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IBD and the Pregnant Patient

IBD and the Pregnant Patient

Crohn's disease and ulcerative colitis are the two main forms of inflammatory bowel disease (IBD), which are incurable, chronic, idiopathic autoimmune conditions that primarily affect the digestive tract. IBD presents a number of concerns for women during pregnancy, particularly when it comes to managing medications and any related conditions. However, there have been great strides in making pregnancy and birth safer for mothers and their babies. Women with IBD who become pregnant will need to be followed closely by both their gastroenterologists and their obstetricians.

Reproductive Choices for Women with IBD

In previous years, women with IBD were counseled against becoming pregnant and having children. It was thought that women with Crohn's disease, in particular, may experience an unfavorable outcome, such as premature birth, birth defects, and a worsening of the IBD. It was thought that ulcerative colitis was associated with infertility. It is now known that the risks are not as significant as was once thought, especially when the IBD is managed properly.1

These misperceptions still exist in the public consciousness, and some women with IBD may delay or forgo pregnancy, thinking that their chances of having a healthy baby are low,2 or that they will be passing their disease on to a child. Women with IBD tend to have smaller families than women who do not have IBD, although this may be attributable in part to the racial and educational status of IBD patients.3

Family members of patients with IBD do have a higher risk (anywhere from 3 to 20 times greater) of developing the disease than the general population. Even so, most patients (greater than 80%) have no family members with IBD.4 However, women who have a recent diagnosis of IBD (between 0 and 6 months) should be counseled to delay a pregnancy for about 6 months because of a risk of preterm birth.5

Disease Activity at Conception

IBD is often spoken of as a "disease of young people." There is a spike in the diagnosis of IBD in adolescents and young men and women between the ages of 15 and 25 years. These are some of the prime childbearing years for women, and given that IBD is not an uncommon condition, obstetricians are likely to see young pregnant patients with Crohn's disease and ulcerative colitis.

IBD is characterized by periods of flare-ups and remission, with the goal of treatment being the induction of remission with mucosal healing in the digestive tract. The state of the IBD (the presence of either remission or active disease) at the time of conception is important to the course of the pregnancy.6 Because patients and their babies may do best when IBD is in remission, planning for conception when the IBD is quiescent should be recommended to patients considering a pregnancy.

Disease Activity during Pregnancy

In general, studies on pregnant women with IBD show that when the disease is active at the time of conception, it tends to continue to be active during the course of the pregnancy.6 For women with IBD who are experiencing remission at the time of conception, the remission tends to continue.7 Women who have severely active Crohn's disease during pregnancy have been shown to have an increased risk of experiencing preterm birth.5 However, pregnant women with active Crohn's disease do not appear to have a higher risk of having a baby with low birth weight, intrauterine growth restriction, or congenital defects.5 Women with IBD should be counseled to avoid a pregnancy within at least 3 months of their last active disease flare-up.

The evidence is conflicting regarding how disease activity during pregnancy affects IBD after delivery, but the largest study done to date reports that women may experience fewer flare-ups after a pregnancy.8 Women with long-standing Crohn's disease and those with ulcerative colitis may have a higher risk of experiencing an IBD flare-up during pregnancy.9 There is also a risk that ulcerative colitis may flare up again after delivery.9

Women who experience a flare-up of IBD during pregnancy will need treatment to have the best possible outcome and to avoid complications such as low birth weight and preterm birth. There are several treatments for IBD (with the exception of methotrexate and thalidomide) that can be used relatively safely during pregnancy.10

Medication in Pregnancy

5-Aminosalicylates (sulfasalazine, mesalamine). Sulfasalazine and mesalamine are in Pregnancy Category B, and it is generally thought that these medications can safely be used to treat IBD in pregnant women. Several studies done on women with IBD taking sulfasalazine during pregnancy have not been able to discern between the effects of the medication versus the effects of the disease on pregnancy outcome. While a few of these studies have shown a slight increase in stillbirth, preterm birth, congenital malformation, and preterm delivery,11,12 others have shown no association with poor pregnancy outcomes.13,14 However, sulfasalazine interferes with the body's ability to absorb folic acid, and both pregnant women with IBD and those women considering pregnancy who take sulfasalazine should receive appropriate folic acid supplements. 

6-Mercaptopurine and azathioprine. Some studies have shown that the use of 6-MP and azathioprine in pregnant women with IBD is associated with an increased risk of preterm birth, congenital defects, and perinatal mortality, but the effects of the disease versus the effects of the drug could be confounding the results.5,15 Several other studies have not found any relationship between 6-MP or azathioprine and preterm birth, low birth weight, neonatal adverse outcomes, or congenital abnormalities.16,17,18 These immunosuppresive drugs are Pregnancy Category D, are known to cross the placenta, and have been found in cord blood. There is some concern that this exposure during pregnancy can result in babies being born anemic.19 It is generally accepted that 6-MP or azathioprine should be continued during pregnancy if these drugs are determined to be effective in keeping the pregnant patient with IBD in remission.

Corticosteroids. This class of drugs is in Pregnancy Category C. There has been some concern over the increased risk of cleft palate in women taking corticosteroids during their first trimester,20 but a recent, large, case-control study shows no association.21 These drugs have not been associated with other fetal abnormalities, and they may be helpful in treating IBD flare-ups in pregnant women.

Methotrexate and thalidomide. These two immunosuppressive drugs are in Pregnancy Category X and should not be used during pregnancy. Methotrexate is associated with fetal skeletal abnormalities and fetal loss.22 Thalidomide is well known for causing limb defects and major organ complications.23 Methotrexate should be discontinued in women for at least three months (and more conservatively, 6 months) before attempting a pregnancy. Both of these drugs are available for treating patients with IBD under close supervision by a physician and only in conjunction with rigorous birth control and frequent pregnancy testing. Women who become pregnant while taking methotrexate or thalidomide will need immediate attention to determine the viability of the pregnancy.

Tumor necrosis factor-alpha blockers. The most recent class of drugs to be utilized in treating IBD are the biologics, or anti-TNF drugs such as infliximab, adalimumab, and certolizumab. TNF-alpha is an important component in the development of a fetus, and there is concern that a TNF blocker could interfere with the growth of the fetus' immune system. These drugs have a much shorter timeframe in the use of IBD, and their safety during pregnancy is still being determined. This class of drugs is in Pregnancy Category B, and infliximab and adalimumab have been found to cross the placenta. Therefore, it is currently recommended that these drugs be stopped in pregnant women with IBD before 30 weeks' gestation.24

Certolizumab has not been found to cross the placenta. The largest study to date on women with IBD taking biologics has not shown any association with fetal complications.18 Babies born to women who take biologics (either alone or in combination with immunosuppressive drugs) during pregnancy should not be given any live vaccines until at least 6 months of age.

The Outlook for Pregnant Women with IBD

Today, women with IBD have a greater chance of a healthy pregnancy and baby than ever before. While many women will have concerns about taking any medications while pregnant, they should be urged to consider that keeping IBD quiescent or in remission offers the best possible chance for an uneventful pregnancy and birth. Pregnant patients with IBD should be encouraged to continue their treatment plans during pregnancy, particularly when the plan is effective at preventing flare-ups.

Flare-ups of IBD in pregnant patients should be treated promptly to minimize risks to the fetus. Patients (especially those with ulcerative colitis and long-standing Crohn's disease) should also be counseled that they are at increased risk of a flare-up after delivery.

References

1. Ban L, Tata LJ, Fiaschi L, Card T. Limited risks of major congenital anomalies in children of mothers with IBD and effects of medications. Gastroenterology. 2014 Jan;146(1):76-84. doi: 10.1053/j.gastro.2013.09.061.

2. Mountifield R, Bampton P, Prosser R, Muller K, Andrews JM. Fear and fertility in inflammatory bowel disease: a mismatch of perception and reality affects family planning decisions. Inflamm Bowel Dis. 2009 May;15(5):720-725. doi: 10.1002/ibd.20839.

3. Marri SR, Ahn C, Buchman AL. Voluntary childlessness is increased in women with inflammatory bowel disease. Inflamm Bowel Dis. 2007 May;13(5):591-599.

4. Heyman MB, Kirschner BS, Gold BD, et al. Children with early-onset inflammatory bowel disease (IBD): analysis of a pediatric IBD consortium registry. J Pediatr. 2005 Jan;146(1):35-40.

5. Nørgård BM. Birth outcome in women with ulcerative colitis and Crohn's disease, and pharmacoepidemiological aspects of anti-inflammatory drug therapy. Dan Med Bull. 2011 Dec;58(12):B4360.

6. Abhyankar A, Ham M, Moss AC. Meta-analysis: the impact of disease activity at conception on disease activity during pregnancy in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2013 Sep;38(5):460-466. doi: 10.1111/apt.12417. Epub 2013 Jul 15.

7. Khosla R, Willoughby CP, Jewell DP. Crohn’s disease and pregnancy. Gut. 1984;25:52–56.

8. Riis L, Vind I, Politi P, et al. Does pregnancy change the disease course? A study in a European cohort of patients with inflammatory bowel disease. Am J Gastroenterol. 2006;101:1539–1545.

9. Pedersen N, Bortoli A, Duricova D, et al. The course of inflammatory bowel disease during pregnancy and postpartum: a prospective European ECCO-EpiCom Study of 209 pregnant women. Aliment Pharmacol Ther. 2013 Sep;38(5):501-512. doi: 10.1111/apt.12412. Epub 2013 Jul 15.

10. Reddy D, Murphy SJ, Kane SV, Present DH, Kornbluth AA. Relapses of inflammatory bowel disease during pregnancy: in-hospital management and birth outcomes. Am J Gastroenterol. 2008 May;103(5):1203-1209. doi: 10.1111/j.1572-0241.2007.01756.x. Epub 2008 Apr 16.

11. Nørgård B, Puho E, Pedersen L, Czeizel AE, Sørensen HT. 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.

12. Rahimi R, Nikfar S, Rezaie A, Abdollahi M. Pregnancy outcome in women with inflammatory bowel disease following exposure to 5-aminosalicylic acid drugs: a meta-analysis. Reprod Toxicol. 2008;25:271–275.

13. Mogadam M, Dobbins WO, Korelitz BI, Ahmed SW. Pregnancy in inflammatory bowel disease: effect of sulfasalazine and corticosteroids on fetal outcome. Gastroenterology. 1981;80:72–76.

14. Rahimi R, Nikfar S, Rezaie A, Abdollahi M. Pregnancy outcome in women with inflammatory bowel disease following exposure to 5-aminosalicylic acid drugs: a meta-analysis. Reprod Toxicol. 2008;25:271–275.

15. Hutson JR, Matlow JN, Moretti ME, Koren G. The fetal safety of thiopurines for the treatment of inflammatory bowel disease in pregnancy. J Obstet Gynaecol. 2013 Jan; 33(1):1-8.

16. Stephansson O, Larsson H, Pedersen L, et al. Congenital abnormalities and other birth outcomes in children born to women with ulcerative colitis in Denmark and Sweden.

Inflamm Bowel Dis. 2011 Mar; 17(3):795-801.

17. Moskovitz DN, Bodian C, Chapman ML, et al. The effect on the fetus of medications used to treat pregnant inflammatory bowel-disease patients. Am J Gastroenterol. 2004 Apr; 99(4):656-661.

18. Mahadevan U, Martin CF, Sandler RS, et al. PIANO: A 1000 Patient Prospective Registry of Pregnancy Outcomes in Women with IBD Exposed to Immunomodulators and Biologic Therapy. Gastroenterology. 2012;142 Suppl 1:S149

19. Jharap B, de Boer NK, Stokkers P, et al. Intrauterine exposure and pharmacology of conventional thiopurine therapy in pregnant patients with inflammatory bowel disease. Gut. 2014 Mar; 63(3):451-457.

20. Edwards MJ, Agho K, Attia J, et al. Case-control study of cleft lip or palate after maternal use of topical corticosteroids during pregnancy. Am J Med Genet A. 2003 Aug 1;120A(4):459-463.

21. Skuladottir H, Wilcox AJ, Ma C, et al. Corticosteroid use and risk of orofacial clefts. Birth Defects Res A Clin Mol Teratol. 2014 Apr 29. doi: 10.1002/bdra.23248.

22. Nguyen C, Duhl AJ, Escallon CS, Blakemore KJ. Multiple anomalies in a fetus exposed to low-dose methotrexate in the first trimester. Obstet Gynecol.  2002 Apr;99(4):599-602.

23. Botting J. The History of Thalidomide. Drug News Perspect. 2002 Nov;15(9):604-611.

24. Gisbert JP, Chaparro M. Safety of anti-TNF agents during pregnancy and breastfeeding in women with inflammatory bowel disease. Am J Gastroenterol. 2013 Sep;108(9):1426-1438. doi: 10.1038/ajg.2013.171. Epub 2013 Jun 11.

 
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