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Article: How Should Inflammatory Bowel Disease Be Managed During Pregnancy?

Sunanda V. Kane, MD, MSPH, FACG, Associate Professor of Medicine, Mayo Clinic, Rochester, Minnesota.

Onset and Diagnosis of Inflammatory Bowel Disease During Pregnancy

An early clinical series suggested that the prognosis was poor for women with ulcerative colitis (UC) diagnosed during pregnancy.[1] Since that time, epidemiologic data have failed to show that inflammatory bowel disease (IBD) is worse during pregnancy than at any other time. To date, there has been no large study involving de novo diagnosis of Crohn's disease (CD) during pregnancy; therefore, no conclusion about disease severity under the physiologic condition of pregnancy can be drawn.

Overall, fertility rates for women with IBD are comparable to rates in the normal population. Active CD, however, can reduce fertility in several ways. Voluntary childlessness can result from fear of intimacy and dyspareunia. Active inflammation in the colon as well as any inflammation or scarring directly involving the fallopian tubes or ovaries have been shown to decrease fertility. Women who have had any surgical resection are at risk for adhesions, which can also impair tubal function. In women with a history of ulcerative colitis, restorative proctocolectomy with ileoanal pouch anastomosis (IPAA) has been shown to increase dyspareunia and significantly reduce fertility.[2]

None of the medications used to treat IBD has a direct effect on female fertility, but it is important to remember that in males, sulfasalazine therapy causes a reversible reduction in sperm count and motility.
Effect of IBD on Pregnancy

If a woman is doing well and is in remission from IBD, there is every reason to expect the pregnancy to proceed smoothly. These women appear no more likely to experience spontaneous abortion or stillbirth or to deliver a child with congenital abnormalities. In a pregnant woman with active disease, it is likely that the disease will continue throughout the pregnancy and place the pregnancy at greater risk for complications.[3] This risk appears to be higher in CD than in UC. Therefore, the main priority is to establish and maintain remission prior to conception.

Miscarriage occurs more frequently (in up to 35% of conceptions) in women with active disease.[4] Despite progress in the treatment of IBD, an increased risk for preterm and low-birthweight babies is still observed. As in all pregnancies, smoking cessation is extremely important. With respect to congenital malformations, all reports published to date, except for a single abstract,[5] show no increased risk for malformations in women with IBD above that seen in the general population (1%-4.8%).[6] The presence of IBD does not appear to have an impact on maternal complications of pregnancy, such as hypertension and proteinuria.
Effect of Pregnancy on IBD

In women with quiescent UC, the rate of relapse is approximately the same in pregnant vs nonpregnant patients. In contrast, the presence of active UC at the time of conception is associated with continued or worsening disease activity in approximately 70% of pregnant women.[7] Comparable rates of worsening disease have been documented in pregnant women with Crohn's disease.
Disease Assessment

During pregnancy, hemoglobin and albumin levels decrease and the sedimentation rate increases. Because of these normal physiologic changes, disease assessment during pregnancy should rely more on clinical symptoms than on laboratory parameters. If radiologic imaging is contemplated, both ultrasound and magnetic resonance imaging are safe procedures, but they are rarely used for clinical assessment. It is best to avoid exposure of the fetus to radiation from abdominal x-rays, especially early in the pregnancy. However, the absolute risk to the fetus from abdominal radiography is minimal, and clinical necessity should guide decision making.[8]

There is no evidence that sigmoidoscopy will induce preterm labor. Most patients can be evaluated with sigmoidoscopy without full colonoscopy. However, if colonoscopy is necessary for diagnosis or determination of extent and severity of disease, close fetal monitoring is indicated.
Treatment of IBD During Pregnancy

Corticosteroids have not been associated with teratogenicity in humans and can be used as necessary to control disease activity. Prednisone crosses the placenta less efficiently than betamethasone or dexamethasone; after metabolization, the fetus is exposed to only 10% of the maternal dose. Budesonide has not yet been studied in this clinical setting.

Sulfasalazine and 5-ASA at doses < 3 g/day have not been associated with any increase in birth defects or kernicterus. Given the risk for sulfasalazine-induced folate deficiency, together with the heightened folate requirements in pregnancy and data showing a decrease in neural tube defects with folate supplementation, daily folic acid supplementation is indicated for any woman of childbearing age who takes sulfasalazine. Mesalamine preparations at doses < 2.4 g/day are considered safe and do not affect the rate of live births, miscarriages, terminations, or fetal distress.[9] However, a prospective study of pregnant women on mesalamine showed a significant increase in the rate of preterm deliveries (13% vs 5%), lower mean maternal weight gain (13.1 kg vs 15.6 kg), and lower mean infant birthweight (3.2 kg vs 3.4 kg) compared with the normal population. The safety of larger doses of 5-ASA has not been studied to the same extent as the lower doses. Use of topical 5-ASA agents during pregnancy has not been shown to increase adverse birth outcomes.

Limited data are available on the safety of antibiotics in Crohn's disease. Ampicillin, cephalosporin, erythromycin, and short courses (7-10 days) of metronidazole are believed to be safe. The quinolones are contraindicated in pregnancy because of the arthropathogenicity of these medications in immature animals.

There are no published large, prospective or population-based studies of the use of immunomodulators (azathioprine, 6-mercaptopurine) to treat IBD during pregnancy. Until recently, most of our information came from the transplantation literature and small retrospective series involving IBD patients. It is generally believed by the most experienced IBD clinicians that 6-mercaptopurine, azathioprine, and cyclosporine can be used safely during pregnancy if the mother's health mandates therapy.[10] Of note, a small retrospective study found that the use of 6-mercaptopurine in fathers within 3 months of conception resulted in an increase in pregnancy-related complications,[11] but subsequent data have failed to corroborate these findings. Methotrexate, another immunomodulator, is associated with severe fetal malformations in the first trimester and is contraindicated in pregnancy. Methotrexate should be stopped in women at least 1 month before conception and, in men, at least 3 months before conception (the time required for spermatogenesis). Although anti-tumor necrosis factor agents cross the placenta, they are considered appropriate therapy during pregnancy. If stopped in the third trimester, the fetal exposure to this agent is reduced because IgG transport is most active in the third trimester.

Antidiarrheal agents are used for symptom relief in IBD. Loperamide is not teratogenic in animals but human data are limited. Loperamide use has not been associated with an increased rate of first-trimester fetal malformations, spontaneous abortions, or preterm deliveries. It may, however, be associated with lower than normal birthweights, and use in late pregnancy has been implicated in neonatal intestinal obstructions. Therefore, it is best to avoid large doses of antidiarrheals during pregnancy. Long-term diphenoxylate use during pregnancy is not recommended. Table 1 details the safety of these medications for pregnant women with IBD.

Table 1. Safety of IBD Medications During Pregnancy

tbl 1.jpg

*Category B: May have been studied in animals with no evidence of harm, but studies done on pregnant women may be lacking. Category B may also mean that animal studies may have found adverse effects, but studies of pregnant women found no such risks.
**Category C: Researchers may have found adverse effects in animals, but there are no adequate studies of pregnant women using the drug. Category C may also mean that there are no animal studies or studies on pregnant women.
***Category D: Have been demonstrated to cause adverse effects in pregnant women, but the benefits may outweigh the risks in some cases (eg, if a woman does not take the category D medication, her life or her baby's life might be in danger).
Postpartum Issues

Nearly all drugs used to treat IBD are secreted in breastmilk. The advantages of breastfeeding for both mother and newborn are well known. General recommendations (which reflect consensus of expert opinion but that have not been established in clinical series) are shown in Table 2. Corticosteroids can be used in breastfeeding mothers because the dose ingested by the infant is < 0.1% of the mother's dose. Some physicians recommend that mothers receiving doses > 20 mg/day wait at least 4 hours after a dose before nursing. As of this writing, immunomodulator use during breastfeeding is not recommended because of the theoretical risk for immune suppression, but emerging data suggest that metabolite levels are miniscule and that no increased risk is imparted to nursing infants.

Table 2. Safety of IBD Medications During Breastfeeding

tbl 2.jpg

Surgery for IBD in Pregnancy

The indications for surgery during pregnancy are identical to those of nonpregnant patients and include obstruction, perforation, abscess, and hemorrhage.


1. Dominitz JA, Young JC, Boyko EJ. Outcomes of infants born to mothers with inflammatory bowel disease: a population based cohort study. Am J Gastroenterol. 2002;97:641-648. Abstract
2. Olsen KO, Berndtsson I, Oresland T, et al. Ulcerative colitis: Female fecundity before diagnosis, during disease, and after surgery compared with a population sample. Gastroenterology. 2002;122:15-19. Abstract
3. Kornfeld D, Cnattingius S, Ekbom A. Pregnancy outcomes in women with inflammatory bowel disease -- A population-based cohort study. Am J Obstet Gynecol. 1997;177:942-946. Abstract
4. Fonager K, Sorensen HT, Olsen J, et al. Pregnancy outcome for women with Crohn's disease: A follow-up study based on linkage between national registries. Am J Gastroenterol. 1998;93:2426-2430. Abstract
5. Bortoli A, Tartarella M, Prada A, et al. Inflammatory bowel disease and pregnancy. Gastroenterology. 1997;112:A940 (Abstract).
6. Rogers RG, Katz VL. Course of Crohn's disease during pregnancy and its effect on pregnancy outcome: A retrospective review. Am J Perinatol. 1995;12:262-264. Abstract
7. Porter RJ, Stirrat GM. The effects of inflammatory bowel disease on pregnancy: A case-controlled retrospective analysis. Br J Obstet Gynaecol. 1986;93:1124-1131. Abstract
8. Brent RL. The effect of embryonic and fetal exposure to x-ray, microwaves, and ultrasound: Counseling the pregnant and nonpregnant patient about these risks. Semin Oncol. 1989;16:347-368. Abstract
9. Diav-Citrin O, Park YH, Veerasuntharam G, et al. The safety of mesalamine in human pregnancy: A prospective controlled cohort study. Gastroenterology. 1998;114:23-28. Abstract
10. Francella A, Dayan A, Rubin P, et al. 6-Mercaptopurine is a safe therapy for child bearing patients with inflammatory bowel disease: A case controlled study. Gastroenterology. 1996;110:A909 (Abstract).
11. Rajapakse RO, Korelitz BI, Zlatanic J, et al. Outcome of pregnancies when fathers are treated with 6-mercaptopurine for inflammatory bowel disease. Am J Gastroenterol. 2000;95:684-688. Abstract
The data does show that biologics (remicade, humira, etc) molecules are too big to pass into breastmilk. The testing they have done on breastmilk have not detected any of the drug in breastmilk and that any levels in the newborn are leftover from exposure in the womb.

The video on this site is so very handy.

The Mayo Clinic offers an informative video on how Crohn’s disease can affect a pregnancy. The video is embedded in this post below, but here are some highlights:

* Women with a history of Crohn’s or inflammatory bowel disease should take prenatal vitamins before attempting to conceive. This will allow the woman to be as healthy as possible before getting pregnant
* Fertility rates are slightly lower for women with Crohn’s; however, many couples are unable to have children, so infertility in a Crohn’s patient might be unrelated to the illness.
* Patients are recommended to stay on their medications during pregnancy because the mother’s health is crucial for the development of her baby.
* Among women who are experiencing active disease when they get pregnant, one-third will get better during the pregnancy, one-third will stay the same, and one-third will get worse.
* It is very important for a female patient to tell her doctors if she is having symptoms of Crohn’s or colitis when she becomes pregnant. Active disease can be harmful for the developing fetus, especially during the first trimester, and the effect of active Crohn’s symptoms are considered worse for the baby than most medicines taken for the condition (at the doses typically prescribed for Crohn’s).
* The biologic agents like Remicade and Humira taken by Crohn’s patients cross the placenta during pregnancy, but not until the late second or third trimester. Therefore, most women with Crohn’s should remain on these treatments during the early part of the pregnancy, and if necessary, stop or reduce their usage during the later stages before the baby is born.
* Pregnant women with Crohn’s disease generally are not mandated to have cesarean sections (c-sections) unless they have experienced fistulas or related symptoms.
* For the mother who wishes to breastfeed her newborn, biologics do not pass into breast milk. Small amounts of 5-ASA medicines do pass into the milk of nursing mothers, but not enough to put a baby at risk. On the other hand, breastfeeding moms should avoid antibiotic therapy.
* Typically, it is acceptable for nursing mothers to take 6mp; if a patient wants to be really safe, she can take the drug at night, pump and dump the first milk of the morning, and then breastfeed normally for the rest of the day.
* There is about a seven percent chance that a mother with Crohn’s will have a child with Crohn’s; if both parents have the disease, then the chances rise to around forty percent.
* The main pharmaceutical for expectant mothers to avoid is methotrexate. Women hoping to get pregnant should be off of the drug for at least three months before conception. Similarly, men taking methotrexate should stop for three months before trying to father a child.
I only say this because breastfeeding can protect babies from IBD later on in life. I think its so important to do so, if you can, and many mothers on IBD meds are told they cant.