[en] BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is a chronic disease affecting mainly young people in their reproductive years. IBD therefore has a major impact on patients' family planning decisions. Management of IBD in pregnancy requires a challenging balance between optimal disease control and drug safety considerations. This article aims to provide a framework for clinical decision making in IBD based on review of the literature on pregnancy-related topics. METHODS: Medline searches with search terms 'IBD', 'Crohn's disease' or 'ulcerative colitis' in combination with keywords for the topics fertility, pregnancy, congenital abnormalities and drugs names of drugs used for treatment of IBD. RESULTS: IBD patients have normal fertility, except for women after ileal pouch-anal anastomosis (IPAA) and men under sulfasalazine treatment. Achieving and maintaining disease remission is a key factor for successful pregnancy outcomes in this population, as active disease at conception carries an increased risk of preterm delivery and low birth weight. Clinicians should discuss the need for drug therapy to maintain remission with their patients in order to ensure therapy compliance. Most IBD drugs are compatible with pregnancy, except for methotrexate and thalidomide. If possible, anti-TNF therapy should be stopped by the end of the second trimester and the choice of delivery route should be discussed with the patient. CONCLUSIONS: Disease control prior to conception and throughout pregnancy is the cornerstone of successful pregnancy management in IBD patients.
Khosla R., Willoughby C.P., Jewell D.P. Crohn's disease and pregnancy. Gut 1984, 25:52-56.
Domm S., Cinatl J., Mrowietz U. The impact of treatment with tumour necrosis factor-alpha antagonists on the course of chronic viral infections: a review of the literature. Br J Dermatol 2008, 159:1217-1228.
Hudson M., Flett G., Sinclair T.S., Brunt P.W., Templeton A., Mowat N.A. Fertility and pregnancy in inflammatory bowel disease. Int J Gynaecol Obstet 1997, 58:229-237.
Mayberry J.F., Weterman I.T. European survey of fertility and pregnancy in women with Crohn's disease: a case control study by European collaborative group. Gut 1986, 27:821-825.
Riis L., Vind I., Politi P., Wolters F., Vermeire S., Tsianos E., et al. Does pregnancy change the disease course? A study in a European cohort of patients with inflammatory bowel disease. Am J Gastroenterol 2006, 101:1539-1545.
Ording Olsen K., Juul S., Berndtsson I., Oresland T., Laurberg S. Ulcerative colitis: Female fecundity before diagnosis, during disease, and after surgery compared with a population sample. Gastroenterology 2002, 122:15-19.
Dubinsky M., Abraham B., Mahadevan U. Management of the pregnant IBD patient. Inflamm Bowel Dis 2008, 14:1736-1750.
Olsen K.O., Joelsson M., Laurberg S., Oresland T. Fertility after ileal pouch-anal anastomosis in women with ulcerative colitis. Br J Surg 1999, 86:493-495.
Johnson P., Richard C., Ravid A., Spencer L., Pinto E., Hanna M., et al. Female infertility after ileal pouch-anal anastomosis for ulcerative colitis. Dis Colon Rectum 2004, 47:1119-1126.
Gorgun E., Remzi F.H., Goldberg J.M., Thornton J., Bast J., Hull T.L., et al. Fertility is reduced after restorative proctocolectomy with ileal pouch anal anastomosis: a study of 300 patients. Surgery 2004, 136:795-803.
Lepistö A., Sarna S., Tiitinen A., Järvinen H.J. Female fertility and childbirth after ileal pouch-anal anastomosis for ulcerative colitis. Br J Surg 2007, 94:478-482.
Waljee A., Waljee J., Morris A.M., Higgins P.D.R. Threefold increased risk of infertility: a meta-analysis of infertility after ileal pouch anal anastomosis in ulcerative colitis. Gut 2006, 55:1575-1580.
Mortier P.-E., Gambiez L., Karoui M., Cortot A., Paris J.-C., Quandalle P., et al. Colectomy with ileorectal anastomosis preserves female fertility in ulcerative colitis. Gastroenterol Clin Biol 2006, 30:594-597.
Mahadevan U., Cucchiara S., Hyams J.S., Steinwurz F., Nuti F., Travis S.P.L., et al. The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organisation: pregnancy and pediatrics. Am J Gastroenterol 2011, 106:214-223. [quiz 224].
Oresland T., Palmblad S., Ellström M., Berndtsson I., Crona N., Hultén L. Gynaecological and sexual function related to anatomical changes in the female pelvis after restorative proctocolectomy. Int J Colorectal Dis 1994, 9:77-81.
Indar A.A., Efron J.E., Young-Fadok T.M. Laparoscopic ileal pouch-anal anastomosis reduces abdominal and pelvic adhesions. Surg Endosc 2009, 23:174-177.
Levi A.J., Fisher A.M., Hughes L., Hendry W.F. Male infertility due to sulphasalazine. Lancet 1979, 2:276-278.
Toovey S., Hudson E., Hendry W.F., Levi A.J. Sulphasalazine and male infertility: reversibility and possible mechanism. Gut 1981, 22:445-451.
Toth A. Reversible toxic effect of salicylazosulfapyridine on semen quality. Fertil Steril 1979, 31:538-540.
Riley S.A., Lecarpentier J., Mani V., Goodman M.J., Mandal B.K., Turnberg L.A. Sulphasalazine induced seminal abnormalities in ulcerative colitis: results of mesalazine substitution. Gut 1987, 28:1008-1012.
Fukushima T., Hamada Y., Komiyama M., Matsuno Y., Mori C., Horii I. Early changes in sperm motility, acrosome reaction, and gene expression of reproductive organs in rats treated with sulfasalazine. Reprod Toxicol 2007, 23:153-157.
Alonso V., Linares V., Bellés M., Albina M.L., Sirvent J.J., Domingo J.L., et al. Sulfasalazine induced oxidative stress: a possible mechanism of male infertility. Reprod Toxicol 2009, 27:35-40.
Dejaco C., Mittermaier C., Reinisch W., Gasche C., Waldhoer T., Strohmer H., et al. Azathioprine treatment and male fertility in inflammatory bowel disease. Gastroenterology 2001, 121:1048-1053.
Rajapakse R.O., Korelitz B.I., Zlatanic J., Baiocco P.J., Gleim G.W. Outcome of pregnancies when fathers are treated with 6-mercaptopurine for inflammatory bowel disease. Am J Gastroenterol 2000, 95:684-688.
Nørgård B., Pedersen L., Jacobsen J., Rasmussen S.N., Sørensen H.T. The risk of congenital abnormalities in children fathered by men treated with azathioprine or mercaptopurine before conception. Aliment Pharmacol Ther 2004, 19:679-685.
Francella A., Dyan A., Bodian C., Rubin P., Chapman M., Present D.H. The safety of 6-mercaptopurine for childbearing patients with inflammatory bowel disease: a retrospective cohort study. Gastroenterology 2003, 124:9-17.
Teruel C., Román A.L.-S., Bermejo F., Taxonera C., Pérez-Calle J.L., Gisbert J.P., et al. Outcomes of pregnancies fathered by inflammatory bowel disease patients exposed to thiopurines. Am J Gastroenterol 2010, 105:2003-2008.
Mahadevan U., Terdiman J.P., Aron J., Jacobsohn S., Turek P. Infliximab and semen quality in men with inflammatory bowel disease. Inflamm Bowel Dis 2005, 11:395-399.
Said T.M., Agarwal A., Falcone T., Sharma R.K., Bedaiwy M.A., Li L. Infliximab may reverse the toxic effects induced by tumor necrosis factor alpha in human spermatozoa: an in vitro model. Fertil Steril 2005, 83:1665-1673.
Andrews J.M., Mountifield R.E., Van Langenberg D.R., Bampton P.A., Holtmann G.J. Un-promoted issues in inflammatory bowel disease: opportunities to optimize care. Intern Med J 2010, 40:173-182.
Mountifield R., Bampton P., Prosser R., Muller K., Andrews J.M. Fear and fertility in inflammatory bowel disease: a mismatch of perception and reality affects family planning decisions. Inflamm Bowel Dis 2009, 15:720-725.
Agret F., Cosnes J., Hassani Z., Gornet J.-M., Gendre J.-P., Lémann M., et al. Impact of pregnancy on the clinical activity of Crohn's disease. Aliment Pharmacol Ther 2005, 21:509-513.
Thomas G.A., Rhodes J., Green J.T., Richardson C. Role of smoking in inflammatory bowel disease: implications for therapy. Postgrad Med J 2000, 76:273-279.
Bortoli A., Pedersen N., Duricova D., D'Inca R., Gionchetti P., Panelli M.R., et al. Pregnancy outcome in inflammatory bowel disease: prospective European case-control ECCO-EpiCom study, 2003-2006. Aliment Pharmacol Ther 2011, 34:724-734.
Moser M.A., Okun N.B., Mayes D.C., Bailey R.J. Crohn's disease, pregnancy, and birth weight. Am J Gastroenterol 2000, 95:1021-1026.
Morales M., Berney T., Jenny A., Morel P., Extermann P. Crohn's disease as a risk factor for the outcome of pregnancy. Hepatogastroenterology 2000, 47:1595-1598.
Julsgaard M., Nørgaard M., Hvas C.L., Buck D., Christensen L.A. Self-reported adherence to medical treatment prior to and during pregnancy among women with ulcerative colitis. Inflamm Bowel Dis 2010, 1-8.
Ferrero S., Ragni N. Inflammatory bowel disease: management issues during pregnancy. Arch Gynecol Obstet 2004, 270:79-85.
Castiglione F., Pignata S., Morace F., Sarubbi A., Baratta M.A., D'Agostino L., et al. Effect of pregnancy on the clinical course of a cohort of women with inflammatory bowel disease. Ital J Gastroenterol 1996, 28:199-204.
Nwokolo C.U., Tan W.C., Andrews H.A., Allan R.N. Surgical resections in parous patients with distal ileal and colonic Crohn's disease. Gut 1994, 35:220-223.
Munkholm P. Pregnancy, fertility, and disease course in patients with Crohn's disease and ulcerative colitis. Eur J Intern Med 2000, 11:215-221.
Kane S., Kisiel J., Shih L., Hanauer S. HLA disparity determines disease activity through pregnancy in women with inflammatory bowel disease. Am J Gastroenterol 2004, 99:1523-1526.
Kane S., Lemieux N. The role of breastfeeding in postpartum disease activity in women with inflammatory bowel disease. Am J Gastroenterol 2005, 100:102-105.
Moffatt D.C., Ilnyckyj A., Bernstein C.N. A population-based study of breastfeeding in inflammatory bowel disease: initiation, duration, and effect on disease in the postpartum period. Am J Gastroenterol 2009, 104:2517-2523.
Elbaz G., Fich A., Levy A., Holcberg G., Sheiner E. Inflammatory bowel disease and preterm delivery. Int J Gynaecol Obstet 2005, 90:193-197.
Nørgård B., Hundborg H.H., Jacobsen B.A., Nielsen G.L., Fonager K. Disease activity in pregnant women with Crohn's disease and birth outcomes: a regional Danish cohort study. Am J Gastroenterol 2007, 102:1947-1954.
Reddy S.I., Wolf J.L. Management issues in women with inflammatory bowel disease. J Am Osteopath Assoc 2001, 101:S17-S23.
Cornish J., Tan E., Teare J., Teoh T.G., Rai R., Clark S.K., et al. A meta-analysis on the influence of inflammatory bowel disease on pregnancy. Gut 2007, 56:830-837.
Fonager K., Sørensen H.T., Olsen J., Dahlerup J.F., Rasmussen S.N. Pregnancy outcome for women with Crohn's disease: a follow-up study based on linkage between national registries. Am J Gastroenterol 1998, 93:2426-2430.
Kornfeld D., Cnattingius S., Ekbom A. Pregnancy outcomes in women with inflammatory bowel disease-a population-based cohort study. Am J Obstet Gynecol 1997, 177:942-946.
Bortoli A., Saibeni S., Tatarella M., Prada A., Beretta L., Rivolta R., et al. Pregnancy before and after the diagnosis of inflammatory bowel diseases: retrospective case-control study. J Gastroenterol Hepatol 2007, 22:542-549.
Dominitz J.A., Young J.C.C., Boyko E.J. Outcomes of infants born to mothers with inflammatory bowel disease: a population-based cohort study. Am J Gastroenterol 2002, 97:641-648.
Subhani J.M., Hamiliton M.I. Review article: The management of inflammatory bowel disease during pregnancy. Aliment Pharmacol Ther 1998, 12:1039-1053.
Nørgård B., Puho E., Pedersen L., Czeizel A.E., Sørensen H.T. Risk of congenital abnormalities in children born to women with ulcerative colitis: a population-based, case-control study. Am J Gastroenterol 2003, 98:2006-2010.
Ilnyckyji A., Blanchard J.F., Rawsthorne P., Bernstein C.N. Perianal Crohn's disease and pregnancy: role of the mode of delivery. Am J Gastroenterol 1999, 94:3274-3278.
Mahadevan U., Sandborn W.J., Li D.-K., Hakimian S., Kane S., Corley D.A. Pregnancy outcomes in women with inflammatory bowel disease: a large community-based study from Northern California. Gastroenterology 2007, 133:1106-1112.
Nguyen G.C., Boudreau H., Harris M.L., Maxwell C.V. Outcomes of obstetric hospitalizations among women with inflammatory bowel disease in the United States. Clin Gastroenterol Hepatol 2009, 7:329-334.
Ravid A., Richard C.S., Spencer L.M., O'Connor B.I., Kennedy E.D., MacRae H.M., et al. Pregnancy, delivery, and pouch function after ileal pouch-anal anastomosis for ulcerative colitis. Dis Colon Rectum 2002, 45:1283-1288.
Van Assche G., Dignass A., Reinisch W., van der Woude C.J., Sturm A., De Vos M., et al. The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: Special situations. J Crohns Colitis 2010, 4:63-101.
Moskovitz D.N., Bodian C., Chapman M.L., Marion J.F., Rubin P.H., Scherl E., et al. The effect on the fetus of medications used to treat pregnant inflammatory bowel-disease patients. Am J Gastroenterol 2004, 99:656-661.
Nielsen M.J., Nørgaard M., Holland-Fisher P., Christensen L.A. Self-reported antenatal adherence to medical treatment among pregnant women with Crohn's disease. Aliment Pharmacol Ther 2010, 32:49-58.
Chambers C.D., Tutuncu Z.N., Johnson D., Jones K.L. Human pregnancy safety for agents used to treat rheumatoid arthritis: adequacy of available information and strategies for developing post-marketing data. Arthritis Res Ther 2006, 8:215.
Nørgård B., Pedersen L., Christensen L.A., Sørensen H.T. Therapeutic drug use in women with Crohn's disease and birth outcomes: a Danish nationwide cohort study. Am J Gastroenterol 2007, 102:1406-1413.
Rahimi R., Nikfar S., Rezaie A., Abdollahi M. Pregnancy outcome in women with inflammatory bowel disease following exposure to 5-aminosalicylic acid drugs: a meta-analysis. Reprod Toxicol 2008, 25:271-275.
Hernández-Díaz S., Werler M.M., Walker A.M., Mitchell A.A. Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med 2000, 343:1608-1614.
Hernández-Díaz S., Mitchell A.A., Kelley K.E., Calafat A.M., Hauser R. Medications as a potential source of exposure to phthalates in the U.S. population. Environ Health Perspect 2009, 117:185-189.
Østensen M., Motta M. Therapy insight: the use of antirheumatic drugs during nursing. Nat Clin Pract Rheumatol 2007, 3:400-406.
American Academy of Pediatrics, Committee on Drugs Transfer of drugs and other chemicals into human milk. Pediatrics 2001, 108:776-789.
Branski D., Kerem E., Gross-Kieselstein E., Hurvitz H., Litt R., Abrahamov A. Bloody diarrhea-a possible complication of sulfasalazine transferred through human breast milk. J Pediatr Gastroenterol Nutr 1986, 5:316-317.
Mahadevan U., Kane S. American gastroenterological association institute technical review on the use of gastrointestinal medications in pregnancy. Gastroenterology 2006, 131:283-311.
Czeizel A.E., Rockenbauer M. A population based case-control teratologic study of oral metronidazole treatment during pregnancy. Br J Obstet Gynaecol 1998, 105:322-327.
van der Woude C.J., Kolacek S., Dotan I., Oresland T., Vermeire S., Munkholm P., et al. European evidenced-based consensus on reproduction in inflammatory bowel disease. J Crohns Colitis 2010, 4:493-510.
Gisbert J.P. Safety of immunomodulators and biologics for the treatment of inflammatory bowel disease during pregnancy and breast-feeding. Inflamm Bowel Dis 2010, 16:881-895.
Osadchy A., Koren G. Cyclosporine and lactation: when the mother is willing to breastfeed. Ther Drug Monit 2011, 33:147-148.
Oussalah A., Roblin X., Laharie D., Filippi J., Flamant M., Faure P., et al. Tumour necrosis factor antagonists and inflammatory bowel diseases: a national practice survey. Aliment Pharmacol Ther 2009, 30:854-863.
Marino M.W., Dunn A., Grail D., Inglese M., Noguchi Y., Richards E., et al. Characterization of tumor necrosis factor-deficient mice. Proc Natl Acad Sci U S A 1997, 94:8093-8098.
Torchinsky A., Shepshelovich J., Orenstein H., Zaslavsky Z., Savion S., Carp H., et al. TNF-alpha protects embryos exposed to developmental toxicants. Am J Reprod Immunol 2003, 49:159-168.
Simister N. Placental transport of immunoglobulin G. Vaccine 2003, 21:3365-3369.
Kane S.V., Acquah L.A. Placental transport of immunoglobulins: a clinical review for gastroenterologists who prescribe therapeutic monoclonal antibodies to women during conception and pregnancy. Am J Gastroenterol 2009, 104:228-233.
Martin W.L., West A.P., Gan L., Bjorkman P.J. Crystal structure at 2.8 A of an FcRn/heterodimeric Fc complex: mechanism of pH-dependent binding. Mol Cell 2001, 7:867-877.
Roopenian D.C., Christianson G.J., Sproule T.J., Brown A.C., Akilesh S., Jung N., et al. The MHC class I-like IgG receptor controls perinatal IgG transport, IgG homeostasis, and fate of IgG-Fc-coupled drugs. J Immunol 2003, 170:3528-3533.
Roopenian D.C., Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol 2007, 7:715-725.
Malek A., Sager R., Kuhn P., Nicolaides K.H., Schneider H. Evolution of maternofetal transport of immunoglobulins during human pregnancy. Am J Reprod Immunol 1996, 36:248-255.
Arsenescu R., Arsenescu V., de Villiers W.J.S. TNF-α and the development of the neonatal immune system: implications for inhibitor use in pregnancy. Am J Gastroenterol 2011, 106:559-562.
Carter J.D., Ladhani A., Ricca L.R., Valeriano J., Vasey F.B. A safety assessment of tumor necrosis factor antagonists during pregnancy: a review of the Food and Drug Administration database. J Rheumatol 2009, 36:635-641.
Winger E.E., Reed J.L. Was risk properly assessed in Carter, et al's safety assessment of tumor necrosis factor antagonists during pregnancy?. J Rheumatol 2009, 36:2122. [author reply 2123].
Koren G., Inoue M. Do tumor necrosis factor inhibitors cause malformations in humans?. J Rheumatol 2009, 36:465-466.
Martin P.L., Cornacoff J.B., Treacy G., Eirikas E., Marini J., White K.L., et al. Effects of administration of a monoclonal antibody against mouse tumor necrosis factor alpha during pregnancy and lactation on the pre- and postnatal development of the mouse immune system. Int J Toxicol 2008, 27:341-347.
Martin P.L., 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, 58:138-149.
Cheent K., Nolan J., Shariq S., Kiho L., Pal A., Arnold J. Case Report: Fatal case of disseminated BCG infection in an infant born to a mother taking infliximab for Crohn's disease. J Crohns Colitis 2010, 4:603-605.
Rahier J.F., Ben-Horin S., Chowers Y., Conlon C., De Munter P., D'Haens G., et al. European evidence-based Consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis 2009, 3:47-91.
Rahier J.-F., Moutschen M., Van Gompel A., Van Ranst M., Louis E., Segaert S., et al. Vaccinations in patients with immune-mediated inflammatory diseases. Rheumatology (Oxford) 2010, 49:1815-1827.
Lichtenstein G.R., Feagan B.G., Cohen R.D., Salzberg B.A., Diamond R.H., Chen D.M., et al. Serious infections and mortality in association with therapies for Crohn's disease: TREAT registry. Clin Gastroenterol Hepatol 2006, 4:621-630.
Katz J.A., Antoni C., Keenan G.F., Smith D.E., Jacobs S.J., Lichtenstein G.R. Outcome of pregnancy in women receiving infliximab for the treatment of Crohn's disease and rheumatoid arthritis. Am J Gastroenterol 2004, 99:2385-2392.
Schnitzler F., Fidder H., Ferrante M., Ballet V., Noman M., Van Assche G., et al. Outcome of pregnancy in women with inflammatory bowel disease treated with antitumor necrosis factor therapy. Inflamm Bowel Dis 2011, 17:1846-1854.
Mahadevan U., Kane S., Sandborn W.J., Cohen R.D., Hanson K., Terdiman J.P., et al. Intentional infliximab use during pregnancy for induction or maintenance of remission in Crohn's disease. Aliment Pharmacol Ther 2005, 21:733-738.
Mahadevan U., Kane S. Use of infliximab in pregnancy. Am J Gastroenterol 2010, 105:219. [author reply 219-20].
Vasiliauskas E.A., Church J.A., Silverman N., Barry M., Targan S.R., Dubinsky M.C. Case report: evidence for transplacental transfer of maternally administered infliximab to the newborn. Clin Gastroenterol Hepatol 2006, 4:1255-1258.
Kane S., Ford J., Cohen R., Wagner C. Absence of infliximab in infants and breast milk from nursing mothers receiving therapy for Crohn's disease before and after delivery. J Clin Gastroenterol 2009, 43:613-616.
Ben-Horin S., Yavzori M., Kopylov U., Picard O., Fudim E., Eliakim R., Chowers Y., Lang A. Detection of infliximab in breast milk of nursing mothers with inflammatory bowel disease. J Crohns Colitis. 2011 Dec, 5(6):555-558.
Stengel J.-Z., Arnold H.-L. Is infliximab safe to use while breastfeeding?. World J Gastroenterol 2008, 14:3085-3087.
Coburn L.A., Wise P.E., Schwartz D.A. The successful use of adalimumab to treat active Crohn's disease of an ileoanal pouch during pregnancy. Dig Dis Sci 2006, 51:2045-2047.
Vesga L., Terdiman J.P., Mahadevan U. Adalimumab use in pregnancy. Gut 2005, 54:890.
Mishkin D.S., Van Deinse W., Becker J.M., Farraye F.A. Successful use of adalimumab (Humira) for Crohn's disease in pregnancy. Inflamm Bowel Dis 2006, 12:827-828.
Bayas A., Penzien J., Hellwig K. Accidental natalizumab administration to the third trimester of pregnancy in an adolescent patient with multiple sclerosis. Acta Neurol Scand 2011, 124:290-292.
Hoevenaren I.A., de Vries L.C., Rijnders R.J.P., Lotgering F.K. Delivery of healthy babies after natalizumab use for multiple sclerosis: a report of two cases. Acta Neurol Scand 2011, 123:430-433.
Østensen M., Förger F. Management of RA medications in pregnant patients. Nat Rev Rheumatol 2009, 5:382-390.
Cowchock F.S., Reece E.A., Balaban D., Branch D.W., Plouffe L. Repeated fetal losses associated with antiphospholipid antibodies: a collaborative randomized trial comparing prednisone with low-dose heparin treatment. Am J Obstet Gynecol 1992, 166:1318-1323.
Park-Wyllie L., Mazzotta P., Pastuszak A., Moretti M.E., Beique L., Hunnisett L., et al. Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies. Teratology 2000, 62:385-392.
Gluck P.A., Gluck J.C. A review of pregnancy outcomes after exposure to orally inhaled or intranasal budesonide. Curr Med Res Opin 2005, 21:1075-1084.
Beaulieu D.B., Ananthakrishnan A.N., Issa M., Rosenbaum L., Skaros S., Newcomer J.R., et al. Budesonide induction and maintenance therapy for Crohn's disease during pregnancy. Inflamm Bowel Dis 2009, 15:25-28.
Ogueh O., Johnson M.R. The metabolic effect of antenatal corticosteroid therapy. Hum Reprod Update 2000, 6:169-176.
Breur J.M.P.J., Visser G.H.A., Kruize A.A., Stoutenbeek P., Meijboom E.J. Treatment of fetal heart block with maternal steroid therapy: case report and review of the literature. Ultrasound Obstet Gynecol 2004, 24:467-472.
Bar Oz B., Hackman R., Einarson T., Koren G. Pregnancy outcome after cyclosporine therapy during pregnancy: a meta-analysis. Transplantation 2001, 71:1051-1055.
Reddy D., Murphy S.J., Kane S.V., Present D.H., Kornbluth A.A. Relapses of inflammatory bowel disease during pregnancy: in-hospital management and birth outcomes. Am J Gastroenterol 2008, 103:1203-1209.
Branche J., Cortot A., Bourreille A., Coffin B., de Vos M., de Saussure P., et al. Cyclosporine treatment of steroid-refractory ulcerative colitis during pregnancy. Inflamm Bowel Dis 2009, 15:1044-1048.
Cleary B.J., Källén B. Early pregnancy azathioprine use and pregnancy outcomes. Birth Defects Res A Clin Mol Teratol 2009, 85:647-654.
Peyrin-Biroulet L., Oussalah A., Roblin X., Sparrow M.P. The use of azathioprine in Crohn's disease during pregnancy and in the post-operative setting: a worldwide survey of experts. Aliment Pharmacol Ther 2011, 33:707-713.
Alstead E.M., Ritchie J.K., Lennard-Jones J.E., Farthing M.J., Clark M.L. Safety of azathioprine in pregnancy in inflammatory bowel disease. Gastroenterology 1990, 99:443-446.
Khan Z.H., Mayberry J.F., Spiers N., Wicks A.C. Retrospective case series analysis of patients with inflammatory bowel disease on azathioprine. A district general hospital experience. Digestion 2000, 62:249-254.
Goldstein L.H., Dolinsky G., Greenberg R., Schaefer C., Cohen-Kerem R., Diav-Citrin O., et al. Pregnancy outcome of women exposed to azathioprine during pregnancy. Birth Defects Res A Clin Mol Teratol 2007, 79:696-701.
Langagergaard V., Pedersen L., Gislum M., Nørgard B., Sørensen H.T. Birth outcome in women treated with azathioprine or mercaptopurine during pregnancy: A Danish nationwide cohort study. Aliment Pharmacol Ther 2007, 25:73-81.
Coelho J., Beaugerie L., Colombel J.F., Hébuterne X., Lerebours E., Lémann M., et al. Pregnancy outcome in patients with inflammatory bowel disease treated with thiopurines: cohort from the CESAME Study. Gut 2011, 60:198-203.
de Boer N.K.H., Jarbandhan S.V.A., de Graaf P., Mulder C.J.J., van Elburg R.M., van Bodegraven A.A. Azathioprine use during pregnancy: unexpected intrauterine exposure to metabolites. Am J Gastroenterol 2006, 101:1390-1392.
Sau A., Clarke S., Bass J., Kaiser A., Marinaki A., Nelson-Piercy C. Azathioprine and breastfeeding: is it safe?. BJOG 2007, 114:498-501.
Christensen L.A., Dahlerup J.F., Nielsen M.J., Fallingborg J.F., Schmiegelow K. Azathioprine treatment during lactation. Aliment Pharmacol Ther 2008, 28:1209-1213.
Zelinkova Z., De Boer I.P., Van Dijke M.J., Kuipers E.J., Van Der Woude C.J. Azathioprine treatment during lactation. Aliment Pharmacol Ther 2009, 30:90-91. [author reply 91].
Ostensen M., Hartmann H., Salvesen K. Low dose weekly methotrexate in early pregnancy. A case series and review of the literature. J Rheumatol 2000, 27:1872-1875.
Buckley L.M., Bullaboy C.A., Leichtman L., Marquez M. Multiple congenital anomalies associated with weekly low-dose methotrexate treatment of the mother. Arthritis Rheum 1997, 40:971-973.
Kalb R.E., Strober B., Weinstein G., Lebwohl M. Methotrexate and psoriasis: 2009 National Psoriasis Foundation Consensus Conference. J Am Acad Dermatol 2009, 60:824-837.
Srinivasan R., Akobeng A.K. Thalidomide and thalidomide analogues for induction of remission in Crohn's disease. Cochrane Database Syst Rev 2009, CD007350.
Akobeng A.K., Stokkers P.C. Thalidomide and thalidomide analogues for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev 2009, CD007351.
Wylie A.M. PART 71 - Designation of Class A, Class B, Class C, Class D, and agency action. Fed Regist 2008, 73:18-55.