The management of inflammatory bowel disease in pregnancy

Pregnancy

Coordinated care

A complete team of specialists with coordinated care among all providers is needed for optimal maternal and fetal outcomes.^23,24 A gastroenterologist, ideally an IBD specialist, should follow the patient throughout pregnancy, seeing the patient at least once during the first or second trimester and as needed during pregnancy.¹⁶ A high-risk obstetrician or maternal-fetal medicine specialist should be involved early in pregnancy, as well. Open communication among all disciplines ensures that a common message is conveyed to the patient.^16,24 A nutritionist, mental health provider, and lactation specialist knowledgeable about IBD drugs may be of assistance, as well.¹⁶

Disease activity

While women with IBD are at increased risk of spontaneous abortion, preterm birth, and labor complications, this risk is mitigated by controlling disease activity.²⁵ The risk of preterm birth, small-for-gestational-age birth, and delivery via C-section is much higher in women with moderate-to-high disease activity, compared with those with low disease activity.²⁶ The presence of active perianal disease mandates C-section over vaginal delivery. Fourth-degree lacerations following vaginal delivery are most common among those patients with perianal disease.^26,27 Stillbirths were shown to be increased only in those with active IBD when compared with non-IBD comparators and inactive IBD.^28-31;11

Noninvasive methods for disease monitoring are preferred in pregnancy, but serum markers such as erythrocyte sedimentation rate and C-reactive protein may not be reliable in the pregnant patient (Figure).³² Fecal calprotectin does rise in correlation with disease activity, but exact thresholds have not been validated in pregnancy.^33,34

An unsedated, unprepped flexible sigmoidoscopy can be safely performed throughout pregnancy.³⁵ When there is a strong indication, a complete colonoscopy can be performed in the pregnant patient as well.³⁶ Current American Society for Gastrointestinal Endoscopy (ASGE) guidelines suggest placing the patient in the left lateral tilt position to avoid decreased maternal and placental perfusion via compression of the aorta or inferior vena cava and performing endoscopy during the second trimester, although trimester-specific timing is not always feasible by indication.³⁷
 

Medication use and safety

IBD medications are a priority topic of concern among pregnant patients or those considering conception.³⁸ Comprehensive data from the PIANO (Pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes) registry has shown that most IBD drugs do not result in adverse pregnancy outcomes and should be continued.³⁹ The use of biologics and thiopurines, either in combination or alone, is not related to an increased risk of congenital malformations, spontaneous abortion, preterm birth, low birth weight, or infections during the child’s first year of life.^7,39 Developmental milestones also remain unaffected.³⁹ Here, we will discuss safety considerations during pregnancy (see Table).

5-aminosalycylic acid. 5-aminosalicylic acid (5-ASA) agents are generally low risk during pregnancy and should be continued.^40-41 Sulfasalazine does interfere with folate metabolism, but by increasing folic acid supplementation to 2 grams per day, sulfasalazine can be continued throughout pregnancy, as well.⁴²

Corticosteroids. Intrapartum corticosteroid use is associated with an increased risk of gestational diabetes and adrenal insufficiency when used long term.^43-45 Short-term use may, however, be necessary to control an acute flare. The lowest dose for the shortest duration possible is recommended. Because of its high first-pass metabolism, budesonide is considered low risk in pregnancy.

Methotrexate. Methotrexate needs to be stopped at least 3 months prior to conception and should be avoided throughout pregnancy. Use during pregnancy can result in spontaneous abortions, as well as embryotoxicity.⁴⁶

Thiopurines (6-mercaptopurine and azathioprine). Patients who are taking thiopurines prior to conception to maintain remission can continue to do so. Data on thiopurines from the PIANO registry has shown no increase in spontaneous abortions, congenital malformations, low birth weight, preterm birth, rates of infection in the child, or developmental delays.^47-51

Calcineurin inhibitors (cyclosporine and tacrolimus). Calcineurin inhibitors are reserved for the management of acute severe UC. Safety data on calcineurin inhibitors is conflicting, and there is not enough information at this time to identify risk during pregnancy. Cyclosporine can be used for salvage therapy if absolutely needed, and there are case reports of its successful using during pregnancy.^16,52

Biologic therapies. With the exception of certolizumab, all of the currently used biologics are actively transported across the placenta.^39,53,54 Intrapartum use of biologic therapies does not worsen pregnancy or neonatal outcomes, including the risk for intensive care unit admission, infections, and developmental milestones.^39,47

While drug concentrations may vary slightly during pregnancy, these changes are not substantial enough to warrant more frequent monitoring or dose adjustments, and prepregnancy weight should be used for dosing.^55,56

Antitumor necrosis factor agents used in IBD include infliximab, adalimumab, certolizumab, and golimumab.⁵⁷ All are low risk for pregnant patients and their offspring. Dosage timings can be adjusted, but not stopped, to minimize exposure to the child; however, it cannot be adjusted for certolizumab pegol because of its lack of placental transfer.^58-59

Natalizumab and vedolizumab are integrin receptor antagonists and are also low risk in pregnancy.^57;60-62;39

Ustekinumab, an interleukin-12/23 antagonist, can be found in infant serum and cord blood, as well. Health outcomes are similar in the exposed mother and child, however, compared with those of the general population.^39;63-64

Small molecule drugs. Unlike monoclonal antibodies, which do not cross the placenta in large amounts until early in the second trimester, small molecules can cross in the first trimester during the critical period of organogenesis.

The two small molecule agents currently approved for use in UC are tofacitinib, a janus kinase inhibitor, and ozanimod, a sphingosine-1-phosphate receptor agonist.^65-66 Further data are still needed to make recommendations on the use of tofacitinib and ozanimod in pregnancy. At this time, we recommend weighing the risks (unknown risk to human pregnancy) vs. benefits (controlled disease activity with clear risk of harm to mother and baby from flare) in the individual patient before counseling on use in pregnancy.