When treating patients with inflammatory bowel disease (IBD) who may want to become pregnant, Marla Dubinsky, MD, stressed that “disease control is paramount,” during her presentation on June 11 at the Advances in Inflammatory Bowel Disease Regionals meeting in Boston, Massachusetts.

Dr Dubinksy is a professor of pediatrics and medicine at Icahn School of Medicine, chief of the division of pediatric GI and nutrition, director of the Barry and Marie Lipman IBD Preconception and Pregnancy Clinic, and codirector of the Susan and Leonard Feinstein IBD Clinical Center at Mount Sinai Kravis Children’s Hospital and Icahn School of Medicine at Mount Sinai, in New York, New York.

Because there are many common misconceptions and much misinformation surrounding IBD and pregnancy, Dr Dubinsky pointed out that patients may think that IBD medications are harmful to the baby and will therefore attempt to put up with their symptoms while pregnant. The most common pregnancy-related fears for patients with IBD were that the IBD or the IBD medication would harm the baby, the parent would pass IBD on to the baby, IBD could cause pregnancy complications, and they would be unable to care for the baby because of their IBD. The most common reason for not breastfeeding among women with IBD receiving immunomodulators, biologics, and combination therapies was out of a concern about exposing the baby to the medication.

Evidence has shown, however, that counseling from health care providers about fertility, pregnancy, and lactation was positively associated with the highest number of pregnancies and was inversely associated with the lowest number of patients considering voluntary childlessness, Dr Dubinsky stated. “Education from providers can help debunk patient fears about IBD and pregnancy,” she said.

The American Gastroenterological Association (AGA) Institute Guideline on IBD provides a Pregnancy Clinical Decision Support Tool offering guidance preconception, through the 9 months of pregnancy, into delivery and postpartum.

There is a higher proportion of voluntary childlessness in patients with IBD than in the general population. While there is no data to suggest that IBD medications affect female fertility, Dr Dubinsky stated that “active disease is associated with reduced fertility.” Impacts on fertility can also differ depending on disease state. For patients with ulcerative colitis (UC), fertility was similar to age-matched control, but surgical history could impact fertility. In Crohn disease (CD), there may be decreased fertility because of lower anti-Müllerian hormone levels. Surgical history and chronic pelvic inflammation can impact fertility, while surgery for CD can also cause a delay to pregnancy.

"We can change involuntary childlessness and take whole levels of fears and phobias and alleviate them in 1 hour," Dr Dubinsky said. "That is the joy of these conversations." 

Dr Dubinsky stated that when it comes to reduced fertility in IBD overall, though, “age is still the number 1 factor.” In a retrospective cohort comparing women with IBD ages 15-44 and age-matched controls, once the fertility rates were adjusted for periods on contraceptives, the difference was no longer significant. Dr Dubinsky pointed out that the “voluntary component” must be considered.

Uncontrolled disease during pregnancy can potentially lead to preterm birth, low birth weight, and preterm and infant infection. Despite these complications, many health care providers recommend the discontinuation of therapy before pregnancy. In a survey of different specialists, more than half of dermatologists, OB/GYNs, and primary care providers responded that they would recommendation discontinuation of a tumor necrosis factor inhibitor treatment before pregnancy. For gastroenterologists, the percentage was 36% and rheumatologists, 46%. There is also data showing that the further patients with IBD progressed into their pregnancies, the more likely they were to stop their biologic.

Dr Dubinsky stated that there was no impact of drug exposures on developmental milestones. A recent study found that there was no difference in developmental milestones (as defined by the Ages and Stages Questionnaire) for babies that had been exposed to biologics, thiopurines, or combination therapy when compared to unexposed babies.

Dr Dubinsky added, however, that novel small molecule agents may affect pregnancies. Janus kinase (JAK) inhibitors may cause fetal harm (based on animal studies at doses higher than human dose) and breast feeding is not recommended. However, clinical trials for tofacitinib did not show any increase in the rates of miscarriage or congenital anomaly and the half-life of JAK inhibitors is short. When considering sphingosine-1-phosphate (S1P) modulators, the receptor that ozanimod affects has been demonstrated to be important in the role of embryogenesis. Breastfeeding on S1P modulators is not recommended and, because of these agents’ longer half-life, women of childbearing age should continue to use contraception for 3 months after stopping treatment.

For patients with IBD who are pregnant, there is a decision algorithm to help determine the best mode of delivery (cesarean or vaginal) based on history of rectovaginal fistula, presence of perineal disease, and history of ileal pouch-anal anastomosis (IPAA). This tool also provides suggestions for modes of postpartum venous thromboembolism prophylaxis.

There is increasing evidence that daily 81-mg aspirin can reduce the risk of preeclampsia among patients over 35 with IBD by 40%.

While validation of current findings is needed and ongoing, Dr. Dubinsky reported a recent study found there is no impact from biologic therapy on wound healing after C-section among patients with IBD. In this study, 70% of C-section patients had been exposed to biologics. Exposure to biologics in the peripartum period did not adversely affect wound healing post-C-section, even when the agent was given within 24-72 hours of delivery. While vaginal tears were common, these wound outcomes were not impacted by biologics. However, Crohn internal penetrating disease was associated with wound infection.

The AGA IBD Parenthood Project Working Group recommends that patients not breastfeed when taking methotrexate or tofacitinib. For patients taking 5-aminosalicylic acids, mesalamine, balsalazide, and olsalasine are preferred to sulfasalazine. Biologics have no indication of harm from breastfeeding. The recommendations also note that “pumping and dumping” is discouraged as it is not likely to be effective for most IBD drugs.

For the newborn baby, vaccines should be given on schedule, although any baby exposed to a biologic during the third trimester should not receive live vaccines in the first 6 months; this would only affect the rotavirus vaccine. Babies who are breastfed by mothers taking biologics can still be given the live vaccines indicated at 1 year (measles, mumps, rubella, and varicella).

Dr Dubinsky also stressed the importance of pregnant individuals being included in the development and deployment of COVID-19 vaccines, as there has been documented vertical transmission of COVID-19 to the fetus, and placental injury from COVID-19 could lead to stillbirth and poor neonatal outcomes.

Counseling and education for patients with IBD who may want to get pregnant is key, Dr Dubinsky concluded. Providers should ask what patients already know, what their fears are, and what their sexual health is like. In this counseling, the need for disease control before and during pregnancy for the safety of the patient and the baby should be emphasized. All women of childbearing age should be referred for maternal fetal medicine (MFM) early. If the only way to control the patient’s disease is surgery, then the surgery should be done. However, for patients with UC, it may be beneficial to wait to undergo IPAA until after childbearing years. Dr Dubinsky also added that the threshold for referral to assisted reproduction therapy is lower for patients with IBD than the general population.

"The bottom line is that uncontrolled inflammation is the biggest factor and you can only have this conversation in the preconception phase," Dr Dubinsky said. "The risk of miscarriage is much higher when disease is not under control."

—Allison Casey

Reference:

Dubinsky M. Considerations in managing IBD in pregnancy. Presented at: Advances in Inflammatory Bowel Disease Regionals; June 11, 2022. Boston, MA.