Pregnancy Risks with your IBD Treatment

Many female patients with Inflammatory Bowel Disease (IBD) such as Crohn’s or ulcerative colitis who are thinking of conceiving are concerned about the potential effects of IBD medications on pregnancy. Most IBD medications are safe to use during pregnancy, but there are a few exceptions—make sure you’re aware of any potential pregnancy risks of your IBD treatment.

Pregnancy and IBD Medications Research

Research shows that female patients with Crohn’s or ulcerative colitis do, in general, run a greater risk of negative pregnancy outcomes than their peers without IBD. However, it’s thought that the risk of negative outcomes is not directly caused by IBD medications taken during pregnancy but rather the activity of the disease itself.

While most IBD medications are considered safe for both the mother and the fetus during pregnancy, a few are not.
Below, learn about any pregnancy risks from IBD medications so you can feel confident about using IBD medications during pregnancy without fear of negatively affecting your health or your child’s early development.

The information in this article is drawn from two comprehensive reviews on IBD medications and pregnancy, published in 2015 in the Journal of Crohn's and Colitis and Gastroenterology & Hepatology. Research in this area is ongoing, with the need for more studies examining the long-term effects of IBD medications on offspring after they are born. It’s important for women with IBD who are preparing for pregnancy to remain up-to-date with the latest findings and to speak with their gastroenterologist about their maternal health on an individual basis.

Aminosalicylates and pregnancy

Aminosalicylates were one of the first medications to be used to treat IBD, and there is little debate about their safety for use during pregnancy due to their prolonged use and numerous studies demonstrating their safety during pregnancy. Also worth noting is that women with IBD who are on aminosalicylates already tend to have milder disease symptoms that raise less concern about the effects of the disease and medications on the pregnancy.

This category includes mesalamine, sulfasalazine, and balsalazide. Specifically, sulfasalazine is known to cross the placenta but does not disturb the development of the fetus. Likewise, mesalamine has been observed in the cord blood but is considered low risk in terms of fertility, pregnancy, and lactation.
Thiopurines and pregnancy

Thiopurines are immunomodulators. In IBD, common thiopurines include the drugs 6-mercaptopurine (also called 6-MP or brand name Purinethol) and azathioprine (also called AZA or brand name Imuran).

Previously, there have been concerns about Imuran and Purinethol pregnancy risks, but these largely originated during a time when thiopurines were administered in large doses to treat leukemia, not as they are used today for IBD.
Today, there is less concern about the pregnancy risks of thiopurines, and it is limited to cases where thiopurines have been used for a long time to treat patients with severe activity of IBD. While it’s true that smaller studies that have observed a high incidence of babies born with anaemia to mothers taking thiopurines, these findings have not been replicated in large-scale studies.

The majority of newer studies on thiopurines and pregnancy in IBD show that thiopurines to not increase the risk of negative outcomes such as congenital abnormalities, preterm births, miscarriages, intrauterine growth retardation, or c-sections. Negative outcomes such as these may still occur, but researchers have found that these are more likely a result of disease type or activity and not of the thiopurine treatment. In the breast milk, thiopurine levels are negligible. Likewise, recent analysis of all available studies has also concluded that thiopurine use by fathers at the time of conception is safe. In terms of child development, studies on children exposed to immunomodulators observed no developmental delays in children up to 4 years old.
Methotrexate and pregnancy

Like thiopurines, methotrexate is an immunomodulator. However, methotrexate, as a category X drug in pregnancy, is one of the two IBD medications that poses an extremely high risk of multiple congenital abnormalities in fetuses.

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Women with IBD who are taking methotrexate should discontinue use at least 6 months prior to conception (and men at least 3 months prior) as the drug persists for a long time in the tissues of the body before being fully eliminated. Likewise, methotrexate is contraindicated during breastfeeding.

Cyclosporine and pregnancy

Along with methotrexate, cyclosporine is contraindicated, especially in breastfeeding mothers.

Results from studies on congenital abnormalities are inconclusive—findings suggest that cyclosporine use during pregnancy may increase the risk of preterm births, but the study that found this correlation also found it to be statistically insignificant.

Cyclosporine (an immunomodulator) is known to be unsafe during the lactation period. It is a known teratogen and is passed to the child through breast milk in high concentrations; mothers taking cyclosporine should look for alternatives during the lactation phase.

Thalidomide and pregnancy

Like cyclosporine, thalidomide in an immunomodulator and is contraindicated during breastfeeding. It is a known teratogen and is passed to the child through breast milk in high concentrations; mothers taking thalidomide should look for alternatives during the lactation phase.

Biologics and pregnancy

Biologics include anti-TNF drugs such as infliximab (Remicade), adalimumab (Humira), certolizumab pegol (Cimzia), and golimumab (Simponi) and anti-integrins such as natalizumab (Tysabri) and vedolizumab (Entyvio).

The anti-TNF biologics are considered category B drugs, and studies have shown that they do not increase the risk of complications in pregnancy. Specifically, infliximab, adalimumab, and certolizumab pegol show no increased risk for negative outcomes, neither during pregnancy nor immediately after birth. In fact, the use of anti-TNF medications is associated with fewer complications, which could be attributed to the maintenance of remission in pregnant women who continue with their anti-TNF treatments.

In lactation studies, concentrations of most anti-TNFs are undetectable in breastmilk. Infliximab (Remicade) breastmilk levels are negligible.
Anti-integrin pregnancy effects are not as comprehensively studied as anti-TNFs, but available data indicates that they, like the other biologics, are safe during pregnancy.

Antibiotics and pregnancy

Various antibiotics are used to treat complications of IBD (pouchitis, abscesses, etc.). Most antibiotics are considered category B or C medications in pregnancy and have been used and studied for a long time. They are all considered relatively low risk, with the drugs of choice during pregnancy being penicillins and cephalosporins. Below, find a summary of common IBD antibiotics and pregnancy risk research.

Metronidazole and pregnancy

Short-term use (less than a week) is safe in pregnancy. One study did find a mid increase in cleft lip in children of patients taking metronidazole, but recent analysis have not found any birth defects linked to metronidazole.

Ciprofloxacin and pregnancy

In some studies, Ciprofloxacin has been associated with arthropathies (joint disease) in children. However, a review of available data on ciprofloxacin pregnancy risks concluded that ciprofloxacin is unlikely to be teratogenic (causing disruptions in fetal development).

Rifaximin and pregnancy

Rifaximin (brand names Xifaxan or Salix) is used for IBD but is not well-studied. It is labeled as a category C medication in pregnancy.

Amoxicillin/Clavulanate and pregnancy

As a category B drug, Amoxicillin/clavulanate (brand name Augmentin) is sometimes prescribed as a more desirable alternative to ciprofloxacin during pregnancy and has shown no teratogenic effects.

Fluoroquinolones and pregnancy

Previously there were concerns about the effects of fluoroquinolones on bone and cartilage development, but recent studies have observed no link between congenital abnormalities and fluoroquinolones. Fluoroquinolones is a category C drug and its use is somewhat restricted during pregnancy.

Corticosteroids and pregnancy

Studies on corticosteroid pregnancy risks have produced conflicting results. Most often, corticosteroids are used for short periods of time for treating flares, and therefore the use and impact of corticosteroids during pregnancy is case-dependent and left to the discretion of the physician and patient.

Corticosteroids are considered category C drugs during pregnancy and are generally regarded as safe. Some studies have observed a link between corticosteroid use during pregnancy and cleft palate in offspring, but a large study that followed almost 1000 women who had used corticosteroids during pregnancy resulted in no higher risk for congenital abnormalities.

References
Hashash, J. G., & Kane, S. (2015). Pregnancy and Inflammatory Bowel Disease. Gastroenterology & Hepatology, 11(2), 96–102. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4836574/ ‘
Oriana M. Damas, Amar R. Deshpande, Danny J. Avalos, Maria T. Abreu; Treating Inflammatory Bowel Disease in Pregnancy: The Issues We Face Today, Journal of Crohn's and Colitis, Volume 9, Issue 10, 1 October 2015, Pages 928–936, https://doi.org/10.1093/ecco-jcc/jjv118