00:00:00: Pradeep Mundre: Hello everyone, welcome to this episode of the UEG podcast.

00:00:04: Pradeep Mundre: It's Pradeep Mundre here.

00:00:06: Pradeep Mundre: I'm a gastroenterologist in the UK and a podcast host for this episode.

00:00:11: Pradeep Mundre: This one is actually the part two of my conversation with Mette Julsgaard on IBD and pregnancy.

00:00:19: Pradeep Mundre: Mette is the Associate Professor of Gastroenterology from Aarhus University Hospital in Denmark, specializing in IBD reproduction.

00:00:28: Pradeep Mundre: Be sure you listen to the part one first in order to follow our discussion here.

00:00:34: Pradeep Mundre: Now in part one, we talked about fertility, you talked about preconception counseling, preconception optimization of patients with IBD who wants to conceive.

00:00:46: Pradeep Mundre: And we went through each class of drugs as to which ones to stop, which one to continue, which one to optimize, and use of aspirin, which I was absolutely completely unaware of.

00:00:58: Pradeep Mundre: In this part, we get into the depths of difficult conversations or difficult decisions or special circumstances where standard care may not be enough and you have to go slightly out of the main path, so to say.

00:01:14: Pradeep Mundre: We also talk about acute severe colitis, surgery in acute severe colitis.

00:01:18: Pradeep Mundre: We talk about methods of delivery.

00:01:20: Pradeep Mundre: We also discuss about vaccination in the infants exposed to IBD drugs.

00:01:27: Pradeep Mundre: And we also talk about the postpartum period, which I think is the part we all tend to forget.

00:01:33: Pradeep Mundre: So here's the rest of the conversation.

00:01:35: Pradeep Mundre: Enjoy.

00:01:37: Pradeep Mundre: Can I ask you a slightly uncomfortable question, Mette?

00:01:39: Pradeep Mundre: Let's say a patient's got a flare or active disease and you want to treat her in pregnancy and you don't have a choice of safer drugs, biologicals, newer biologicals, IL-23 inhibitors.

00:01:51: Pradeep Mundre: And the only choice you have is JAK inhibitors.

00:01:54: Pradeep Mundre: What is the trade-off here?

00:01:55: Pradeep Mundre: Would you take a chance and give them JAK inhibitors or would you kind of continue with sort of low-grade active disease, somehow trying to control the symptoms?

00:02:07: Pradeep Mundre: Which is the bad person here, active disease or JAK inhibitors?

00:02:10: Mette Julsgaard: Active disease.

00:02:11: Pradeep Mundre: Okay.

00:02:12: Mette Julsgaard: That's a shorter answer.

00:02:13: Mette Julsgaard: Yeah, so we know active disease poses an increased risk of adverse pregnancy outcome, even like mild active disease, if you could call it that.

00:02:22: Mette Julsgaard: But active disease is active disease.

00:02:24: Mette Julsgaard: Of course, the increase for adverse pregnancy outcome increases with the severity of activity in the disease.

00:02:31: Mette Julsgaard: But I would always aim for obtaining remission.

00:02:35: Mette Julsgaard: And if the biologics have failed and we are dealing with a corticosteroid non-responder or there's previously been side effects to corticosteroids,

00:02:44: Mette Julsgaard: well, then I'll discuss with the patient saying, look, it's too early to induce delivery because it's only like second trimester or beginning of the third trimester.

00:02:55: Mette Julsgaard: And we have other types of drugs, fast-acting drugs, but the limited safety data.

00:03:00: Mette Julsgaard: I would highlight what we know regarding exposure during pregnancy.

00:03:06: Mette Julsgaard: And then keep in mind that for tofacitinib and upadacitinib, there's been no reports of increased risk of fetal death in the animal studies either.

00:03:16: Mette Julsgaard: There was only like the link to malformations.

00:03:19: Mette Julsgaard: Again, malformations, which we haven't seen, in human data.

00:03:24: Mette Julsgaard: So I would definitely, if the patient agrees to it, I would induce and start JAK inhibitors in pregnancy.

00:03:33: Mette Julsgaard: And as I mentioned early on in our talk, I have actually already done so because of a patient in severe active disease at gestation week 28.

00:03:43: Mette Julsgaard: We had no other option and the mother agreed and we initiated upadacitinib.

00:03:48: Mette Julsgaard: And two days after, the patient was actually showing signs of remission, markedly reduced bowel movements, went into remission during the third trimester and gave birth at term.

00:03:59: Mette Julsgaard: So this is really on an individual level,

00:04:02: Mette Julsgaard: we need these types of discussions and preferably refer your patient to a center with expertise in this field,

00:04:10: Mette Julsgaard: or even like a phone consultation if you live far away from that particular expert within this field.

00:04:18: Pradeep Mundre: Okay.

00:04:19: Pradeep Mundre: Mette, on the note of active disease, I think, as clinicians, we're very comfortable continuing drugs that they were on previously.

00:04:27: Pradeep Mundre: It's about initiating new drugs that we get nervous and concerned about.

00:04:30: Pradeep Mundre: So what you're trying to highlight is you would manage them as you would do with any other patient.

00:04:36: Pradeep Mundre: Actually, more importance to managing the active disease because that improves outcomes.

00:04:41: Pradeep Mundre: And you would initiate any treatment as usual.

00:04:43: Pradeep Mundre: But is there anything about any particular, other than the JAK inhibitors, S1Ps, is there any other medication that you would be cautious about initiating during pregnancy?

00:04:54: Mette Julsgaard: So I would never initiate thiopurines.

00:04:57: Mette Julsgaard: We don't really use thiopurines that much anymore because we have so many biologics and I would prefer those in our patients, also in the non-pregnant patients.

00:05:05: Mette Julsgaard: But I would never initiate thiopurines because it's a slow-acting drug, first of all, and then the risk of side effects like pancreatitis, hepatitis.

00:05:14: Mette Julsgaard: But when you have active disease, you really need a drug of choice which works fast.

00:05:20: Mette Julsgaard: Thiopurines, it takes time, it builds up in the system and you don't have that time to wait in a pregnant patient.

00:05:28: Mette Julsgaard: And also the risk of side effects to the drug.

00:05:31: Mette Julsgaard: So never initiate thiopurines.

00:05:34: Mette Julsgaard: If a patient falls pregnant with thiopurines, you can continue it throughout pregnancy in case of monotherapy, as mentioned early on.

00:05:41: Mette Julsgaard: But yeah, never use thiopurines.

00:05:44: Mette Julsgaard: And of course, obviously, as we discussed, methotrexate should be stopped and of course, should never be initiated either.

00:05:51: Mette Julsgaard: But the biologics really keep them in mind.

00:05:54: Mette Julsgaard: Some of them are fast-acting and they should be initiated in case of active disease.

00:05:59: Mette Julsgaard: And in case you have failed a TNF-alpha inhibitor and you want to use another biologic in case of active disease in pregnancy,

00:06:07: Mette Julsgaard: well, initiate those type of biologics in pregnancy and potentially bridging with budesonide for a period of time in order to ensure remission.

00:06:16: Mette Julsgaard: Or if budesonide isn't sufficient for the bridging period, then systemic corticosteroids, but for the shortest possible duration of time.

00:06:25: Pradeep Mundre: And on that note, any words of wisdom in terms of managing patients with acute severe colitis in pregnancy?

00:06:33: Pradeep Mundre: The reason why I ask, I still remember this case where I was a trainee, the first year trainee in gastroenterology, 22-week pregnant lady came in and there was a bit of reluctance to use any drugs beyond steroids.

00:06:46: Pradeep Mundre: But this was a long time ago.

00:06:47: Pradeep Mundre: Eventually, unfortunately, you know, even the reluctance to do surgery on this patient to an extent that the surgery was only conducted when her colon had toxic dilatation.

00:06:58: Pradeep Mundre: It was like five, six centimeters wide and she was not responding.

00:07:02: Pradeep Mundre: Luckily, you know, she recovered well and the baby was born healthy at term and all that.

00:07:07: Pradeep Mundre: So any words of wisdom or anything the trainees or any of us general gastroenterologists need to know in managing the acute severe colitis?

00:07:15: Mette Julsgaard: So the worst thing we can do is under-treatment.

00:07:20: Mette Julsgaard: I think I've said that quite a few times now.

00:07:22: Mette Julsgaard: So, but in cases, especially in case of acute severe ulcerative colitis, you need to be aggressive.

00:07:27: Mette Julsgaard: So high dose corticosteroids, definitely intravenous admission to the department so you can monitor mom and infant.

00:07:35: Mette Julsgaard: While being admitted to the inpatient ward, you can get obstetrician to see the patient, monitor the fetal heart rate and so on.

00:07:44: Mette Julsgaard: So high dose intravenous corticosteroids induce biologics.

00:07:49: Mette Julsgaard: So we have like a bridging to ensure remission, not just in pregnancy, but also postpartum.

00:07:55: Mette Julsgaard: That's a very important period of time as well.

00:07:58: Mette Julsgaard: So you need a management plan and not just here and now, but also moving on onwards.

00:08:02: Mette Julsgaard: So treat active disease aggressively, just as in the non-pregnant patients.

00:08:07: Mette Julsgaard: When it comes to surgery, it is so important that we not just try and wait to see how it goes.

00:08:13: Mette Julsgaard: We need to, first of all, highly recommendable, refer pregnant patients with acute severe ulcerative colitis to, to a referral hospital

00:08:22: Mette Julsgaard: because those centers, they have the knowledge and the capability of performing these high risk operations.

00:08:31: Mette Julsgaard: We know the perfect timing for doing like colectomy and operations in general on the bowel in pregnancy is during the second trimester, but that should never guide our decision when to perform surgery.

00:08:45: Mette Julsgaard: It is really the patient's clinical conditions, which should guide us.

00:08:49: Mette Julsgaard: So if surgery during the first trimester is needed, it should be performed then.

00:08:54: Mette Julsgaard: And also if needed early in the third trimester,

00:08:57: Mette Julsgaard: or if it's later in the third trimester, again, in sort of a multidisciplinary approach with our obstetricians as well,

00:09:06: Mette Julsgaard: surgery in combination with elective cesarean section or emergency cesarean section, it all depends on gestational week.

00:09:14: Mette Julsgaard: What is important though, to note is that both maternal and neonatal mortality, in case of surgery has decreased during the past decades.

00:09:24: Mette Julsgaard: We showed that in a large European study, and that is most likely due to, we are best at referring to tertiary referral hospitals, skilled surgical surgeons,

00:09:34: Mette Julsgaard: and also more like less invasive surgery with laparoscopic surgery as well in the pregnant patient.

00:09:40: Mette Julsgaard: So, and another important point is that risk of abortion and stillbirth in case of surgery in pregnancy is highest during the first trimester.

00:09:52: Mette Julsgaard: So, the first two weeks are really the period of time where we should monitor our patient clearly,

00:09:58: Mette Julsgaard: but also inform the patient that after two weeks post-surgery, she is sort of out of the woods, but of course monitor these patients clearly, but never postpone time for surgery.

00:10:10: Mette Julsgaard: Refer to tertiary referral centers.

00:10:14: Pradeep Mundre: Yeah, I guess a point to highlight is to involve the obstetricians all along because monitoring of the baby.

00:10:19: Mette Julsgaard: And surgeons.

00:10:21: Pradeep Mundre: Yeah, and surgery of course, yeah.

00:10:23: Pradeep Mundre: And anything to consider in terms of mode of delivery?

00:10:26: Pradeep Mundre: Sort of any advice?

00:10:27: Pradeep Mundre: I know it's a forte of obstetricians, but anything that we need to know in terms of IBD itself?

00:10:35: Mette Julsgaard: Yeah, well, I think the most important thing is multidisciplinary management.

00:10:40: Mette Julsgaard: Have a great dialogue with the patient, like patient involvement and with the obstetric department.

00:10:45: Mette Julsgaard: But there are, of course, special considerations for our IBD patients.

00:10:50: Mette Julsgaard: So, in case of active perianal disease, there is a 10-time increased risk of sphincter tear.

00:10:57: Mette Julsgaard: So, in case of active perianal disease, always cesarean section.

00:11:01: Mette Julsgaard: But also in case of women with a pouch or those who are high likelihood of having a pouch in the future, you should discuss having a cesarean section.

00:11:11: Mette Julsgaard: I personally always recommend cesarean section in my patient for the pouch because you need to take extra care of the sphincter in those patients.

00:11:21: Mette Julsgaard: But it all comes down to that our patients need to feel safe and secure going into delivery.

00:11:29: Mette Julsgaard: So, one size doesn't fit all.

00:11:32: Mette Julsgaard: That's why the MDT is so important and multidisciplinary involvement and patient involvement, deciding on mode of delivery.

00:11:41: Pradeep Mundre: Okay.

00:11:42: Pradeep Mundre: Maybe it's time to move on to vaccinations, Mette.

00:11:47: Pradeep Mundre: In brief, what are the things, what advice would you give?

00:11:50: Pradeep Mundre: Because that's one of the concerns brought up and I'm always confused and I'm just looking at guidelines and things.

00:11:56: Pradeep Mundre: So, just some in brief, what are the vaccination to avoid?

00:11:59: Pradeep Mundre: How do you counsel patients?

00:12:01: Pradeep Mundre: How do you counsel pregnant women?

00:12:03: Mette Julsgaard: Yeah.

00:12:04: Mette Julsgaard: So, I think the concern really rise because we have seen that in infants exposed to biologics, there's been five cases of death in infants exposed to a TNF-alpha inhibitor.

00:12:16: Mette Julsgaard: These infants were exposed to either infliximab or adalimumab during pregnancy and received the live attenuated BCG vaccine and those infants died of disseminated BCG infection.

00:12:30: Mette Julsgaard: So, that really raised a huge concern when we saw the first case published more than a decade ago.

00:12:36: Mette Julsgaard: So, when it comes to biologics, infants exposed to biologics, we know the biologics are present for the first six months after delivery.

00:12:45: Mette Julsgaard: for infliximab up to a small percentage will have detectable infliximab levels at a very low concentration up to the age of 12 months.

00:12:54: Mette Julsgaard: But for all the other biologics, it will be cleared within the first six months of life.

00:12:59: Mette Julsgaard: So, when it comes to inactive vaccines, like all the standard inactive vaccines, those can be given on schedule to all infants exposed to biologics.

00:13:10: Mette Julsgaard: So, follow the National Immunization Program and I highly recommend that.

00:13:14: Mette Julsgaard: And another good thing is that we have seen when it comes to the inactive vaccines, no adverse risk of adverse events and we have seen adequate serologic response to vaccines as well.

00:13:24: Mette Julsgaard: And that's important to highlight to the moms or to the parents overall.

00:13:29: Mette Julsgaard: When it comes to live attenuated vaccines, except rotavirus vaccine, avoid these vaccines for the first six months of life.

00:13:39: Mette Julsgaard: Of course, like regional risk should be taken into account if you live in a country with a high risk of tuberculosis, then pros and cons should be weighed and being exposed to infliximab where we have this prolonged clearance.

00:13:53: Mette Julsgaard: And if a BCG vaccine is needed, well, you could also after the six months of age, we could also measure if there is any like levels detectable still and like test the immunological assessments.

00:14:05: Mette Julsgaard: But really most, even in Europe, BCG vaccine is recommended in some countries or at least in populations highly at risk of tuberculosis.

00:14:15: Mette Julsgaard: So, to keep it simple, avoid live vaccines for the first six months of life in case of biological exposure.

00:14:23: Mette Julsgaard: When it comes to rotavirus vaccine, and that's new and we have really explained this in detail in our new global consensus that, but rotavirus vaccine can actually be given on schedule in infants exposed to biologics.

00:14:38: Mette Julsgaard: And that's because the Canadian Immunization Research Network, they did a splendid study.

00:14:43: Mette Julsgaard: They included nearly 200 infants exposed to biologics in pregnancy, the vast majority exposed during the third trimester as well.

00:14:51: Mette Julsgaard: And they did extensive immunological assessment and they found completely normal immunological assessment in 98% of infants.

00:15:00: Mette Julsgaard: And they recommended rotavirus vaccine, most received it and they saw no adverse reactions.

00:15:07: Mette Julsgaard: Even those infants, who had a high level of biologicals at the time of vaccine.

00:15:14: Mette Julsgaard: So, really rotavirus vaccine can be given on schedule if it's a part of the national immunization program.

00:15:21: Pradeep Mundre: Okay, that's well summarized.

00:15:22: Pradeep Mundre: That actually makes it much more simpler, right?

00:15:24: Pradeep Mundre: It seems much more simpler than I thought.

00:15:26: Mette Julsgaard: That's what we need.

00:15:27: Mette Julsgaard: We need simple advice and so simple recommendations.

00:15:30: Mette Julsgaard: So, clinicians remember it and the patients remember it as well.

00:15:35: Pradeep Mundre: Absolutely.

00:15:36: Pradeep Mundre: Moving on to briefly about the postpartum period.

00:15:39: Pradeep Mundre: Can you think of any special points to highlight?

00:15:42: Pradeep Mundre: Because that's something I think patients don't come to you because they're very busy with their lives.

00:15:48: Pradeep Mundre: Moms are very busy.

00:15:49: Pradeep Mundre: It's probably the most busiest time and they will not come to your appointments and things.

00:15:53: Pradeep Mundre: So, something you need to plan before delivery, I guess.

00:15:57: Pradeep Mundre: So, any words of wisdom?

00:15:59: Mette Julsgaard: Yeah.

00:16:00: Mette Julsgaard: So, I always address the postpartum period for the exact same reason as I just highlighted.

00:16:05: Mette Julsgaard: So, I discuss the postpartum period already during pregnancy because it seems to me that our patients accept that medical treatment during pregnancy is needed to ensure both maternal but also fetal health.

00:16:18: Mette Julsgaard: But once you're giving birth and you sit there and they're breastfeeding, they get all concerned about the drugs and the likelihood of non-adherence to medical treatment increases during the postpartum period.

00:16:30: Mette Julsgaard: So, I can highlight the importance of staying on the drugs in order to ensure remission because women with IBD, they are at increased risk of postpartum flaring, especially in case of, of course, non-compliance to medical treatment.

00:16:45: Mette Julsgaard: Also, if they have discontinued biologics in the third trimester in pregnancy.

00:16:50: Mette Julsgaard: And again, off note, one should never discontinue biologics in pregnancy.

00:16:54: Mette Julsgaard: We used to say that in the old days in Europe, but we do not recommend this anymore because we have so much safety data on newborn exposure.

00:17:04: Mette Julsgaard: So, really continue biologics throughout pregnancy to ensure remission, not just in pregnancy, but also during the postpartum period.

00:17:13: Mette Julsgaard: And again, because of the hormonal changes and stress of becoming a mom, sleep deprivation and so on, they are at increased risk of flaring.

00:17:21: Mette Julsgaard: So, staying adherent to medical treatment is of utmost importance.

00:17:26: Mette Julsgaard: Another important aspect I always address to my patients, especially if the partner is in the consultation as well during pregnancy,

00:17:35: Mette Julsgaard: is that women with IBD are actually at a slight increased risk of postpartum depression compared to the background population.

00:17:44: Mette Julsgaard: And it's just important that the women, and especially the spouse, is aware of this.

00:17:51: Mette Julsgaard: So, precautions can be taken in case our patients show signs of depression.

00:17:58: Mette Julsgaard: Early intervention is, of course, of utmost importance also in that matter.

00:18:02: Mette Julsgaard: It is not us as gastroenterologists, that's the DEP, maternal health nurse coming to their home and so on,

00:18:09: Mette Julsgaard: And relatives and so on should be aware of how the mom is doing, but we just need to raise awareness regarding this point.

00:18:18: Pradeep Mundre: Mette, with that, it brings us towards the end of the conversation.

00:18:21: Pradeep Mundre: Thanks for your time for the last hour.

00:18:23: Pradeep Mundre: You made it very clear, simple for us to understand.

00:18:26: Pradeep Mundre: And thanks for the amazing guidelines, the consensus statement the team of you have put up, which is very simple, succinct, and makes it much easier for others to follow.

00:18:37: Pradeep Mundre: Any final thoughts, words of wisdom, a piece of advice?

00:18:41: Mette Julsgaard: Yeah, so really one sentence, healthy mom, healthy baby.

00:18:46: Mette Julsgaard: And in order to ensure a healthy baby, remission in maternal disease is of utmost importance.

00:18:53: Mette Julsgaard: So, please, aggressiveness in order with the different medical drugs is of great importance.

00:19:00: Mette Julsgaard: Use biologics also as induction in pregnancy, always patient involvement.

00:19:06: Mette Julsgaard: That is really the key message.

00:19:07: Mette Julsgaard: Healthy mom, healthy baby.

00:19:09: Pradeep Mundre: Okay.

00:19:10: Pradeep Mundre: Thanks for your time.

00:19:11: Pradeep Mundre: Good day.

00:19:12: Mette Julsgaard: Thank you.