related pituitary-adrenal axis hormones in fetal and maternal blood during the second half of pregnancy. J Perinat Med 1996; 24:243.
  42. Petri M. Immunosuppressive drug use in pregnancy. Autoimmunity 2003; 36:51.
  43. Ost L, Wettrell G, Björkhem I, Rane A. Prednisolone excretion in human milk. J Pediatr 1985; 106:1008.
  44. Saarikoski S, Seppälä M. Immunosuppression during pregnancy: transmission of azathioprine and its metabolites from the mother to the fetus. Am J Obstet Gynecol 1973; 115:1100.
  45. Nørgård B, Pedersen L, Christensen LA, Sørensen HT. Therapeutic drug use in women with Crohn's disease and birth outcomes: a Danish nationwide cohort study. Am J Gastroenterol 2007; 102:1406.
  46. Francella A, Dyan A, Bodian C, et al. The safety of 6-mercaptopurine for childbearing patients with inflammatory bowel disease: a retrospective cohort study. Gastroenterology 2003; 124:9.
  47. Moskovitz DN, Bodian C, Chapman ML, et al. The effect on the fetus of medications used to treat pregnant inflammatory bowel-disease patients. Am J Gastroenterol 2004; 99:656.
  48. Armenti VT, Ahlswede KM, Ahlswede BA, et al. National transplantation Pregnancy Registry--outcomes of 154 pregnancies in cyclosporine-treated female kidney transplant recipients. Transplantation 1994; 57:502.
  49. WHO Working Group on Drugs and Human Lactation. Drugs and Human Lactation. Elsevier; Amsterdam, 1988.
  50. EBPG Expert Group on Renal Transplantation. European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.10. Pregnancy in renal transplant recipients. Nephrol Dial Transplant 2002; 17 Suppl 4:50.
  51. Moretti ME, Verjee Z, Ito S, Koren G. Breast-feeding during maternal use of azathioprine. Ann Pharmacother 2006; 40:2269.
  52. Sau A, Clarke S, Bass J, et al. Azathioprine and breastfeeding: is it safe? BJOG 2007; 114:498.
  53. Coulam CB, Moyer TP, Jiang NS, Zincke H. Breast-feeding after renal transplantation. Transplant Proc 1982; 14:605.
  54. Grekas DM, Vasiliou SS, Lazarides AN. Immunosuppressive therapy and breast-feeding after renal transplantation. Nephron 1984; 37:68.
  55. Roux CH, Brocq O, Breuil V, et al. Pregnancy in rheumatology patients exposed to anti-tumour necrosis factor (TNF)-alpha therapy. Rheumatology (Oxford) 2007; 46:695.
  56. Vinet E, Pineau C, Gordon C, et al. Biologic therapy and pregnancy outcomes in women with rheumatic diseases. Arthritis Rheum 2009; 61:587.
  57. Ali YM, Kuriya B, Orozco C, et al. Can tumor necrosis factor inhibitors be safely used in pregnancy? J Rheumatol 2010; 37:9.
  58. Chambers C, Johnson DL, Jones KL, the OTIS Collaborative Research Group. Pregnancy outcome in women exposed to anti-TNF-alpha medications: The OTIS Rheumatoid Arthritis in Pregnancy Study. Arthritis Rheum 2004; 50:S479.
  59. Hyrich KL, Symmons DP, Watson KD, et al. Pregnancy outcome in women who were exposed to anti-tumor necrosis factor agents: results from a national population register. Arthritis Rheum 2006; 54:2701.
  60. Katz JA, Antoni C, Keenan GF, et al. Outcome of pregnancy in women receiving infliximab for the treatment of Crohn's disease and rheumatoid arthritis. Am J Gastroenterol 2004; 99:2385.
  61. Ventura SJ, Mosher WD, Curtin SC, et al. Trends in pregnancies and pregnancy rates by outcome: estimates for the United States, 1976-96. Vital Health Stat 21 2000; :1.
  62. Coburn LA, Wise PE, Schwartz DA. The successful use of adalimumab to treat active Crohn's disease of an ileoanal pouch during pregnancy. Dig Dis Sci 2006; 51:2045.
  63. Strangfeld A. Pregnancy outcome after exposure to biologics: results from the German biologics register RABBIT. Arthritis Rheum 2007; 56:S311.
  64. Clowse ME, Wolf DC, Förger F, et al. Pregnancy Outcomes in Subjects Exposed to Certolizumab Pegol. J Rheumatol 2015; 42:2270.
  65. Treacy G. Using an analogous monoclonal antibody to evaluate the reproductive and chronic toxicity potential for a humanized anti-TNFalpha monoclonal antibody. Hum Exp Toxicol 2000; 19:226.
  66. Reprotox Agent Detail - Adalimumab www.reprotox.org/Members/AgentDetail.aspx?a=4262 (Accessed on March 25, 2010).
  67. Carter JD, Valeriano J, Vasey FB. Tumor necrosis factor-alpha inhibition and VATER association: a causal relationship. J Rheumatol 2006; 33:1014.
  68. Carter JD, Ladhani A, Ricca LR, et al. A safety assessment of tumor necrosis factor antagonists during pregnancy: a review of the Food and Drug Administration database. J Rheumatol 2009; 36:635.
  69. Koren G, Inoue M. Do tumor necrosis factor inhibitors cause malformations in humans? J Rheumatol 2009; 36:465.
  70. Crijns HJ, Jentink J, Garne E, et al. The distribution of congenital anomalies within the VACTERL association among tumor necrosis factor antagonist-exposed pregnancies is similar to the general population. J Rheumatol 2011; 38:1871.
  71. Weber-Schoendorfer C, Oppermann M, Wacker E, et al. Pregnancy outcome after TNF-α inhibitor therapy during the first trimester: a prospective multicentre cohort study. Br J Clin Pharmacol 2015; 80:727.
  72. Brown D, Nesbitt A, Stephens S, Foulkes R. Lack of placental transfer and accumulation in milk of an anti-TNF PEGylated Fab fragment in rats. Inflamm Bowel Dis 2007; 13:656.
  73. Mahadevan U, Wolf DC, Dubinsky M, et al. Placental transfer of anti-tumor necrosis factor agents in pregnant patients with inflammatory bowel disease. Clin Gastroenterol Hepatol 2013; 11:286.
  74. Martin PL, Oneda S, Treacy G. Effects of an anti-TNF-alpha monoclonal antibody, administered throughout pregnancy and lactation, on the development of the macaque immune system. Am J Reprod Immunol 2007; 58:138.
  75. Ostensen M, Eigenmann GO. Etanercept in breast milk. J Rheumatol 2004; 31:1017.
  76. Stengel JZ, Arnold HL. Is infliximab safe to use while breastfeeding? World J Gastroenterol 2008; 14:3085.
  77. Flint J, Panchal S, Hurrell A, et al. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatology (Oxford) 2016; 55:1693.
  78. van der Woude CJ, Ardizzone S, Bengtson MB, et al. The second European evidenced-based consensus on reproduction and pregnancy in inflammatory bowel disease. J Crohns Colitis 2015; 9:107.
  79. Sheibani S, Cohen R, Kane S, et al. The effect of maternal peripartum anti-TNFa use on infant immune response. Dig Dis Sci 2016.
  80. Bakimer R, Guilburd B, Zurgil N, Shoenfeld Y. The effect of intravenous gamma-globulin on the induction of experimental antiphospholipid syndrome. Clin Immunol Immunopathol 1993; 69:97.
  81. Höckel M, Kaufmann R. Placental transfer of class G immunoglobulins treated with beta-propiolactone (beta-PL) for intravenous application--a case report. J Perinat Med 1986; 14:205.
  82. Potter M, Stockley R, Storry J, Slade R. ABO alloimmunisation after intravenous immunoglobulin infusion. Lancet 1988; 1:932.
  83. Reznikoff-Etievant MF, de Lachaux Y, Marpeau L, Couroucé A. Intravenous immunoglobulins and hepatitis C transmission in healthy pregnant women. Lancet 1992; 340:986.
  84. Palmeira P, Costa-Carvalho BT, Arslanian C, et al. Transfer of antibodies across the placenta and in breast milk from mothers on intravenous immunoglobulin. Pediatr Allergy Immunol 2009; 20:528.
  85. Tanaka H, Haba R, Itoh S, et al. Prenatal high-dose immunoglobulin treatment for neonatal hemochromatosis: a case report and review of the literature. J Obstet Gynaecol Res 2011; 37:1891.
  86. Bäckman L, Brandt I, Appelkvist EL, Dallner G. Tissue and subcellular localizations of 3H-cyclosporine A in mice. Pharmacol Toxicol 1988; 62:110.
  87. Schmid BP. Monitoring of organ formation in rat embryos after in vitro exposure to azathioprine, mercaptopurine, methotrexate or cyclosporin A. Toxicology 1984; 31:9.
  88. Mason RJ, Thomson AW, Whiting PH, et al. Cyclosporine-induced fetotoxicity in the rat. Transplantation 1985; 39:9.
  89. Nandakumaran M, Eldeen AS. Transfer of cyclosporine in the perfused human placenta. Dev Pharmacol Ther 1990; 15:101.
  90. Venkataramanan R, Koneru B, Wang CC, et al. Cyclosporine and its metabolites in mother and baby. Transplantation 1988; 46:468.
  91. Di Paolo S, Monno R, Stallone G, et al. Placental imbalance of vasoactive factors does not affect pregnancy outcome in patients treated with Cyclosporine A after transplantation. Am J Kidney Dis 2002; 39:776.
  92. Lewis GJ, Lamont CA, Lee HA, Slapak M. Successful pregnancy in a renal transplant recipient taking cyclosporin A. Br Med J (Clin Res Ed) 1983; 286:603.
  93. Flechner SM, Katz AR, Rogers AJ, et al. The presence of cyclosporine in body tissues and fluids during pregnancy. Am J Kidney Dis 1985; 5:60.
  94. Burrows DA, O'Neil TJ, Sorrells TL. Successful twin pregnancy after renal transplant maintained on cyclosporine A immunosuppression. Obstet Gynecol 1988; 72:459.
  95. Löwenstein BR, Vain NW, Perrone SV, et al. Successful pregnancy and vaginal delivery after heart transplantation. Am J Obstet Gynecol 1988; 158:589.
  96. Ziegenhagen DJ, Crombach G, Dieckmann M, et al. [Pregnancy during cyclosporin medication following a kidney transplant]. Dtsch Med Wochenschr 1988; 113:260.
  97. al-Khader AA, Absy M, al-Hasani MK, et al. Successful pregnancy in renal transplant recipients treated with cyclosporine. Transplantation 1988; 45:987.
  98. Sims CJ, Porter KB, Knuppel RA. Successful pregnancy after a liver transplant. Am J Obstet Gynecol 1989; 161:532.
  99. Kossoy LR, Herbert CM 3rd, Wentz AC. Management of heart transplant recipients: guidelines for the obstetrician-gynecologist. Am J Obstet Gynecol 1988; 159:490.
  100. Munoz-Flores-Thiagarajan KD, Easterling T, Davis C, Bond EF. Breast-feeding by a cyclosporine-treated mother. Obstet Gynecol 2001; 97:816.
  101. Moretti ME, Sgro M, Johnson DW, et al. Cyclosporine excretion into breast milk. Transplantation 2003; 75:2144.
  102. Cockburn I, Krupp P, Monka C. Present experience of Sandimmun in pregnancy. Transplant Proc 1989; 21:3730.
  103. Bar Oz B, Hackman R, Einarson T, Koren G. Pregnancy outcome after cyclosporine therapy during pregnancy: a meta-analysis. Transplantation 2001; 71:1051.
  104. Nyberg G, Haljamäe U, Frisenette-Fich C, et al. Breast-feeding during treatment with cyclosporine. Transplantation 1998; 65:253.
  105. Osadchy A, Koren G. Cyclosporine and lactation: when the mother is willing to breastfeed. Ther Drug Monit 2011; 33:147.
  106. American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001; 108:776.
  107. Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation, 9th, Lippincott Williams & Wilkins, Philadelphia 2011. p.1381.
  108. Kainz A, Harabacz I, Cowlrick IS, et al. Review of the course and outcome of 100 pregnancies in 84 women treated with tacrolimus. Transplantation 2000; 70:1718.
  109. Jain A, Venkataramanan R, Fung JJ, et al. Pregnancy after liver transplantation under tacrolimus. Transplantation 1997; 64:559.
  110. Jain AB, Shapiro R, Scantlebury VP, et al. Pregnancy after kidney and kidney-pancreas transplantation under tacrolimus: a single center's experience. Transplantation 2004; 77:897.
  111. French AE, Soldin SJ, Soldin OP, Koren G. Milk transfer and neonatal safety of tacrolimus. Ann Pharmacother 2003; 37:815.
  112. Gardiner SJ, Begg EJ. Breastfeeding during tacrolimus therapy. Obstet Gynecol 2006; 107:453.
  113. Kart Köseoglu H, Yücel AE, Künefeci G, et al. Cyclophosphamide therapy in a serious case of lupus nephritis during pregnancy. Lupus 2001; 10:818.
  114. Berry DL, Theriault RL, Holmes FA, et al. Management of breast cancer during pregnancy using a standardized protocol. J Clin Oncol 1999; 17:855.
  115. Ring AE, Smith IE, Jones A, et al. Chemotherapy for breast cancer during pregnancy: an 18-year experience from five London teaching hospitals. J Clin Oncol 2005; 23:4192.
  116. Clowse ME, Magder L, Petri M. Cyclophosphamide for lupus during pregnancy. Lupus 2005; 14:593.
  117. Wiernik PH, Duncan JH. Cyclophosphamide in human milk. Lancet 1971; 1:912.
  118. Skalko RG, Gold MP. Teratogenicity of methotrexate in mice. Teratology 1974; 9:159.
  119. Buckley LM, Bullaboy CA, Leichtman L, Marquez M. Multiple congenital anomalies associated with weekly low-dose methotrexate treatment of the mother. Arthritis Rheum 1997; 40:971.
  120. Milunsky A, Graef JW, Gaynor MF Jr. Methotrexate-induced congenital malformations. J Pediatr 1968; 72:790.
  121. Kozlowski RD, Steinbrunner JV, MacKenzie AH, et al. Outcome of first-trimester exposure to low-dose methotrexate in eight patients with rheumatic disease. Am J Med 1990; 88:589.
  122. Ostensen M, Hartmann H, Salvesen K. Low dose weekly methotrexate in early pregnancy. A case series and review of the literature. J Rheumatol 2000; 27:1872.
  123. Chakravarty EF, Sanchez-Yamamoto D, Bush TM. The use of disease modifying antirheumatic drugs in women with rheumatoid arthritis of childbearing age: a survey of practice patterns and pregnancy outcomes. J Rheumatol 2003; 30:241.
  124. Lewden B, Vial T, Elefant E, et al. Low dose methotrexate in the first trimester of pregnancy: results of a French collaborative study. J Rheumatol 2004; 31:2360.
  125. Johns DG, Rutherford LD, Leighton PC, Vogel CL. Secretion of methotrexate into human milk. Am J Obstet Gynecol 1972; 112:978.
  126. Sifontis NM, Coscia LA, Constantinescu S, et al. Pregnancy outcomes in solid organ transplant recipients with exposure to mycophenolate mofetil or sirolimus. Transplantation 2006; 82:1698.
  127. www.rocheusa.com/products/cellcept/pregnancy_notice.pdf (Accessed on September 14, 2011).
  128. Hoeltzenbein M, Elefant E, Vial T, et al. Teratogenicity of mycophenolate confirmed in a prospective study of the European Network of Teratology Information Services. Am J Med Genet A 2012; 158A:588.
  129. Klieger-Grossmann C, Chitayat D, Lavign S, et al. Prenatal exposure to mycophenolate mofetil: an updated estimate. J Obstet Gynaecol Can 2010; 32:794.
  130. US Food and Drug Administration Information for Healthcare Professionals: Mycophenolate Mofetil (marketed as CellCept) and Mycophenolic Acid (marketed as Myfortic) http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm124776.htm (Accessed on June 02, 2014).
  131. Perez-Aytes A, Ledo A, Boso V, et al. In utero exposure to mycophenolate mofetil: a characteristic phenotype? Am J Med Genet A 2008; 146A:1.
  132. Downs SM. Induction of meiotic maturation in vivo in the mouse by IMP dehydrogenase inhibitors: effects on the developmental capacity of ova. Mol Reprod Dev 1994; 38:293.
  133. Brent RL. Teratogen update: reproductive risks of leflunomide (Arava); a pyrimidine synthesis inhibitor: counseling women taking leflunomide before or during pregnancy and men taking leflunomide who are contemplating fathering a child. Teratology 2001; 63:106.
  134. De Santis M, Straface G, Cavaliere A, et al. Paternal and maternal exposure to leflunomide: pregnancy and neonatal outcome. Ann Rheum Dis 2005; 64:1096.
  135. Heine K, Poets CF. A pair of twins born after maternal exposure to leflunomide. J Perinatol 2008; 28:841.
  136. Neville CE, McNally J. Maternal exposure to leflunomide associated with blindness and cerebral palsy. Rheumatology (Oxford) 2007; 46:1506.
  137. Chambers CD, Johnson DL, Robinson LK, et al. Birth outcomes in women who have taken leflunomide during pregnancy. Arthritis Rheum 2010; 62:1494.
  138. Cassina M, Johnson DL, Robinson LK, et al. Pregnancy outcome in women exposed to leflunomide before or during pregnancy. Arthritis Rheum 2012; 64:2085.
  139. Fukushima R, Kanamori S, Hirashiba M, et al. Teratogenicity study of the dihydroorotate-dehydrogenase inhibitor and protein tyrosine kinase inhibitor Leflunomide in mice. Reprod Toxicol 2007; 24:310.
  140. Physician's Desk Reference, Edition 58. Montvale, NJ, Thomson PDR, 2004; 31:1017.
  141. Friedrichs B, Tiemann M, Salwender H, et al. The effects of rituximab treatment during pregnancy on a neonate. Haematologica 2006; 91:1426.
  142. Kimby E, Sverrisdottir A, Elinder G. Safety of rituximab therapy during the first trimester of pregnancy: a case history. Eur J Haematol 2004; 72:292.
  143. Herold M, Schnohr S, Bittrich H. Efficacy and safety of a combined rituximab chemotherapy during pregnancy. J Clin Oncol 2001; 19:3439.
  144. Abatacept (Orencia) for rheumatoid arthritis. Med Lett Drugs Ther 2006; 48:17.
  145. Full prescribing information for Actemra (tocilizumab) www.gene.com/gene/products/information/actemra/pdf/pi.pdf (Accessed on June 09, 2010).
  146. Rubbert-Roth A, Goupile PM, Moosavi S, et al. First experiences with pregnancies in RA patients receiving tocilizumab therapy (abstract). Arthritis Rheum 2010; Suppl:384.
  147. Marren A, Chen Y, Frazier D, Geier J. Pregnancy outcomes in the tofacitinib RA safety database through April 2014, American College of Rheumatology Annual Meeting, Boston, November 2014.