Chronisch entzündliche Darmerkrankungen und Reproduktion - Aktuelles zu Datenlage und Behandlungskonzepten

M. K. Bohlmann; D. W. Luedders; R. Speer; A. Hornemann; I. Bohlmann; K. Diedrich

doi:10.1055/s-2007-989410

Geburtshilfe und Frauenheilkunde, Table of Contents

Geburtshilfe Frauenheilkd 2008; 68(1): 40-51
DOI: 10.1055/s-2007-989410

Übersicht

Chronisch entzündliche Darmerkrankungen und Reproduktion - Aktuelles zu Datenlage und Behandlungskonzepten

Chronic Inflammatory Bowel Diseases and Reproduction - Current State of Knowledge and Treatment OptionsM. K. Bohlmann¹ , D. W. Luedders¹ , R. Speer² , A. Hornemann¹ , I. Bohlmann³ , K. Diedrich¹

¹Universitäts-Frauenklinik Lübeck
²Klinik für Geburtsmedizin, Campus Virchow-Klinikum der Charité-Universitätsmedizin Berlin
³Klinik und Poliklinik für Gynäkologie, Universitätsklinikum Hamburg-Eppendorf

Abstract

Zusammenfassung

Die Inzidenzen der chronisch entzündlichen Darmerkrankungen Morbus Crohn und Colitis ulcerosa sind ansteigend. Aufgrund der relativ hohen Inzidenz bei Patientinnen im reproduktiven Alter sowie verbesserter medikamentöser und chirurgischer Methoden sind geburtshilflich Tätige häufiger mit Fragestellungen zur optimalen Betreuung vor und während einer Schwangerschaft konfrontiert. Die vorliegende Übersichtsarbeit soll einerseits den aktuellen Kenntnisstand im Hinblick auf Kinderwunsch und Schwangerschaftsbetreuung von Patientinnen mit chronisch entzündlichen Darmerkrankungen darstellen, andererseits therapeutische Optionen im Hinblick auf ihre Anwendbarkeit in Gravidität und Stillzeit überprüfen.

Abstract

The incidence of inflammatory bowel diseases such as ulcerative colitis and Crohn's disease is rising. Due to their relatively high incidence in the reproductive period and improved conservative and surgical options, obstetricians are more frequently being confronted with questions concerning the optimal therapy before and during the pregnancy of patients with inflammatory bowel diseases. It is the aim of this review to present the current state of knowledge on fertility and medical care during pregnancy and to discuss the therapeutic options with regard to their applicability in pregnancy and during the period of breast feeding in patients with ulcerative colitis and Crohn's disease.

Schlüsselwörter

Morbus Crohn - Colitis ulcerosa - chronisch entzündliche Darmerkrankung - Fertilität - Schwangerschaft - therapeutische Optionen

Key words

Crohn's disease - ulcerative colitis - inflammatory bowel disease - fertility - pregnancy - therapeutic options

Full Text

References

Literatur

1 Binder V. Genetic epidemiology in inflammatory bowel disease. Dig Dis. 1998; 16 351-355
2 Binder V. Epidemiology of IBD during the twentieth century: an integrated view. Best Pract Res Clin Gastroenterol. 2004; 18 463-479
3 Leitlinie der Deutschen Gesellschaft für Verdauungs- und Stoffwechselerkrankungen. Diagnostik und Therapie der Colitis ulcerosa. http://www.uni-duesseldorf.de/AWMF/ll/021-009.htm .
4 Shivananda S, Lennard-Jones J, Logan R, Fear N, Price A, Carpenter L, van Blankenstein M. Incidence of inflammatory bowel disease across Europe: is there a difference between north and south? Results of the European Collaborative Study on Inflammatory Bowel Disease (EC‐IBD). Gut. 1996; 39 690-697
5 Leitlinie der Deutschen Gesellschaft für Verdauungs- und Stoffwechselerkrankungen. Diagnostik und Therapie des Morbus Crohn. Zeitschrift für Gastroenterologie. 2003; 41 19-68
6 McLeod R S. Surgery for inflammatory bowel diseases. Dig Dis. 2003; 21 168-179
7 Schröder O, Sohn C, Stein J. Gastrointestinal and hepatobiliary complications during pregnancy. Geburtsh Frauenheilk. 2000; 60 333-344
8 Peeters M, Nevens H, Baert F, Hiele M, de Meyer A M, Vlietinck R, Rutgeerts P. Familial aggregation in Crohn's disease. Increased age, adjusted risk and concordance in clinical characteristics. Gastroenterology. 1996; 111 597-603
9 Ferrero S, Ragni N. Inflammatory bowel disease: management issues during pregnancy. Arch Gynecol Obstet. 2004; 270 79-85
10 Alstead E M, Nelson-Piercy C. Inflammatory bowel disease in pregnancy. Gut. 2003; 52 159-161
11 Willoughby C P, Truelove S C. Ulcerative colitis and pregnancy. Gut. 1980; 21 469-474
12 Baird D D, Narendranathan M, Sandler R S. Increased risk of preterm birth for women with inflammatory bowel disease. Gastroenterology. 1990; 99 987-994
13 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
14 Baiocco P J, Korelitz B I. The influence of inflammatory bowel disease and its treatment on pregnancy and fetal outcome. J Clin Gastroenterol. 1984; 6 211-216
15 Bradley R J, Rosen M P. Subfertility and gastrointestinal disease: “unexplained” is often undiagnosed. Obstet Gynecol Surv. 2004; 59 108-117
16 Ording Olsen K, Juul S, Berndtsson I, Oresland T, Laurberg S. Ulcerative colitis: female fecundity before diagnosis, during disease and after surgery compared to a population sample. Gastroenterology. 2002; 122 15-19
17 Johnson P, Richard C, Ravid A, Spencer L, Pinto E, Hanna M, Cohen Z, McLeod R. Female infertility after ileal pouch-anal anastomosis for ulcerative colitis. Dis Colon Rectum. 2004; 47 1119-1126
18 Oresland T, Palmblad S, Ellstrom M, Berndtsson I, Crona N, Hulten L. Gynaecological and sexual function related to anatomical changes in the female pelvis after restorative proctocolectomy. Int J Colorectal Dis. 1994; 9 77-81
19 Asztély M, Palmblad S, Wikland M, Hultén L. Radiological study of changes in the pelvis in women following proctocolectomy. Int J Colorectal Dis. 1991; 6 103-107
20 Mortier P E, Gambiez L, Karoui M, Cortot A, Paris J C, Quandalle P, Colombel J F. Colectomy with ileorectal anastomosis preserves female fertility in ulcerative colitis. Gastroenterol Clin Biol. 2006; 30 594-597
21 Cornish J A, Tan E, Teare J, Teoh T G, Rai R, Darzi A W, Paraskevas P, Clark S K, Tekkis P P. The effect of restorative proctocolectomy on sexual function, urinary function, fertility, pregnancy and delivery: a systematic review. Dis Colon Rectum. 2007; 50 1128-1138
22 Marri S R, Ahn C, Buchman A L. Voluntary childlessness is increased in women with inflammatory bowel disease. Inflamm Bowel Dis. 2007; 13 591-599
23 Fielding J F, Cooke W T. Pregnancy and Crohn's disease. Br Med J. 1970; 2 76-77
24 Moody G, Probert C S, Srivastava E M, Rhodes J, Mayberry J F. Sexual dysfunction amongst women with Crohn's disease: a hidden problem. Digestion. 1992; 52 179-183
25 Hueting W E, Gooszen H G, van Laarhoven C J. Sexual function and continence after ileo pouch anal anastomosis: a comparison between a meta-analysis and a questionnaire survey. Int J Colorectal Dis. 2004; 19 215-218
26 Bambrick M, Fazio V W, Hull T L, Pucel G. Sexual function following restorative proctocolectomy in women. Dis Colon Rectum. 1996; 39 610-614
27 Berndtsson I, Oresland T, Hulten L. Sexuality in patients with ulcerative colitis before and after restorative proctocolectomy: a prospective study. Scand J Gastroenterol. 2004; 39 374-379
28 Damgaard B, Wettergren A, Kirkegaard P. Social and sexual function following ileal pouch-anal anastomosis. Dis Colon Rectum. 1995; 38 286-289
29 Nielsen O H, Andreasson B, Bondesen S, Jarnum S. Pregnancy in ulcerative colitis. Scand J Gastroenterol. 1983; 18 735-742
30 Nielsen O H, Andreasson B, Bondesen S, Jacobsen O, Jarnum S. Pregnancy in Crohn's disease. Scand J Gastroenterol. 1984; 19 724-732
31 Miller J P. Inflammatory bowel disease in pregnancy. A review. J Royal Soc Med. 1986; 79 221-229
32 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
33 Castiglione F, Pignata S, Morace F, Sarubbi A, Baratta M A, D'Agostino L, D'Arienzo A, Mazzacca G. Effect of pregnancy on the clinical course of a cohort of women with inflammatory bowel disease. Ital J Gastroenterol. 1996; 28 199-204
34 Caprilli R, Gassull M A, Escher J C, Moser G, Munkholm P, Forbes A, Hommes D W, Lochs H, Angelucci E, Cocco A, Vucelic B, Hildebrand H, Kolacek S, Riis L, Lukas M, de Franchis R, Hamilton M, Jantschek G, Michetti P, O'Morain C, Anwar M M, Freitas J L, Mouzas I A, Baert F, Mitchell R, Hawkey C J. European Crohn's and Colitis Organisation . European evidence based consensus on the diagnosis and management of Crohn's disease: special situations. Gut. 2006; 55 i36-i58
35 Buyon J P. The effects of pregnancy on autoimmune diseases. J Leukoc Biol. 1998; 63 281-287
36 Riis L, Vind I, Politi P, Wolters F, Vermeire S, Tsianos E, Freitas J, Mouzas I, Ruiz Ochoa V, O'Morain C, Odes S, Binder V, Moum B, Stockbrugger R, Langholz E, Munkholm P. European Collaborative study group on Inflammatory Bowel Disease . 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
37 Kitayama T, Funayama Y, Fukushima K, Shibata C, Takahashi K, Ogawa H, Ueno T, Hashimoto A, Sasaki I. Anal function during pregnancy and postpartum after ileal pouch anal anastomosis for ulcerative colitis. Surg Today. 2005; 35 211-215
38 Lamah M, Scott H J. Inflammatory bowel disease and pregnancy. Int J Colorectal Dis. 2002; 17 216-222
39 Fedorkow D M, Persaud D, Nimrod C A. Inflammatory bowel disease: A controlled study of late pregnancy outcome. Am J Obstet Gynecol. 1989; 160 998-1001
40 Zeldis J B. Pregnancy and inflammatory bowel disease. West J Med. 1989; 151 168-171
41 Anderson J B, Turner G M, Williamson R C. Fulminant ulcerative colitis in late pregnancy and the puerperium. J R Soc Med. 1987; 80 492-494
42 Mahadevan U. Fertility and pregnancy in the patient with inflammatory bowel disease. Gut. 2006; 55 1198-1206
43 Korelitz B I. Inflammatory bowel disease and pregnancy. Gastroenterol Clin North Am. 1998; 27 213-224
44 Lang E, Schäfer W, Steegmüller K W, Höckel M, Junginger T. Die Perforation bei Morbus Crohn als Komplikation in der Schwangerschaft. Geburtsh Frauenheilk. 1991; 51 241-243
45 Roether M, Reichardt H D, Oechsner M G. Erstmanifestation eines Morbus Crohn in der Spätschwangerschaft: Indikation zur Ileozäkalresektion mit nachfolgendem Spontanpartus. Geburtsh Frauenheilk. 2005; 65 974-977
46 Subhani J M, Hamiliton M I. Review article: The management of inflammatory bowel disease during pregnancy. Aliment Pharmacol Ther. 1998; 12 1039-1053
47 Hanan I M, Kirsner J B. Inflammatory bowel disease in the pregnant woman. Clin Perinatol. 1985; 12 669-682
48 Schade R R, Thiel D HV, Gavaler J S. Chronic idiopathic ulcerative colitis. Pregnancy and fetal outcome. Dig Dis Sci. 1984; 29 614-619
49 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
50 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
51 Norgard B, Fonager K, Sørensen H T, Olsen J. Birth outcomes of women with ulcerative colitis: A nationwide Danish cohort study. Am J Gastroenterol. 2000; 95 3165-3170
52 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
53 Bortoli A, Saibeni S, Tatarella M, Prada A, Beretta L, Rivolta R, Politi P, Ravelli P, Imperiali G, Colombo E, Pera A, Daperno M, Carnovali M, de Franchis R, Vecchi M. the Study Group for Inflammatory Bowel Diseases GSMII . Pregnancy before and after the diagnosis of inflammatory bowel diseases: retrospective case-control study. J Gastroenterol Hepatol. 2007; 22 542-549
54 Rogers R G, Katz V L. Course of Crohn's disease during pregnancy and its effect on pregnancy outcome: A retrospective review. Am J Perinatol. 1995; 12 262-264
55 Cornish J A, Tan E K, Teare J, Teoh T G, Rai R, Clark S K, Tekkis P P. A Meta-analysis on the influence of inflammatory bowel disease on pregnancy. Gut. 2007; 56 830-837
56 Dominitz J A, Young J CC, 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
57 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
58 Teahon K, Pearson M, Levi A J, Bjarnason I. Elemental diet in the management of Crohn's disease during pregnancy. Gut. 1991; 32 1079-1081
59 Tresadern J C, Falconer G F, Turnberg L A, Irving M H. Successful completed pregnancy in a patient maintained on home parenteral nutrition. BMJ. 1983; 286 602-603
60 Czeizel A E, Toth M, Rockenbauer M. Population-based case-control study of folic acid supplementation during pregnancy. Teratology. 1996; 53 345-351
61 Reddy S I, Wolf J L. Management issues in women with inflammatory bowel disease. J Am Osteopath Assoc. 2001; 101 (12 Suppl Pt 2) S17-23
62 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 (Paris). 2005; 34 581-588
63 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
64 Brandt L J, Estabrook S G, Reinus J F. 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
65 Remzi F H, Gorgun E, Bast J, Schroeder T, Hammel J, Philipson E, Hull T L, Church J M, Fazio V W. Vaginal delivery after ileal pouch-anal anastomosis: a word of caution. Dis Colon Rectum. 2005; 48 1691-1699
66 Hahnloser D, Pemberton J H, Wolff B G, Larson D, Harrington J, Farouk R, Dozois R R. 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; 47 1127-1135
67 Katz J A, Pore G. Inflammatory bowel disease and pregnancy. Inflamm Bowel Dis. 2001; 7 146-157
68 Donaldson R M. Management of medical problems in pregnancy - inflammatory bowel disease. N Engl J Med. 1985; 312 1616-1619
69 Warrell D W, Taylor R. Outcome for the foetus of mothers receiving prednisolone during pregnancy. Lancet. 1968; 1 117-118
70 Khosla R, Willoughby C P, Jewell D P. Crohn's disease and pregnancy. Gut. 1984; 25 52-56
71 Porter R J, Stirrat G M. The effects of inflammatory bowel disease on pregnancy: A case-controlled retrospective analysis. Br J Obstet Gynecol. 1986; 93 1124-1131
72 Wolfson K, Cohen Z, McLeod R S. Crohn's disease and pregnancy. Dis Colon Rectum. 1990; 33 869-873
73 Travis S. Advances in therapeutic approaches to ulcerative colitis and Crohn's disease. Curr Gastroenterol Rep. 2005; 7 475-484
74 Stein R B, Hanauer S B. Comparative tolerability of treatments for inflammatory bowel disease. Drug Saf. 2000; 23 429-448
75 Craxi A, Pagliarello F. Possible embryotoxicity of sulfasalazine. Arch Intern Med. 1980; 140 1674
76 Newman N M, Correy J F. Possible teratogenicity of sulphasalazine. Med J Aust. 1983; 1 528-529
77 Hoo J J, Hadro T A, Von Behren P. Possible teratogenicity of sulfasalazine. N Engl J Med. 1988; 318 1128
78 Norgard B, Czeizel A E, Rockenbauer M, Olsen J, Sørensen H T. Population-based case control study of the safety of sulfasalazine use during pregnancy. Aliment Pharmacol Ther. 2001; 15 483-486
79 Czeizel E A, Dudas I. Prevention of the first occurrence of neuraltube defects with folic acid supplementation. N Engl J Med. 1992; 327 1832-1835
80 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; 76 137-142
81 Mogadam M, Dobbins W O, Korelitz B I, Ahmed S W. Pregnancy in inflammatory bowel disease: effect of sulfasalazine and corticosteroids on fetal outcome. Gastroenterology. 1981; 80 72-76
82 Diav-Citrin O, Park Y H, Veerasuntharam G, Polachek H, Bologa M, Pastuszak A, Koren G. The safety of mesalamine in human pregnancy: a prospective controlled cohort study. Gastroenterology. 1998; 114 23-28
83 Marteau P, Tennenbaum R, Elefant E, Lémann M, Cosnes J. Foetal outcome in women with inflammatory bowel disease treated during pregnancy with oral mesalazine microgranules. Aliment Pharmacol Ther. 1998; 12 1101-1108
84 Schroeder K W. Role of mesalazine in acute and long-term treatment of ulcerative colitis and its complications. Scand J Gastroenterol Suppl. 2002; 236 42-44
85 Bell C M, Habal F M. Safety of topical 5-aminosalicylic acid in pregnancy. Am J Gastroenterol. 1997; 92 2201-2202
86 Marteau P, Crand J, Devaux C B. Mesalazine in pregnancy: fetal outcome in 76 IBD patients treated with Pentasa. Gastroenterology. 1995; 108 A871
87 Habal F M, Hui G, Greenberg G R. Oral 5-aminosalicylic acid for inflammatory bowel disease in pregnancy: safety and clinical course. Gastroenterology. 1993; 105 1057-1060
88 http://www.fda.gov/cder/foi/label/2000/20610lbl.pdf
89 Hanauer S B. Review article: high-dose aminosalicylates to induce and maintain remissions in ulcerative colitis. Aliment Pharmacol Ther. 2006; 24 37-40
90 Bressler B, Sands B E. Review article: Medical therapy for fistulizing Crohn's disease. Aliment Pharmacol Ther. 2006; 24 1283-1293
91 Roe F J. Toxicologic evaluation of metronidazole with particular reference to carcinogenic, mutagenic, and teratogenic potential. Surgery. 1983; 93 158-164
92 Greenberg F. Possible metronidazole teratogenicity and clefting. Am J Med Genet. 1985; 22 825
93 Burtin P, Taddio A, Ariburnu O, Einarson T R, Koren G. Safety of metronidazole in pregnancy: a meta-analysis. Am J Obstet Gynecol. 1995; 172 525-529
94 Caro-Paton T, Carvajal A, Diego I M, Martin-Arias L H, Alvarez Requejo A, Rodriguez Pinilla E. Is metronidazole teratogenic? A meta-analysis. Br J Clin Pharmacol. 1997; 44 179-183
95 Heisterberg L, Branebjerg P E. Blood and milk concentrations of metronidazole in mothers and infants. J Perinat Med. 1983; 11 114-120
96 Passmore C M, McElnay J C, Rainey E A, D'Arcy P F. Metronidazole excretion in human milk and its effect on the suckling neonate. Br J Clin Pharmacol. 1988; 26 45-51
97 Loebstein R, Addis A, Ho E, Andreou R, Sage S, Donnenfeld A E, Schick B, Bonati M, Moretti M, Lalkin A, Pastuszak A, Koren G. Pregnancy outcome following gestational exposure to fluoroquinolones: A multicenter prospective controlled study. Antimicrob Agents Chemother. 1998; 42 1336-1339
98 Niebyl J R. Antibiotics and other anti-infective agents in pregnancy and lactation. Am J Perinatol. 2003; 20 405-414
99 Linseman D A, Hampton L A, Branstetter D G. Quinolone-induced arthropathy in the neonatal mouse. Morphological analysis of articular lesions produced by pipemidic acid and ciprofloxacin. Fundam Appl Toxicol. 1995; 28 59-64
100 Berkovitch M, Pastuszak A, Garzarian M, Lewis M, Koren G. Safety of the new quinolones in pregnancy. Obstet Gynecol. 1994; 84 535-538
101 Harmon T, Burkhart G, Applebaum H. Perforated pseudomembranous colitis in the breast-fed infant. J Pediatr Surg. 1992; 27 744-746
102 Gardner D K, Gabbe S G, Harter C. Simultaneous concentrations of ciprofloxacin in breast milk and in serum in mother and breast-fed infant. Clin Pharm. 1992; 11 352-354
103 Briggs G G, Freeman F R, Yaffe S J. Drugs in Pregnancy and Lactation. 7th ed. Philadelphia, PA; Lippincott, Williams and Wilkins 2005
104 Nahum G G, Uhl K, Kennedy D L. Antibiotic use in pregnancy and lactation: what is and is not known about teratogenic and toxic risks. Obstet Gynecol. 2006; 107 1120-1138
105 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
106 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
107 Ramsey-Goldman R, Schilling E. Immunosuppressive drug use during pregnancy. Rheum Clin NA. 1997; 23 149-167
108 Present D H, Meltzer S J, Krumholz M P, Wolke A, Korelitz B I. 6-Mercaptopurine in the management of inflammatory bowel disease. Ann Intern Med. 1989; 111 641-649
109 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
110 Mottet C, Juillerat P, Gonvers J J, Froehlich F, Burnand B, Vader J P, Michetti P, Felley C. Pregnancy and Crohn's disease. Digestion. 2005; 71 54-61
111 Donnenfeld A E, Pastuszak A, Noah J S, Schick B, Rose N C, Koren G. Methotrexate exposure prior to and during pregnancy. Teratology. 1994; 49 79-81
112 Briggs G G, Freeman R K, Yaffe S J. Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk. 5th ed. Baltimore; Williams & Wilkins 1998: 702-705
113 Lloyd M E, Carr M, McElhatton P, Hall G M, Hughes R A. The effects of methotrexate on pregnancy, fertility and lactation. QJM. 1999; 92 551-563
114 Connell W R. Safety of drug therapy for inflammatory bowel disease in pregnant and nursing women. Inflamm Bowel Dis. 1996; 2 33-47
115 Kane S. Managing pregnancy in IBD. Inflamm Bowel Dis Monitor. 2002; 4 2-11
116 Johns D G, Rutherford L D, Leighton P C, Vogel C L. Secretion of methotrexate into human milk. Am J Obstet Gynecol. 1972; 112 978-980
117 American Academy of Pediatrics . Transfer of drugs and other chemicals into human milk. Pediatrics. 2001; 108 776-779
118 Lichtiger A, Present D, Kornbluth A, Gelernt I, Bauer J, Galler G, Michelassi F, Hanauer S. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med. 1994; 330 1841-1845
119 Cohen R D, Stein R, Hanauer S B. Intravenous cyclosporine in ulcerative colitis: a five year experience. Am J Gastrorenterol. 1999; 94 1587-1592
120 Nguyen G C, Harris M L, Dassopoulos T. Insights in immunomodulatory therapies for ulcerative colitis and Crohn's disease. Curr Gastroenterol Rep. 2006; 8 499-505
121 Armenti V T, Moritz M J, Davison J M. Drug safety issues in pregnancy following transplantation and immunosuppression: effects and outcomes. Drug Saf. 1998; 19 219-232
122 Bertschinger P, Himmelmann A, Risti B, Follath F. Cyclosporine treatment of severe ulcerative colitis during pregnancy. Am J Gastroenterol. 1995; 90 330
123 Marion J F, Rubin P H, Lichtiger S. et al . Cyclosporine is safe for severe colitis complicating pregnancy. Am J Gastroenterol. 1996; 91 1975
124 Flechner S M, Katz A R, Rogers A J, van Buren C, Kahan B D. The presence of cyclosporin in body tissues and fluids during pregnancy. Am J Kidney Dis. 1985; 5 60-63
125 Munoz-Flores-Thiagarajan K D, Easterling T, Davis C, Bond E F. Breast-feeding by a cyclosporine-treated mother. Obstet Gynecol. 2001; 97 816-818
126 Thiru Y, Bateman D N, Coulthard M G. Successful breast feeding while mother was taking cyclosporin. BMJ. 1997; 315 463
127 Gonzalez-Lama Y, Gisbert J P, Mate J. The role of tacrolimus in inflammatory bowel disease: a systematic review. Dig Dis Sci. 2006; 51 1833-1840
128 Ng S C, Arebi N, Kamm M A. Medium-term results of oral tacrolimus treatment in refractory inflammatory bowel disease. Inflamm Bowel Dis. 2007; 13 129-134
129 Kainz A, Harabacz I, Cowlrick I S, Gadgil S D, Hagiwara D. Review of the course and outcome of 100 pregnancies in 84 women treated with tacrolimus. Transplantation. 2000; 70 1718-1721
130 Jain A, Venkataramanan R, Fung J J, Gartner J C, Lever J, Balan V, Warty V, Starzl T E. Pregnancy after liver transplantation under tacrolimus. Transplantation. 1997; 64 559-565
131 French A E, Soldin S J, Soldin O P, Koren G. Milk transfer and neonatal safety of tacrolimus. Ann Pharmacother. 2003; 37 815-818
132 Gardiner S J, Begg E J. Breastfeeding during tacrolimus therapy. Obstet Gynecol. 2006; 107 453-455
133 Korelitz B I. Pregnancy, fertility, and inflammatory bowel disease. Am J Gastroenterol. 1985; 80 365-370
134 Modigliani R. Drug therapy for ulcerative colitis during pregnancy. Eur J Gastroenterol Hepatol. 1997; 9 854-857
135 Bulmash J M. Systemic lupus erythematosus and pregnancy. Obstet Gynecol Ann. 1978; 7 153-194
136 Bulmash J M. Rheumatoid arthritis and pregnancy. Obstet Gynecol Ann. 1979; 8 223-276
137 Fitzsimons R, Greenberger P A, Patterson R. Outcome of pregnancy in women requiring corticosteroids for severe asthma. J Allergy Clin Immunol. 1986; 78 349-353
138 Pinsky L, DiGeorge A M. Cleft palate in the mouse: a teratogenic index of glucocorticoid potency. Science. 1965; 147 402-403
139 Fraser F C, Sajoo A. Teratogenic potential of corticosteroids in humans. Teratology. 1995; 51 45-46
140 Rodriguez-Pinella E, Martinez-Frias M L. Corticosteroids during pregnancy and oral clefts: a case control study. Teratology. 1998; 58 2-5
141 Beitens I Z, Bayarrd F, Ances I G, Kowarski A, Migeon C J. The transplacental passage of prednisone and prednisolone in pregnancy near term. J Pediatr. 1972; 81 936-945
142 Armenti V T, Moritz M J, Cardonick E H, Davison J M. Immunosuppression in pregnancy: choices for infant and maternal health. Drugs. 2002; 62 2361-2375
143 Burakoff R, Opper F. Pregnancy and nursing. Gastroenterol Clin N Am. 1995; 24 689-698
144 Khanna D, McMahon M, Furst D E. Safety of tumor necrosis factor-alpha antagonists. Drug Saf. 2004; 27 307-324
145 Osterman M T, Lichtenstein G R. Current and future anti-TNF therapy for inflammatory bowel disease. Curr Treat Options Gastroenterol. 2007; 10 195-207
146 Baumgart D C, Sandborn W J. Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet. 2007; 369 1641-1657
147 Vesga L, Terdiman J P, Mahadevan U. Adalimumab use in pregnancy. Gut. 2005; 54 890
148 Roux C H, Brocq O, Breuil V, Albert C, Euller-Ziegler L. Pregnancy in rheumatology patients exposed to anti-tumour necrosis factor (TNF)-alpha therapy. Rheumatology (Oxford). 2007; 46 695-698
149 Lichtenstein G, Cohen R D, Feagan B G, Sandborn W, Salzberg B, Chen D, Diamond R. Safety of infliximab in Crohn's disease: data from the 5000-patient TREAT registry. Gastroenterology. 2004; 126 A54
150 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
151 Mahadevan U, Kane S, Sandborn W J, Cohen R D, Hanson K, Terdiman J P, Binion D G. Intentional infliximab use during pregnancy for induction or maintenance of remission in Crohn's disease. Aliment Pharmacol Ther. 2005; 21 733-738
152 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
153 Shrim A, Koren G. Tumour necrosis factor alpha and use of infliximab. Safety during pregnancy. Can Fam Physician. 2005; 51 667-668
154 Einarson A, Mastroiacovo P, Arnon J, Ornoy A, Addis A, Malm H, Koren G. Prospective, controlled, multicentre study of loperamide in pregnancy. Can J Gastroenterol. 2000; 14 185-187
155 Hagemann T M. Gastrointestinal medications and breastfeeding. J Hum Lact. 1998; 14 259-262
156 Levi A J, Fisher A M, Hughes L, Hendry W F. Male infertility due to sulphasalazine. Lancet. 1979; 2 276-278
157 Toth A. Reversible toxic effect of salicylazosulfapyridine on semen quality. Fertil Steril. 1979; 31 538-540
158 Birnie G G, McLeod T I, Watkinson G. Incidence of sulphasalazine-induced male infertility. Gut. 1981; 22 452-455
159 Shaffer J L, Kershaw A, Berrisford M H. Sulphasalazine-induced infertility reversed on transfer to 5-aminosalicylic acid. Lancet. 1984; 1 1240
160 Zelissen P M, van Hattum J, Poen H, Scholten P, Gerritse R, te Velde E R. Influence of salazosulphapyridine and 5-aminosalicylic acid on seminal qualities and male sex hormones. Scand J Gastroenterol. 1988; 23 1100-1104
161 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
162 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
163 Kane S V. What's good for the goose should be good for the gander - 6-MP use in fathers with inflammatory bowel disease. Am J Gastroenterol. 2000; 95 581-582
164 Burnell D, Mayberry J, Calcraft B J, Morris J S, Rhodes J. Male fertility in Crohn's disease. Postgrad Med J. 1986; 62 269-272
165 Narendranathan M, Sandler R S, Suchindran C M, Savitz D A. Male infertility in inflammatory bowel disease. J Clin Gastroenterol. 1989; 11 403-406
166 Farthing M J, Dawson A M. Impaired semen quality in Crohn's disease - drugs, ill health, or undernutrition?. Scand J Gastroenterol. 1983; 18 57-60
167 El-Tawil A M. Zinc deficiency in men with Crohn's disease may contribute to poor sperm function and male infertility. Andrologia. 2003; 35 337-341

Michael K. Bohlmann

Klinik für Frauenheilkunde und Geburtshilfe
Universitätsklinikum Schleswig-Holstein - Campus Lübeck

Ratzeburger Allee 160

23538 Lübeck

Email: michael.bohlmann@uk-sh.de