GI in Pregnancy: Inflammatory Bowel Disease in Pregnancy

0:00Welcome to Board Pearls. This is episode five of six of the GI in Pregnancy chapter, in the Special Populations and Acute or Supportive Care module. In this episode we cover inflammatory bowel disease in pregnancy: biologic continuation through delivery as the standard rather than holding biologics in the third trimester, and the FcRn-mediated placental transfer that distinguishes the anti-TNF agents from certolizumab.

0:26Start with the central teaching, because it flips a deeply intuitive instinct. The intuition is that pregnancy is a time to back off immunosuppression, to give the fetus a clean drug environment, to let the disease ride while the patient grows a baby. That instinct is wrong, and the wrongness has been measured. A large prospective registry followed roughly fifteen hundred completed pregnancies in women with IBD on thiopurines, biologics, or combinations of the two. There was no increase in congenital malformations or spontaneous abortion. There was no increase in preterm birth or low birth weight. There was no increase in infant infections. What did predict adverse outcomes was active disease at conception. Active ulcerative colitis at conception doubles the rate of disease activity through pregnancy. Active Crohn disease at conception does the same. Patients in remission at conception flare during pregnancy in about one in seven. Patients with active disease at conception remain active in about one in four.

1:28That gives you the single organizing principle for IBD in pregnancy. The greatest risk to the fetus is active maternal disease, not active maternal medicine. Once that principle is in place, the medication rules stop being a list and start being predictable. Anything that maintained remission is continued. The exceptions are a small set of drugs with mechanism-level fetal toxicity, and you keep those exceptions in mind not by memorizing a list but by understanding why each one is different.

1:57The safe-to-continue group includes mesalamine in oral and topical forms, sulfasalazine, the thiopurines azathioprine and 6-mercaptopurine, corticosteroids, the anti-TNF agents, vedolizumab, and ustekinumab. Sulfasalazine carries one practical adjustment. The sulfa moiety acts as a folate antagonist and sulfasalazine itself inhibits intestinal folate absorption. The folic acid supplementation is bumped to two to three milligrams daily to bring neural tube defect risk back to baseline. The thiopurines have a clean mechanistic story that is worth teaching directly. Azathioprine and 6-mercaptopurine are prodrugs that require hepatic enzymes for activation into the cytotoxic thioguanine nucleotides. The fetal liver lacks those activating enzymes, so even though maternal drug crosses the placenta, the fetus is exposed to inactive parent compound. That is why a category D label and continued safe use can coexist.

2:58Now the molecular detail that the boards return to. Anti-TNF agents are safe to continue through pregnancy, but they are not all the same at the placenta, and the difference is mechanistic. Infliximab, adalimumab, and golimumab are full IgG-class monoclonal antibodies. The neonatal Fc receptor, FcRn, sits on the syncytiotrophoblast and binds the Fc region of IgG at acidic endosomal pH, then transcytoses the antibody across to the fetal circulation. That transport is minimal in the first trimester, accelerates after about week twenty-two, and by term cord blood drug levels can actually exceed maternal levels. Certolizumab pegol is the exception, and the exception is structural. Certolizumab is a PEGylated Fab prime fragment. It does not have an Fc region. FcRn has nothing to bind. Placental transfer is minimal in any trimester. That is the testable distinguishing fact.

3:59The downstream consequence of FcRn transfer matters for two decisions. The first is dose timing near term. For the IgG anti-TNF agents, the last dose is often timed six to ten weeks before expected delivery. Dose schedules drift out to roughly week thirty-two through thirty-eight. Birth then happens at presumed drug trough to lower cord blood concentration. Note what this is not. It is not stopping the biologic in the third trimester. The drug is continued through pregnancy. Only the spacing of the final dose is shifted. The biologic is resumed twenty-four hours after vaginal delivery and forty-eight hours after cesarean if there is no infection. For certolizumab, none of this dose-spacing logic applies because placental transfer is already minimal.

4:47The second consequence is infant live virus vaccination. Infants exposed in utero to IgG anti-TNF carry detectable maternal drug for months after birth. A live attenuated vaccine in that window could in principle produce vaccine-strain disease. The board-relevant vaccine is rotavirus, given at two months. The conservative approach has been to delay live virus vaccination through the first six to twelve months in infants exposed to IgG biologics. That includes infliximab, adalimumab, golimumab, vedolizumab, and ustekinumab. The 2025 global IBD pregnancy consensus has loosened this and now permits rotavirus vaccine in infants of mothers on anti-TNF, IL-23 inhibitor, or vedolizumab based on accumulating safety data. Certolizumab-exposed infants were never restricted because there is no maternal drug in the infant to interact with. MMR and varicella at age one are safe across the board because by then any residual maternal antibody is negligible.

5:53Now the small set of drugs that are not safe, and each carries a mechanism-level reason. Methotrexate is absolutely contraindicated. It inhibits dihydrofolate reductase, which arrests DNA synthesis in rapidly dividing tissue. The fetus is the most rapidly dividing tissue in the maternal compartment. Methotrexate is teratogenic and abortifacient and is stopped at least three to six months before conception to allow elimination and tissue washout. Tofacitinib and the other JAK inhibitors like upadacitinib are avoided because broad cytokine signaling inhibition during organogenesis raises theoretical concern about fetal immunologic and hematopoietic development. Human data are too limited to argue against the concern. Ozanimod, a sphingosine-1-phosphate modulator, is avoided on similar caution. Thalidomide is teratogenic by long-established history. Rifaximin is avoided in pregnancy.

6:47Disease activity assessment in pregnancy carries its own pregnancy-specific logic. CRP is unreliable because it rises physiologically with pregnancy, so an elevated CRP cannot be cleanly attributed to a flare. Fecal calprotectin is reliable as a non-invasive activity marker and does not shift with pregnancy. Clostridioides difficile is more common in pregnant IBD patients than non-pregnant ones, and the symptoms overlap with an IBD flare, so a stool test for C. difficile gets sent whenever a flare presentation comes through the door. Imaging follows the chapter's general framework. Ultrasound is safe. MR enterography is preferred over CT enterography, without gadolinium. Flexible sigmoidoscopy without sedation is safe through pregnancy. Full colonoscopy with anesthesia and fetal monitoring is reserved for indications that cannot wait until postpartum, ideally timed to the second trimester.

7:43Two more practical pieces close the IBD section. Mesalamine, thiopurines, and biologic monoclonal antibodies are compatible with breastfeeding because the large molecules transfer minimally into breast milk and what does transfer is degraded by infant gut acid and proteolysis. Tofacitinib and methotrexate are not used during breastfeeding because small molecules cross into milk readily and reach the infant systemically. Postpartum venous thromboembolism prophylaxis matters because pregnancy and IBD are each independently prothrombotic and the puerperium is the peak-risk window. Low-dose aspirin from week eleven is recommended in IBD pregnancy under the 2025 global consensus to lower preeclampsia risk. Vaginal delivery is generally appropriate. Cesarean delivery is reserved for active perianal disease or rectovaginal fistula, where sphincter or fissure trauma would be unacceptable.

8:38So the way to hold IBD in pregnancy is this. Treat active disease as the danger, not the treatment, which is why biologic therapy is continued through delivery rather than held in the third trimester. Continue what worked. Know the structural reason certolizumab is different at the placenta, a Fab fragment with no Fc region for FcRn to bind, and the consequence that follows for dose-spacing near term and for infant vaccine timing. Recognize that CRP cannot do the work it does in non-pregnant patients and lean on calprotectin instead. And send the C. diff stool when the picture looks like a flare.

9:14The next episode takes the other two luminal problems of pregnancy, both governed by anatomy and timing: post-bariatric pregnancy with the internal hernia that defines right upper quadrant pain after gastric bypass, and cholelithiasis with the second-trimester surgical window and the radiation-minimization stack for ERCP.

9:34For the full chapter, the practice vignettes, and the topic-tagged question bank, head to board pearls dot com. You'll find the rest of the series on Apple Podcasts, Spotify, or wherever you listen to podcasts. That brings us to the end of episode five of six of chapter thirty five, and I'll see you in the next one.