Inflammatory Bowel Disease, Crohn’s Disease, Ulcerative Colitis
1. What every clinician should know
Inflammatory bowel disease is broken down into two conditions, Ulcerative colitis (UC) and Crohn’s disease (CD). Both conditions commonly present during the reproductive years and require counseling and management prior, during, and after pregnancy. Estimates for the incidence of UC and CD in North America range widely from 1-15 cases per 100,000 person-years. Prevalence ranges between 25-250 cases per 100,000 persons.
Both conditions are inflammatory disorders of the gastrointestinal tract. The pathogenesis of both remains elusive. UC is characterized by colitis and proctitis, ascending proximally from the rectum in a predictably continuous manner. Pathology is limited to the mucosa and submucosa of the colon and frequently presents as bloody diarrhea. Although emergency surgery is not required commonly, it is curative.
Crohn’s disease can be more unpredictable and more challenging to manage during pregnancy. Unlike UC, it is characterized by skipped lesions throughout the gut, most commonly the ileum and proximal colon, while sparing the rectum. Disease is transmural, which explains the more concerning sequelae, such as intra-abdominal abscesses from perforation, intestinal strictures, fistulas (including perineal involvement and fistulas), and obstruction. Emergency surgery may be required at any time, but is not curative.
There are genetic and environmental risk factors that predispose individuals to inflammatory bowel disease. Family history of disease is an important risk factor for the offspring of IBD adults, especially if Jewish. Twin studies have also demonstrated the importance of genetic concordance in the development of IBD, particularly with CD.
Environmental exposures may play a role, though this continues to be challenging to prove with certainty. Some exposures that have been proposed include NSAIDs, antibiotics, and oral contraceptive use. Smoking could be a risk factor for CD that may contribute towards disease activity, and some have suggested it could have the opposite effect on UC activity. Exposure to breast milk as a child may be protective.
2. Diagnosis and differential diagnosis
The diagnosis of either UC or CD is commonly made during the reproductive years. If presenting during pregnancy, a multidisciplinary team may be required. Ultimately, the process of diagnosis during and outside of pregnancy should not differ significantly. Although management may be initiated by the clinical picture, endoscopy with biopsy diagnosis continues to be the gold standard. Although there has not been an extensive experience with endoscopy during pregnancy, flexible sigmoidoscopy and colonoscopy have been performed safely.
Radiographic studies may be required during pregnancy and should not be withheld if it changes clinical management, especially when there is concern for an intra-abdominal infection or other surgical emergency. Both MRI and CT are useful in these cases, especially when evaluating the small intestine, which cannot be easily accessed by endoscopy.
Inflammatory bowel disease may present in a variety of ways, but commonly has some component of bowel habit changes and/or abdominal pain. The differential diagnosis if initially presenting during pregnancy may be extremely broad and evaluation should depend on the presenting signs and symptoms. Entities can range from conditions without significant concerns towards pregnancy, such as irritable bowel syndrome, or as surgical emergencies, such as appendicitis.
Preconception consultation is a critical aspect of IBD management. It is the opportunity to review optimal pregnancy timing as well as the risks/benefits of current pharmacotherapy to minimize clinical flares and fetal risks. A woman with quiescent disease is less likely to have disease flares during pregnancy and would be expected to have a less complicated pregnancy course. Supplemental folic acid should be prescribed, and medications for IBD should not be discontinued without discussing with a physician.
Given the frequency of using pharmacotherapies for disease control, it is prudent to perform a detailed anatomical survey at 18 – 20 weeks gestation, as is done for a variety of high-risk conditions that co-mingle with pregnancy. Given the risks of growth abnormalities in the fetus, interval ultrasounds to assess fetal growth in the second and third trimesters of pregnancy may be helpful.
Attention to nutrition is important, as many women with IBD, especially CD, who have had significant ileal disease are at risk for nutritional deficiencies. In particular, deficiencies in folate, B12, and iron are common. Attention to oral or parenteral supplementation is important to prevent significant maternal anemia prior to delivery and to promote overall health. For women receiving chronic steroids, attention to early screening for gestational diabetes may be indicated.
Women with concurrent disease may continue most therapies that control flares at the minimal dosing to achieve clinical stability. Disease should be monitored carefully, and we suggest a multidisciplinary team to manage these complex patients. Therapies should be tailored to manage clinical symptoms, and surgery should be reserved for complications that are not amenable or appropriate for medical therapy escalation. Decisions regarding surgery in a pregnant woman should not be delayed when there is concern for emergencies such as intestinal perforation, hemorrhage, and intestinal obstruction.
In most cases, labor can be routinely managed. The mode of delivery (cesarean versus vaginal delivery) in women with Crohn’s disease afflicted with perianal involvement does require discussion. Many experts routinely make the option of an elective cesarean section available to these women to avoid further perineal trauma and concerns for disease progression with vaginal delivery. Vaginal birth is appropriate and perhaps preferable with previous intestinal surgery or the presence of a colostomy or ileostomy without additional complications.
In general, the postpartum period should be managed routinely. However, some attention to breast feeding may be required given that this population typically has lower than optimal rate of breast feeding that is slightly higher than 50%. The reasons for this are unclear but may be related to medication concerns. There continue to be concerns for breast feeding in women receiving cyclosporin due to high concentrations in the breast milk.
Complications from the disease
Inflammatory bowel disease may complicate pregnancy and is associated with adverse pregnancy outcomes. Observational studies have demonstrated concerns, including risks for prematurity, small for gestational age (SGA) babies, and spontaneous abortion or miscarriage. Whether these are due to medication exposure, disease flares, or merely the presence of disease remain unclear. Moreover, there is an increased frequency of cesarean section and deep vein thrombosis.
Finally, complications from UC or CD disease flares may occur at any time and may result in an unstable maternal condition, such as bowel obstruction, abscess and/or sepsis, placing mother and fetus at risk for adverse pregnancy outcomes. Often, these cases require invasive intervention.
Complications from the management of the disease
The management of IBD can have consequences on pregnancy, although a lack of management likely has far greater consequences. There are a variety of anti-inflammatory and immunosuppressive agents utilized that are commonly maintained throughout pregnancy. Although some have been used extensively, many of the newer therapies do not have decades of experience to assure safety.
Sulfasalzine and 5-amniosalicylic acid cross the placenta towards the fetal compartment but are considered safe to use during pregnancy. Glucocortiocoids are thought to be low risk and should not be withheld from pregnant women with treatment indications. However, delays beyond the first trimester may be reasonable, as oral clefting, although rare, has been associated with first trimester exposure. Prolonged glucocorticoid use may predispose pregnancy to adverse outcomes, such as hypertension, gestational diabetes, and preterm premature rupture of membranes. Breast feeding is acceptable.
Cyclosporine is used for recalcitrant disease. To date there is no increased birth defect risk but there remains some concern that use may be linked to prematurity and small for gestational age babies. Moreover, there are concerns for breast feeding given high concentrations of cyclosporin in breast milk. Azathioprine and Mercaptopurine are thiopurines that are not known to cause significant issues. There may be an association with prematurity, but at this time no concerns for an increased risk for small for gestational age or birth defects.
Anti-tumor necrosis factor therapies such as infliximab, adalimumab, and certolizumab have not been extensively used during pregnancy, but no significant concerns have been noted, especially in the first and second trimesters. Due to the limited experience, some experts suggest discontinuing therapy in the third trimester as placental transport to the fetal compartment seems to increase. There has been a concern for neonatal immune suppression. However, if therapy is required, it should not be discontinued and can be restarted if previously deferred.
Methotrexate is known to cause spontaneous abortion and should be discontinued prior to pregnancy, as a high rate of congenital birth defects has been associated with its use. Given the concerns, many experts would suggest contraception for a few months after discontinuation. There has been concern for diphenoxylate exposure and fetal birth defects, but this has not been confirmed. As such, it would be prudent to avoid first trimester exposure until more information is available.
5. Prognosis and outcome
Although many women can have a successful pregnancy, large cohort studies have demonstrated increased adverse pregnancy outcomes, such as prematurity, spontaneous abortion, and growth restriction. Prognosis for IBD during pregnancy may be dependent on baseline activity at the commencement of pregnancy.
Quiescent disease predicts activity throughout pregnancy. Two thirds of women with active disease at conception will have additional flares, while only a third of women with stable disease would be anticipated to flare during pregnancy, and these would be less severe.
Long term prognosis
Pregnancy has been thought to offer some disease stability. Some have found that pregnancy has a protective effect on future disease activity and future need for surgical intervention. Beyond pregnancy, both conditions are chronic diseases that typically do not resolve completely with pregnancy. Both disorders have an increased risk of further intestinal cancer, with UC greater than CD.
6. What is the evidence for specific management and treatment recommendations
Ilnyckyji, A, Blanchard, JF, Rawsthorne, P. “Perinatal Crohn's disease and pregnancy: role of mode of delivery”. Am J Gastroenterol. vol. 94. 1999. pp. 3274-8. (Canadian experience with vaginal delivery and perianal involvement.)
Kornfeld, D, Cnattingius, S, Ekbom, A. “Pregnancy outcomes in women with inflammatory bowel disease—A population based cohort”. Am J Obstet Gynecol. vol. 177. 1997. pp. 942-6. (Large cohort from the Swedish Birth Registry demonstrating increased risks for SGA LGA, preterm birth, and cesarean section.)
Mahadevan, U, Cucchiara, S, Hyams, JS. “The London position statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organisation: pregnancy and pediatrics”. Am J Gastrolenterol. vol. 106. 2011. pp. 214-23. (Review of anti-tumor necrosis factor therapy during pregnancy.
Nguyen, GC, Boudreau, H, Harris, ML. “Outcomes of obstetric hospitalizations among women with inflammatory bowel disease in the United States”. Clin Gastroenerol Hepatol. vol. 7. 2009. pp. 329-34. (Large database study evaluating maternal complications using the 2005 Nationwide Inpatient Sample.
VanHorn , C, Barrett, P. “Pregnancy, delivery, and postpartum experiences of fifty-four women with ostomies”. J Wound Ostomy Conference Nurs. vol. 24. 1997. pp. 151-62. (Experience with pregnancy and women that required ostomies.
Yang, H, McElree, C, Roth, MP. “Familial empirical risks for inflammatory bowel disease: differences between Jews and non-Jews”. Gut. vol. 34. 1993. pp. 517-24. (Study exploring genetic/ethnic risk factors for IBD.)
Yarur, AJ, Kane, SV. “Update on pregnancy and breastfeeding in the era of biologics”. Dig Liver Dis. 2013 Mar 5. (Comprehensive review of IBD and pregnancy.)
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- Inflammatory Bowel Disease, Crohn’s Disease, Ulcerative Colitis
- 1. What every clinician should know
- 2. Diagnosis and differential diagnosis
- 3. Management
- 4. Complications
- 5. Prognosis and outcome
- 6. What is the evidence for specific management and treatment recommendations