Management and treatment of pregnancy complicated with inflammatory bowel disease_West China Medical Journal

Authors：

WU Jiaqi , WANG Yi ,  YE Bai

Department of Gastroenterology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P. R. China;

Corresponding author：

YE Bai, Email: yeb1961@163.com

Keywords：

Inflammatory bowel disease; Pregnancy; Drug safety; Management and treatment

DOI：

10.7507/1002-0179.201912243

Video：

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Inflammatory bowel disease (IBD) is a group of chronic, recurrent, and non-specific intestinal inflammatory diseases. It usually occurs between 20 and 40 years old, overlapping with the patient’s childbearing age. Active IBD may lead to decreased fertility and adverse pregnancy outcomes, and pregnancy may also lead to recurrence of IBD. Through studying domestic and foreign related literature on pregnancy and IBD, this article elaborates on the guidance and management of IBD before pregnancy, the disease management of IBD during pregnancy, the disease management of IBD during lactation, and the current status and prospects of traditional Chinese medicine treatment. It aims to provide references for patients and clinicians to have a more scientific understanding of pregnancy with IBD.

Citation： WU Jiaqi, WANG Yi, YE Bai. Management and treatment of pregnancy complicated with inflammatory bowel disease. West China Medical Journal, 2021, 36(2): 271-275. doi: 10.7507/1002-0179.201912243 Copy

1.	Salari P, Nikfar S, Abdollahi M. Current opinion on treatment of inflammatory bowel disease in pregnant women. Arch Med Sci, 2012, 8(6): 983-986.
2.	Druvefors E, Landerholm K, Hammar U, et al. Impaired fertility in women with inflammatory bowel disease: a national cohort study from Sweden. J Crohns Colitis, 2020, 19: jjaa191.
3.	Jølving LR, Nielsen J, Beck-Nielsen SS, et al. The association between maternal chronic inflammatory bowel disease and long-term health outcomes in children-a nationwide cohort study. Inflamm Bowel Dis, 2017, 23(8): 1440-1446.
4.	Elten M, Benchimol EI, Fell DB, et al. Ambient air pollution and the risk of pediatric-onset inflammatory bowel disease: a population-based cohort study. Environ Int, 2020, 138: 105676.
5.	谭蓓, 钱家鸣. 炎症性肠病妊娠期管理与治疗. 中国实用内科杂志, 2018, 38(3): 200-203.
6.	戴萌, 金雷, 熊毅敏, 等. 炎症性肠病患者的妊娠相关问题. 世界华人消化杂志, 2016, 24(3): 382-389.
7.	Ørding Olsen K, 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(1): 15-19.
8.	Moscandrew M, Kane S. Inflammatory bowel diseases and management considerations: fertility and pregnancy. Curr Gastroenterol Rep, 2009, 11(5): 395-399.
9.	Marri SR, Ahn C, Buchman AL. Voluntary childlessness is increased in women with inflammatory bowel disease. Inflamm Bowel Dis, 2007, 13(5): 591-599.
10.	Ali MF, He H, Friedel D. Inflammatory bowel disease and pregnancy: fertility, complications and treatment. Ann Gastroenterol, 2020, 33(6): 579-590.
11.	Bell SJ, Flanagan EK. Updates in the management of inflammatory bowel disease during pregnancy. Med J Aust, 2019, 210(6): 276-280.
12.	Heetun ZS, Byrnes C, Neary P, et al. Review article: reproduction in the patient with inflammatory bowel disease. Aliment Pharmacol Ther, 2007, 26(4): 513-533.
13.	中华医学会消化病学分会炎症性肠病学组. 炎症性肠病妊娠期管理的专家共识意见. 协和医学杂志, 2019, 10(5): 465-475.
14.	Perez-Garcia LF, Dolhain RJEM, Vorstenbosch S, et al. The effect of paternal exposure to immunosuppressive drugs on sexual function, reproductive hormones, fertility, pregnancy and offspring outcomes: a systematic review. Hum Reprod Update, 2020, 26(6): 961-1001.
15.	Peng X, Zhi M, Wei M, et al. Thalidomide results in diminished ovarian reserve in reproductive age female IBD patients. Medicine (Baltimore), 2017, 96(21): e6540.
16.	Grosen A, Kelsen J, Hvas CL, et al. The influence of methotrexate treatment on male fertility and pregnancy outcome after paternal exposure. Inflamm Bowel Dis, 2017, 23(4): 561-569.
17.	Shannahan SE, Erlich JM, Peppercorn MA. Insights into the treatment of inflammatory bowel disease in pregnancy. Therap Adv Gastroenterol, 2019, 12: 1756284819852231.
18.	Rahimi R, Nikfar S, Rezaie A, et al. Pregnancy outcome in women with inflammatory bowel disease following exposure to 5-aminosalicylic acid drugs: a meta-analysis. Reprod Toxicol, 2008, 25(2): 271-275.
19.	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(11): 1101-1108.
20.	Diav-Citrin O, Park YH, Veerasuntharam G, et al. The safety of mesalamine in human pregnancy: a prospective controlled cohort study. Gastroenterology, 1998, 114(1): 23-28.
21.	Mahood IK, Scott HM, Brown R, et al. In utero exposure to di(n-butyl) phthalate and testicular dysgenesis: comparison of fetal and adult end points and their dose sensitivity. Environ Health Perspect, 2007, 115(Suppl 1): 55-61.
22.	Nguyen GC, Seow CH, Maxwell C, et al. The Toronto consensus statements for the management of inflammatory bowel disease in pregnancy. Gastroenterology, 2016, 150(3): 734-757. e1.
23.	Pradat P, Robert-Gnansia E, Di Tanna GL, et al. First trimester exposure to corticosteroids and oral clefts. Birth Defects Res A Clin Mol Teratol, 2003, 67(12): 968-970.
24.	Xiao WL, Liu XY, Liu YS, et al. The relationship between maternal corticosteroid use and orofacial clefts-a meta-analysis. Reprod Toxicol, 2017, 69: 99-105.
25.	Hviid A, Mølgaard-Nielsen D. Corticosteroid use during pregnancy and risk of orofacial clefts. CMAJ, 2011, 183(7): 796-804.
26.	Bay Bjørn AM, Ehrenstein V, Hundborg HH, et al. Use of corticosteroids in early pregnancy is not associated with risk of oral clefts and other congenital malformations in offspring. Am J Ther, 2014, 21(2): 73-80.
27.	Beaulieu DB, Ananthakrishnan AN, Issa M, et al. Budesonide induction and maintenance therapy for Crohn’s disease during pregnancy. Inflamm Bowel Dis, 2009, 15(1): 25-28.
28.	Saulnier PJ, Piguel X, Perault-Pochat MC, et al. Hypoglycaemic seizure and neonatal acute adrenal insufficiency after maternal exposure to prednisone during pregnancy: a case report. Eur J Pediatr, 2010, 169(6): 763-765.
29.	Coelho J, Beaugerie L, Colombel JF, et al. Pregnancy outcome in patients with inflammatory bowel disease treated with thiopurines: cohort from the CESAME Study. Gut, 2011, 60(2): 198-203.
30.	de Meij TG, Jharap B, Kneepkens CM, et al. Long-term follow-up of children exposed intrauterine to maternal thiopurine therapy during pregnancy in females with inflammatory bowel disease. Aliment Pharmacol Ther, 2013, 38(1): 38-43.
31.	Komoto S, Motoya S, Nishiwaki Y, et al. Pregnancy outcome in women with inflammatory bowel disease treated with anti-tumor necrosis factor and/or thiopurine therapy: a multicenter study from Japan. Intest Res, 2016, 14(2): 139-145.
32.	Shihab Z, Yeomans ND, De Cruz P. Anti-tumour necrosis factor α therapies and inflammatory bowel disease pregnancy outcomes: a meta-analysis. J Crohns Colitis, 2016, 10(8): 979-88.
33.	Bar-Gil Shitrit A, Grisaru-Granovsky S, Ben Ya’acov A, et al. Management of inflammatory bowel disease during pregnancy. Dig Dis Sci, 2016, 61(8): 2194-2204.
34.	管丽芳, 胡博文, 孙琳, 等. 妊娠期炎症性肠病的治疗策略与动态管理. 世界华人消化杂志, 2016, 24(28): 3978-3984.
35.	张修礼, 令狐恩强, 刘庆森, 等. 妊娠期炎症性肠病的处理-多伦多共识意见(2015)解读. 中华胃肠内镜电子杂志, 2016, 3(2): 49-53.
36.	吴开春, 梁洁, 冉志华, 等. 炎症性肠病诊断与治疗的共识意见(2018 年·北京). 中国实用内科杂志, 2018, 38(9): 796-813.
37.	王亿鹏, 谢小超, 王燕, 等. 内外兼治治疗妊娠期溃疡性结肠炎 1 例. 中国民间疗法, 2017, 25(10): 63-64.
38.	Klajnbard A, Szecsi PB, Colov NP, et al. Laboratory reference intervals during pregnancy, delivery and the early postpartum period. Clin Chem Lab Med, 2010, 48(2): 237-248.
39.	Flanagan E, Wright EK, Begun J, et al. Monitoring inflammatory bowel disease in pregnancy using gastrointestinal ultrasonography. J Crohns Colitis, 2020, 14(10): 1405-1412.
40.	ASGE Standard of Practice Committee, Shergill AK, Ben-Menachem T, et al. Guidelines for endoscopy in pregnant and lactating women. Gastrointest Endosc, 2012, 76(1): 18-24.
41.	Moretti ME, Verjee Z, Ito S, et al. Breast-feeding during maternal use of azathioprine. Ann Pharmacother, 2006, 40(12): 2269-2272.
42.	Cheent K, Nolan J, Shariq S, et al. 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(5): 603-605.
43.	王志斌, 陈晨, 郭一, 等. 清肠温中方治疗轻中度溃疡性结肠炎的临床研究. 中国中西医结合杂志, 2018, 38(1): 15-19.
44.	郑依玲, 梅全喜, 戴卫波, 等. 妊娠禁忌中药研究概述. 中国药房, 2018, 29(3): 421-424.
45.	梅全喜. 现代中药药理与临床应用手册. 3 版. 北京: 中国中医药出版社, 2016: 795, 865-868.

1. Salari P, Nikfar S, Abdollahi M. Current opinion on treatment of inflammatory bowel disease in pregnant women. Arch Med Sci, 2012, 8(6): 983-986.
2. Druvefors E, Landerholm K, Hammar U, et al. Impaired fertility in women with inflammatory bowel disease: a national cohort study from Sweden. J Crohns Colitis, 2020, 19: jjaa191.
3. Jølving LR, Nielsen J, Beck-Nielsen SS, et al. The association between maternal chronic inflammatory bowel disease and long-term health outcomes in children-a nationwide cohort study. Inflamm Bowel Dis, 2017, 23(8): 1440-1446.
4. Elten M, Benchimol EI, Fell DB, et al. Ambient air pollution and the risk of pediatric-onset inflammatory bowel disease: a population-based cohort study. Environ Int, 2020, 138: 105676.
5. 谭蓓, 钱家鸣. 炎症性肠病妊娠期管理与治疗. 中国实用内科杂志, 2018, 38(3): 200-203.
6. 戴萌, 金雷, 熊毅敏, 等. 炎症性肠病患者的妊娠相关问题. 世界华人消化杂志, 2016, 24(3): 382-389.
7. Ørding Olsen K, 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(1): 15-19.
8. Moscandrew M, Kane S. Inflammatory bowel diseases and management considerations: fertility and pregnancy. Curr Gastroenterol Rep, 2009, 11(5): 395-399.
9. Marri SR, Ahn C, Buchman AL. Voluntary childlessness is increased in women with inflammatory bowel disease. Inflamm Bowel Dis, 2007, 13(5): 591-599.
10. Ali MF, He H, Friedel D. Inflammatory bowel disease and pregnancy: fertility, complications and treatment. Ann Gastroenterol, 2020, 33(6): 579-590.
11. Bell SJ, Flanagan EK. Updates in the management of inflammatory bowel disease during pregnancy. Med J Aust, 2019, 210(6): 276-280.
12. Heetun ZS, Byrnes C, Neary P, et al. Review article: reproduction in the patient with inflammatory bowel disease. Aliment Pharmacol Ther, 2007, 26(4): 513-533.
13. 中华医学会消化病学分会炎症性肠病学组. 炎症性肠病妊娠期管理的专家共识意见. 协和医学杂志, 2019, 10(5): 465-475.
14. Perez-Garcia LF, Dolhain RJEM, Vorstenbosch S, et al. The effect of paternal exposure to immunosuppressive drugs on sexual function, reproductive hormones, fertility, pregnancy and offspring outcomes: a systematic review. Hum Reprod Update, 2020, 26(6): 961-1001.
15. Peng X, Zhi M, Wei M, et al. Thalidomide results in diminished ovarian reserve in reproductive age female IBD patients. Medicine (Baltimore), 2017, 96(21): e6540.
16. Grosen A, Kelsen J, Hvas CL, et al. The influence of methotrexate treatment on male fertility and pregnancy outcome after paternal exposure. Inflamm Bowel Dis, 2017, 23(4): 561-569.
17. Shannahan SE, Erlich JM, Peppercorn MA. Insights into the treatment of inflammatory bowel disease in pregnancy. Therap Adv Gastroenterol, 2019, 12: 1756284819852231.
18. Rahimi R, Nikfar S, Rezaie A, et al. Pregnancy outcome in women with inflammatory bowel disease following exposure to 5-aminosalicylic acid drugs: a meta-analysis. Reprod Toxicol, 2008, 25(2): 271-275.
19. 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(11): 1101-1108.
20. Diav-Citrin O, Park YH, Veerasuntharam G, et al. The safety of mesalamine in human pregnancy: a prospective controlled cohort study. Gastroenterology, 1998, 114(1): 23-28.
21. Mahood IK, Scott HM, Brown R, et al. In utero exposure to di(n-butyl) phthalate and testicular dysgenesis: comparison of fetal and adult end points and their dose sensitivity. Environ Health Perspect, 2007, 115(Suppl 1): 55-61.
22. Nguyen GC, Seow CH, Maxwell C, et al. The Toronto consensus statements for the management of inflammatory bowel disease in pregnancy. Gastroenterology, 2016, 150(3): 734-757. e1.
23. Pradat P, Robert-Gnansia E, Di Tanna GL, et al. First trimester exposure to corticosteroids and oral clefts. Birth Defects Res A Clin Mol Teratol, 2003, 67(12): 968-970.
24. Xiao WL, Liu XY, Liu YS, et al. The relationship between maternal corticosteroid use and orofacial clefts-a meta-analysis. Reprod Toxicol, 2017, 69: 99-105.
25. Hviid A, Mølgaard-Nielsen D. Corticosteroid use during pregnancy and risk of orofacial clefts. CMAJ, 2011, 183(7): 796-804.
26. Bay Bjørn AM, Ehrenstein V, Hundborg HH, et al. Use of corticosteroids in early pregnancy is not associated with risk of oral clefts and other congenital malformations in offspring. Am J Ther, 2014, 21(2): 73-80.
27. Beaulieu DB, Ananthakrishnan AN, Issa M, et al. Budesonide induction and maintenance therapy for Crohn’s disease during pregnancy. Inflamm Bowel Dis, 2009, 15(1): 25-28.
28. Saulnier PJ, Piguel X, Perault-Pochat MC, et al. Hypoglycaemic seizure and neonatal acute adrenal insufficiency after maternal exposure to prednisone during pregnancy: a case report. Eur J Pediatr, 2010, 169(6): 763-765.
29. Coelho J, Beaugerie L, Colombel JF, et al. Pregnancy outcome in patients with inflammatory bowel disease treated with thiopurines: cohort from the CESAME Study. Gut, 2011, 60(2): 198-203.
30. de Meij TG, Jharap B, Kneepkens CM, et al. Long-term follow-up of children exposed intrauterine to maternal thiopurine therapy during pregnancy in females with inflammatory bowel disease. Aliment Pharmacol Ther, 2013, 38(1): 38-43.
31. Komoto S, Motoya S, Nishiwaki Y, et al. Pregnancy outcome in women with inflammatory bowel disease treated with anti-tumor necrosis factor and/or thiopurine therapy: a multicenter study from Japan. Intest Res, 2016, 14(2): 139-145.
32. Shihab Z, Yeomans ND, De Cruz P. Anti-tumour necrosis factor α therapies and inflammatory bowel disease pregnancy outcomes: a meta-analysis. J Crohns Colitis, 2016, 10(8): 979-88.
33. Bar-Gil Shitrit A, Grisaru-Granovsky S, Ben Ya’acov A, et al. Management of inflammatory bowel disease during pregnancy. Dig Dis Sci, 2016, 61(8): 2194-2204.
34. 管丽芳, 胡博文, 孙琳, 等. 妊娠期炎症性肠病的治疗策略与动态管理. 世界华人消化杂志, 2016, 24(28): 3978-3984.
35. 张修礼, 令狐恩强, 刘庆森, 等. 妊娠期炎症性肠病的处理-多伦多共识意见(2015)解读. 中华胃肠内镜电子杂志, 2016, 3(2): 49-53.
36. 吴开春, 梁洁, 冉志华, 等. 炎症性肠病诊断与治疗的共识意见(2018 年·北京). 中国实用内科杂志, 2018, 38(9): 796-813.
37. 王亿鹏, 谢小超, 王燕, 等. 内外兼治治疗妊娠期溃疡性结肠炎 1 例. 中国民间疗法, 2017, 25(10): 63-64.
38. Klajnbard A, Szecsi PB, Colov NP, et al. Laboratory reference intervals during pregnancy, delivery and the early postpartum period. Clin Chem Lab Med, 2010, 48(2): 237-248.
39. Flanagan E, Wright EK, Begun J, et al. Monitoring inflammatory bowel disease in pregnancy using gastrointestinal ultrasonography. J Crohns Colitis, 2020, 14(10): 1405-1412.
40. ASGE Standard of Practice Committee, Shergill AK, Ben-Menachem T, et al. Guidelines for endoscopy in pregnant and lactating women. Gastrointest Endosc, 2012, 76(1): 18-24.
41. Moretti ME, Verjee Z, Ito S, et al. Breast-feeding during maternal use of azathioprine. Ann Pharmacother, 2006, 40(12): 2269-2272.
42. Cheent K, Nolan J, Shariq S, et al. 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(5): 603-605.
43. 王志斌, 陈晨, 郭一, 等. 清肠温中方治疗轻中度溃疡性结肠炎的临床研究. 中国中西医结合杂志, 2018, 38(1): 15-19.
44. 郑依玲, 梅全喜, 戴卫波, 等. 妊娠禁忌中药研究概述. 中国药房, 2018, 29(3): 421-424.
45. 梅全喜. 现代中药药理与临床应用手册. 3 版. 北京: 中国中医药出版社, 2016: 795, 865-868.

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