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Sunanda Kane, MD, MSPH: Hello. I'm Dr Sunanda Kane. Welcome to the Medscape InDiscussion series on ulcerative colitis (UC). Today we'll be discussing pregnancy and UC with our guest, Dr Uma Mahadevan. Dr Mahadevan is a gastroenterologist and director of the UCSF Colitis and Crohn's Disease Center. She's an expert on inflammatory bowel disease (IBD), particularly as it relates to pregnancy and fertility, and on managing patients with complex Crohn's disease and UC. Welcome to InDiscussion.
Uma Mahadevan, MD: Hi, Susie.
Kane: As the principal investigator for the largest prospective registry for pregnancy and IBD in the world, what are the top two or three takeaway points that you want every patient with UC to know?
Mahadevan: When we started Pregnancy Inflammatory bowel disease And Neonatal Outcomes (PIANO) in 2007, it was really about drug safety. What's come out over and over and over again is that it's disease activity that's the biggest risk to the pregnancy. Women with UC are more likely to flare during pregnancy than women with Crohn's disease, and they're also more likely to need steroids. We now know that disease activity is the driver of pregnancy loss, preterm birth, small for gestational age, etc.
Kane: I remember when we were having those discussions and you presented those data to us as subinvestigators. It was surprising because you think about UC as being less severe or less complicated than Crohn's. That's a really important thing for people to know — that UC in the setting of pregnancy is not less severe or less dangerous.
Mahadevan: It's really interesting. The patients with UC were less likely to be on biologics in PIANO, but I have patients who are well managed on good medications going into pregnancy and they still flare. There is probably something about pregnancy itself or the cytokines the placenta secretes that seem to be a trigger for UC.
Kane: Interesting. You mentioned that patients with UC are less likely to be on biologics. That was 2007. Do you think that's still true?
Mahadevan: It's absolutely still true. You see this among all patients and certainly among pregnant patients.
Kane: How do you feel about biologics if a patient is flaring during her pregnancy — do you start one rather than give her more steroids?
Mahadevan: I always prefer to use a biologic rather than steroids in pregnancy for two reasons. The first reason is, again, that the biggest risk to the pregnancy is active disease. The quicker you get a patient into remission, the less the impact on the pregnancy. In PIANO, we looked at the impact of steroids on pregnancy outcome. Yes, it's very hard to separate steroids from active disease, but women who required steroids had more adverse pregnancy outcomes, including preterm birth, ICU stay for the baby, and even birth defects in the first trimester.
Kane: Wow. Is your recommendation to practitioners who are listening to actually get a biologic rather than pull the trigger on prednisone?
Mahadevan: It is. I mean, everything is situational. If the patient has always been on mesalamine their whole life and they're having a flare at 37 weeks' gestation, at that point I probably give them a course of prednisone, see if you they deliver, and see how they do. If they're in their first trimester and have moderate to severe disease, that's a long time to require steroids. And in that setting, if I can, I will try to go to the most effective and appropriate biologic right away.
Kane: Got it. We talked about prednisone. Do you give budesonide during pregnancy?
Mahadevan: I do. Budesonide foam, in particular, I have no concerns about. We do use low-dose budesonide or budesonide in pregnancy, 9 mg and otherwise. But as always, we're trying to treat the underlying disease activity. So if it's something they need as a bridge for a couple of weeks, fine. If this is going to be a long-term treatment, I really prefer to control the underlying disease with a better medication.
Kane: Got it. Okay. So that's pregnancy. Let's talk a little bit about fertility and the data about a woman who has a J pouch. She's told she could have infertility. Where are we at with that? Can you dispel or tease out the fact from the fiction?
Mahadevan: Sure. Most of the larger studies have looked at women who had an open colectomy during staged J-pouch surgery. The surgeon made the midline incision, took out the colon, went into the peritoneum, and created a J pouch. In that setting, we did see significant reductions in the ability of women to conceive on their own over the course of a year. It could be anywhere from 30% to 80%, depending on the study. Now, the argument is that if you're using a laparoscopic approach, you'll have less adhesions, so you should have better outcomes. Unfortunately, we haven't had the large-scale studies to show that. There are some smaller retrospective studies that have suggested the time to conception is shorter with a laparoscopic approach. There are two options there; one option we offer to women who have a partner is to do the subtotal colectomy and have the surgeon not go into the peritoneum, leave the rectum in place until they have their children, and then go back and create the J pouch. That, of course, doesn't work for everyone.
Kane: Because doesn't that mean they have a stoma during that time?
Kane: Maybe that option is only for a woman who is in a very stable relationship, right?
Mahadevan: Yes, definitely. This works for people who feel like as soon as they're better, they are going to get pregnant, and they already have their life partner. It's easier for them to make that decision. Remember that in vitro fertilization or assisted reproduction is very expensive, emotionally challenging, doesn't even always work, and may work less effectively in patients with IBD based on some studies out of Denmark.
Kane: So does it matter in terms of fertility whether there's pouchitis, or is it just the pouch itself that seems to be an issue?
Mahadevan: It seems to be more related to the surgery and scar tissue that forms or adhesions that may affect the reproductive organs, as opposed to pouchitis. Now, if they have pouchitis, they have active inflammation. In theory, it would be more difficult for them to conceive, but most of these people don't have active pouchitis and still have difficulty. We think it's related to scarring of the fallopian tubes.
Kane: Okay. What about a patient who has UC who doesn't have a pouch? In terms of fertility, what do you tell that patient?
Mahadevan: Well, if they're in remission, we tell them that their chances of conceiving are equal to other women their age. That's something to think about, too.
Kane: Right. What about men? We talk so much about women, and obviously they're the ones who are carrying the child, but in terms of fertility, what sort of counseling do you offer to a man who says they just got married and now wants to start a family?
Mahadevan: For men, we do want them to be in remission as well. Sperm are very, very delicate. Get in a hot tub, go on a long bike ride, and they're shot. Having active disease also impacts semen quality. You have your best shot at achieving conception if the patient is in remission. Most of the medications we use in UC are compatible with attempting conception. I think the exception would be sulfasalazine, which can reduce semen quality. Methotrexate is probably fine, but if I can, I try to take people off it prior to attempting conception.
Kane: What I'm hearing is that you're not worried about any of the biologics. And then we heard when we were both fellows in 2005 or so, out of New York, about that very controversial study about 6-mercaptopurine and sperm health and poor outcomes. It has never been scrubbed from the internet. How do you feel about that?
Mahadevan: I remember being at that presentation, and I got a very animated response from the audience. I think there was so much bias in who they measured. People were quite sick. It was pre-biologics, and having active disease, and surgery plays a role, and even statistically, who they picked. One of the biggest studies came out of the University of California system, and Joe Meserve and Sid Singh along with all of the University of California epidemiologists used the database from the university. They did not see an increase based on 6-mercaptopurine use and adverse outcomes among multiple disease types.
Kane: Great. Not everything you read on the internet is either true or even up to date at this point. All right, so we talked about fertility. We've talked a little bit about pregnancy. I know we say that patients with IBD who get pregnant should be followed by high-risk OB. How firm of a recommendation is that? Do they have to be followed through their whole pregnancy? Or maybe just a consult? Because here in the depths of the Midwest farming communities, it's midwives who are delivering these kids. How do you feel about this?
Mahadevan: I do recommend that all of our pregnant patients with IBD be seen by a maternal-fetal medicine (MFM) specialist. It's not just a high-risk OB who may be the person in the practice to take on the more complicated cases. It's somebody who's actually done additional training in MFM. And so our MFMs will decide if a patient needs ongoing visits with them or if they can co-follow with their local OB. For many of our patients, like yours, they come from all over the Pacific Northwest and all over California, which is a giant state with many rural communities, and they don't have access to MFMs. They will often deliver in their local community but be followed through their pregnancy by the MFM specialist. First, that helps the OB and makes them more comfortable with some of the medicines their patients are on. The patients get monitored for complications. And then in a patient we're worried about, we do a scheduled induction or C-section at UCSF. They come in for that.
Kane: Okay. But does every patient who has UC have to have a C-section? What if they want to have a natural delivery?
Mahadevan: I think most patients should have vaginal delivery. The only time I, as a gastroenterologist, say you need a C-section is if you have active perianal disease or rectal vaginal fistula. In patients with UC, even a J pouch, patients can be considered for vaginal delivery. I would say if you had a J pouch, you probably shouldn't be delivering in a rural community in the event that you do need a C-section. It can be complicated.
Kane: For pregnant patients, do you recommend any special diets for them to be on while they're pregnant with UC?
Mahadevan: So, there are two things. One is that they have adequate maternal weight gain. Bente Mertz Nørgård, using the IBSEN cohort in Norway, and also the PIANO study showed that women with UC who don't gain appropriate weight during pregnancy have worse pregnancy outcomes. Again, that's probably linked with how they're doing overall with their disease. Maternal weight gain is important to measure, so they need to be able to eat and gain weight. In terms of special diet, we recommend a Mediterranean-type diet. There was a recent paper that looked globally in pregnancy and found that a Mediterranean-type diet led to better pregnancy outcomes. It is an anti-inflammatory diet, and pregnancy can be a proinflammatory state. And you add that to the IBD — to the UC — and it can be cumulative. We want them to eat well, but first of all, we want them to eat. If fruits and vegetables make you throw up, it's okay, eat what you can.
Kane: This is not the time to be on your special elimination, only-eat-white-things diet. When do you start a prenatal vitamin in these folks?
Mahadevan: Generally, I will check vitamin levels and iron ahead of time. Ideally, they should be on a prenatal at least 3-6 months prior to attempting conception.
Kane: That's what I tell them.
Mahadevan: It doesn't always work out that way.
Kane: Okay. So, they've delivered. We talked about vaginal births and such. What about breastfeeding?
Mahadevan: I tell all my patients that they should be able to breastfeed with UC. There's nothing about UC that prohibits breastfeeding. There may be certain medications such as JAK inhibitors or methotrexate where a patient should not breastfeed if they're taking them, but everything else can be continued on schedule.
Kane: Got it. I remind my patients that I want to hear if they are being recommended to be on fenugreek, which is the lactation enhancer. It certainly works for milk production but can cause bleeding in and of itself. I don't know whether you've seen this come up, Uma.
Mahadevan: I learned that from you, and I tell all my patients that, as well.
Kane: And turmeric too. You take too much turmeric, and you can have bleeding because of the warfarin-like component of it. I learn things from my patients on a regular basis. We think that we know a lot, and there's still lots to learn. That baby who may have been exposed to a biologic, what do you recommend in counsel for the care of that child?
Mahadevan: If a patient was on a biologic, we recommend that the child not get live vaccines for at least the first 6 months of life unless they're on certolizumab because that does not cross the placenta.
Kane: That's not FDA approved for UC. I have seen folks who try to get it for their colitis patients because of that reason.
Mahadevan: Yes, but don't worry about the placental transfer. That's not a big deal. Use the best biologic, and the baby shouldn't get a live vaccine for the first 6 months. In the United States, that's just rotavirus. In some communities where they have a measles epidemic, they'll get the MMR (measles, mumps, and rubella) vaccine at 6 months and that's fine. The amount of any biologic at that point from placental exposure is very low. I also tell my patients that if their baby has fevers and other things, particularly in the first couple of months when they have high levels of biologic in their system, they need to be very vigilant — and people are that way anyway with a newborn. The pediatrician should be aware of the placental exposure.
Kane: Sure. So Sonia Friedman has done some really nice work showing that you can use fecal calprotectin during pregnancy as a potentially noninvasive way to monitor patients. When do you use that and when do you potentially use a scope?
Mahadevan: There have been some good papers looking at that. Ariella Shitrit had one as well. Even for the patients who are clinically in remission, their median and mean calprotectin can be in the inflammatory range. I don't do mandatory calprotectin throughout pregnancy if somebody's feeling well, but if they have increased symptoms, I will check the calprotectin. If I'm going to make a major change in their therapy, I want to scope, and it's almost always a flexible sigmoidoscopy, which is low risk at any point in pregnancy. For UC, you never really need a full colonoscopy for disease assessment, and so an unprepped and unsedated flex sig, no problem.
Kane: That's the study that you guys did that's really helped practitioners understand that again, it's unprepped and unsedated flex sig because there's a lot of logistics and hoops to run through if you're trying to scope with propofol. Then you have to have fetal monitoring, which means OB has to be there, and it's a big headache. Thank you for that work to show us that it's safe to do those flex sigs. I believe it was Sonia who did the paper that showed the disease activity — that you have to be mindful for a flare upward of a year out after delivery. What is it that you might counsel after the patient has delivered, and the pregnancy is done? What do you tell them about watching what they do after they deliver?
Mahadevan: We make sure they know that they are to continue their IBD medications postpartum. I think some of the studies have suggested one of the most common causes of flares is women stopping their medication at the tail end of pregnancy and then never restarting it. This is not really shown, but I've had patients who've struggled with breastfeeding being associated with their flares, and then when they stopped breastfeeding, they got better. That's anecdotal because, overall, breastfeeding has not been associated with flares. The main thing is that we continue to monitor pregnant women in the peripartum period for an increased risk of C diff (Clostridioides difficile). I always check for that.
Mahadevan: Yes. Pregnancy in the peripartum period is an increased C diff period. We have had some people with C diff in that setting with and without UC. But overall, in PIANO, we did not see an increased risk of flare in the postpartum, particularly in people who continued their medication.
Kane: Great. Okay. Can you believe it's been 20 minutes?
Mahadevan: Oh my goodness.
Kane: We've had a great discussion and dialogue, and a lot of really great information that has come out of the PIANO registry that you are principal investigator for. We very much appreciate all of your hard work and seeing this through. We've talked about quite a few things in pregnancy and fertility. The key takeaway is that disease activity is the main driver here. Whatever it takes to get that mom well, do it. There may be some special personnel involved like the MFM specialist. But honestly, it's being very cognizant of what can happen and thinking about it — not necessarily having to go out of your way for any kind of special care. Thank you so much for joining us today. This has been Dr Sunanda Kane for InDiscussion.
PIANO (Pregnancy Inflammatory bowel disease And Neonatal Outcomes)
Does Laparoscopic IIeal Pouch–Anal Anastomosis Reduce Infertility Compared With Open Approach?
The Impact of Medical Therapies and Factors Related to Treatment Procedures in Women With Rheumatoid Arthritis and Inflammatory Bowel Disease Receiving Assisted Reproduction: A Nationwide Cohort Study
Effects of 6-Mercaptopurine Treatment on Sperm Production and Reproductive Performance: A Study in Male Mice
Paternal Exposure to Immunosuppressive and/or Biologic Agents and Birth Outcomes in Patients With Immune-Mediated Inflammatory Diseases
Child-Mother Index: A New Risk Factor for Selected Adverse Maternal Birth Outcomes
Association of a Mediterranean Diet Pattern With Adverse Pregnancy Outcomes Among US Women
Fecal Calprotectin During Pregnancy in Women With Moderate-Severe Inflammatory Bowel Disease
Fecal Calprotectin as a Predictor of Abnormal Colonic Histology
Safety of Flexible Sigmoidoscopy in Pregnant Patients With Known or Suspected Inflammatory Bowel Disease
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Cite this: Pregnancy, Fertility, Ulcerative Colitis: Facts vs Fiction - Medscape - Mar 21, 2023.