IBD & Pregnancy

Inflammatory bowel disease (IBD) frequently aﬀects young people in their reproductive years, and can have a major impact on patients’ family planning decisions. The majority of women with IBD can have healthy pregnancies and healthy babies. One of the most important factors for having a healthy pregnancy is to ensure that your IBD is well controlled both prior to becoming pregnant, as well as throughout your pregnancy. It is important to discuss your plans for starting a family with your IBD doctor and team. The following information sheet will answer some of the most commonly asked questions about pregnancy and IBD.

How does IBD aﬀect Fertility?

Many patients with IBD are concerned about how their disease can aﬀect fertility. An Australian study found that 43% of women with IBD were worried about infertility. Fortunately, women with inactive IBD, both Crohn’s disease (CD) and ulcerative colitis (UC), have fertility rates similar to the general population. However, some women with active IBD, especially CD, can have decreased fertility.

Does surgery have an impact on fertility?

Women with UC who have had their colon removed and had a pouch created (colectomy and ileal pouch‐anal anastomosis (IPAA)) may have reduced fertility. See the pictogram below to see the risk of infertility for the general population, medically treated IBD, and after IPAA. If possible, women who are planning on having children may want to consider alternative surgical procedures, such as colectomy and the formation of an ileostomy, which does not aﬀect fertility, and wait until after child‐ birth to have the pouch surgery. Similarly, women with CD that have had significant surgery in the pelvic region may also have reduced fertility. Women with IBD who are having problems with infertility should ask about a referral to a fertility specialist.

Do IBD medications have an impact on fertility?

To date, IBD medications do not appear to impact fertility in women. Men with IBD may have decreased fertility when taking sulfasalazine. Fertility returns to normal within 3 months of stopping the medications and good alter‐ natives, such as mesalazine, can be taken instead. Methotrexate can aﬀect sperm production and quality, and should be stopped 3‐6 months prior to conception. Methotrexate should also be stopped in women considering pregnancy due to an increased risk of birth defects.

What are the chances of my child having IBD?

Patients with IBD are slightly more likely to have a child with IBD compared to parents without IBD, although the overall risk is still quite low. If one parent has UC, the risk of their child having IBD is 1.6%. If one parent has CD, the risk of their child having IBD is 5.2%. Or, to put this in other terms, less than 2 out of 100 children born to a parent with UC or 5 out of 100 children born to a parent with CD, will get IBD. If both parents have IBD, the risk of their child developing IBD in 36 out of 100, or 36%.

How does pregnancy aﬀect IBD?

The most important factor in predicting how active your IBD will be throughout pregnancy appears to be how active your disease is when you become pregnant. If you conceive during remission, rates of flare are similar to rates for non‐pregnant patients. However, if you become pregnant when your disease is active, your disease is more likely to remain active or get worse.

Interestingly, it appears that pregnancy may have a beneficial eﬀect on the course of IBD, with a lower rate of flares in the years after pregnancy, compared to the years before pregnancy.

What if I have a flare during pregnancy?

Most of the medications used to treat IBD are safe to use in pregnancy, but some are not. It is therefore very important that you discuss your plans to become pregnant with your IBD team, and let them know as soon as possible once you become pregnant. More details on the most common IBD drugs are given in the next section.

If you start to have symptoms of IBD during your pregnancy, let your IBD team know as soon as possible. Investigations may need to be done to determine what is happening. Endoscopic procedures such as flexible sigmoidoscopy and colonoscopy are considered safe in pregnancy, but should only be done if clearly necessary, and in the second trimester if possible. Elective procedures should be delayed until after delivery. MRI and ultrasound are also considered safe, but other radiology tests that involve radiation, such as x‐rays, CT scans, and barium tests, should be avoided.

How does IBD aﬀect pregnancy?

The eﬀect IBD has on pregnancy depends on whether the disease is active or in remission. Current evidence indicates that well controlled disease has minimal impact on the course and outcome of pregnancy. However, it appears that if a woman with active IBD becomes pregnant, or if the disease flares in pregnancy, the risk for adverse outcomes is higher. Several studies have shown that there is an increased risk of preterm delivery and low birth weight babies in women with IBD, particularly in patients who have had active disease either at conception, or throughout their pregnancy. The risk of congenital malformations may be slightly higher in children of mothers with UC, although a number of other studies did not show any increased risk. As active disease is associated with increased risk of adverse outcomes in pregnancy, we therefore recommend, if possible, that women with IBD who are considering becoming pregnant wait until their disease is in remission.

Does IBD influence the route of delivery?

Women with IBD are more likely to have caesarean (C) sections compared to the general population. There are only 2 situations where your gastroenterologist might recommend a C‐section: active perianal disease (inactive peri‐ anal disease does not require a C‐section), and in patients who have a pouch (IPAA). Although the route of delivery was not found to influence whether there were complications with the pouch, the recommendation is based on the theoretical increased risk of incontinence from damage to the anal sphincter with a vaginal delivery.

How do IBD medications aﬀect pregnancy?

The decision whether to continue taking medications for IBD during pregnancy can be a diﬃcult one. Most of the medications that are used to treat IBD are considered safe in pregnancy. As complications and adverse outcomes in pregnancy are usually associated with active disease, the benefits of keeping IBD in remission usually outweigh the potential risks. However, some medications should not be used in pregnancy. It is therefore very important to review your medications with your IBD team if you are pregnant, or if you are considering pregnancy. Table 1 describes the Category System used by the Food and Drug Administration for drug safety during pregnancy. Details on the most common IBD medications are given below and are summarized in Table 2.

Table 1. US Food and Drug Administration categories for drug safety during

FDA Category	Description
A	Controlled human studies show no risk. Controlled studies in animals and women have shown no risk to the fetus during the first trimester of pregnancy (and there is no evidence of risk in later trimesters).
B	No evidence of risk in studies. Either animal studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women, OR, animal studies have shown an adverse eﬀect that was not confirmed in controlled studies in women in the first trimester (and there is no evidence of a risk in later trimesters).
C	Risk cannot be ruled out. Either there are no animal or human studies OR animal studies have shown an adverse eﬀect and there are no well controlled studies in humans AND the benefit from the use of the drug in pregnant women may be acceptable despite its potential risks.
D	Positive evidence of risk. Positive evidence of human fetal risk, but the potential benefits from the use of the drug in pregnant women may be acceptable despite its potential risks.
X	Contraindicated in pregnancy. Studies in animals or humans have demonstrated fetal abnormali‐ ties. The risk of the use of the drug in pregnant women clearly outweighs any possible benefit.

Aminosalicylates (5‐ASAs)

5‐ASA medications are generally considered safe to use in pregnancy. All 5‐ASA formulations available in Canada are FDA category B drugs, except Asacol, which is a category C drug. The coating of Asacol contains dibutyl phthalate (DBP). In animal studies, DBP was associated with abnormalities of the kidneys and genital organs when given in doses greater than 80 times the human dose. Your IBD team may therefore recommend switching to a diﬀerent 5‐ASA medication if you are planning on becoming pregnant.

Sulfasalazine, is safe to use in pregnancy. However, it interferes with folate synthesis so increased supplementation with 2‐5 mg of folate per day is therefore recommended.

Antibiotics

Metronidazole (Flagyl®), ciprofloxacin (Cipro®), and amoxicillin‐clavulanic acid (Clavulin®), are some of the antibiotics most frequently used in the treatment of IBD. Metronidazole and amoxicillin‐clavulanate are category B medications and can be used during pregnancy. However, antibiotics use should be limited to short‐term use.

Ciprofloxacin is a category C drug. Although the overall risk is limited, animal studies have shown an increased risk of musculoskeletal abnormalities, so use should be avoided during pregnancy.

Corticosteroids

Steroids (for example Prednisone®, Budesonide®) are category C medications. Corticosteroid use in the first trimester has been associated with a small increase in the risk of oral clefts (3.35 times more likely). The magnitude of this risk is shown in the adjacent pictogram. As the risk of steroid use is very small, and the potential benefits of treating a significant flare are great, steroids may be recommended to treat IBD flares throughout pregnancy. If steroids are used near the time of delivery, your baby will be monitored to make sure their adrenal glands (which make natural steroid) are working properly. Much less is known regarding the safety of budesonide in pregnancy. Very small case series have not shown any adverse events.

Thiopurines

Thiopurines (Azathioprine/Imuran®, 6‐mercaptopurine) are category D medications. This designation is from the 1960s when animal studies using extremely high doses of these medications showed adverse eﬀects. However, multiple studies of IBD patients treated with thiopurines throughout pregnancy have not shown any increased risk of congenital anomalies. Also, the risk of relapse is high when azathioprine is stopped, even in patients who are in remission. For these reasons, 9 out of 10 experts recommend continuing azathioprine throughout pregnancy.22 We do not recommend starting thiopurines for the first time in pregnancy due to the delay in the onset of action, and the risk of pancreatitis, which can be more serious in pregnancy.

Methotrexate

Methotrexate is contraindicated during pregnancy—category X. Methotrexate can remain in the body even after it is stopped. It should therefore be stopped 3‐6 months prior to attempting conception.

Biologics

Infliximab (Remicade®) and adalimumab (Humira®) are category B medications. Both of these medications are antibodies, which are unlikely to cross the placenta in the first trimester, but very eﬃciently cross the placenta in the late second and third trimesters. Two large safety studies have not shown any increased risk of fetal malformations or neonatal complications with infliximab use in pregnancy compared to the general population. Less data is available for adalimumab. However, small case series show that rates of congenital malformations and ad‐ verse pregnancy outcomes are similar in patients treated with adalimumab compared to IBD patients not receiving adalimumab and the general population.

We therefore recommend, that if possible (you are well, with no symptoms of active disease), infliximab and adalimumab be stopped in the late 2nd or early 3rd trimester. However, if there is evidence of ongoing active disease, it may be safer to continue with anti‐TNF medications as active IBD carries risks of adverse pregnancy outcomes.

These decisions can be diﬃcult to make, and must be discussed in detail with you IBD team. Babies exposed to anti‐TNFs during pregnancy should not receive any live vaccines (common ones are measles, mumps, rubella (MMR), rotavirus, varicella zoster), until at least 6 months of age.

Table 2. IBD Medications and Risks During Pregnancy

Drug Class	Example	Safety	Recommendations
Aminosalicylates	Sulfalazine	Low risk	Increase folate supplementation to 2‐5mg per day
	Mesalamine	Low risk	Class B apart from Asacol® (Class C) ‐can consider switching to diﬀerent 5‐ASA
Antibiotics	Metronidazole	Low risk	Safe for short term use
	Amoxicillin‐ Clavulanic acid	Low risk	Safe for short term use
	Ciprofloxacin	Avoid	Should be avoided (Class C)—potential in‐ creased risk of joint problems (arthropathy)
Corticosteroids	Prednisone®, Budesonide®	Low risk	Class C—very small increased risk of oral cleft with 1st trimester use. However, use in treating IBD flare has significant benefits.
Thiopurines	Azathioprine, 6‐mercaptopurine	Low risk	Class D based on animal studies and human studies for treatment of cancer. Studies in IBD patients suggest low risk.
Methotrexate	Infliximab	Contraindicated	Stop 3‐6 months prior to conception
Biological agents	Methotrexate	Low Risk	If possible, last dose in late 2nd or early 3rd trimester. No live vaccines to infants until after 6 months of age.
	Adalimumab	Low Risk	Similar to infliximab

What are the recommendations for breastfeeding and IBD?

In 2009‐2010, 87.3% of Canadian women who had a live birth initiated breastfeeding, and 25.9% of women exclusively breastfed for 6 months. Although one large study found that women with IBD were less likely to breastfeed than women in the general population, a recent study from the University of Manitoba showed similar rates in their IBD patients compared to the general population. Breastfeeding has many benefits for both mother and child, and is recommended as the primary form of nutrition for the first six months by Health Canada, the Canadian Paediatric Society, Dieticians of Canada, and the Breastfeeding Committee for Canada. For example, breast milk can help keep your infant healthy by protecting them from illness and it also promotes optimal brain development. In addition, breastfeeding helps to develop and strengthen the bond between mother and child. Breastfeeding may also decrease the risk of developing IBD later in life. Only certain IBD medications are absolutely contraindicated in breastfeeding (see Table 3).

Table 3. IBD Medications and Recommendations for Breastfeeding

Medication	Recommendation in Breastfeeding
Aminosalicylates	Compatible. Reports of infant diarrhea.
Antibiotics	Metronidazole—not recommended Ciprofloxacin—probably compatible Amoxicillin/clavulanic acid—compatible
Corticosteroids	Compatible
Thiopurines	Low levels found in breast milk (<1% of maternal dose) and majority excreted in first 4 hours after taking medication. Breast feeding probably safe. Can wait 4 hours between taking medication and breastfeeding to be safe.
Methotrexate	Contraindicated
Anti‐TNFs	Limited human data, probably compatible

What else should I do to prepare for pregnancy?

All women who are considering becoming pregnant should:

Avoid alcohol and smoking as they negatively aﬀect infant development.
Proper nutrition is a very important part of a healthy pregnancy.
Follow Eating Well with Canada’s Food Guide.
Take a maternal multivitamin.
Limiting caﬀeine to a maximum of 200 mg per day (about 1 cup of coﬀee).
In addition, for women with IBD, supplementation with 2‐5 mg of folic acid per day both before and during pregnancy is recommended to help prevent neural tube defects.

Your IBD team can provide you with additional nutritional advice for before, during and after pregnancy.

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Handout designed by Sharyle Fowler, MD and Megan Sander, MSc RD, University of Saskatchewan. Reviewed by: Natasha Haskey MSc RD and Jennifer Jones, MD, MSc, University of Saskatchewan. Funding for this project provided by the Interprofessional Health Collaborative of Saskatchewan and the Saskatoon Health Region.