Clinical Review
Management of the pregnant IBD patient
Marla Dubinsky MD,
Bincy Abraham MD,
Uma Mahadevan MD,
Corresponding Author
Marla Dubinsky MD
Department of Pediatrics, Inflammatory Bowel Disease Center, Cedars Sinai Medical Center, Los Angeles, California
Cedars Sinai Medical Center, 1165W, 8700 Beverly Blvd., Los Angeles, CA 90048Search for more papers by this authorBincy Abraham MD
Department of Medicine, Baylor College of Medicine, Houston Texas
Search for more papers by this authorUma Mahadevan MD
Departmemt of Medicine, Inflammatory Bowel Disease Center, University of California San Francisco, San Francisco, California
Search for more papers by this authorMarla Dubinsky MD,
Bincy Abraham MD,
Uma Mahadevan MD,
Corresponding Author
Marla Dubinsky MD
Department of Pediatrics, Inflammatory Bowel Disease Center, Cedars Sinai Medical Center, Los Angeles, California
Cedars Sinai Medical Center, 1165W, 8700 Beverly Blvd., Los Angeles, CA 90048Search for more papers by this authorBincy Abraham MD
Department of Medicine, Baylor College of Medicine, Houston Texas
Search for more papers by this authorUma Mahadevan MD
Departmemt of Medicine, Inflammatory Bowel Disease Center, University of California San Francisco, San Francisco, California
Search for more papers by this authorAbstract
Women with inflammatory bowel disease (IBD) and the physicians who care for them must make difficult decisions on issues of conception, pregnancy, and breastfeeding with very limited and often contradictory information. This review provides the most current information on the inheritance of IBD, fertility, pregnancy outcomes, the management of disease during pregnancy, and the safety of medications in pregnancy and breastfeeding. We would like to emphasize that the information presented here must be individualized to the specific situation of each patient, their acceptance of risk, and their degree of disease severity.
(Inflamm Bowel Dis 2008)
REFERENCES
- 1 Yang H, McElree C, Roth M-P, et al. Familial empricial risk for inflammatory bowel disease: diffrences between Jews and non-Jews. Gut. 1993; 34: 517–524.
- 2 Orholm M. Fonager K. Sorensen HT. Risk of ulcerative colitis and Crohn's disease among offspring of patients with chronic inflammatory bowel disease. Am J Gastroenterol. 1999; 94: 3236–3238.
- 3 Peeters M, Nevens H, Baert F, et al. Familial aggregation in Crohn's disease: increased age-adjusted risk and concordance in clinical characteristics. Gastroenterology. 1996; 111: 597–603.
- 4 Bennett R, Rubin P, Present D. Frequency of inflammatory bowel disease in offspring of couples both presenting with inflammatory bowel disease. Gastroenterology. 1991; 100: 1638–1643.
- 5 Fielding JF, Cooke WT. Pregnancy and Crohn's disease. Br Med J. 1970; 2: 76–77.
- 6 Willoughby CP, Truelove SC. Ulcerative colitis and pregnancy. Gut. 1980; 21: 469–474.
- 7 Baird DD, Narendranathan M, Sandler RS. Increased risk of preterm birth for women with inflammatory bowel disease. Gastroenterology. 1990; 99: 987–994.
- 8 Hudson M, Flett G, Sinclair TS, et al. Fertility and pregnancy in inflammatory bowel disease. Int J Gynaecol Obstet. 1997; 58: 229–237.
- 9 Olsen KO, Joelsson M, Laurberg S, et al. Fertility after ileal pouch-anal anastamosis in women with ulcerative colitis. Br J Surg. 1999; 86: 493–495.
- 10 Olsen KO, Juul S, Berndtsson I, et al. Ulcerative colitis: female fecundity before diagnosis, during disease, and after surgery compared with a population sample. Gastroenterology. 2002; 122: 15–19.
- 11 Olsen KØ, Juul S, Bulow S, et al. Female fecundity before and after operation for familial adenomatous polyposis. Br J Surg. 2003; 90: 227–231.
- 12 Gorgun E, Remzi FH, Goldberg JM, et al. Fertility is reduced after restorative proctocolectomy with ileal pouch anal anastomosis: a study of 300 patients. Surgery. 2004; 136: 795–803.
- 13 Lepisto A, Sarna S, Tiitinen A, et al. Female fertility and childbirth after ileal pouch-anal anastomosis for ulcerative colitis. Br J Surg. 2007; 94: 478–482.
- 14 Cornish JA, Tan E, Teare J, et al. The effect of restorative proctocolectomy on sexual function, urinary function, fertility, pregnancy and delivery: a systematic review. Dis Colon Rectum. 2007; 50: 1128–1138.
- 15 Khosla R, Willoughby CP, Jewell DP. Crohn's disease and pregnancy. Gut. 1984; 25: 52–56.
- 16 Baiocco PJ, Korelitz BI. The influence of inflammatory bowel disease and its treatment on pregnancy and fetal outcome. J Clin Gastroenterol. 1984; 6: 211–216.
- 17 Mayberry JF, Weterman IT. 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.
- 18 Hudson M, Flett G, Sinclair TS, et al. Fertility and pregnancy in inflammatory bowel disease. Int J Gynaecol Obstet. 1997; 58: 229–237.
- 19 Arkuran, C. McComb, P. Crohn's disease and tubal infertility: the effect of adhesion formation. Clin Exp Obstet Gynecol. 2000; 27: 12–13.
- 20 Nielsen OH, Andreasson B, Bondesen S, et al. Pregnancy in ulcerative colitis. Scand J Gastroenterol. 1983; 18: 735–742.
- 21 Nielsen OH, Andreasson B, Bondesen S, et al. Pregnancy in Crohn's disease. Scand J Gastroenterol. 1984; 19: 724–732.
- 22 Mahadevan U SW, Li DK. Pregnancy outcomes in women with inflammatory bowel disease: a population based cohort study. Gastroenterology. 2007; 113: 1106–1112.
- 23 Mogadam M, Korelitz BI, Ahmed SW, et al. The course of inflammatory bowel disease during pregnancy and postpartum. Am J Gastroenterol. 1981; 75: 265–269.
- 24 Morales M, Berney T, Jenny A, et al. Crohn's disease as a risk factor for the outcome of pregnancy. Hepatogastroenterology. 2000; 47: 1595–1598.
- 25 Agret F, Cosnes J, Hassani Z, et al. Impact of pregnancy on the clinical activity of Crohn's disease. Aliment Pharmacol Ther. 2005; 21: 509–513.
- 26 Castiglione F, Pignata S, Morace F, 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.
- 27 Riis L, Vind I, Politi P, 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.
- 28 Nelson JL, Hughes KA, Smith AG, et al. Maternal-fetal disparity in HLA class II alloantigens and the pregnancy-induced amelioration of rheumatoid arthritis. N Engl J Med. 1993; 329: 466–471.
- 29 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.
- 30 Bush MC, Patel S, Lapinski RH, et al. Perinatal outcomes in inflammatory bowel disease. J Matern Fetal Neonatal Med. 2004; 15: 237–241.
- 31 Fedorkow DM, Persaud D, Nimrod CA. Inflammatory bowel disease: a controlled study of late pregnancy outcome. Am J Obstet Gynecol. 1989; 160: 998–1001.
- 32 Moser MA, Okun NB, Mayes DC, et al. Crohn's disease, pregnancy, and birth weight. Am J Gastroenterol. 2000; 95: 1021–1026.
- 33 Norgard B, Hundborg HH, Jacobsen BA, et al. Disease activity in pregnant women with Crohn's disease and birth outcomes: a regional Danish cohort study. Am J Gastroenterol. 2007; 102: 1947–1954.
- 34 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.
- 35 Fonager K, Sorensen HT, Olsen J, et al. 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.
- 36 Norgard B, Fonager K, Sorensen HT, et al. Birth outcomes of women with ulcerative colitis: a nationwide Danish cohort study. Am J Gastroenterol. 2000; 95: 3165–3170.
- 37 Dominitz JA, Young JC, Boyko EJ. Outcomes of infants born to mothers with inflammatory bowel disease: a population-based cohort study. Am J Gastroenterol. 2002; 97: 641–648.
- 38 Norgard B, Puho E, Pedersen L, et al. 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.
- 39 Bortoli A, Saibeni S, Tatarella M, et al. Pregnancy before and after the diagnosis of inflammatory bowel diseases: retrospective case-control study. J Gastroenterol Hepatol. 2007; 22: 542–549.
- 40 Cornish J, Tan E, Teare J, et al. A meta-analysis on the influence of inflammatory bowel disease on pregnancy. Gut. 2007; 56: 830–837.
- 41 Larzilliere I, Beau P. [ Chronic inflammatory bowel disease and pregnancy. Case control study.] Gastroenterol Clin Biol. 1998; 22: 1056–1060.
- 42 Craxi A, Pagliarello F. Possible embryotoxicity of sulfasalazine. Arch Intern Med. 1980; 140: 1674.
- 43 Hoo JJ, Hadro TA, Von Behren P. Possible teratogenicity of sulfasalazine. N Engl J Med. 1988; 318: 1128.
- 44 Newman NM, Correy JF. Possible teratogenicity of sulphasalazine. Med J Aust. 1983; 1: 528–529.
- 45 Mogadam M, Dobbins WO 3rd, Korelitz BI, et al. Pregnancy in inflammatory bowel disease: effect of sulfasalazine and corticosteroids on fetal outcome. Gastroenterology. 1981; 80: 72–76.
- 46 Norgard B, Czeizel AE, Rockenbauer M, et al. Population-based case control study of the safety of sulfasalazine use during pregnancy. Aliment Pharmacol Ther. 2001; 15: 483–486.
- 47 Esbjorner E, Jarnerot G, Wranne L. Sulphasalazine and sulphapyridine serum levels in children to mothers treated with sulphasalazine during pregnancy and lactation. Acta Paediatr Scand. 1987; 76: 137–142.
- 48 Habal FM, Hui G, Greenberg GR. Oral 5-aminosalicylic acid for inflammatory bowel disease in pregnancy: safety and clinical course. Gastroenterology. 1993; 105: 1057–1060.
- 49 Marteau P, Tennenbaum R, Elefant E, et al. Foetal outcome in women with inflammatory bowel disease treated during pregnancy with oral mesalazine microgranules. Aliment Pharmacol Ther. 1998; 12: 1101–1108.
- 50 Trallori G, d'Albasio G, Bardazzi G, et al. 5-Aminosalicylic acid in pregnancy: clinical report. Ital J Gastroenterol. 1994; 26: 75–78.
- 51 Diav-Citrin O, Park YH, Veerasuntharam G, et al. The safety of mesalamine in human pregnancy: a prospective controlled cohort study. Gastroenterology. 1998; 114: 23–28.
- 52 Norgard B, Fonager K, Pedersen L, et al. Birth outcome in women exposed to 5-aminosalicylic acid during pregnancy: a Danish cohort study. Gut. 2003; 52: 243–247.
- 53 Burtin P, Taddio A, Ariburnu O, et al. Safety of metronidazole in pregnancy: a meta-analysis. Am J Obstet Gynecol. 1995; 172: 525–529.
- 54 Caro-Paton T, Carvajal A, Martin de Diego I, et al. Is metronidazole teratogenic? A meta-analysis. Br J Clin Pharmacol. 1997; 44: 179–182.
- 55 Piper JM, Mitchel EF, Ray WA. Prenatal use of metronidazole and birth defects: no association. Obstet Gynecol. 1993; 82: 348–352.
- 56 Sorensen HT, Larsen H, Jensen ES, et al. Safety of metronidazole during pregnancy: a cohort study of risk of congenital abnormalities, preterm delivery and low birth weight in 124 women. J Antimicrob Chemother. 1999; 44: 854–856.
- 57 Diav-Citrin O, Shechtman S, Gotteiner T, et al. Pregnancy outcome after gestational exposure to metronidazole: a prospective controlled cohort study. Teratology. 2001; 63: 186–192.
- 58 Czeizel AE, Rockenbauer M. A population based case-control teratologic study of oral metronidazole treatment during pregnancy. Br J Obstet Gynaecol. 1998; 105: 322–327.
- 59 Niebyl JR. Antibiotics and other anti-infective agents in pregnancy and lactation. Am J Perinatol. 2003; 20: 405–414.
- 60 Loebstein R, Addis A, Ho E, et al. Pregnancy outcome following gestational exposure to fluoroquinolones: a multicenter prospective controlled study. Antimicrob Agents Chemother. 1998; 42: 1336–1339.
- 61 Larsen H, Nielsen GL, Schonheyder HC, et al. Birth outcome following maternal use of fluoroquinolones. Int J Antimicrob Agents. 2001; 18: 259–262.
- 62 Bertoli D, Borelli G. Fertility study of rifaximin (L/105) in rats. Chemioterapia. 1986; 5: 204–207.
- 63 Bertoli D, Borelli G. [ Teratogenic action of Rifaximin in the rat and rabbit and its effect on perinatal development in the rat.] Boll Soc Ital Biol Sper. 1984; 60: 1079–1085.
- 64 Adams CA. Anderson LS, Juanengo JC, et al. Effect of medications on semen analysis and sperm chromatin structure assay (SCSA) parameters. Presented at the American Association of Bioanalysts, Las Vegas, 2004.
- 65 Czeizel AE, Rockenbauer M, Sorensen HT, et al. Augmentin treatment during pregnancy and the prevalence of congenital abnormalities: a population-based case-control teratologic study. Eur J Obstet Gynecol Reprod Biol. 2001; 97: 188–192.
- 66 Berkovitch M, Diav-Citrin O, Greenberg R, et al. First-trimester exposure to amoxycillin/clavulanic acid: a prospective, controlled study. Br J Clin Pharmacol. 2004; 58: 298–302.
- 67
Rodriguez-Pinilla E,
Martinez-Frias ML.
Corticosteroids during pregnancy and oral clefts: a case-control study.
Teratology.
1998;
58:
2–5.
10.1002/(SICI)1096-9926(199807)58:1<2::AID-TERA2>3.0.CO;2-4 CAS PubMed Web of Science® Google Scholar
- 68
Carmichael SL,
Shaw GM.
Maternal corticosteroid use and risk of selected congenital anomalies.
Am J Med Genet.
1999;
86:
242–244.
10.1002/(SICI)1096-8628(19990917)86:3<242::AID-AJMG9>3.0.CO;2-U CAS PubMed Web of Science® Google Scholar
- 69 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: 385–392.
- 70 Gur C, Diav-Citrin O, Shechtman S, et al. Pregnancy outcome after first trimester exposure to corticosteroids: a prospective controlled study. Reprod Toxicol. 2004; 18: 93–101.
- 71 Armenti VT, Moritz MJ, Cardonick EH, et al. Immunosuppression in pregnancy: choices for infant and maternal health. Drugs. 2002; 62: 2361–2375.
- 72 Beaulieu WL, Issa M, Newcomer JR, et al. Budesonide induction and maintenance therapy for Crohn's disease during pregnancy. Am J Gastroenterol. 2006; 101: S463.
- 73 Gluck PA, Gluck JC. A review of pregnancy outcomes after exposure to orally inhaled or intranasal budesonide. Curr Med Res Opin. 2005; 21: 1075–1084.
- 74 Norjavaara E, de Verdier MG. Normal pregnancy outcomes in a population-based study including 2,968 pregnant women exposed to budesonide. J Allergy Clin Immunol. 2003; 111: 736–742.
- 75
Patlas N,
Golomb G,
Yaffe P, et al.
Transplacental effects of bisphosphonates on fetal skeletal ossification and mineralization in rats.
Teratology.
1999;
60:
68–73.
10.1002/(SICI)1096-9926(199908)60:2<68::AID-TERA10>3.0.CO;2-H CAS PubMed Web of Science® Google Scholar
- 76 Ornoy A, Wajnberg R, Diav-Citrin O. The outcome of pregnancy following pre-pregnancy or early pregnancy alendronate treatment. Reprod Toxicol. 2006; 22: 578–579.
- 77 Briggs. Drugs in Pregnancy and Lactation. Philadelphia: Lippincott, Williams & Wilkins; 2005.
- 78
Del Campo M,
Kosaki K,
Bennett FC, et al.
Developmental delay in fetal aminopterin/methotrexate syndrome.
Teratology.
1999;
60:
10–12.
10.1002/(SICI)1096-9926(199907)60:1<10::AID-TERA5>3.0.CO;2-H CAS PubMed Web of Science® Google Scholar
- 79 Polifka JE, Friedman JM. Teratogen update: azathioprine and 6-mercaptopurine. Teratology. 2002; 65: 240–261.
- 80 de Boer NK, Jarbandhan SV, de Graaf P, et al. Azathioprine use during pregnancy: unexpected intrauterine exposure to metabolites. Am J Gastroenterol. 2006; 101: 1390–1392.
- 81 Norgard B, Pedersen L, Fonager K, et al. Azathioprine, mercaptopurine and birth outcome: a population-based cohort study. Aliment Pharmacol Ther. 2003; 17: 827–834.
- 82 Alstead EM, Ritchie JK, Lennard-Jones JE, et al. Safety of azathioprine in pregnancy in inflammatory bowel disease. Gastroenterology. 1990; 99: 443–446.
- 83 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: 9–17.
- 84 Khan ZH, Mayberry JF, Spiers N, et al. Retrospective case series analysis of patients with inflammatory bowel disease on azathioprine. A district general hospital experience. Digestion. 2000; 62: 249–254.
- 85 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: 656–661.
- 86 Zlatanic J, Korelitz BI, Rajapakse R, et al. Complications of pregnancy and child development after cessation of treatment with 6-mercaptopurine for inflammatory bowel disease. J Clin Gastroenterol. 2003; 36: 303–309.
- 87 Norgard B, Pedersen L, Christensen LA, et al. Therapeutic drug use in women with Crohn's disease and birth outcomes: a Danish nationwide cohort study. Am J Gastroenterol. 2007; 102: 1406–1413.
- 88 Goldstein LH, Dolinsky G, Greenberg R, et al. Pregnancy outcome of women exposed to azathioprine during pregnancy. Birth Defects Res A Clin Mol Teratol. 2007; 79: 696–701.
- 89 Bar Oz B, Hackman R, Einarson T, et al. Pregnancy outcome after cyclosporine therapy during pregnancy: a meta-analysis. Transplantation. 2001; 71: 1051–1055.
- 90 Nagy S, Bush MC, Berkowitz R, et al. Pregnancy outcome in liver transplant recipients. Obstet Gynecol. 2003; 102: 121–128.
- 91 Angelberger S, Reinisch W, Dejaco C. Prevention of abortion by ciclosporin treatment of fulminant ulcerative colitis during pregnancy. Gut. 2006; 55: 1364–1365.
- 92 Bertschinger P, Himmelmann A, Risti B, et al. Cyclosporine treatment of severe ulcerative colitis during pregnancy. Am J Gastroenterol. 1995; 90: 330.
- 93 Reindl W, Schmid RM, Huber W. Cyclosporin A treatment of steroid-refractory ulcerative colitis during pregnancy: report of two cases. Gut. 2007; 56: 1019.
- 94 Jain A, Venkataramanan R, Fung JJ, et al. Pregnancy after liver transplantation under tacrolimus. Transplantation. 1997; 64: 559–565.
- 95 Kainz A, Harabacz I, Cowlrick IS, et al. Analysis of 100 pregnancy outcomes in women treated systemically with tacrolimus. Transpl Int. 2000; 13(suppl 1): S299–300.
- 96 Jain AB, Reyes J, Marcos A, et al. Pregnancy after liver transplantation with tacrolimus immunosuppression: a single center's experience update at 13 years. Transplantation. 2003; 76: 827–832.
- 97 Baumgart DC, Sturm A, Wiedenmann B, et al. Uneventful pregnancy and neonatal outcome with tacrolimus in refractory ulcerative colitis. Gut. 2005; 54: 1822–1823.
- 98 Ehrenpreis ED, Kane SV, Cohen LB, et al. Thalidomide therapy for patients with refractory Crohn's disease: an open-label trial. Gastroenterology. 1999; 117: 1271–1277.
- 99 Celgene Corp. Thalomid. Product Information 2000.
- 100 Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet. 2002; 359: 1541–1549.
- 101 Rutgeerts P, Diamond, RH, Bala, M, et al. Scheduled maintenance treatment with infliximab is superior to episodie treatment for the healing of mucosal ulceration associated with Crohn's Disease. Gastrointest Endosc. 2006; 63: 433–442.
- 102 Simister NE. Placental transport of immunoglobulin G. Vaccine. 2003; 21: 3365–3369.
- 103 Srinivasan R. Infliximab treatment and pregnancy outcome in active Crohn's disease. Am J Gastroenterol. 2001; 96: 2274–2275.
- 104 Bank L HB. Unexpected dramatic clinical repsonse of psoriasis lesions and unexpected pregnancy in an infertile patient in reponse to treatment with anti-tumor necrosis factor monoclonal antibody for Crohn's disease. Am J Gastroenterol. 2002; 97: S260.
- 105 Burt MJ, Frizelle FA, Barbezat GO. Pregnancy and exposure to infliximab (anti-tumor necrosis factor-alpha monoclonal antibody). J Gastroenterol Hepatol. 2003; 18: 465–466.
- 106
James RL PL.
Successful treatment of pregnancy-triggered Crohn's disease complicated by severe recurrent life-threatening gastrointestinal bleeding.
Am J Gastroenterol.
2001;
96:
S295.
10.1016/S0002-9270(01)03714-5 Google Scholar
- 107 Lichtenstein GR, Feagan BG, Cohen RD, et al. Serious infections and mortality in association with therapies for Crohn's disease: TREAT registry. Clin Gastroenterol Hepatol. 2006; 4: 621–630.
- 108 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: 2385–2392.
- 109 Mahadevan U, Kane S, Sandborn WJ, et al. Intentional infliximab use during pregnancy for induction or maintenance of remission in Crohn's disease. Aliment Pharmacol Ther. 2005; 21: 733–738.
- 110 Schnitzler F FH, Ferrante M, Noman M, et al. Intentional treatment with infliximab during pregnancy in women with inflammatory bowel disease (Abstract). Gastroenterology. 2007; 132:Abstract 958.
- 111 Vasiliauskas EA, Church JA, Silverman N, et al. Case report: evidence for transplacental transfer of maternally administered infliximab to the newborn. Clin Gastroenterol Hepatol. 2006; 4: 1255–1258.
- 112 Mahadevan U TJ, Church, J, et al. Infliximab levels in infants born to women with inflammatory bowel disease. Gastroenterology. 2007; 132: A144.
- 113 Hanauer SB, Stromberg U. Oral Pentasa in the treatment of active Crohn's disease: A meta-analysis of double-blind, placebo-controlled trials. Clin Gastroenterol Hepatol. 2004; 2: 379–388.
- 114 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: 2045–2047.
- 115 Mishkin DS, Van Deinse W, Becker JM, et al. Successful use of adalimumab (Humira) for Crohn's disease in pregnancy. Inflamm Bowel Dis. 2006; 12: 827–828.
- 116 Vesga L, Terdiman JP, Mahadevan U. Adalimumab use in pregnancy. Gut. 2005; 54: 890.
- 117 Chambers CD JD, Jones KL. Pregnancy outcomes in women exposed to adalimumab: the OTIS Autoimmune Diseases in Pregnancy Project. Personal communication July 13, 2007.
- 118 Sandborn WJ, Feagan BG, Stoinov S, et al. Certolizumab pegol for the treatment of Crohn's disease. N Engl J Med. 2007; 357: 228–238.
- 119 Schreiber S, Khaliq-Kareemi M, Lawrance IC, et al. Maintenance therapy with certolizumab pegol for Crohn's disease. N Engl J Med. 2007; 357: 239–250.
- 120 Nesbitt A BD, Stephens S, Foulkes R. Placental transfer and accumulation in milk of the anti-TNF antibody TN3 in rats: immunoglobulin G1 versus PEGylated Fab'. Am J Gastroenterol. 2006;Abstract 119.
- 121 Olsen SF, Sorensen JD, Secher NJ, et al. Randomised controlled trial of effect of fish-oil supplementation on pregnancy duration. Lancet. 1992; 339: 1003–1007.
- 122 Rossi E, Costa M. Fish oil derivatives as a prophylaxis of recurrent miscarriage associated with antiphospholipid antibodies (APL): a pilot study. Lupus. 1993; 2: 319–323.
- 123 FDA. Regulations. 1980;44: 37434–37467.
- 124 Kilpatrick CC, Monga M. Approach to the acute abdomen in pregnancy. Obstet Gynecol Clin North Am. 2007; 34: 389–402.
- 125 Upadhyay A, Stanten S, Kazantsev G, et al. Laparoscopic management of a nonobstetric emergency in the third trimester of pregnancy. Surg Endosc. 2007; 21: 1344–1348.
- 126 Dozois EJ, Wolff BG, Tremaine WJ, et al. Maternal and fetal outcome after colectomy for fulminant ulcerative colitis during pregnancy: case series and literature review. Dis Colon Rectum. 2006; 49: 64–73.
- 127 Watson WJ, Gaines TE. Third-trimester colectomy for severe ulcerative colitis. A case report. J Reprod Med. 1987; 32: 869–872.
- 128 Bohe MG, Ekelund GR, Genell SN, et al. Surgery for fulminating colitis during pregnancy. Dis Colon Rectum. 1983; 26: 119–122.
- 129 Boulton R, Hamilton M, Lewis A, et al. Fulminant ulcerative colitis in pregnancy. Am J Gastroenterol. 1994; 89: 931–933.
- 130 Ooi BS, Remzi FH, Fazio VW. Turnbull-Blowhole colostomy for toxic ulcerative colitis in pregnancy: report of two cases. Dis Colon Rectum. 2003; 46: 111–115.
- 131 Haq AI, Sahai A, Hallwoth S, et al. Synchronous colectomy and caesarean section for fulminant ulcerative colitis: case report and review of the literature. Int J Colorectal Dis. 2006; 21: 465–469.
- 132 Martimbeau PW. Welch JS. Weiland LH. Crohn's disease and pregnancy. Am J Obstet Gynecol. 1975; 122: 746–749.
- 133 Hill J, Clark A, Scott NA. Surgical treatment of acute manifestations of Crohn's disease during pregnancy. J Roy Soc Med. 1997; 90: 64–66.
- 134 Brandt LJ. Estabrook SG. Reinus JF. Results of a survey to evaluate whether vaginal delivery and episiotomy lead to perineal involvement in women with Crohn's disease. Am J Gastroenterol. 1995; 90: 1918–1922.
- 135 Ilnyckyji A, Blanchard JF, Rawsthorne P, et al. Perianal Crohn's disease and pregnancy: role of the mode of delivery. Am J Gastroenterol. 1999; 94: 3274–3278.
- 136 Beniada A. Benoist G. Maurel J. Dreyfus M. Inflammatory bowel disease and pregnancy: report of 76 cases and review of the literature. J Gynecol Obstet Biol Reprod. 2005; 34: 581–588.
- 137 Rogers RG. Katz VL. Course of Crohn's disease during pregnancy and its effect on pregnancy outcome: a retrospective review. Am J Perinatol. 1995; 12: 262–264.
- 138 Ravid A, Richard CS, et al. Pregnancy, delivery, and pouch function after ileal pouch-anal anastomosis for ulcerative colitis. Dis Colon Rectum. 2002; 45: 1283–1288.
- 139 Juhasz ES, Fozard B, Dozois RR, et al. Ileal pouch-anal anastomosis function following childbirth. Dis Colon Rectum. 1995; 38: 158–165.
- 140 Kitayama T, Funayama Y, Fukushima K, et al. Anal function during pregnancy and postpartum after ileal pouch anal anastomosis for ulcerative colitis. Surg Today. 2005; 35: 211–215.
- 141 Hahnloser D, Pemberton JH, Wolff BG, et al. Pregnancy and delivery before and after ileal pouch-anal anastomosis for inflammatory bowel disease: immediate and long term consequences and outcomes. Dis Colon Rectum. 2004; 7: 1127–1135.
- 142 Kane S, Lemieux N, et al. The role of breastfeeding in postpartum disease activity in women with inflammatory bowel disease. Am J Gastroenterol. 2005; 100: 102–105.
- 143 Ubina-Aznar E, De Sola-Earle C, Rivera-Irigoin R, et al. Crohn's disease and pregnancy. A descriptive and retrospective study. Gastroenterol Hepatol. 2006; 29: 277–280.
- 144 Ackerman Z, Einbinder Y, Stalnikowicz, et al. Recurrent postpartum exacerbation of chronic ulcerative colitis. J Clin Gastroenterol. 2004; 38: 914.
- 145 Ostensen M, Forger F, Nelson JL, et al. Pregnancy in patients with rheumatic disease: anti-inflammatory cytokines increase in pregnancy and decrease postpartum. Ann Rheum Dis. 2005; 64: 839–844.
- 146 Salem ML. Estrogen, a double-edged sword: modulation of TH1- and TH2-mediated inflammations by differential regulation of TH1/TH2 cytokine production. Curr Drug Targets Inflamm Allergy. 2004; 3: 97–104.
- 147 Mogadam M, Korelitz BI, Ahmed SW, et al. The course of inflammatory bowel disease during pregnancy and postpartum. Am J Gastroenterol. 1981; 75: 265–269.
- 148 Barrett JH, Brennan P, Fiddler M, et al. Breast-feeding and postpartum relapse in women with rheumatoid and inflammatory arthritis. Arthritis Rheumatism. 2000; 43: 1010–1015.
- 149 Draca S, Levic Z. The possible role of prolactin in the immunopathogenesis of multiple sclerosis. Med Hypotheses. 1996; 47: 89–92.
- 150 Berczi I. The role of the growth and iatogenic hormone family in immune function. Neuroimmunomodulation. 1994; 1: 201–216.
- 151 Klement E, Cohen RV, Boxman J, et al. Breastfeeding and risk of inflammatory bowel disease: a systematic review with meta-analysis. Am J Clin Nutr. 2004; 80: 1342–1352.
- 152 Jantchou P, Turck D. Breastfeeding and risk of inflammatory bowel disease: results of a pediatric, population-based, case-control study. Am J Clin Nutr. 2005; 82: 485–486.
- 153 Nelis GF. Diarrhoea due to 6-aminosalicyclic acid in breast milk. Lancet. 1989; 1: 383.
- 154 American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics. 2001; 108: 776–789.
- 155 Kroser J, Srinivasan R. Drug therapy of inflammatory bowel disease in fertile women. Am J Gastroenterol. 2006; 101: S633–S639.
- 156 Miller LG, Hopkinson JM, Motil KJ, et al. Disposition of olsalazine and metabolites in breast milk. J Clin Pharmacol. 1993; 33: 703–706.
- 157 Silverman DA, Ford J, Shaw I, et al. Is mesalazine really safe for use in breastfeeding mothers? Gut. 2005; 54: 170–171.
- 158 Branski D, Kerem E, Gross-Kieselsterin E, et al. Bloody diarrhea—a possible complication of sulfasalazine tansferred through human breast milk. J Pediatr Gastroenterol Nutr. 1986; 5: 316–317.
- 159 Jarnerot G, Into-Malmberg MB, Esbjorner E. Placental transfer of sulphasalazine and sulphapyridine and some of its metabolites. Scand J Gastroenterol. 1981; 16: 693–697.
- 160 Cover DL. Mueller BA. Ciprofloxacin penetration into human breast milk: a case report. DICP. 1990; 24: 703–704.
- 161 Physicians Desk Reference. Edition 62; Published by Thomson Health Care Inc., Montvale, NJ. 2008.
- 162 Passmore CM, McElnay JC, Rainey EA, et al. Metronidazole excretion in human milk and its effect on the suckling neonate. Br J Clin Pharmacol. 1988; 26: 45–51.
- 163 Heisterberg L. Branebjerg PE. Blood and milk concentrations of metronidazole in mothers and infants. J Perinat Med. 1983; 11: 114–120.
- 164 Mogadam M, Dobbins WO 3rd, Korelitz BI, et al. Pregnancy in inflammatory bowel disease: Effect of sulfasalazine and corticosteroids on fetal outcome. Gastroenterology. 1981; 80: 72–76.
- 165 Ost L, Wettrell G, Bjorkhem I, et al. Prednisolone excretion in human milk. J Pediatr. 1985; 106: 1008–1011.
- 166 Coulam CB, Moyer TP, Jiang NS, et al. Breast-feeding after renal transplantation. Transplant Proc. 1982; 14: 605–609.
- 167 Christensen LA, Dahlerup JF, Schmiegelow K. Excretion of azathioprine metabolites in maternal milk. Gut. 2005; 54(suppl VII): A45.
- 168 Moretti ME, Verjee Z, Ito S, et al. Breast-feeding during maternal use of azathioprine. Ann Pharmacother. 2006; 40: 2269–2272.
- 169 Gardiner SJ, Gearry RB, Roberts RL, et al. Exposure to thiopurine drugs through breast milk is low based on metabolite concentrations in mother-infant pairs. Br J Clin Pharmacol. 2006; 62: 453–456.
- 170 Sau A, Clarke S, Bass J, et al. Azathioprine and breastfeeding: is it safe? Br J Obstet Gynaecol. 2007; 114: 498–501.
- 171 Moretti ME, Sgro M, Johnson DW, et al. Cyclosporine excretion into breast milk. Transplantation. 2003; 75: 2144–2146.
- 172 Johns DG, Rutherford LD, Keighton PC, et al. Secretion of methotrexate into human milk. Am J Obstet Gynecol. 1972; 112: 978–980.
- 173 Hunt JS, Chen HL, Miller L. Tumour necrosis factor: pivotal components of pregnancy? Biol Reprod. 1996; 54: 554–562.
- 174 Mahadevan U, Kane S, Church JA, et al. The effect of maternal peripartum infliximab use on neonatal immune response. Gastroenterology. Abstract. Digest Dis Week (in press).
- 175 Maryin, O, Oneda S, Treacy G. Effects of 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.
