Neha Pathak, MD, FACP, DipABLM: Welcome to the WebMD Health Discovered Podcast. I'm Dr Neha Pathak, WebMD's Chief Physician Editor for Health and Lifestyle Medicine. Today we're going to discuss a longstanding treatment challenge within the healthcare system: managing inflammatory bowel disease, or IBD, which most commonly includes Crohn's disease and ulcerative colitis, while also preparing for or being pregnant.

If you're pregnant or hoping to be and living with IBD, you probably have a million questions, including: What should I do to prepare for pregnancy? Is my pregnancy high risk just because I have IBD? Can I safely stay on my medications? Will it be safe to breastfeed my child after pregnancy? If you've asked yourself any of these questions or had concerns about pregnancy, you are not alone.

The goal of this episode is to dispel myths and misconceptions around IBD and pregnancy and to help you be informed, supported, and safe in your family-planning journey. Today we'll cover what matters most: why disease remission before and during pregnancy is one of the most important predictors for healthy outcomes. We'll also talk about which IBD therapies are considered low risk to continue and which aren't, how to think about high-risk OB care and delivery planning, and what breastfeeding safety really looks like with modern treatments.

First, let me introduce my guest, Dr Uma Mahadevan. Dr Mahadevan is a gastroenterologist and Director of the UCSF Colitis and Crohn's Disease Center. She's one of the world's leading experts on inflammatory bowel disease, particularly as it relates to pregnancy and fertility. And she recently led an international team to develop the first global consensus guidelines on managing IBD in pregnancy. Welcome to the WebMD Health Discovered Podcast, Dr Mahadevan.

Uma Mahadevan, MD: Thank you for having me on. Delighted to be here.

Pathak: Well, I am very excited for this conversation — one, because my husband is a gastroenterologist, so as soon as I saw your consensus guidelines, I forwarded them to him and said, “Hey, have you seen this?” So that was exciting. But I think it really speaks to a need that we have in medicine, particularly around the care of pregnant patients.

Before we jump into all of my questions around that work, I'd love to start by asking: What's been your most meaningful health discovery recently? Something you've learned from your research or your patients that has changed how you think about care.

Mahadevan: There are so many things that go into the care of the pregnant patient, and I think my biggest discovery from this population is how much fear and how much unsolicited advice they're exposed to. When you have a patient who's considering pregnancy, is pregnant, or even is a young mom, everybody — from the mother-in-law to the manicurist to the person at the grocery store — has something to say and is very adamant about it.

And there's a lot of guilt in the moms. So if you don't get in there first and have a plan and give them the data so that they're comfortable, a lot of their reactions are very fear- and society-, or societal pressure–based.

Pathak: I definitely want to dig into that more because mom guilt is real for so many of us. But to start more broadly, can you help us understand how common IBD — so that's ulcerative colitis and Crohn's disease — is among women, particularly among women of childbearing age?

Mahadevan: In the United States, there are about 3 million people with inflammatory bowel disease. Of those, half are women, and most of them will be diagnosed during their childbearing years or will carry the diagnosis during their childbearing years if they were diagnosed in childhood. So for pretty much every patient with inflammatory bowel disease, the potential for conception is there and something they need to consider.

Pathak: And have you seen any change in this prevalence over the course of your career?

Mahadevan: Yes. In the United States, it's fairly stable. There’s definitely more prevalence now because people who are diagnosed live longer with it. But where we're really seeing a dramatic change is around the world. When I started in inflammatory bowel disease 20 years ago, this was really considered a disease of Western populations — so the U.S., Canada, Australia, Western Europe.

Now we have inflammatory bowel disease clinics in Bangalore, China, and Taiwan, and that is where the biggest change has been — that this is now a global disease.

Pathak: When we kicked off our discussion, you mentioned that there are a lot of myths and misconceptions that you have to address in your practice, particularly with pregnant women. Can you share some of those common fears or misconceptions that you find yourself addressing again and again?

Mahadevan: The first thing is that they believe they cannot get pregnant or should not get pregnant. Data from about 20 years ago looked at surveys, and many women said that their doctor told them they should not get pregnant if they have IBD — and that certainly is not correct.

The second misconception is that the safest thing for the pregnancy is for them to be off all medications. That goes back to societal pressure, but it also goes back to fear in the medical profession, because we as gastroenterologists are afraid of pregnancy. Whatever profession you are within medicine, people are afraid of harming the fetus.

However, in IBD, the biggest risk to the fetus is inflammation in the mother. So if you stop the medicine, the mother’s inflamed — she’s less likely to get pregnant, more likely to miscarry, and more likely to have preterm birth and other complications. So when people talk about the medication, they often don’t balance it by talking about the risk of the disease itself.

Pathak: Thinking about the patient who’s pregnant or considering pregnancy, I’d love for you to tell her, her family members, and others: What are some of the key questions she should bring into the office setting to ensure that she has those questions answered — so that the mom guilt around all of the other information she hears from others can be put to rest a little bit?

Mahadevan: She should ask: What is my disease status? Meaning, am I in remission? How are we confirming it? Because symptoms aren’t enough. Do you need a colonoscopy, an intestinal ultrasound, or a calprotectin test?

She should be asking: Are the medications I’m on compatible with use in pregnancy and lactation? And if not, what changes do I need to make?

She should be asking for a high-risk OB referral from her OB or her gastroenterologist.

And then she should also talk about mode of delivery. Most women with IBD can have vaginal delivery. The exceptions are if they have active perianal fistulas or disease at the time of delivery, or if they have a current or past rectovaginal fistula — because those are so hard to close.

And then they would discuss, if they had an ileoanal J-pouch, that in our center we tend to do more C-sections.

Finally, if they've had a lot of complications, they should be asking: Where should I deliver? Because, you know, in California, if you're north of Lake Tahoe in a small community hospital but have complex IBD with a lot of surgeries, we'd rather bring you in and induce here than take our chances in a small community hospital without the resources you may need.

Pathak: I think those are really helpful questions to really get that personalized shared decision-making that we're hoping for with this guidance. In order to address this major gap in care for pregnant women, you just led the development of this first global guidance for managing IBD in pregnancy. Can you tell us a little bit about which gaps you were hoping to fill, and how do you feel about the fact that this guideline is now out there?

Mahadevan: I'm so excited it's out there, 'cause it was like a year of my life between getting the consensus done, writing it, doing the revisions, getting it out there. So a lot of physicians around the world got together to put this out.
In pregnancy, you have nine months to get it right, and so there's less room for mistakes. What we were seeing is that people would look at the same data and view it through the lens of fear — again, that concern about hurting the fetus without really balancing the health of the mother. And so we wanted to have one universal guideline so that there wasn’t confusion for both the patient and the provider.

So now let's dig into some of the guidance. We know that pregnancy — and having an optimal pregnancy — really starts in the planning for the pregnancy, so the preconception counseling. Can you help us understand some of the recommendations for women who are planning to conceive? How long should they be in remission with regard to their IBD journey?

Pathak: Can you talk a little bit about that preconception counseling phase?

Mahadevan: Sure. One thing I always bring up with my patients is: are you planning on pregnancy soon? If not, definitely, let's talk about it beforehand. But this medicine “X” that I'm putting you on is or is not safe in pregnancy. So in one sentence, plant the seed early. Then the ideal patient is someone who comes to you and says, “I am ready to start family planning.”
We look at their medications, make sure they're optimized, make sure they're not on something that they shouldn’t be, and then we check to make sure they're in remission. Confirm that. They go on to pregnancy where they're monitored from the beginning, they see a high-risk obstetrician, etc. It doesn’t always work out that way.
We can’t achieve full remission in every single patient — there’s a lot of complexity — but that is the ideal. When we look at medications: mesalamine, five-ASAs, mercaptopurine, azathioprine, all the biologics — these are considered low risk in pregnancy and can be continued throughout pregnancy.
Methotrexate is a known abortifacient and teratogen and should be stopped at least one month prior to attempting to conceive. The S1Ps, ozanimod and etrasimod, should be avoided in pregnancy. Usually with that drug, there are other options you can switch them to, so that’s okay.
The JAK inhibitors, tofacitinib and upadacitinib, are a lot more challenging. Animal studies for tofacitinib showed birth defects at supratherapeutic doses — much higher than what we use in humans. For upadacitinib, the birth defects were seen at the 30-milligram and 45-milligram dose equivalents, which is what we use in humans, so that’s more concerning.
However, if you're on upadacitinib, chances are you didn’t respond to anti-TNF, and you've tried other medications, and this is the one thing that’s keeping you going. So if you don’t have another option, what do we do? For that particular population, we talk about surrogacy, we talk about trying to switch the medicine and seeing what happens — understanding there may be a risk of colectomy — or continuing it if there’s no other option for maternal health.
And so that is the shared decision-making that goes into that agent.

Pathak: Just listening to you — and I hope anyone listening to our conversation recognizes — this is a complex decision and a complex conversation that needs to happen with your gastroenterologist and your medical team. The amazing thing about this consensus is that now you're all sort of working with the same framework and the same foundation.

Mahadevan: Correct.

Pathak: I’d love to also talk a little bit about how the report highlights that we really need to be thinking about women with IBD who are entering pregnancy as following with a care team that considers their pregnancy a high-risk pregnancy — even though many of these women are young and otherwise healthy. That was something I took away from the recommendations. But there were other novel things, like low-dose aspirin during pregnancy to reduce preterm preeclampsia risk. So can you talk a little bit about some of these other pieces?

Mahadevan: Sure. Some of the key things that came out of the consensus, as you already noted, were the need for preconception counseling, which is ideal, and the idea of being followed as high risk. One of the things about having a global consensus is understanding that resources vary around the world — and even around the United States.
So for us in San Francisco, we’ll say, “Okay, we’re going to refer you to a maternal-fetal medicine specialist,” which is an OB who’s done additional training in high-risk patients. They get additional monitoring and are followed more closely. So all my IBD patients are followed as high risk.
It’s a hard sell sometimes because you see this 27-year-old who’s otherwise healthy and looks great, but statistically they have a higher rate of preeclampsia and other complications. We’ve had patients have very bad outcomes when they weren’t followed closely. In resource-limited areas, that may just mean you see the OB instead of the midwife — or if it’s only a midwife, they’re trained on what high-risk monitoring for this patient population looks like. But they need closer care.

The idea of baby aspirin comes from the ASPRE study (A-S-P-R-E), which was in The New England Journal of Medicine and is out of Australia. They looked at patients who were at risk for preterm preeclampsia and started them on aspirin, 150 milligrams daily, beginning around week 12 to 16 of pregnancy, and continued it throughout pregnancy. They found that those patients had a lower risk of preeclampsia.
Patients with IBD, particularly if they have active disease, have a higher risk of preterm preeclampsia and therefore qualify. Our center and Mount Sinai have shown that being on baby aspirin during pregnancy did not increase the risk of flare, so that’s reassuring. Women should take it with food, but they can continue it through week 12 through at least week 36.

That’s the second thing. The third thing: continue your biologic throughout pregnancy without any breaks. And that’s new, because we used to do all of these contortions to try to stop at eight weeks, which led to a lot of flares and bad outcomes. So now we just continue it. If you’re due for your dose the day you deliver, maybe you want to wait until afterward, but otherwise just continue it on schedule.

And then finally, the vaccines. This was a big one. In Canada, they had a prospective study where they took infants exposed to biologics, measured their immune function, and found it was normal. They gave them the live rotavirus vaccine — and they all did fine. So within the first six months, you can get all your vaccines on schedule. In the U.S., outside the U.S., oral polio should be avoided in the first six months. We don’t use that here. BCG, which is a TB vaccine, should also be avoided in the first six months. 

Pathak: What did you learn about infant outcomes? Anything around infections, growth, or developmental milestones after in utero exposure to the low-risk IBD medications?

Mahadevan: So that's a great question. When we started the PIANO registry in 2007, it was really about birth defects. And we looked in that first year of life, and then we said, well, what happens after that? What happens at four years? What happens at 18 years? So we've been following these children out.

Exposure to a biologic — so monoclonal antibody — and most of the data's in anti-TNF because they're the oldest. But we also have IL-23 data and vedolizumab data. No increased risk of infection in the first year of life, and beyond that, no increased risk of lymphoma or other malignancies. No increased risk of autism or neurodegenerative disorders. No impact on developmental milestones.

What was interesting is there was a signal — and I always laugh about this — but when you use the Ages and Stages, which is a validated questionnaire for development, if you take your child to the pediatrician, they ask you, “Can they turn their head? Can they catch a ball?” So we used that. When we found that compared to the national average, patients in the PIANO study had a higher achievement of developmental milestones with anti-TNFs in every category.

And you can argue, well, higher socioeconomic status — because they're insured, they're in an IBD center, et cetera. But even within PIANO, the anti-TNF babies did better than the thiopurine babies. And it's not to say that the anti-TNFs make your kids smarter, but reducing inflammation in pregnancy improves neural pathway development and achievement in milestones.

Pathak: Can you give us a little bit more of a high-level statement around what you found with breastfeeding?

Mahadevan: Yes, and so here again, we use the science of breast milk transfer, and there is a ratio called the relative infant dose, which is the amount of drug in the infant serum versus the mother. Anything less than 10% in theory is considered acceptable. Again, here we have the FCRN receptor, so if the mother's on a monoclonal antibody — infliximab, ustekinumab, et cetera — 100% in the mother's serum, when you go through breast milk, it's like 0.01%. It's very low.

And then that goes in the infant digestive tract — half of that gets digested. So the relative infant dose is 0.001%. It's really nothing. And so we don't worry at all about breastfeeding on a monoclonal antibody. And again, why the EMA letter truly made no sense.

However, with a small molecule — again, thiopurines we know cross, but at a low rate — they have not been associated with harm. So they can breastfeed on thiopurines. Five-ASAs are fine. But going back to the JAK inhibitors, data from tofacitinib showed a relative infant dose closer to 5%. And because these medications can have significant impact on infection risk, et cetera, we do want to avoid exposure in the infant, so we say don't breastfeed on the JAK inhibitors and the S1Ps.

Pathak: Very, very helpful. So now I want to envision us in the office with a woman who is beginning this journey and has been hearing about, “Oh, you shouldn't be on X medication,” or “You shouldn't be taking this,” or “You need to avoid all kinds of chemicals in your body and your system.”

So for that woman with IBD who wants to get pregnant or who is pregnant right now, what's the most important message you want her to take away from these new guidelines?

Mahadevan: Healthy mother equals healthy baby. I think that really boils down to that. And then of course, knowledge is power. The more you learn, the more you understand, the more comfortable you feel with your plan. Depending on who you work with, the gastroenterologist can say one thing, and the OB will say, “No, you’ve got to stop all your medicines.”

And in fact, 20 years ago when I started in San Francisco, some OBs refused to take care of my patients if they continued their IBD medications during pregnancy. So it is a battle, and that’s where having a maternal-fetal medicine specialist on our consensus really helped with the OB part of it. I would say the key thing is to understand that you need to be in remission.

You need to understand which medications are safe, and you need to feel confident in your plan so that all the people you meet along the way who are going to give you advice aren’t going to be able to shake you from the right path.

Pathak: And then looking ahead, what unanswered questions are you most excited to study next?

Mahadevan: I really want to understand the safety of upadacitinib and the JAK inhibitors, because for the patients who are sick, it is such an effective medication. And are we withholding this without due cause? All we really have is animal data. The human data is fine, but I think my next, or my current big research project, is understanding the role of the placenta.

So the placenta is a highly immunologic organ, and humans are the only creatures where the placenta actually embeds in the uterus and the blood supply intertwines. This is why the infant brain can develop at the rate it does, but it's also why human pregnancies are higher risk than animal pregnancies.

And because it's an immune organ, when you have active inflammation, the placenta can be abnormal, and that’s where you get the preterm birth and the preeclampsia and some of the other complications. Really understanding the role of the placenta and how we can support the placenta during these pregnancies is key — not just to IBD, but all immune-mediated disease.

Pathak: Well, I'm looking forward to any research that you are working on and the results that you are able to share. Thank you so much for your time and for really cutting through and sharing the high-level takeaways with us.

Mahadevan: Thank you. My pleasure.

Pathak: Before we close our episode today, I'd like to highlight three key clinical takeaways from our discussion.

First, if you have IBD, staying in remission is one of the most important factors for a healthy pregnancy. The safest thing you can do for a baby is to keep your IBD under control, and that usually means staying on your prescribed treatment regimen. Active inflammation, not your medication, is the biggest risk to fertility, miscarriage, preterm birth, and complications.

Second, most modern IBD medications are considered low risk in pregnancy and while breastfeeding. Biologics don't cross the placenta during early development and are considered low risk to continue throughout pregnancy and breastfeeding. But certain medications are potentially higher risk, so it's critical to always talk with your gastroenterologist before making any medication changes, since stopping treatment abruptly can increase risks to both you and your baby.

And finally, you deserve coordinated, high-quality pregnancy care and clear communication. Ask your gastroenterologist and obstetrician to work together — ideally with a maternal-fetal medicine specialist. Discuss prenatal planning, delivery options, and postpartum follow-up, including how to safely manage vaccines in your newborn and breastfeeding.

With the right team and plan, women with IBD can have safe, healthy pregnancies and thriving babies. To find out more information about Dr Uma Mahadevan, her work, and about IBD, make sure to check out our show notes.

Thank you so much for listening. Please take a moment to follow, rate, and review this podcast on your favorite listening platform. If you'd like to send me an email about topics you are interested in or questions for future guests, please send me a note at [email protected].

This is Dr Neha Pathak for the WebMD Health Discovered Podcast.