Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Inflammatory bowel disease in pregnancy and breastfeeding

Nature Reviews Gastroenterology & Hepatology volume 20, pages 504–523 (2023)Cite this article

Subjects

Abstract

Inflammatory bowel disease (IBD) has a peak age of diagnosis before the age of 35 years. Concerns about infertility, adverse pregnancy outcomes, and heritability of IBD have influenced decision-making for patients of childbearing age and their care providers. The interplay between the complex physiology in pregnancy and IBD can affect placental development, microbiome composition and responses to therapy. Current evidence has shown that effective disease management, including pre-conception counselling, multidisciplinary care and therapeutic agents to minimize disease activity, can improve pregnancy outcomes. This Review outlines the management of IBD in pregnancy and the safety of IBD therapies, including novel agents, with regard to both maternal and fetal health. The vast majority of IBD therapies can be used with low risk during pregnancy and lactation without substantial effects on neonatal outcomes.

Key points

  • Placental and lactation physiology involves a complicated milieu of cells, and includes immune-mediated effects, with implications for inflammatory bowel disease (IBD) and medication pharmacokinetics.

  • Both maternal and fetal microbiomes are influenced by pregnancy and IBD, and investigation into the role these interactions play in disease pathogenesis is ongoing.

  • Patients with no prior abdominal surgery and quiescent disease can anticipate similar rates of fertility and pregnancy outcomes to the general population.

  • Pre-conception counselling and multidisciplinary care, including maternal–fetal medicine where available, can help address patient concerns and improve pregnancy outcomes.

  • The vast majority of IBD therapies, including biologic therapies, can be used with low risk during pregnancy and breastfeeding, and uninterrupted therapy can help mitigate the risk of adverse outcomes.

  • Investigation to address knowledge gaps regarding the safety of new and evolving therapies is needed, particularly small-molecule medications.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Active transport of maternal IgG across the human placenta from maternal blood to the fetal circulation.
Fig. 2: Transfer of maternal IgG from breast tissue into breast milk.
Fig. 3: A proposed care pathway for monitoring and management of IBD during pregnancy.

Similar content being viewed by others

References

  1. Shivashankar, R., Tremaine, W. J., Harmsen, W. S. & Loftus, E. V. Incidence and prevalence of Crohn’s disease and ulcerative colitis in Olmsted County, Minnesota from 1970 through 2010. Clin. Gastroenterol. Hepatol. 15, 857–863 (2017).

    PubMed  Google Scholar 

  2. Coward, S. et al. Past and future burden of inflammatory bowel diseases based on modeling of population-based data. Gastroenterology 156, 1345–1353.e4 (2019).

    PubMed  Google Scholar 

  3. Erlebacher, A. & Fisher, S. J. Baby’s first organ. Sci. Am. 317, 46–53 (2017).

    PubMed  Google Scholar 

  4. Huhn, O. et al. How do uterine natural killer and innate lymphoid cells contribute to successful pregnancy? Front. Immunol. 12, 607669 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Romanowska-Próchnicka, K. et al. The role of TNF-α and anti-TNF-α agents during preconception, pregnancy, and breastfeeding. Int. J. Mol. Sci. https://doi.org/10.3390/ijms22062922 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Pavlov, O., Selutin, A., Pavlova, O. & Selkov, S. Macrophages are a source of IL-17 in the human placenta. Am. J. Reprod. Immunol. 80, e13016 (2018).

    PubMed  Google Scholar 

  7. Alijotas-Reig, J., Esteve-Valverde, E., Ferrer-Oliveras, R., Llurba, E. & Gris, J. M. Tumor necrosis factor-alpha and pregnancy: focus on biologics. An updated and comprehensive review. Clin. Rev. Allergy Immunol. 53, 40–53 (2017).

    CAS  PubMed  Google Scholar 

  8. Blaisdell, A., Zhou, Y., Kattah, M. G., Fisher, S. J. & Mahadevan, U. Vedolizumab antagonizes MAdCAM-1-dependent human placental cytotrophoblast adhesion and invasion in vitro. Inflamm. Bowel Dis. https://doi.org/10.1093/ibd/izac056 (2022).

    Article  PubMed  Google Scholar 

  9. Maltepe, E. & Fisher, S. J. Placenta: the forgotten organ. Annu. Rev. Cell Dev. Biol. 31, 523–552 (2015).

    CAS  PubMed  Google Scholar 

  10. Simister, N. E. Placental transport of immunoglobulin G. Vaccine 21, 3365–3369 (2003).

    CAS  PubMed  Google Scholar 

  11. Roopenian, D. C. & Akilesh, S. FcRn: the neonatal Fc receptor comes of age. Nat. Rev. Immunol. 7, 715–725 (2007).

    CAS  PubMed  Google Scholar 

  12. Porter, C. et al. Certolizumab pegol does not bind the neonatal Fc receptor (FcRn): consequences for FcRn-mediated in vitro transcytosis and ex vivo human placental transfer. J. Reprod. Immunol. 116, 7–12 (2016).

    CAS  PubMed  Google Scholar 

  13. Gisbert, J. P. & Chaparro, M. Safety of new biologics (vedolizumab and ustekinumab) and small molecules (tofacitinib) during pregnancy: a review. Drugs 80, 1085–1100 (2020).

    CAS  PubMed  Google Scholar 

  14. Datta, P., Baker, T. & Hale, T. W. Balancing the use of medications while maintaining breastfeeding. Clin. Perinatol. 46, 367–382 (2019).

    PubMed  Google Scholar 

  15. Anderson, G. D. Using pharmacokinetics to predict the effects of pregnancy and maternal-infant transfer of drugs during lactation. Expert. Opin. Drug Metab. Toxicol. 2, 947–960 (2006).

    CAS  PubMed  Google Scholar 

  16. Fleishaker, J. C., Desai, N. & McNamara, P. J. Factors affecting the milk-to-plasma drug concentration ratio in lactating women: physical interactions with protein and fat. J. Pharm. Sci. 76, 189–193 (1987).

    CAS  PubMed  Google Scholar 

  17. Hunt, K. M. et al. Mastitis is associated with increased free fatty acids, somatic cell count, and interleukin-8 concentrations in human milk. Breastfeed. Med. 8, 105–110 (2013).

    PubMed  PubMed Central  Google Scholar 

  18. Tuaillon, E. et al. Subclinical mastitis occurs frequently in association with dramatic changes in inflammatory/anti-inflammatory breast milk components. Pediatr. Res. 81, 556–564 (2017).

    CAS  PubMed  Google Scholar 

  19. Ansell, C., Moore, A. & Barrie, H. Electrolyte pH changes in human milk. Pediatr. Res. 11, 1177–1179 (1977).

    CAS  PubMed  Google Scholar 

  20. Syversen, G. B. & Ratkje, S. K. Drug distribution within human milk phases. J. Pharm. Sci. 74, 1071–1074 (1985).

    CAS  PubMed  Google Scholar 

  21. Koshimichi, H., Ito, K., Hisaka, A., Honma, M. & Suzuki, H. Analysis and prediction of drug transfer into human milk taking into consideration secretion and reuptake clearances across the mammary epithelia. Drug Metab. Dispos. 39, 2370–2380 (2011).

    CAS  PubMed  Google Scholar 

  22. Anderson, P. O. Drugs in lactation. Pharm. Res. 35, 45 (2018).

    PubMed  Google Scholar 

  23. Matro, R., Martin, C. F., Wolf, D., Shah, S. A. & Mahadevan, U. Exposure concentrations of infants breastfed by women receiving biologic therapies for inflammatory bowel diseases and effects of breastfeeding on infections and development. Gastroenterology 155, 696–704 (2018).

    PubMed  Google Scholar 

  24. Atyeo, C. & Alter, G. The multifaceted roles of breast milk antibodies. Cell 184, 1486–1499 (2021).

    CAS  PubMed  Google Scholar 

  25. Sartor, R. B. Microbial influences in inflammatory bowel diseases. Gastroenterology 134, 577–594 (2008).

    CAS  PubMed  Google Scholar 

  26. Glover, L. E., Fennimore, B. & Wingfield, M. Inflammatory bowel disease: influence and implications in reproduction. Inflamm. Bowel Dis. 22, 2724–2732 (2016).

    PubMed  Google Scholar 

  27. Edwards, S. M., Cunningham, S. A., Dunlop, A. L. & Corwin, E. J. The maternal gut microbiome during pregnancy. MCN Am. J. Matern. Child. Nurs. 42, 310–317 (2017).

    PubMed  PubMed Central  Google Scholar 

  28. Koren, O. et al. Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell 150, 470–480 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Santacruz, A. et al. Gut microbiota composition is associated with body weight, weight gain and biochemical parameters in pregnant women. Br. J. Nutr. 104, 83–92 (2010).

    CAS  PubMed  Google Scholar 

  30. Mulak, A., Taché, Y. & Larauche, M. Sex hormones in the modulation of irritable bowel syndrome. World J. Gastroenterol. 20, 2433–2448 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Fuhler, G. M. The immune system and microbiome in pregnancy. Best. Pract. Res. Clin. Gastroenterol. 44-45, 101671 (2020).

    CAS  PubMed  Google Scholar 

  32. Machiels, K. et al. A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut 63, 1275–1283 (2014).

    CAS  PubMed  Google Scholar 

  33. Torres, J. et al. Infants born to mothers with IBD present with altered gut microbiome that transfers abnormalities of the adaptive immune system to germ-free mice. Gut 69, 42–51 (2020).

    CAS  PubMed  Google Scholar 

  34. Satokari, R., Grönroos, T., Laitinen, K., Salminen, S. & Isolauri, E. Bifidobacterium and Lactobacillus DNA in the human placenta. Lett. Appl. Microbiol. 48, 8–12 (2009).

    CAS  PubMed  Google Scholar 

  35. Aagaard, K. et al. The placenta harbors a unique microbiome. Sci. Transl. Med. 6, 237ra265 (2014).

    Google Scholar 

  36. Ferretti, P. et al. Mother-to-infant microbial transmission from different body sites shapes the developing infant gut microbiome. Cell Host Microbe 24, 133–145.e5 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 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. 15, 720–725 (2009).

    PubMed  Google Scholar 

  38. Walldorf, J., Brunne, S., Gittinger, F. S. & Michl, P. Family planning in inflammatory bowel disease: childlessness and disease-related concerns among female patients. Eur. J. Gastroenterol. Hepatol. 30, 310–315 (2018).

    PubMed  Google Scholar 

  39. Aboubakr, A., Riggs, A. R., Jimenez, D., Mella, M. T. & Dubinsky, M. C. Identifying patient priorities for preconception and pregnancy counseling in IBD. Dig. Dis. Sci. 66, 1829–1835 (2021).

    PubMed  Google Scholar 

  40. de Lima, A., Zelinkova, Z., Mulders, A. G. & van der Woude, C. J. Preconception care reduces relapse of inflammatory bowel disease during pregnancy. Clin. Gastroenterol. Hepatol. 14, 1285–1292.e1 (2016).

    PubMed  Google Scholar 

  41. Laube, R., Paramsothy, S. & Leong, R. W. Review of pregnancy in Crohn’s disease and ulcerative colitis. Ther. Adv. Gastroenterol. 14, 17562848211016242 (2021).

    Google Scholar 

  42. De Dombal, F. T., Watts, J. M., Watkinson, G. & Goligher, J. C. Ulcerative colitis and pregnancy. Lancet 2, 599–602 (1965).

    PubMed  Google Scholar 

  43. Hudson, M. et al. Fertility and pregnancy in inflammatory bowel disease. Int. J. Gynaecol. Obstet. 58, 229–237 (1997).

    CAS  PubMed  Google Scholar 

  44. Korelitz, B. I. Inflammatory bowel disease and pregnancy. Gastroenterol. Clin. North. Am. 27, 213–224 (1998).

    CAS  PubMed  Google Scholar 

  45. Ørding 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 122, 15–19 (2002).

    PubMed  Google Scholar 

  46. Waljee, A., Waljee, J., Morris, A. M. & Higgins, P. D. Threefold increased risk of infertility: a meta-analysis of infertility after ileal pouch anal anastomosis in ulcerative colitis. Gut 55, 1575–1580 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Oresland, T. et al. Gynaecological and sexual function related to anatomical changes in the female pelvis after restorative proctocolectomy. Int. J. Colorectal Dis. 9, 77–81 (1994).

    CAS  PubMed  Google Scholar 

  48. Friedman, S., Nielsen, J., Nøhr, E. A., Jølving, L. R. & Nørgård, B. M. Comparison of time to pregnancy in women with and without inflammatory bowel diseases. Clin. Gastroenterol. Hepatol. 18, 1537–1544.e1 (2020).

    PubMed  Google Scholar 

  49. Ban, L., Tata, L. J., Humes, D. J., Fiaschi, L. & Card, T. Decreased fertility rates in 9639 women diagnosed with inflammatory bowel disease: a United Kingdom population-based cohort study. Aliment. Pharmacol. Ther. 42, 855–866 (2015).

    CAS  PubMed  Google Scholar 

  50. Zhao, Y. et al. Risk factors associated with impaired ovarian reserve in young women of reproductive age with Crohn’s disease. Intest. Res. 18, 200–209 (2020).

    PubMed  PubMed Central  Google Scholar 

  51. Hernandez-Nieto, C. et al. Infertile patients with inflammatory bowel disease have comparable in vitro fertilization clinical outcomes to the general infertile population. Gynecol. Endocrinol. 36, 554–557 (2020).

    CAS  PubMed  Google Scholar 

  52. Friedman, S., Larsen, P. V., Fedder, J. & Nørgård, B. M. The efficacy of assisted reproduction in women with inflammatory bowel disease and the impact of surgery – a nationwide cohort study. Inflamm. Bowel Dis. 23, 208–217 (2017).

    PubMed  Google Scholar 

  53. Laube, R., Tran, Y., Paramsothy, S. & Leong, R. W. Assisted reproductive technology in Crohn’s disease and ulcerative colitis: a systematic review and meta-analysis. Am. J. Gastroenterol. 116, 2334–2344 (2021).

    PubMed  Google Scholar 

  54. Kim, M. A. et al. The influence of disease activity on pregnancy outcomes in women with inflammatory bowel disease: a systematic review and meta-analysis. J. Crohns Colitis 15, 719–732 (2021).

    PubMed  Google Scholar 

  55. Mahadevan, U. et al. Pregnancy outcomes in women with inflammatory bowel disease: a large community-based study from Northern California. Gastroenterology 133, 1106–1112 (2007).

    PubMed  Google Scholar 

  56. Shand, A. W., Chen, J. S., Selby, W., Solomon, M. & Roberts, C. L. Inflammatory bowel disease in pregnancy: a population-based study of prevalence and pregnancy outcomes. BJOG 123, 1862–1870 (2016).

    CAS  PubMed  Google Scholar 

  57. Mahadevan, U. et al. Pregnancy and neonatal outcomes after fetal exposure to biologics and thiopurines among women with inflammatory bowel disease. Gastroenterology 160, 1131–1139 (2021).

    CAS  PubMed  Google Scholar 

  58. Abdul Sultan, A. et al. Adverse pregnancy outcomes among women with inflammatory bowel disease: a population-based study from England. Inflamm. Bowel Dis. 22, 1621–1630 (2016).

    PubMed  Google Scholar 

  59. Boyd, H. A., Basit, S., Harpsøe, M. C., Wohlfahrt, J. & Jess, T. Inflammatory bowel disease and risk of adverse pregnancy outcomes. PLoS ONE 10, e0129567 (2015).

    PubMed  PubMed Central  Google Scholar 

  60. Lee, H. H. et al. Pregnancy outcomes in women with inflammatory bowel disease: a 10-year nationwide population-based cohort study. Aliment. Pharmacol. Ther. 51, 861–869 (2020).

    CAS  PubMed  Google Scholar 

  61. Bröms, G. et al. Birth outcomes in women with inflammatory bowel disease: effects of disease activity and drug exposure. Inflamm. Bowel Dis. 20, 1091–1098 (2014).

    PubMed  Google Scholar 

  62. Miller, J. P. Inflammatory bowel disease in pregnancy: a review. J. R. Soc. Med. 79, 221–225 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Abhyankar, A., Ham, M. & Moss, A. C. Meta-analysis: the impact of disease activity at conception on disease activity during pregnancy in patients with inflammatory bowel disease. Aliment. Pharmacol. Ther. 38, 460–466 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. de Lima-Karagiannis, A., Zelinkova-Detkova, Z. & van der Woude, C. J. The effects of active IBD during pregnancy in the era of novel IBD therapies. Am. J. Gastroenterol. 111, 1305–1312 (2016).

    PubMed  Google Scholar 

  65. Rottenstreich, A. et al. Factors associated with inflammatory bowel disease flare during pregnancy among women with preconception remission. Dig. Dis. Sci. 66, 1189–1194 (2021).

    PubMed  Google Scholar 

  66. Nguyen, G. C. et al. The Toronto consensus statements for the management of inflammatory bowel disease in pregnancy. Gastroenterology 150, 734–757.e1 (2016).

    PubMed  Google Scholar 

  67. Mahadevan, U. et al. Inflammatory bowel disease in pregnancy clinical care pathway: a report from the American Gastroenterological Association IBD Parenthood Project Working Group. Gastroenterology 156, 1508–1524 (2019).

    PubMed  Google Scholar 

  68. Jharap, B. et al. Intrauterine exposure and pharmacology of conventional thiopurine therapy in pregnant patients with inflammatory bowel disease. Gut 63, 451–457 (2014).

    CAS  PubMed  Google Scholar 

  69. Flanagan, E. et al. Maternal thiopurine metabolism during pregnancy in inflammatory bowel disease and clearance of thiopurine metabolites and outcomes in exposed neonates. Aliment. Pharmacol. Ther. 53, 810–820 (2021).

    CAS  PubMed  Google Scholar 

  70. Flanagan, E. et al. Infliximab, adalimumab and vedolizumab concentrations across pregnancy and vedolizumab concentrations in infants following intrauterine exposure. Aliment. Pharmacol. Ther. 52, 1551–1562 (2020).

    CAS  PubMed  Google Scholar 

  71. Bell, S. J. & Flanagan, E. K. Updates in the management of inflammatory bowel disease during pregnancy. Med. J. Aust. 210, 276–280 (2019).

    PubMed  Google Scholar 

  72. Klajnbard, A. et al. Laboratory reference intervals during pregnancy, delivery and the early postpartum period. Clin. Chem. Lab. Med. 48, 237–248 (2010).

    CAS  PubMed  Google Scholar 

  73. Friedman, S., McElrath, T. F. & Wolf, J. L. Management of fertility and pregnancy in women with inflammatory bowel disease: a practical guide. Inflamm. Bowel Dis. 19, 2937–2948 (2013).

    PubMed  Google Scholar 

  74. Julsgaard, M. et al. Fecal calprotectin is not affected by pregnancy: clinical implications for the management of pregnant patients with inflammatory bowel disease. Inflamm. Bowel Dis. 23, 1240–1246 (2017).

    PubMed  Google Scholar 

  75. Rottenstreich, A. et al. Clinical utility of fecal calprotectin in monitoring disease activity and predicting relapse in pregnant patients with inflammatory bowel diseases. Eur. J. Intern. Med. 77, 105–110 (2020).

    CAS  PubMed  Google Scholar 

  76. de Lima, A., Zelinkova, Z. & van der Woude, C. J. A prospective study of the safety of lower gastrointestinal endoscopy during pregnancy in patients with inflammatory bowel disease. J. Crohns Colitis 9, 519–524 (2015).

    PubMed  Google Scholar 

  77. De Voogd, F. et al. Intestinal ultrasound to evaluate treatment response during pregnancy in patients with inflammatory bowel disease. Inflamm. Bowel Dis. https://doi.org/10.1093/ibd/izab216 (2021).

    Article  PubMed Central  Google Scholar 

  78. Ko, M. S., Rudrapatna, V. A., Avila, P. & Mahadevan, U. Safety of flexible sigmoidoscopy in pregnant patients with known or suspected inflammatory bowel disease. Dig. Dis. Sci. 65, 2979–2985 (2020).

    CAS  PubMed  Google Scholar 

  79. Shergill, A. K. et al. Guidelines for endoscopy in pregnant and lactating women. Gastrointest. Endosc. 76, 18–24 (2012).

    PubMed  Google Scholar 

  80. Savas, N. Gastrointestinal endoscopy in pregnancy. World J. Gastroenterol. 20, 15241–15252 (2014).

    PubMed  PubMed Central  Google Scholar 

  81. Bernstein, C. N. et al. Increased burden of psychiatric disorders in inflammatory bowel disease. Inflamm. Bowel Dis. 25, 360–368 (2019).

    PubMed  Google Scholar 

  82. Vigod, S. N. et al. Inflammatory bowel disease and new-onset psychiatric disorders in pregnancy and post partum: a population-based cohort study. Gut 68, 1597–1605 (2019).

    PubMed  Google Scholar 

  83. Selinger, C. et al. Standards for the provision of antenatal care for patients with inflammatory bowel disease: guidance endorsed by the British Society of Gastroenterology and the British Maternal and Fetal Medicine Society. Frontline Gastroenterol. 12, 182–187 (2021).

    PubMed  Google Scholar 

  84. Ota, K. et al. Vitamin D deficiency may be a risk factor for recurrent pregnancy losses by increasing cellular immunity and autoimmunity. Hum. Reprod. 29, 208–219 (2014).

    CAS  PubMed  Google Scholar 

  85. Holick, M. F. et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 96, 1911–1930 (2011).

    CAS  PubMed  Google Scholar 

  86. Lee, S. et al. Pregnant women with inflammatory bowel disease are at increased risk of vitamin D insufficiency: a cross-sectional study. J. Crohns Colitis 12, 702–709 (2018).

    PubMed  PubMed Central  Google Scholar 

  87. van der Woude, C. J. et al. The second European evidenced-based consensus on reproduction and pregnancy in inflammatory bowel disease. J. Crohns Colitis 9, 107–124 (2015).

    PubMed  Google Scholar 

  88. 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. 343, 1608–1614 (2000).

    PubMed  Google Scholar 

  89. Sauk, J. & Kane, S. The use of medications for inflammatory bowel disease during pregnancy and nursing. Expert. Opin. Pharmacother. 6, 1833–1839 (2005).

    CAS  PubMed  Google Scholar 

  90. Milman, N. Prepartum anaemia: prevention and treatment. Ann. Hematol. 87, 949–959 (2008).

    CAS  PubMed  Google Scholar 

  91. Lopez, A., Cacoub, P., Macdougall, I. C. & Peyrin-Biroulet, L. Iron deficiency anaemia. Lancet 387, 907–916 (2016).

    CAS  PubMed  Google Scholar 

  92. Pavord, S. et al. UK guidelines on the management of iron deficiency in pregnancy. Br. J. Haematol. 188, 819–830 (2020).

    PubMed  Google Scholar 

  93. Auerbach, M. et al. Results of the first American prospective study of intravenous iron in oral iron-intolerant iron-deficient gravidas. Am. J. Med. 130, 1402–1407 (2017).

    CAS  PubMed  Google Scholar 

  94. US Food and Drug Administration. Pregnancy and lactation labeling (drugs) final rule. FDA https://www.fda.gov/drugs/labeling-information-drug-products/pregnancy-and-lactation-labeling-drugs-final-rule (2021).

  95. Caro-Patón, T. et al. Is metronidazole teratogenic? A meta-analysis. Br. J. Clin. Pharmacol. 44, 179–182 (1997).

    PubMed  PubMed Central  Google Scholar 

  96. Bar-Oz, B., Moretti, M. E., Boskovic, R., O’Brien, L. & Koren, G. The safety of quinolones–a meta-analysis of pregnancy outcomes. Eur. J. Obstet. Gynecol. Reprod. Biol. 143, 75–78 (2009).

    CAS  PubMed  Google Scholar 

  97. Afzali, A. Inflammatory bowel disease during pregnancy: management of a disease flare or remission. Curr. Opin. Gastroenterol. 35, 281–287 (2019).

    PubMed  Google Scholar 

  98. Khanna, S., Shin, A. & Kelly, C. P. Management of Clostridium difficile infection in inflammatory bowel disease: expert review from the Clinical Practice Updates Committee of the AGA Institute. Clin. Gastroenterol. Hepatol. 15, 166–174 (2017).

    PubMed  Google Scholar 

  99. ViroPharma. Highlights of prescribing information: Vancocin capsules (vancomycin hydrochloride). FDA https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/050606s028lbl.pdf (2011).

  100. Restellini, S. et al. Update on the management of inflammatory bowel disease during pregnancy and breastfeeding. Digestion 101, 27–42 (2020).

    PubMed  Google Scholar 

  101. Jarde, A. et al. Pregnancy outcomes in women taking probiotics or prebiotics: a systematic review and meta-analysis. BMC Pregnancy Childbirth 18, 14 (2018).

    PubMed  PubMed Central  Google Scholar 

  102. De Felice, K. M. & Kane, S. V. Inflammatory bowel disease in women of reproductive age. Expert. Rev. Gastroenterol. Hepatol. 8, 417–425 (2014).

    PubMed  Google Scholar 

  103. Nørgård, B., Fonager, K., Pedersen, L., Jacobsen, B. A. & Sørensen, H. T. Birth outcome in women exposed to 5-aminosalicylic acid during pregnancy: a Danish cohort study. Gut 52, 243–247 (2003).

    PubMed  PubMed Central  Google Scholar 

  104. 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. 102, 1406–1413 (2007).

    PubMed  Google Scholar 

  105. Mahadevan, U. Fertility and pregnancy in the patient with inflammatory bowel disease. Gut 55, 1198–1206 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. 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. 25, 271–275 (2008).

    CAS  PubMed  Google Scholar 

  107. Katz, J. A. & Pore, G. Inflammatory bowel disease and pregnancy. Inflamm. Bowel Dis. 7, 146–157 (2001).

    CAS  PubMed  Google Scholar 

  108. Hashash, J. G. & Kane, S. Pregnancy and inflammatory bowel disease. Gastroenterol. Hepatol. 11, 96–102 (2015).

    Google Scholar 

  109. Bandoli, G., Palmsten, K., Forbess Smith, C. J. & Chambers, C. D. A review of systemic corticosteroid use in pregnancy and the risk of select pregnancy and birth outcomes. Rheum. Dis. Clin. North. Am. 43, 489–502 (2017).

    PubMed  PubMed Central  Google Scholar 

  110. Park-Wyllie, L. et al. Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies. Teratology 62, 385–392 (2000).

    CAS  PubMed  Google Scholar 

  111. Odufalu, F. D., Long, M., Lin, K. & Mahadevan, U. Exposure to corticosteroids in pregnancy is associated with adverse perinatal outcomes among infants of mothers with inflammatory bowel disease: results from the PIANO registry. Gut https://doi.org/10.1136/gutjnl-2021-325317 (2021).

    Article  PubMed  Google Scholar 

  112. Beaulieu, D. B. et al. Budesonide induction and maintenance therapy for Crohn’s disease during pregnancy. Inflamm. Bowel Dis. 15, 25–28 (2009).

    PubMed  Google Scholar 

  113. Murphy, V. E. et al. Metabolism of synthetic steroids by the human placenta. Placenta 28, 39–46 (2007).

    CAS  PubMed  Google Scholar 

  114. Gluck, P. A. & Gluck, J. C. A review of pregnancy outcomes after exposure to orally inhaled or intranasal budesonide. Curr. Med. Res. Opin. 21, 1075–1084 (2005).

    CAS  PubMed  Google Scholar 

  115. de Boer, N. K. et al. Azathioprine use during pregnancy: unexpected intrauterine exposure to metabolites. Am. J. Gastroenterol. 101, 1390–1392 (2006).

    PubMed  Google Scholar 

  116. Kanis, S. L. et al. Health outcomes of 1000 children born to mothers with inflammatory bowel disease in their first 5 years of life. Gut 70, 1266–1274 (2021).

    PubMed  Google Scholar 

  117. Nasser, R. et al. Thiopurine hepatotoxicity can mimic intrahepatic cholestasis of pregnancy. Clin. Res. Hepatol. Gastroenterol. 44, e29–e31 (2020).

    PubMed  Google Scholar 

  118. Akbari, M., Shah, S., Velayos, F. S., Mahadevan, U. & Cheifetz, A. S. Systematic review and meta-analysis on the effects of thiopurines on birth outcomes from female and male patients with inflammatory bowel disease. Inflamm. Bowel Dis. 19, 15–22 (2013).

    PubMed  Google Scholar 

  119. Hutson, J. R., Matlow, J. N., Moretti, M. E. & Koren, G. The fetal safety of thiopurines for the treatment of inflammatory bowel disease in pregnancy. J. Obstet. Gynaecol. 33, 1–8 (2013).

    CAS  PubMed  Google Scholar 

  120. Casanova, M. J. et al. Safety of thiopurines and anti-TNF-α drugs during pregnancy in patients with inflammatory bowel disease. Am. J. Gastroenterol. 108, 433–440 (2013).

    CAS  PubMed  Google Scholar 

  121. Koslowsky, B. et al. Thiopurine therapy for inflammatory bowel disease during pregnancy is not associated with anemia in the infant. Dig. Dis. Sci. 64, 2286–2290 (2019).

    CAS  PubMed  Google Scholar 

  122. Sheikh, M., Nelson-Piercy, C., Duley, J., Florin, T. & Ansari, A. Successful pregnancies with thiopurine-allopurinol co-therapy for inflammatory bowel disease. J. Crohns Colitis 9, 680–684 (2015).

    PubMed  Google Scholar 

  123. van den Berg, S. A. et al. Safety of tioguanine during pregnancy in inflammatory bowel disease. J. Crohns Colitis 10, 159–165 (2016).

    PubMed  Google Scholar 

  124. Martínez Lopez, J. A., Loza, E. & Carmona, L. Systematic review on the safety of methotrexate in rheumatoid arthritis regarding the reproductive system (fertility, pregnancy, and breastfeeding). Clin. Exp. Rheumatol. 27, 678–684 (2009).

    PubMed  Google Scholar 

  125. Weber-Schoendorfer, C. et al. Pregnancy outcome after methotrexate treatment for rheumatic disease prior to or during early pregnancy: a prospective multicenter cohort study. Arthritis Rheumatol. 66, 1101–1110 (2014).

    CAS  PubMed  Google Scholar 

  126. Feldkamp, M. & Carey, J. C. Clinical teratology counseling and consultation case report: low dose methotrexate exposure in the early weeks of pregnancy. Teratology 47, 533–539 (1993).

    CAS  PubMed  Google Scholar 

  127. Bar Oz, B., Hackman, R., Einarson, T. & Koren, G. Pregnancy outcome after cyclosporine therapy during pregnancy: a meta-analysis. Transplantation 71, 1051–1055 (2001).

    CAS  PubMed  Google Scholar 

  128. Jain, A. B. et al. Pregnancy after liver transplantation with tacrolimus immunosuppression: a single center’s experience update at 13 years. Transplantation 76, 827–832 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Branche, J. et al. Cyclosporine treatment of steroid-refractory ulcerative colitis during pregnancy. Inflamm. Bowel Dis. 15, 1044–1048 (2009).

    PubMed  Google Scholar 

  130. Baumgart, D. C., Sturm, A., Wiedenmann, B. & Dignass, A. U. Uneventful pregnancy and neonatal outcome with tacrolimus in refractory ulcerative colitis. Gut 54, 1822–1823 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Ponticelli, C. & Glassock, R. J. Prevention of complications from use of conventional immunosuppressants: a critical review. J. Nephrol. 32, 851–870 (2019).

    PubMed  Google Scholar 

  132. Chaparro, M. et al. Long-term safety of in utero exposure to anti-TNFα drugs for the treatment of inflammatory bowel disease: results from the multicenter European TEDDY study. Am. J. Gastroenterol. 113, 396–403 (2018).

    CAS  PubMed  Google Scholar 

  133. Luu, M. et al. Continuous anti-TNFα use throughout pregnancy: possible complications for the mother but not for the fetus. a retrospective cohort on the French National Health Insurance Database (EVASION). Am. J. Gastroenterol. 113, 1669–1677 (2018).

    CAS  PubMed  Google Scholar 

  134. Torres, J. et al. European Crohn’s and colitis guidelines on sexuality, fertility, pregnancy, and lactation. J. Crohns Colitis https://doi.org/10.1093/ecco-jcc/jjac115 (2022).

    Article  PubMed  Google Scholar 

  135. Julsgaard, M. et al. Concentrations of adalimumab and infliximab in mothers and newborns, and effects on infection. Gastroenterology 151, 110–119 (2016).

    CAS  PubMed  Google Scholar 

  136. Hellwig, K., Haghikia, A. & Gold, R. Pregnancy and natalizumab: results of an observational study in 35 accidental pregnancies during natalizumab treatment. Mult. Scler. 17, 958–963 (2011).

    PubMed  Google Scholar 

  137. Landi, D. et al. Continuation of natalizumab versus interruption is associated with lower risk of relapses during pregnancy and postpartum in women with MS [abstract 338]. Mult. Scler. J. 25 (Suppl. 2), 892–894 (2019).

    Google Scholar 

  138. Moens, A. et al. Pregnancy outcomes in inflammatory bowel disease patients treated with vedolizumab, anti-TNF or conventional therapy: results of the European CONCEIVE study. Aliment. Pharmacol. Ther. 51, 129–138 (2020).

    CAS  PubMed  Google Scholar 

  139. Wils, P. et al. Safety of ustekinumab or vedolizumab in pregnant inflammatory bowel disease patients: a multicentre cohort study. Aliment. Pharmacol. Ther. 53, 460–470 (2021).

    CAS  PubMed  Google Scholar 

  140. Bar-Gil Shitrit, A. et al. Exposure to vedolizumab in IBD pregnant women appears of low risk for mother and neonate: a first prospective comparison study. Am. J. Gastroenterol. 114, 1172–1175 (2019).

    PubMed  Google Scholar 

  141. Bell, C., Tandon, P., Lentz, E., Marshall, J. K. & Narula, N. Systematic review and meta-analysis: safety of vedolizumab during pregnancy in patients with inflammatory bowel disease. J. Gastroenterol. Hepatol. 36, 2640–2648 (2021).

    CAS  PubMed  Google Scholar 

  142. Ferrante, M. et al. Long-term safety and efficacy of risankizumab treatment in patients with Crohn’s disease: results from the phase 2 open-label extension study. J. Crohns Colitis 15, 2001–2010 (2021).

    PubMed  PubMed Central  Google Scholar 

  143. Volger, S. et al. Pregnancy outcomes in women with psoriasis, psoriatic arthritis, Crohn’s disease and ulcerative colitis treated with ustekinumab [abstract Sa1827]. Gastroenterology 158 (6 Suppl. 1), S-442 (2020).

    Google Scholar 

  144. Chugh, R. et al. Maternal and neonatal outcomes in vedolizumab and ustekinumab exposed pregnancies: results from the PIANO registry [abstract S719]. Am. J. Gastroenterol. 117(10S), e502–e503 (2022).

    Google Scholar 

  145. Owczarek, W. et al. The use of biological drugs in psoriasis patients prior to pregnancy, during pregnancy and lactation: a review of current clinical guidelines. Postepy Dermatol. Alergol. 37, 821–830 (2020).

    PubMed  Google Scholar 

  146. Danese, S. et al. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials. Lancet 399, 2113–2128 (2022).

    CAS  PubMed  Google Scholar 

  147. Pfizer. Highlights of prescribing information: Xeljanz/Xeljanz XR (tofacitinib). FDA https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/203214s018lbl.pdf (2018).

  148. Mahadevan, U. et al. Outcomes of pregnancies with maternal/paternal exposure in the tofacitinib safety databases for ulcerative colitis. Inflamm. Bowel Dis. 24, 2494–2500 (2018).

    PubMed  PubMed Central  Google Scholar 

  149. Abbvie. Highlights of prescribing information: Rinvoq (upadacitinib). FDA https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211675s000lbl.pdf (2019).

  150. Dubinsky, M. C. et al. Pregnancy outcomes in the ozanimod clinical development program in relapsing multiple sclerosis, ulcerative colitis, and Crohn’s disease [abstract DOP53]. J. Crohns Colitis 15 (Suppl. 1), S088–S089 (2021).

    Google Scholar 

  151. Celgene. Highlights of prescribing information: Zeposia (ozanimod). FDA https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209899s000lbl.pdf (2020).

  152. Lopez-Leon, S. et al. A systematic review and meta-analyses of pregnancy and fetal outcomes in women with multiple sclerosis: a contribution from the IMI2 ConcePTION project. J. Neurol. 267, 2721–2731 (2020).

    PubMed  PubMed Central  Google Scholar 

  153. Seah, D. & De Cruz, P. Review article: the practical management of acute severe ulcerative colitis. Aliment. Pharmacol. Ther. 43, 482–513 (2016).

    CAS  PubMed  Google Scholar 

  154. Ollech, J. E. et al. Effective treatment of acute severe ulcerative colitis in pregnancy is associated with good maternal and fetal outcomes. Clin. Gastroenterol. Hepatol. 19, 2444–2446.e2 (2021).

    CAS  PubMed  Google Scholar 

  155. Chaparro, M. et al. Surgery due to inflammatory bowel disease during pregnancy: mothers and offspring outcomes from an Ecco Confer Multicentre Case Series (Scar Study). J. Crohns Colitis https://doi.org/10.1093/ecco-jcc/jjac050 (2022).

    Article  PubMed  Google Scholar 

  156. Killeen, S., Gunn, J. & Hartley, J. Surgical management of complicated and medically refractory inflammatory bowel disease during pregnancy. Colorectal Dis. 19, 123–138 (2017).

    CAS  PubMed  Google Scholar 

  157. Novacek, G. et al. Inflammatory bowel disease is a risk factor for recurrent venous thromboembolism. Gastroenterology 139, 779–787 (2010).

    PubMed  Google Scholar 

  158. 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. 7, 329–334 (2009).

    PubMed  Google Scholar 

  159. Foulon, A. et al. Defining the most appropriate delivery mode in women with inflammatory bowel disease: a systematic review. Inflamm. Bowel Dis. 23, 712–720 (2017).

    PubMed  Google Scholar 

  160. Friedman, S., Zegers, F. D., Jølving, L. R., Nielsen, J. & Nørgård, B. M. Postpartum surgical complications in women with inflammatory bowel disease after caesarian section: a Danish nationwide cohort study. J. Crohns Colitis https://doi.org/10.1093/ecco-jcc/jjab187 (2021).

    Article  PubMed  Google Scholar 

  161. Lever, G., Chipeta, H., Glanville, T. & Selinger, C. Perineal outcomes after delivery in 179 mothers with inflammatory bowel disease compared to 31 258 controls: a single-centre cohort study. J. Crohns Colitis 16, 511–514 (2022).

    PubMed  Google Scholar 

  162. Remzi, F. H. et al. Vaginal delivery after ileal pouch–anal anastomosis: a word of caution. Dis. Colon. Rectum 48, 1691–1699 (2005).

    PubMed  Google Scholar 

  163. Hahnloser, D. 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 47, 1127–1135 (2004).

    PubMed  Google Scholar 

  164. Van Horn, C. & Barrett, P. Pregnancy, delivery, and postpartum experiences of fifty-four women with ostomies. J. Wound Ostomy Cont. Nurs. 24, 151–162 (1997).

    Google Scholar 

  165. PAPooSE Study Group. Pregnancy outcomes after stoma surgery for inflammatory bowel disease: the results of a retrospective multicentre audit. Colorectal Dis. 24, 838–844 (2022).

    Google Scholar 

  166. Aukamp, V. & Sredl, D. Collaborative care management for a pregnant woman with an ostomy. Complement. Ther. Nurs. Midwifery 10, 5–12 (2004).

    PubMed  Google Scholar 

  167. Peeters, M. et al. Familial aggregation in Crohn’s disease: increased age-adjusted risk and concordance in clinical characteristics. Gastroenterology 111, 597–603 (1996).

    CAS  PubMed  Google Scholar 

  168. Laharie, D. et al. Inflammatory bowel disease in spouses and their offspring. Gastroenterology 120, 816–819 (2001).

    CAS  PubMed  Google Scholar 

  169. Barclay, A. R. et al. Systematic review: the role of breastfeeding in the development of pediatric inflammatory bowel disease. J. Pediatr. 155, 421–426 (2009).

    PubMed  Google Scholar 

  170. Penders, J. et al. Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study. Gut 56, 661–667 (2007).

    CAS  PubMed  Google Scholar 

  171. Turfkruyer, M. & Verhasselt, V. Breast milk and its impact on maturation of the neonatal immune system. Curr. Opin. Infect. Dis. 28, 199–206 (2015).

    CAS  PubMed  Google Scholar 

  172. Meng, X. et al. The profile of human milk metabolome, cytokines, and antibodies in inflammatory bowel diseases versus healthy mothers, and potential impact on the newborn. J. Crohns Colitis 13, 431–441 (2019).

    PubMed  Google Scholar 

  173. Section on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics 129, e827–e841 (2012).

    Google Scholar 

  174. 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. 26, 45–51 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  175. Biedermann, L., Rogler, G., Vavricka, S. R., Seibold, F. & Seirafi, M. Pregnancy and breastfeeding in inflammatory bowel disease. Digestion 86, 45–54 (2012).

    PubMed  Google Scholar 

  176. Drugs and Lactation Database (LactMed). Vancomycin (National Institute of Child Health and Human Development, 2022).

  177. Klotz, U. & Harings-Kaim, A. Negligible excretion of 5-aminosalicylic acid in breast milk. Lancet 342, 618–619 (1993).

    CAS  PubMed  Google Scholar 

  178. Ost, L., Wettrell, G., Björkhem, I. & Rane, A. Prednisolone excretion in human milk. J. Pediatr. 106, 1008–1011 (1985).

    CAS  PubMed  Google Scholar 

  179. Christensen, L. A., Dahlerup, J. F., Nielsen, M. J., Fallingborg, J. F. & Schmiegelow, K. Azathioprine treatment during lactation. Aliment. Pharmacol. Ther. 28, 1209–1213 (2008).

    CAS  PubMed  Google Scholar 

  180. Moretti, M. E. et al. Cyclosporine excretion into breast milk. Transplantation 75, 2144–2146 (2003).

    CAS  PubMed  Google Scholar 

  181. Lahiff, C. & Moss, A. C. Cyclosporine in the management of severe ulcerative colitis while breast-feeding. Inflamm. Bowel Dis. 17, E78 (2011).

    PubMed  Google Scholar 

  182. Drugs and Lactation Database (LactMed). Cyclosporine (National Institute of Child Health and Human Development, 2021).

  183. Fritzsche, J., Pilch, A., Mury, D., Schaefer, C. & Weber-Schoendorfer, C. Infliximab and adalimumab use during breastfeeding. J. Clin. Gastroenterol. 46, 718–719 (2012).

    PubMed  Google Scholar 

  184. Bar-Gil Shitrit, A. et al. Detection of ustekinumab in breast milk of nursing mothers with Crohn disease. Inflamm. Bowel Dis. 27, 742–745 (2021).

    PubMed  Google Scholar 

  185. Flanagan, E. et al. Ustekinumab levels in pregnant women with inflammatory bowel disease and infants exposed in utero. Aliment. Pharmacol. Ther. 55, 700–704 (2022).

    CAS  PubMed  Google Scholar 

  186. Angelberger, S. et al. Long-term follow-up of babies exposed to azathioprine in utero and via breastfeeding. J. Crohns Colitis 5, 95–100 (2011).

    PubMed  Google Scholar 

  187. Beaulieu, D. B. et al. Use of biologic therapy by pregnant women with inflammatory bowel disease does not affect infant response to vaccines. Clin. Gastroenterol. Hepatol. 16, 99–105 (2018).

    PubMed  Google Scholar 

  188. Cheent, K. 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 4, 603–605 (2010).

    PubMed  Google Scholar 

  189. Takeda. Highlights of prescribing information: Entyvio (vedolizumab). FDA https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125476Orig1s046lbl.pdf (2022).

  190. European Medicines Agency. Direct healthcare professional communication (DHPC): Infliximab (Remicade, Flixabi, Inflectra, Remsima and Zessly): Use of live vaccines in infants exposed in utero or during breastfeeding. EMA https://www.ema.europa.eu/en/documents/dhpc/direct-healthcare-professional-communication-dhpc-infliximab-remicade-flixabi-inflectra-remsima_en.pdf (2022).

  191. Lim, J., Hammami, M. B. & Mahadevan, U. Infliximab use in a child with ulcerative colitis and prior in utero exposure to infliximab. Gastroenterology 158, 1834–1835 (2020).

    CAS  PubMed  Google Scholar 

  192. Ban, L., Tata, L. J., Fiaschi, L. & Card, T. Limited risks of major congenital anomalies in children of mothers with IBD and effects of medications. Gastroenterology 146, 76–84 (2014).

    CAS  PubMed  Google Scholar 

  193. Bengtson, M. B. et al. Relationships between inflammatory bowel disease and perinatal factors: both maternal and paternal disease are related to preterm birth of offspring. Inflamm. Bowel Dis. 16, 847–855 (2010).

    PubMed  Google Scholar 

  194. Bortoli, A. et al. Pregnancy before and after the diagnosis of inflammatory bowel diseases: retrospective case-control study. J. Gastroenterol. Hepatol. 22, 542–549 (2007).

    PubMed  Google Scholar 

  195. Bortoli, A. et al. Pregnancy outcome in inflammatory bowel disease: prospective European case-control ECCO-EpiCom study, 2003-2006. Aliment. Pharmacol. Ther. 34, 724–734 (2011).

    CAS  PubMed  Google Scholar 

  196. Bröms, G., Granath, F., Stephansson, O. & Kieler, H. Preterm birth in women with inflammatory bowel disease – the association with disease activity and drug treatment. Scand. J. Gastroenterol. 51, 1462–1469 (2016).

    PubMed  Google Scholar 

  197. Bush, M. C., Patel, S., Lapinski, R. H. & Stone, J. L. Perinatal outcomes in inflammatory bowel disease. J. Matern. Fetal Neonatal Med. 15, 237–241 (2004).

    CAS  PubMed  Google Scholar 

  198. Cleary, B. J. & Källén, B. Early pregnancy azathioprine use and pregnancy outcomes. Birth Defects Res. A Clin. Mol. Teratol. 85, 647–654 (2009).

    CAS  PubMed  Google Scholar 

  199. Clowse, M. E. et al. Pregnancy outcomes in subjects exposed to certolizumab pegol. J. Rheumatol. 42, 2270–2278 (2015).

    CAS  PubMed  Google Scholar 

  200. Coelho, J. et al. Pregnancy outcome in patients with inflammatory bowel disease treated with thiopurines: cohort from the CESAME study. Gut 60, 198–203 (2011).

    PubMed  Google Scholar 

  201. Dominitz, J. A., Young, J. C. & Boyko, E. J. Outcomes of infants born to mothers with inflammatory bowel disease: a population-based cohort study. Am. J. Gastroenterol. 97, 641–648 (2002).

    PubMed  Google Scholar 

  202. Elbaz, G., Fich, A., Levy, A., Holcberg, G. & Sheiner, E. Inflammatory bowel disease and preterm delivery. Int. J. Gynaecol. Obstet. 90, 193–197 (2005).

    PubMed  Google Scholar 

  203. Francella, A. et al. The safety of 6-mercaptopurine for childbearing patients with inflammatory bowel disease: a retrospective cohort study. Gastroenterology 124, 9–17 (2003).

    CAS  PubMed  Google Scholar 

  204. Goldstein, L. H. et al. Pregnancy outcome of women exposed to azathioprine during pregnancy. Birth Defects Res. A Clin. Mol. Teratol. 79, 696–701 (2007).

    CAS  PubMed  Google Scholar 

  205. Kammerlander, H. et al. The effect of disease activity on birth outcomes in a nationwide cohort of women with moderate to severe inflammatory bowel disease. Inflamm. Bowel Dis. 23, 1011–1018 (2017).

    PubMed  Google Scholar 

  206. Kanis, S. L., de Lima-Karagiannis, A., de Boer, N. K. H. & van der Woude, C. J. Use of thiopurines during conception and pregnancy is not associated with adverse pregnancy outcomes or health of infants at one year in a prospective study. Clin. Gastroenterol. Hepatol. 15, 1232–1241.e1 (2017).

    CAS  PubMed  Google Scholar 

  207. Koslowsky, B. et al. Pregnancy-onset inflammatory bowel disease: a subtle diagnosis. Inflamm. Bowel Dis. 24, 1826–1832 (2018).

    PubMed  Google Scholar 

  208. Lichtenstein, G. R. et al. Pregnancy outcomes reported during the 13-year TREAT registry: a descriptive report. Am. J. Gastroenterol. 113, 1678–1688 (2018).

    CAS  PubMed  Google Scholar 

  209. Lin, H. C. et al. Ulcerative colitis and pregnancy outcomes in an Asian population. Am. J. Gastroenterol. 105, 387–394 (2010).

    PubMed  Google Scholar 

  210. Meyer, A., Drouin, J., Weill, A., Carbonnel, F. & Dray-Spira, R. Pregnancy in women with inflammatory bowel disease: a French nationwide study 2010-2018. Aliment. Pharmacol. Ther. 52, 1480–1490 (2020).

    PubMed  Google Scholar 

  211. Meyer, A., Drouin, J., Weill, A., Carbonnel, F. & Dray-Spira, R. Comparative study of pregnancy outcomes in women with inflammatory bowel disease treated with thiopurines and/or anti-TNF: a French nationwide study 2010-2018. Aliment. Pharmacol. Ther. 54, 302–311 (2021).

    CAS  PubMed  Google Scholar 

  212. Moskovitz, D. N. et al. The effect on the fetus of medications used to treat pregnant inflammatory bowel-disease patients. Am. J. Gastroenterol. 99, 656–661 (2004).

    PubMed  Google Scholar 

  213. Naganuma, M. et al. Conception and pregnancy outcome in women with inflammatory bowel disease: a multicentre study from Japan. J. Crohns Colitis 5, 317–323 (2011).

    PubMed  Google Scholar 

  214. Nørgård, B., Fonager, K., Sørensen, H. T. & Olsen, J. Birth outcomes of women with ulcerative colitis: a nationwide Danish cohort study. Am. J. Gastroenterol. 95, 3165–3170 (2000).

    PubMed  Google Scholar 

  215. Padhan, R. K. et al. Long-term disease course and pregnancy outcomes in women with inflammatory bowel disease: an Indian cohort study. Dig. Dis. Sci. 62, 2054–2062 (2017).

    PubMed  Google Scholar 

  216. Raatikainen, K., Mustonen, J., Pajala, M. O., Heikkinen, M. & Heinonen, S. The effects of pre- and post-pregnancy inflammatory bowel disease diagnosis on birth outcomes. Aliment. Pharmacol. Ther. 33, 333–339 (2011).

    CAS  PubMed  Google Scholar 

  217. Schnitzler, F. et al. Outcome of pregnancy in women with inflammatory bowel disease treated with antitumor necrosis factor therapy. Inflamm. Bowel Dis. 17, 1846–1854 (2011).

    PubMed  Google Scholar 

  218. Seirafi, M. et al. Factors associated with pregnancy outcome in anti-TNF treated women with inflammatory bowel disease. Aliment. Pharmacol. Ther. 40, 363–373 (2014).

    CAS  PubMed  Google Scholar 

  219. Smink, M., Lotgering, F. K., Albers, L. & de Jong, D. J. Effect of childbirth on the course of Crohn’s disease; results from a retrospective cohort study in the Netherlands. BMC Gastroenterol. 11, 6 (2011).

    PubMed  PubMed Central  Google Scholar 

  220. Stephansson, O. et al. Crohn’s disease is a risk factor for preterm birth. Clin. Gastroenterol. Hepatol. 8, 509–515 (2010).

    PubMed  Google Scholar 

  221. Stephansson, O. et al. Congenital abnormalities and other birth outcomes in children born to women with ulcerative colitis in Denmark and Sweden. Inflamm. Bowel Dis. 17, 795–801 (2011).

    PubMed  Google Scholar 

  222. Tandon, P., Diong, C., Chong, R. Y. & Nguyen, G. C. Regional variation in pregnancy outcomes amongst women in inflammatory bowel disease: a population-based cohort study. Can. J. Gastroenterol. Hepatol. 2021, 3037128 (2021).

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank D. Johnson and J. Sauberan for their clinical insights.

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA

    Max N. Brondfield & Uma Mahadevan

Authors
  1. Max N. Brondfield
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Uma Mahadevan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The authors contributed equally to all aspects of the article.

Corresponding author

Correspondence to Uma Mahadevan.

Ethics declarations

Competing interests

U.M. has acted as a consultant for Abbvie, Bristol Myers Squibb, Gilead, Janssen and Pfizer, Takeda. M.N.B. declares no competing interests.

Peer review

Peer review information

Nature Reviews Gastroenterology & Hepatology thanks Vivian Huang, Parul Tandon, Sally Bell, Ralley Prentice and Christian Selinger for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Brondfield, M.N., Mahadevan, U. Inflammatory bowel disease in pregnancy and breastfeeding. Nat Rev Gastroenterol Hepatol 20, 504–523 (2023). https://doi.org/10.1038/s41575-023-00758-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41575-023-00758-3

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research