Summary
Women with rheumatic diseases frequently need treatment throughout pregnancy and lactation. Physicians must confront the dual challenge of monitoring the possible effects of the underlying maternal disease and the medications on both mother and child. It is essential that the maternal disease is well controlled before, during and after pregnancy to ensure the best possible outcome for the mother and child.
Glucocorticoids have been used extensively in pregnant patients with systemic lupus erythematosus and rheumatoid arthritis; there have been no reports of congenital malformations in the exposed infants. There is limited information on the safety of disease-modifying antirheumatic drugs, including hydroxychloroquine, cyclosporin, oral and parenteral gold and sulfasalazine, during pregnancy. However, penicillamine, another disease-modifying antirheumatic drug, is contra-indicated during pregnancy.
There is considerable experience with the use of azathioprine during pregnancy if the maternal condition requires a cytotoxic drug. There has been no increased risk of congenital malformations in the exposed infants. The other cytotoxic drugs frequently used in the treatment of rheumatic diseases, chlorambucil, cyclophosphamide and methotrexate, are contraindicated during pregnancy.
Glucocorticoids (such as prednisone and methylprednisolone) and hydroxychloroquine are considered to be safe during lactation. Oral and parenteral gold and sulfasalazine can be used with caution during lactation. Penicillamine, cyclosporin and all cytotoxic drugs are contraindicated during lactation.
Similar content being viewed by others
References
Briggs GG, Freeman RK, Yaffe SJ, editors. Drugs in pregnancy and lactation. Baltimore: Williams and Wilkins, 1989
Urowitz MB, Gladman DD, Farewell VT, et al. Lupus and pregnancy studies. Arthritis Rheum 1993; 36: 1392–7
Cecere PA, Persellin RH. The interaction of pregnancy and the rheumatic diseases. Clin Rheumatol 1981; 7: 747–68
Needs C, Brooks P. Drugs, pregnancy, and rheumatoid arthritis. In: Klippel JH, Dieppe PA, editors. Rheumatology. London: Mosby Year Book, 1994; 18: 4–6
Hazes JMW. Pregnancy and its effect on the risk of developing rheumatoid arthritis. Ann Rheum Dis 1991; 50: 71–4
Lockshin MD, Druzin ML. Rheumatic disease. In: Barron WM, Lindheimer MD, editors. Medical disorders during pregnancy. St Louis: Mosby Year Book, 1991; 366–99
Palit J, Clague RB. Wegener’s granulomatous presenting during first trimester of pregnancy. Br J Rheumatol 1990; 29: 389–90
Barron WB, Lindheimer MD, editors. Medical disorders during pregnancy. St Louis: Mosby Year Book, 1991
Corby DG. Aspirin in pregnancy: maternal and fetal effects. Pediatrics 1978; 62: 930–7
Brooks PM, Needs CJ. The use of antirheumatic medication during pregnancy and in the Puerperium. Rheum Dis Clin North Am 1989; 15: 789–806
Werler MM, Mitchell AA, Shapiro S. The relation of aspirin use during the first trimester of pregnancy to congenital cardiac defects. N Engl J Med 1989; 321: 1639–42
Barton JR, Sibal BM. Low-dose aspirin to improve perinatal outcome. Clin Obstet Gynecol 1991; 34: 251–61
Pritchard JA. Changes in blood volume during pregnancy and delivery. Anaesthesia 1965; 26: 293
Mendenhall HW. Serum protein concentrations in pregnancy. 1. Concentration in maternal serum. Am J Obstet Gynecol 1970; 106: 388
Dettli L, Spring P. The modifying effect of physiologic variables and disease upon pharmacokinetics. In: Pharmacology and the future of man. Proceedings of the Fifth International Congress on Pharmacology; San Francisco, 1992: Basel, Karger: 3: 165–73
The Nutrition Committee of the Canadian Pediatric Society and the Committee on Nutrition of the American Academy of Pediatrics. Breast feeding. Pediatrics 1978; 62: 591–601
Berlin CM. Pharmacological considerations of drug use in the lactating mother. Obstet Gynecol 1981; 58 Suppl.: 17–23
Maksymowych W, Russell AS. Antimalarials in rheumatology: efficacy and safety. Semin Arthritis Rheum 1987; 3: 206–21
Tett S, Cutler D, Day R. Antimalarials in rheumatic diseases. Balliere’s Clin Rheumatol 1990; 4: 467–89
Fox RI, Kang H-I. Mechanism of action of antimalarial drugs: inhibition of antigen processing and presentation. Lupus 1993; 2 Suppl.: S9–S12
Fox R. Antimalarial drugs: mechanisms of action in autoimmune disease and prospects for drug development. Clin Immunother 1995; 4(3): 219–34
Buchanan NMM, Toubi E, Khamashta MA, et al. The safety of hydroxychloroquine in lupus pregnancy: experience in 24 pregnancies. Br J Rheumatol 1995; 35 Suppl. 1: 14
Dencker L, Lindquist NJ, Ullberg S, et al. Distribution of an I-125 labelled chloroquin analogue in a pregnant macaca monkey. Toxicology 1975; 5: 255–64
Ullberg S, Lindquist NJ, Siostrand SE. Accumulation of chorioretinotoxic drugs in the foetal eye. Nature 1970; 227: 1257–8
Mgbodile MU. Effects of perinatal exposure of albino rats to chloroquin. Biol Neonate 1987; 51: 273–6
Campbell PM, Wilske K. In: Weaver AL, editor. Guidelines for reviewers of rheumatic disease care. 2nd ed. Atlanta: American College of Rheumatology, 1989
O’Day R. SAARDS-I. In: Klippel JH, Dieppe PA, editors. Rheumatology. London: Mosby Year Book, 1994; 12: 1–9
Akintonwa A. Placental and milk transfer of chloroquine in humans. Ther Drug Monit 1988; 10: 147–9
Neill WA, Panay GS, Duthie JJR, et al. Action of chloroquine phosphate in rheumatoid arthritis. II. chromosomal damaging effect. Ann Rheum Dis 1972; 32: 547–50
Wolfe MS, Cordero JF. Safety of chloroquine in chemosuppression of malaria during pregnancy. BMJ 1985; 290: 1466–7
Paufique L, Magnard P. Retinal degeneration in 2 children following preventive antimalarial treatment of mother during pregnancy. Bull Soc Ophthalmol Fr 1969; 69: 466–77
Parke AL. Antimalarial drugs, systemic lupus erythematosus and pregnancy. J Rheumatol 1988; 15: 607–10
Hart CN, Naunton RF. The ototoxicity of chloroquine phosphate. Arch Otolaryngol Head Neck Surg 1964; 80: 407–12
Ross JB, Garatsos S. Absence of chloroquine-induced ototoxicity in a fetus. Arch Dermatol 1974; 109: 573
MacKenzie AH. Antimalarial drugs for rheumatoid arthritis (oral gold symposium). Am J Med 1983; 75: 48–58
Roubenoff R, Hoyt I, Petri M, et al. Effects of antiinflammatory and immunosuppressive drugs on pregnancy and fertility. Semin Arthritis Rheum 1988; 18: 88–110
The Canadian Hydroxychloroquine Study Group. A randomized study of the effect of withdrawing hydroxychloroquine sulfate in systemic lupus erythematosus. N Engl J Med 1991; 324: 150–4
Merland R, Creste M. Study of the elimination and estimation of nivaquine in human milk. Med Trop 1951; 11: 793
Nation RL, Hackett LP, Dusci LG, et al. Excretion of hydroxychloroquine in human milk. Br J Clin Pharmacol 1984; 17: 368–9
Ostensen M, Brown ND, Chiang PK, et al. Hydroxychloroquine in human breast milk. Eur J Clin Pharmacol 1985; 28: 357
Anderson PO. Drugs and breast feeding. Drug Intell Clin Pharm 1977; 11: 210–1
American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 1989; 84: 924–36
Tsokos GC. Immunomodulatory treatments in patients with rheumatic diseases: mechanism of action. Semin Arthritis Rheum 1987; 17: 24–38
Britton S, Palacios R. Cyclosporin A — usefulness, risks and mechanism of action. Immunol Rev 1982; 65: 5–22
Mason RJ, Thomson AW, Whiting PH, et al. Cyclosporine-induced fetotoxicity in the rat. Transplantation 1985; 39: 9–12
Brown PAJ, Gray ES, Whiting PH, et al. Effects of cyclosporin A on fetal development in the rat. Biol Neonate 1985; 48: 172–80
Tugwell P, Bombardier C, Geut M, et al. Low-dose cyclosporin versus placebo in patients with rheumatoid arthritis. Lancet 1990; 335: 1051–5
Yocum DE, Klippel JH, Wilder RL, et al. Cyclosporin A in severe, treatment refractory rheumatoid arthritis. Ann Intern Med 1988; 109: 863–9
Kowal A, Carstens Jr JH, Schnitzer TJ. Cyclosporine in rheumatoid arthritis. In: Furst DE, Weinblatt ME, editors. Immunomodulators in the rheumatic diseases. New York: Marcel Dekker, 1990
Tokuda M, Kurata N, Mizoguchi A, et al. Effect of low-dose cyclosporin A on systemic lupus erythematosus disease activity. Arthritis Rheum 1994; 37: 551–8
Lewis GJ, Larmont CAR, Lee HA, et al. Successful pregnancy in a renal transplant recipient taking cyclosporin A. BMJ 1983; 286: 603
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: 60–3
Burrows DA, O’Neil TJ, Sorrells TL. Successful twin pregnancy after renal transplant maintained on cyclosporine A immunosuppression. Obstet Gynecol 1988; 72: 459–61
Lowenstein BR, Vain NW, Perrone SV, et al. Successful pregnancy after and vaginal delivery after heart transplantation. Am J Obstet Gynecol 1988; 158: 589–90
Ostensen M. Treatment with immunosuppressive and disease modifying drugs during pregnancy and lactation. Am J Reprod Immunol 1992; 28: 148–52
Cockburn I, Krupp P, Monka C. Present experience of Sandimmun in pregnancy. Transplant Proc 1989; 21: 3730–2
Pujals JM, Figueras G, Puig JM, et al. Osseous malformation in baby born to woman on cyclosporin. Lancet 1989; 1: 667
Hussein MM, Mooij JMV, Roujouleh H. Cyclosporine in the treatment of lupus nephritis including two patients treated during pregnancy. Clin Nephrol 1993; 40: 160–3
Calne RY, Brons IGM, Williams PF, et al. Successful pregnancy after paratropic segmental pancreas and kidney transplantation. BMJ 1988; 296: 1709
Baarsna R, Kamps WA. Immunological responses in an infant after cyclosporine A exposure during pregnancy. Eur J Pediatr 1993; 152: 476–7
Product information. Sandimmune. Sandoz Pharmaceutical Corporation, 1991
Joyce DA. D-Penicillamine. Clin Rheumatol 1990; 4: 553–74
Keen CL, Mark-Savage P, Lormerdal BO, et al. Teratogenic effects of d-penicillamine in rats: relation to copper deficiency. Drug Nutr Interact 1983; 2: 17–34
Steffek AJ, Verussio AC, Watkins CA. Cleft palate in rodents after maternal treatment with lathyrogenic agents. Teratology 1972; 5: 33–8
Stivers FE, Steffek AJ, Yarington CT. Effect of lathyrogens on developing midfacial structures in the rat. J Surg Res 1971; 11: 415–20
Harpey JP, Jandon MC, Clavel JP, et al. Cutis laxa and low serum zinc after antenatal exposure to d-penicillamine in rats. Lancet 1983; 2: 858
Steen VD, Blair S, Medsger TAJ. The toxicity of d-penicillamine in systemic sclerosis. Ann Intern Med 1986; 104: 699–705
Steen VD. When and how to use penicillamine for systemic sclerosis. J Musculoskeletal Med 1989; 4: 72–87
Lyle WH. Penicillamine in pregnancy. Lancet 1978; 1: 606–7
Mjolnerod OK, Rasmussen K, Dommerud SA, et al. Congenital connective-tissue defect probably due to d-penicillamine treatment in pregnancy. Lancet 1971; 1: 673–4
Solomon L, Abrams G, Dinner M, et al. Neonatal abnormalities associated with d-penicillamine treatment during pregnancy. N Engl J Med 1977; 296: 54–5
Gregory MC, Mansell MA. Pregnancy and cystinuria. Lancet 1983; 2: 1158–60
Paulus HE, Bulpitt KJ. Nonsteroidal antiinflammatory agents and corticosteroids. In: Schumacher HR, Klippel JH, Koopman WJ, editors. Primer on the rheumatic diseases. Atlanta: Arthritis Foundation, 1993: 298–303
Walker B. Induction of cleft palate in rats with antiinflammatory drugs. Teratology 1971; 4: 39–42
Pinsky L, DiGeorge AM. Cleft palate in the mouse: a teratogenic index of glucocorticoid potency. Science 1965; 147: 402–3
Walker BE. Induction of cleft palate in rabbits by several glucocorticoids. Proc Soc Exp Biol Med 1967; 125: 1281–4
Reinisch JM, Simon NG. Prenatal exposure to prednisone in humans and animals retards intrauterine growth. Science 1978; 202: 436–8
Petri M. Systemic lupus erythematosus and pregnancy. Rheum Dis Clin North Am 1994; 20: 87–118
Blanford AT, Murphy BEP. In vitro metabolism of prednisone, dexamethasone, and cortisol by the human placenta. Am J Obstet Gynecol 1977; 127: 264–7
Schardein JL. Chemically induced birth defects. New York: Marcel Dekker, 1985
Connolly ME. The pharmacologic management of systemic lupus erythematosus in pregnancy. Ann Intern Med 1981; 94: 671–2
Scott JR. Fetal growth retardation associated with maternal administration of immunosuppressives. Am J Obstet Gynecol 1977; 128: 668–76
Kraus AM. Congenital cataract and maternal steroid injection. J Pediatr Ophthalmol Strabismus 1975; 12: 107–8
Cote CJ, Meuwissen HJ, Pickering RJ, et al. Effects on the neonate of prednisone and azathioprine administered to the mother during pregnancy. J Pediatr 1974; 85: 324–8
Cederqvist LL, Merkatz IR, Litwin SD, et al. Fetal immunoglobulin synthesis following maternal immunosuppression. Am J Obstet Gynecol 1977; 129: 687–90
Ramsey-Goldman R. Pregnancy in systemic lupus erythematosus. Rheum Dis Clin North Am 1988; 14: 169–85
Grigor RR, Shervington PC, Hughes GRV, et al. Outcome of pregnancy in systemic lupus erythematosus. Proc Soc Exp Biol Med 1977; 70: 99–100
Ost L, Wettrell G, Bjorkhem I, et al. Prednisolone excretion in human milk. J Pediatr 1985; 106: 1008–111
Szabo KT, Difebb ME, Phelan DG. The effect of gold containing compounds on pregnant rabbits and their fetuses. Vet Pathol 1978; 15: 95–8
Anonymous. Drugs for rheumatoid arthritis. Med Lett Drugs Ther 1994; 36: 101–6
Richards AJ. Transfer of gold from mother to foetus. Lancet 1977; 1: 99
Rocker I, Hendeson MJH. Transfer of gold from mother to foetus. Lancet 1976; 2: 1246
Miyamoto T, Miyaji S, Horiuchi T, et al. Gold therapy in bronchial asthma: special emphasis upon blood levels of gold and its teratogenicity. Nippon Naika Gakkai Zasshi 1974; 63: 190–7
Tozman ECS, Gottlieb NL. Adverse reactions with oral and parenteral gold preparations. Med Toxicol Adverse Drug Exper 1987; 2: 177–89
Blau SP. Metabolism of gold during lactation. Arthritis Rheum 1973; 16: 777–8
Xiong JM, Liang B, Mo YQ, et al. Teratologic studies of methyl 5-aminosalicylate and salicylazopyridine. Acta Pharmacol Sin 1992; 13: 265–7
Folb PI, Graham Dukes MN, editors. Drug safety in pregnancy. Amsterdam: Elsevier, 1990
Jarnerot G, Into-Malmberg MB, Esbjorner E. Placental transfer of sulphasalazine and sulphapyridine and some of its metabolites. Scand J Gastroenterol 1981; 16: 693–7
Mogadam M, Dobbins WOIII, Korelitz BI, et al. Pregnancy in IBD: effect of sulphasalazine and corticosteroids on fetal outcome. Gastroenterology 1981; 80: 72–6
Craxi A, Pagliarello F. Possible embryotoxicity of sulfasalazine [letter]. Arch Intern Med 1980; 140: 1674
Hoo JJ, Hadro TA, von Behren P. Possible teratogenicity of sulfasalazine. N Engl J Med 1988; 318: 1128
Newman NM, Correy JF. Possible teratogenicity of sulphasalazine. Med J Aust 1983; 1: 528–9
Levi S, Liberman M, Levi AJ, et al. Reversible congenital neutropenia associated with maternal sulphasalazine therapy [letter]. Eur J Pediatr 1988; 148: 174–5
Branski D, Kerem E, Gross-Kieselstein E, et al. Bloody diarrhea — a possible complication of sulphasalazine transferred through human breast milk. J Pediatr Gastroenterol Nutr 1986; 5: 316–7
McKendry RJR. Purine analogs. In: Dixon JS, Furst DE, editors. Second line agents in the treatment of rheumatic diseases. New York: Marcel Dekker, 1991
Clements PJ. Cytotoxic immunosuppressive drugs. In: Paulus HE, Furst DE, Dromgooles H, editors. Drugs for rheumatic disease. New York: Marcel Dekker, 1987: 135–6
Furst DE, Clements PJ. SAARDs-II. In: Klippel JH, Dieppe PE, editors. Rheumatology. London: Mosby Year Book, 1994; 13: 1–7
Githens JH, Rosencrantz JG, Tunnock SM, et al. Teratogenic effects of azathioprine (Imuran). J Pediatr 1965; 66: 962–3
Fujii TM, Kowa Y. Teratogenesis of azathioprine (Imuran) in mice and rats. Oyo Yakuri 1968; 2: 401
Tuchmann-Duplessis H, Mercier-Parot L. Production in rabbits of malformations of the extremities by administration of azathioprine and 6-mercaptopurine. C R Seances Soc Biol Fil 1966; 160: 501–6
Davison JM, Dellagrammatikas H, Parkin JM, et al. Maternal azathioprine therapy and depressed haematopoiesis in the babies of renal allograft patients. Br J Obstet Gynaecol 1985; 92: 233–9
Rudolph JE, Schweizer RT, Bartkus SA. Pregnancy in renal transplant patients. Transplantation 1979; 27: 26–9
The Registration Committee of the European Dialysis and Transplant Association. Successful pregnancies in women treated by dialysis and kidney transplantation. Br J Obstet Gynaecol 1980; 87: 839–45
Felson DT, Anderson J. Evidence for the superiority of immunosuppressive drugs and prednisone over prednisone alone in lupus nephritis. Results of a pooled analysis. N Engl J Med 1984; 311: 1528–33
Leb DE, Weisskopf B, Kanovitz BS. Chromosome aberrations in the child of a kidney transplant recipient. Arch Intern Med 1971; 128: 441–4
Marushak A, Weber T, Bock J, et al. Pregnancy following kidney transplantation. Acta Obstet Gynecol Scand 1986; 65: 557–9
Davison JM, Lindheimer MD. Pregnancy in renal transplant recipients. J Reprod Med 1982; 27: 613–21
Williamson RA, Karp LE. Azathioprine teratogenicity: review of the literature and case report. Obstet Gynecol 1981; 58: 247–50
Nishimura H, Tanimura T. Clinical aspects of the teratogenicity of drugs. New York: American Elsevier, 1976
Burleson RL, Sunderji SG, Aubry RH, et al. Renal allotransplantation during pregnancy: successful outcome for mother, child, and kidney. Transplantation 1983; 36: 334
Ogburn PLJ, Kitzmiller JL, Hare JW, et al. Pregnancy following renal transplantation in class T diabetes mellitus. JAMA 1986; 255: 911–5
De Witte DB, Buick MK, Cyran SE, et al. Neonatal pancytopenia and severe combined immunodeficiency associated with antenatal administration of azathioprine and prednisone. J Pediatr 1984; 105: 625–8
Haagsma EB, Visser GH, Klompmaker IJ, et al. Successful pregnancy after orthotropic transplantation. Obstet Gynecol 1989; 74: 442–3
Coulam CB, Moyer TP, Jiang NS, et al. Breast-feeding after renal transplantation. Transplant Proc 1982; 14: 605–9
Cannon GW, Ward JR. Cytotoxic drugs and sulfasalazine. In: McCarty D, editor. Arthritis and allied conditions. 2nd ed. Philadelphia: Lea and Febiger, 1989
Klinenberg JR, Reichman R, Clements PJ. Investigational therapy for rheumatoid arthritis. In: Progress in clinical immunology, vol. 1. New York: Grune and Stratton, 1984
Lawler SD, Lele KP. Chromosomal damage induced by chlorambucil and chronic lymphocytic leukemia. Scand J Haematol 1972; 17: 197–204
Westin J. Chromosome abnormalities after chlorambucil therapy of polycythemia vera. Scand J Haematol 1976; 17: 197–204
Clements PJ. Alkylating agents. In: Dixon JS, Furst DE, editors. Second line agents in the treatment of rheumatic diseases. New York: Marcel Dekker, 1991
Kahn MF, Arlet J, Bloch-Michel H, et al. Leucemies aigues apres traitement par agents cytotoxiques en rheumatologies: 19 observations chez 2006 patients. Nouv Presse Med 1979; 8: 1393–7
Monie IW. Chlorambucil-induced abnormalities of urogenital system of rat fetuses. Anat Rec 1961; 139: 145
Takacs SE, Warkany J. Chromosome changes in embryos treated with various teratogens. J Embryol Exp Morphol 1967; 18: 215–26
Brummett ES, Johnson EM. Morphological alterations in the developing fetal rat limb due to maternal injection of chlorambucil. Teratology 1979; 20: 279–88
Chapman RM, Sutcliffe SB. Protection of ovarian function by oral contraceptives in women receiving chemotherapy for Hodgkin’s disease. Blood 1981; 58: 849–51
Glode LM, Robinson J, Gould SF. Protection from cyclophosphamide-induced testicular damage with an analogue of gonadotropin releasing hormone. Lancet 1981; 1: 1132–4
Ataya KM, McKanna JA, Weintraub AM, et al. A luteinizing hormone-releasing hormone agonist for the prevention of chemotherapy-induced ovarian follicular loss in rats. Cancer Treat Rev 1985; 45: 3651–6
Nseyo UO, Huben RP, Klioze SS, et al. Protection of germinal epithelium with luteinizing hormone-releasing hormone analogue. J Urol 1985; 34: 187–90
Sokal JE, Lessmann EM. Effects of cancer chemotherapeutic agents on the human fetus. JAMA 1960; 172: 1765–71
Shotton D, Monie IW. Possible teratogenic effect of chlorambucil on a human fetus. JAMA 1963; 186: 74–5
Steege JF, Caldwell DS. Renal agenesis after first trimester exposure to chlorambucil. South Med J 1980; 73: 1414–5
Thompson J, Conklin KA. Anesthetic management of a pregnant patient with scleroderma. Anaesthesiology 1983; 59: 69–71
Austin HA, Klippel JH, Balow JE, et al. Therapy of lupus nephritis: controlled trial of prednisone and cytotoxic drugs. N Engl J Med 1986; 314: 614–9
Hackenberger I, Kreybig T. Vergleichende teratologische Untersuchungen bei der maus und der ratte. Arzneimittel Forschung 1965; 15: 1456–60
Chaube S, Kury G, Murphy ML, et al. Teratogenic effects of cyclophosphamide in the rat. Cancer Chemother Biol Response Modif 1967; 51: 363–76
Gerlinger P, Clavert J. Anomalies observees chez des lapins issus de meres traitees au cyclophosphamide. C R Seances Soc Biol Fil 1965; 159: 1462–6
Fritz H, Hess R. Effects of cyclophosphamide on embryonic development in the rabbit. Agents Actions 1971; 2: 83–6
Wilk A, McClure HM, Horigan EA, et al. Induction of craniofacial malformations in the rhesus monkey with cyclophosphamide. Teratology 1978; 17: 24A
Koyama H, Wada T, Nishizawa Y. Induced ovarian failure and its therapeutic significance in patients with breast cancer. Cancer 1977; 39: 1403–9
Boumpas DT, Austin HA III, Vaughn EM, et al. Risk of sustained amenorrhea in patients with systemic lupus erythematosus receiving intermittent pulse cyclophosphamide therapy. Ann Intern Med 1993; 119: 366–9
Nicholson HO. Cytotoxic drugs in pregnancy: review of reported cases. J Obstet Gynaecol 1968; 75: 307–12
Kirshon B, Wasserstrum N, Willis R, et al. Teratogenic effects of first-trimester cyclophosphamide therapy. Obstet Gynecol 1988; 72: 462–4
Pizzuto J, Aviles A, Noriega L, et al. Treatment of acute leukemia during pregnancy: presentation of nine cases. Cancer Treat Rep 1980; 64: 679–83
Greenberg LH, Tanaka KR. Congenital anomalies probably induced by cyclophosphamide. JAMA 1964; 188: 423–6
Toledo TM, Harper RC, Moser RH. Fetal effects during cyclophosphamide and irradiation therapy. Ann Intern Med 1971; 74: 87–91
Coates A. Cyclophosphamide in pregnancy. Aust J Obstet Gynaecol 1970; 10: 33–4
Murray CL, Reichert JA, Anderson J, et al. Multimodal cancer therapy for breast cancer in the first trimester of pregnancy. JAMA 1984; 252: 2607–8
Sweet DL, Kinzie J. Consequences of radiotherapy and antineoplastic therapy for the fetus. J Reprod Med 1976; 17: 241–6
Wiernik PH, Duncan JH. Cyclophosphamide in human milk. Lancet 1971; 1: 912
Mullarkey MF, Blumenstein BA, Andrade P, et al. Methotrexate in the treatment of corticosteroid-dependent asthma. N Engl J Med 1988; 318: 603–7
Songstridey N, Furst DE. Methotrexate — the rapidly acting drug. Clin Rheumatol 1990; 4: 575–94
Rothenberg RJ, Graziano FM, Grandone JT, et al. The use of methotrexate in steroid-resistant SLE. Arthritis Rheum 1988; 31: 612–5
DePaola DP, Mandella RD. Folate deficiency and in vitro palatogenesis II: effects of methotrexate on rabbit palate fusion, folate pools, and dihydrofolate reductase activity. J Craniofac Genet Dev Biol 1984; 4: 321–7
Zamenhof S. Differential effects of antifolate on the development of brain parts in chick embryos. Growth 1985; 49: 28–33
Skalko RG, Gold MP. Teratogenicity of methotrexate in mice. Teratology 1974; 9: 159–64
Schmid BP. Monitoring of organ formation in rat embryos after in vitro exposure to azathioprine, mercaptopurine, methotrexate, or cyclosporine A. Toxicology 1984; 31: 9–21
Adams CE, Hay M, Lutwak-Mann C, et al. The actions of various agents on the rabbit embryo. J Embryol Exper Morphol 1961; 9: 468–91
Wilson JG, Scott WJ, Ritter EJ, et al. Comparative distribution and embryotoxicity of methotrexate in pregnant rats and Rhesus monkeys. Teratology 1979; 19: 71–80
Groenendal H, Rampen FH. Methotrexate and trimethoprim-sulphamethoxazole — a potentially hazardous combination. Clin Exp Dermatol 1990; 15: 358–60
Bower C, Stanley FJ. Dietary folate as a risk factor for neural-tube defects: evidence from a case-control study in Western Australia. Med J Aust 1989; 150: 613–9
Milunsky A, Jick H, Jick SS. Multivitamin/folic acid supplementation in early pregnancy reduces the prevalence of neural tube defects. JAMA 1989; 262: 2847–52
Kremer JM, Alarcon GS, Lightfoot RW, et al. Methotrexate for rheumatoid arthritis: suggested guidelines for monitoring liver toxicity. Arthritis Rheum 1994; 37: 316–28
Chotiner HC. Nonsurgical management of ectopic pregnancy associated with severe hyperstimulation syndrome. Obstet Gynecol 1985; 66: 740–3
Oyer R. Treatment of cervical pregnancy with methotrexate. Obstet Gynecol 1988; 71: 469–71
Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk. Baltimore: Williams and Wilkins, 1986
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: 589–92
Waiden PAM, Bagshawe KD. Pregnancies after chemotherapy for gestational trophoblastic tumours. Lancet 1979; 2: 1241
Turchi JJ, Villasis C. Anthracyclines in the treatment of malignancy in pregnancy. Cancer 1988; 61: 435–40
Barnes AB, Link DA. Childhood dermatomyositis and pregnancy. Am J Obstet Gynecol 1983; 146: 335–6
Sivanesaratnam V, Sen DK. Normal pregnancy after successful treatment of choriocarcinoma with cerebral metastases: a case report. J Reprod Med 1988; 33: 402–3
Schleuning M, Clemm C. Chromosomal aberrations in a newborn whose mother received cytotoxic treatment during pregnancy. N Engl J Med 1987; 317: 1666–7
Author information
Authors and Affiliations
Additional information
An erratum to this article is available at http://dx.doi.org/10.1007/BF03259510.
Rights and permissions
About this article
Cite this article
Ramsey-Goldman, R., Schilling, E. Optimum Use of Disease-Modifying and Immunosuppressive Antirheumatic Agents During Pregnancy and Lactation. Clin Immunother 5, 40–58 (1996). https://doi.org/10.1007/BF03259314
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03259314