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

00:00:03: Pradeep Mundre: It's Pradeep Mundre here.

00:00:05: Pradeep Mundre: I'm a gastroenterologist from the UK and podcast host for this episode.

00:00:09: Pradeep Mundre: Now today's episode is about IBD and pregnancy.

00:00:13: Pradeep Mundre: From a clinician's point of view, I feel there's generally a sense of unease, a bit of uncomfortableness and nervousness amongst clinicians in dealing with patients with IBD and pregnancy.

00:00:25: Pradeep Mundre: And I suspect that's probably driven by our lack of knowledge in this topic, a lot of uncertainty in this area, and probably high stakes that are involved in managing such patients.

00:00:37: Pradeep Mundre: There are two lives involved in this.

00:00:38: Pradeep Mundre: However, I think things are becoming more and more comfortable.

00:00:41: Pradeep Mundre: Things are changing for us with new evidence and release of various guidelines which are making it much more simpler and clearer in this topic.

00:00:50: Pradeep Mundre: But there's still a significant challenge of counselling our patients prior to conception and counselling them about the safety of medications.

00:00:58: Pradeep Mundre: And I guess from the patient's perspective, there's significant voluntary childlessness amongst women with IBD.

00:01:06: Pradeep Mundre: That's probably driven by various concerns and probably by far the most important one is about the safety of the drugs and the outcome for the newborns.

00:01:14: Pradeep Mundre: Today we are discussing about this topic.

00:01:19: Pradeep Mundre: We are delving into how IBD affects pregnancy outcomes, how pregnancy affects IBD course.

00:01:26: Pradeep Mundre: We'll also touch upon fertility, maybe touch briefly on safety of the investigations in a pregnant IBD patient, and of course, all important aspects of medications in pregnancy and breastfeeding, and hopefully end by talking briefly on vaccinations.

00:01:42: Pradeep Mundre: And to discuss all this today, we have our wonderful guest, Dr.

00:01:45: Pradeep Mundre: Mette Julsgaard, who is Associate Professor of Gastroenterology Specializing in IBD and reproduction from Aarhus University Hospital in Denmark.

00:01:58: Pradeep Mundre: Mette is also Director of National Centre for Preconception and Pregnancy in Autoimmune Diseases and was one of the authors for the Global Consensus Statement on IBD and Pregnancy, which was published in GUT last year.

00:02:12: Pradeep Mundre: Welcome to the podcast, Mette.

00:02:15: Mette Julsgaard: Thank you very much, Prad, and thank you for the warm welcome.

00:02:18: Pradeep Mundre: Lovely, Mette.

00:02:20: Pradeep Mundre: Let's start with pregnancy.

00:02:21: Pradeep Mundre: Pregnancy is unique, and I guess most of our efforts and energy is focused on teratogenicity of the drugs, but there's a lot more to IBD and there's a lot more to IBD in pregnancy.

00:02:33: Pradeep Mundre: Can you explain, sort of in various domains, how IBD in pregnancy is different?

00:02:40: Mette Julsgaard: Yeah, you're so.

00:02:40: Mette Julsgaard: right.

00:02:41: Mette Julsgaard: We talk a lot about drugs and risk or congenital abnormalities, but really pregnancy is a period of profound physiological changes involving metabolic, hormonal, immunological and microbiome adaptions, and these changes can influence the course of IBD during pregnancy.

00:03:01: Mette Julsgaard: Conversely, IBD may also

00:03:02: Mette Julsgaard: affect pregnancy outcome, and in particular, and of great, great importance, that active disease during pregnancy is associated with an increased risk of adverse pregnancy outcome.

00:03:17: Mette Julsgaard: Hence, it is of utmost importance to keep our patients in remission.

00:03:21: Mette Julsgaard: But pregnancy itself can also alter biological pharmacokinetics, thereby affecting both maternal and infant drug exposure.

00:03:31: Mette Julsgaard: We have seen that

00:03:33: Mette Julsgaard: when it comes to the biologics.

00:03:34: Mette Julsgaard: Some biologics have increased clearance in pregnancy, whereas others have decreased clearance.

00:03:40: Mette Julsgaard: So, and in addition, I think that's the most important thing, that misperceptions during the conception period and pregnancy is also very common among our patients.

00:03:52: Mette Julsgaard: Like, for instance, one-third of women with IBD consider all IBD medication harmful during pregnancy.

00:04:00: Mette Julsgaard: And around 75% of our patients are concerned about passing on IBD.

00:04:08: Mette Julsgaard: And really, the risk of passing on IBD is, the absolute risk is really low.

00:04:13: Mette Julsgaard: 2 to 5% if only one of the parents have IBD.

00:04:18: Mette Julsgaard: Of course, 35% in case of both parents have Crohn's or Colitis.

00:04:24: Mette Julsgaard: But these are very important aspects to talk with our patients about.

00:04:29: Mette Julsgaard: doing preconception counseling.

00:04:31: Pradeep Mundre: Mette, I think what you're talking there is you're shifting the focus from teratogenicity or concerns for drugs towards managing active disease or keeping the disease at the control.

00:04:44: Pradeep Mundre: How important is that?

00:04:45: Pradeep Mundre: As in, you know, what does active disease do to pregnancy outcomes in IBD?

00:04:51: Mette Julsgaard: So, firstly, just want to highlight that in case we keep the mother during pregnancy in remission, her likelihood of giving normal, like giving birth to a normal infant is really high.

00:05:05: Mette Julsgaard: Whereas in case of active disease during pregnancy, the risk of adverse pregnancy outcome and for Crohn's disease, such as stillbirth, but for both Crohn's and Colitis, risk of low birth weight, infant small for gestational age, and giving birth preterm, are significantly higher than compared to women in remission during pregnancy.

00:05:27: Mette Julsgaard: That's why keeping the woman in remission, both prior to pregnancy, but also during pregnancy, is of utmost.

00:05:34: Mette Julsgaard: importance.

00:05:36: Mette Julsgaard: But again, we are already now discussing like the pregnancy period.

00:05:40: Mette Julsgaard: We also have to keep in mind the preconception period, because that is also of utmost importance.

00:05:47: Pradeep Mundre: So, Mette, let's talk about fertility.

00:05:50: Pradeep Mundre: A sort of preconception.

00:05:52: Pradeep Mundre: Maybe you can explain both in relation to men and women, and how does the disease affect fertility in patients?

00:05:59: Mette Julsgaard: Yeah, so we know that active IBD during the preconception period in women, in case you have active disease, those women have higher infertility rates compared to those with being in remission.

00:06:12: Mette Julsgaard: So, this large British study studied nearly 10,000 women with IBD, and they showed that fertility rate was reduced to 70% in the presence of active disease.

00:06:24: Mette Julsgaard: So, this clearly underscores that keeping our women in remission during the preconception period is also of utmost importance.

00:06:33: Mette Julsgaard: We have very limited data when it comes to men and fertility.

00:06:37: Mette Julsgaard: In ulcerative colitis, it seems that the fertility rate in men with ulcerative colitis is similar, both prior to and after being diagnosed with ulcerative colitis.

00:06:48: Mette Julsgaard: However, in men with Crohn's disease, it seems that the fertility rate or the likelihood of becoming a father is lower in men.

00:06:57: Mette Julsgaard: diagnosed with Crohn's disease compared to men without Crohn's disease.

00:07:02: Pradeep Mundre: Mette, I know active disease is a big factor, but let's say patients with inactive disease, patients with disease under control, is fertility affected if their disease is in remission compared to general population?

00:07:16: Mette Julsgaard: Well, there are other factors affecting fertility in women with IBD, and those we, of course, have to take into consideration.

00:07:24: Mette Julsgaard: So, we know that women who have undergone pouch surgery experience reduced fertility, and new data actually indicate that this is also the case in case of less invasive laparoscopic surgery.

00:07:39: Mette Julsgaard: But on the other hand, we know that IVF treatment is very effective in women with IBD, so that's a very good option.

00:07:46: Mette Julsgaard: So, we need to refer our patients to fertility experts in case of pouch surgery or previous pouch surgery.

00:07:54: Mette Julsgaard: And then there's another aspect, which is of great importance, that we know that women with IBD who are older than 30 years of age, they might have a lower ovarian reserve.

00:08:06: Mette Julsgaard: And this is indicated by a lower anti-Mullerian hormone levels compared to women without IBD.

00:08:13: Mette Julsgaard: And this has been shown in two small studies.

00:08:15: Mette Julsgaard: And then, of course, this.

00:08:17: Mette Julsgaard: adds to that women in this day and age, we delay becoming moms.

00:08:22: Mette Julsgaard: So, delayed childbearing is, of course, also a factor that affects fertility and the likelihood of becoming a mom.

00:08:29: Pradeep Mundre: So, it looks like getting disease under control seems to be the keystone, or getting disease into remission seems be the keystone.

00:08:36: Pradeep Mundre: And the other take-home point there is IVF treatments are equally effective, or very effective in patients compared to the general population.

00:08:46: Mette Julsgaard: Exactly.

00:08:47: Mette Julsgaard: So, IVF treatment is just as effective in women with IBD as in the background population.

00:08:53: Mette Julsgaard: So, yes, it's all about keeping the patient in remission, thereby increasing the likelihood of falling pregnant.

00:09:00: Pradeep Mundre: Okay, well, that's a good point to note, Mette.

00:09:02: Pradeep Mundre: Let's go back to a sort of preconception management.

00:09:06: Pradeep Mundre: Let's say you have a young woman with IBD in your clinic, and you come across, and they, mostly they don't mention all these things in IBD clinic for some reason, but let's say they discuss about conception.

00:09:18: Pradeep Mundre: So, what's going on in your mind?

00:09:20: Pradeep Mundre: What are the things that you would do?

00:09:21: Pradeep Mundre: Maybe on a practical note, how you run your service, and what sort of things are going on in terms of medications?

00:09:28: Pradeep Mundre: What do you think, what are you thinking about in such patients, optimizing them before conception?

00:09:33: Mette Julsgaard: So, before moving to the medical treatment aspect, I always review and discuss with the patient whether she's been pregnant before, because we know that if you've been pregnant before, and you had active disease in that previous pregnancy, the likelihood of experiencing disease activity in a subsequent pregnancy is actually increased by threefold.

00:09:58: Mette Julsgaard: So, that's sort of a red flag that I need to keep extra care, take extra care of this patient in pregnancy in order to ensure remission.

00:10:07: Mette Julsgaard: And then, of course, I review how the patient is doing on the particular drug they are receiving, like measuring like calprotectin, reviewing the charts, when had this patient endoscopy the last time, is it time just to do a checkup?

00:10:21: Mette Julsgaard: If everything is looking fine, then as a rule of thumb, she stay on that particular drug.

00:10:26: Mette Julsgaard: There are a few exceptions, I'll address that, but it's all about keeping the patient in remission.

00:10:31: Mette Julsgaard: If there are signs of flaring, then you need to address that, and potential changing the medical therapy, dose optimization, whatever it.

00:10:40: Mette Julsgaard: takes to ensure remission.

00:10:42: Mette Julsgaard: That's what's needed.

00:10:44: Mette Julsgaard: And another important aspect is, of course, micronutrition.

00:10:47: Mette Julsgaard: In women who mention they want to fall pregnant or who are pregnant, I always check iron level, because women with IBD are at increased risk of iron deficiency compared to the background population.

00:11:01: Mette Julsgaard: But I also check vitamin D levels, B12 and B9, and optimize those micronutrition in case they are lacking.

00:11:11: Mette Julsgaard: Because that is also a very important part of taking care of women who want to fall pregnant or who are pregnant.

00:11:18: Mette Julsgaard: It gives a better course of the pregnancy, reduces the risk of maternal morbidity and complications during pregnancy, ensures sufficient growth of placenta and the fetus.

00:11:30: Pradeep Mundre: Okay.

00:11:31: Pradeep Mundre: So the two key points there, I picked up is optimizing nutrition and optimizing to ensure that the disease is in remission before you think about conception.

00:11:42: Mette Julsgaard: Yes.

00:11:43: Pradeep Mundre: And in terms of medications, maybe I don't know whether we could talk about it now, or maybe later, but in the preconception medications, what are the medications to avoid?

00:11:53: Pradeep Mundre: What are the ones to continue?

00:11:55: Mette Julsgaard: Yeah.

00:11:56: Mette Julsgaard: So the main issue is really that the JAK inhibitors and the S1Ps should be avoided during pregnancy.

00:12:05: Mette Julsgaard: Hence, you need to discontinue treatment with those type of drugs prior to pregnancy.

00:12:10: Mette Julsgaard: And of course, it's easy to state that in the guideline, you need to avoid JAK inhibitors.

00:12:14: Mette Julsgaard: But if you have failed all other types of treatment, and you are now in remission on a JAK inhibitor, what to do then?

00:12:21: Mette Julsgaard: So as we have also stated in our new global consensus that JAK inhibitors and S1Ps for that matter, should only be used if there are no other viable option for maternal health.

00:12:34: Mette Julsgaard: So in case a woman has failed all of the biologics, any of our other standard treatments, then you need to have a detailed discussion regarding pros and cons for continuing the drug during the conception period.

00:12:47: Mette Julsgaard: Because if you decide to continue that particular drug during the conception period, then you are also going to continue in pregnancy because you have no other medical option to ensure remission.

00:13:00: Mette Julsgaard: The reason why we are concerned about the JAK inhibitors are that the animal studies, again, bear in mind, those were conducted in rabbits and rats, but they indicated increased risk of malformations.

00:13:14: Mette Julsgaard: And for some of the drugs,

00:13:15: Mette Julsgaard: also fetal death.

00:13:17: Mette Julsgaard: We have not seen that in human data.

00:13:19: Mette Julsgaard: That's important for me to stress.

00:13:22: Mette Julsgaard: We, of course, have limited safety data.

00:13:25: Mette Julsgaard: The drugs we have most data on are tofacitinib and UPA, the two JAK inhibitors.

00:13:31: Mette Julsgaard: But again, the data we have available is primarily first trimester exposure, but that is also during the organogenesis.

00:13:40: Mette Julsgaard: And again, the data we have not shown any signals of increased risk of malformations.

00:13:46: Mette Julsgaard: And we have so far, an American colleague and I have collected more than 60 cases now, not published only, preliminary data at conferences, but 60 cases of exposure to JAK inhibitors throughout pregnancy, where we haven't seen increased risk of either maternal or adverse pregnancy outcome.

00:14:07: Mette Julsgaard: So those data, although limited, are reassuring.

00:14:11: Mette Julsgaard: And that needs to be discussed with our patients.

00:14:14: Mette Julsgaard: Pros and cons for continuation of these drugs during the preconception period and pregnancy.

00:14:20: Mette Julsgaard: And then, of course, clearly documentations in the medical files, what you have agreed on with your patients.

00:14:26: Mette Julsgaard: For all the other drugs, there are no negative effects on fertility when it comes to 5-ASA.

00:14:33: Mette Julsgaard: Corticosteroids, antibiotics can be used, used for a short period of time, thiopurines as well, and all of the biologics, also the newer biologics and thiopurines as well.

00:14:45: Mette Julsgaard: And that's for women.

00:14:47: Mette Julsgaard: When it comes to, we should never forget men when we talk about fertility and pregnancy as well.

00:14:53: Mette Julsgaard: When it comes to men, one needs to keep in mind that sulfasalazine, although we don't use it as frequent, but in patients with arthritis as well, then sulfasalazine is still a drug.

00:15:06: Mette Julsgaard: Which is being used.

00:15:07: Mette Julsgaard: That actually results in reversible oligospermia.

00:15:12: Mette Julsgaard: But in case you discontinue sulfasalazine, the sperm count will be within normal range for that particular male within three months.

00:15:22: Mette Julsgaard: So that's important to keep in mind.

00:15:25: Mette Julsgaard: And another key thing is, because previously we said methotrexate had to be discontinued.

00:15:31: Mette Julsgaard: That is only the case in women, because it increases the risk of malformations.

00:15:35: Mette Julsgaard: But in men, new data has shown that a low-dose methotrexate therapy does not affect semen parameters or sperm DNA.

00:15:45: Mette Julsgaard: So men on methotrexate who wants to become fathers can continue this particular drug.

00:15:51: Pradeep Mundre: Okay.

00:15:52: Pradeep Mundre: So the bottom line on that is, in the preconception period, stop JAK or if there's an alternative.

00:15:58: Pradeep Mundre: Of course, methotrexate.

00:15:59: Pradeep Mundre: should be stopped.

00:16:00: Pradeep Mundre: And all other drugs can be continued if patients are stable on them.

00:16:06: Mette Julsgaard: Exactly.

00:16:07: Pradeep Mundre: And with the JAK inhibitors, if there's no other alternative, an individual decision and probably a sort of consultation with somebody who specializes in this.

00:16:15: Pradeep Mundre: And counseling, I guess, is the most important thing on this one.

00:16:19: Pradeep Mundre: For the audience, can you just remind us what S1P inhibitors are?

00:16:24: Mette Julsgaard: The etrasimod

00:16:24: Mette Julsgaard: and ozanimod.

00:16:26: Mette Julsgaard: So we are not using those drugs that much, but they are definitely being used in, especially ozanimod in a patient who has MS as well, because ozanimod can be used in both sclerosis, but also in ulcerative colitis.

00:16:41: Mette Julsgaard: So that's definitely an option there.

00:16:44: Mette Julsgaard: So an etrasimod as well can be used in ulcerative colitis.

00:16:48: Mette Julsgaard: But we, I actually, I have experience using JAK-inhibitors both prior to and during pregnancy.

00:16:55: Mette Julsgaard: So far, I haven't had any patients on an S1P during pregnancy for now.

00:17:02: Pradeep Mundre: And Mette, this applies to all the new drugs, IL-23.

00:17:06: Pradeep Mundre: I don't use these terms, I use the drug names.

00:17:09: Pradeep Mundre: But anyway, the new drugs, guselkumab, mirikizumab and risankizumab.

00:17:14: Pradeep Mundre: So this applies, this rule applies to them as well?

00:17:17: Mette Julsgaard: No, definitely not.

00:17:18: Mette Julsgaard: So the new anti-IL-23 inhibitors, risankizumab, mirikizumab, guselkumab, they are all biologics.

00:17:26: Mette Julsgaard: So large immunoglobulins, which doesn't pass placenta during the first trimester, they start passing actively from around gestation week, 15, 16 and throughout pregnancy, exponential increase during the third trimester.

00:17:43: Mette Julsgaard: Just like we know for infliximab, adalimumab, ustekinumab and vedolizumab, they are all biologics.

00:17:49: Mette Julsgaard: And of course, we have so far limited safety data with these newer biologics, but I am completely at ease by using them in pregnancy because we have such a great knowledge regarding the other biologics, which we have used like infliximab have been in use since around the year 2000.

00:18:09: Mette Julsgaard: And we have really seen an exponential increase in the use of TNF-alpha inhibitors like the biologics since 2010 and up until now.

00:18:18: Mette Julsgaard: And we have a lot of safety data regarding its use in pregnancy.

00:18:23: Mette Julsgaard: We have seen no increased risk of congenital malformations for any of the biologics, no increased risk of adverse pregnancy overall.

00:18:31: Mette Julsgaard: Infants of mothers exposed to biologics are doing really well.

00:18:35: Mette Julsgaard: Normal development, we have seen that across different studies.

00:18:40: Mette Julsgaard: And also in case of monotherapy, no increased risk of infections.

00:18:46: Mette Julsgaard: And bear in mind, infants, they do get infections.

00:18:49: Mette Julsgaard: And we have seen infections in infants exposed to biologics as well.

00:18:54: Mette Julsgaard: But in case of infections, they respond just as well to antibiotics and other treatments like other infants.

00:19:00: Mette Julsgaard: So definitely continue these drugs in pregnancy.

00:19:03: Mette Julsgaard: And that also goes for the newer biologics like the anti-IL-23.

00:19:09: Pradeep Mundre: Excellent, Mette.

00:19:10: Pradeep Mundre: Let's move on to pregnancy.

00:19:12: Pradeep Mundre: And let's say the patients are exhibiting signs of active disease and you do need to investigate them.

00:19:18: Pradeep Mundre: Can you talk about the investigations during pregnancy?

00:19:20: Pradeep Mundre: Which ones are safe?

00:19:21: Pradeep Mundre: Which ones are to avoid in patients?

00:19:24: Mette Julsgaard: Well, to keep it simple, most investigations are safe in pregnancy.

00:19:29: Mette Julsgaard: Basically, it's only a capsule endoscopy which should be avoided.

00:19:33: Mette Julsgaard: But you can perform endoscopy throughout all trimesters in pregnancy.

00:19:38: Mette Julsgaard: It's

00:19:38: Mette Julsgaard: low risk.

00:19:39: Mette Julsgaard: But of course, it should only be performed when needed to guide clinical decision.

00:19:43: Mette Julsgaard: One important point regarding endoscopy is that the patient should always be in the left lateral position to avoid compression of the inferior vena cava.

00:19:54: Mette Julsgaard: And I guess most of the patients are always in the left lateral position.

00:19:57: Mette Julsgaard: But sometimes you do change the position.

00:19:59: Mette Julsgaard: And that's where you need to keep in mind in case of a pregnant patient, especially during the second part of the pregnancy, always left lateral position.

00:20:08: Mette Julsgaard: Because if you do suppress the inferior vena cava, it may lead to maternal hypotension and reduced placental perfusion.

00:20:18: Mette Julsgaard: And you really need to avoid that.

00:20:19: Mette Julsgaard: I want to highlight, I think it was in the Red Journal, American Journal of Gastroenterology in 2025.

00:20:26: Mette Julsgaard: There is an excellent article on endoscopy in pregnancy.

00:20:30: Mette Julsgaard: So highly recommendable to search for that article if you do a lot of endoscopy in pregnant patients.

00:20:38: Mette Julsgaard: So when it comes to CT and MRI without gadolinium.

00:20:44: Mette Julsgaard: Those can also be performed in pregnancy to guide clinical decision.

00:20:49: Mette Julsgaard: And in intestinal ultrasound, we use that increase in our IBD patient.

00:20:55: Mette Julsgaard: And it's very accurate during the first and the second trimester of pregnancy.

00:20:59: Mette Julsgaard: It's more challenging in the third trimester, especially when it's difficult to visualize the sigmoid colon and the terminal ileum.

00:21:08: Mette Julsgaard: But it's a great tool to visualize also for the patients that look, there's actually signs of active disease.

00:21:16: Mette Julsgaard: And we need to also the medical treatment based on these findings.

00:21:20: Pradeep Mundre: But if you have a choice.

00:21:21: Pradeep Mundre: between the, you said CT was safe and you absolutely need to do some imaging on this patient.

00:21:26: Pradeep Mundre: And you have a choice.

00:21:27: Pradeep Mundre: You work in a center where you can get an MRI scan in a day.

00:21:30: Pradeep Mundre: Would you choose an MRI scan versus a CT?

00:21:33: Mette Julsgaard: Yeah, well, if there's no waiting list and it's easy to get and you can get a description of it shortly after it's been performed, then an MRI without gadolinium would, of course, be the choice of scan.

00:21:45: Mette Julsgaard: But again, if that's not feasible, then a CT is still, it's a very, very low dose exposure of mom and infant.

00:21:53: Mette Julsgaard: And if you are in doubt whether there might be an abcess or anything, then perform the CT.

00:21:59: Mette Julsgaard: Really, it's important that you get the right sort of answers.

00:22:02: Mette Julsgaard: To guide your clinical decision and treatment of the patient.

00:22:07: Pradeep Mundre: And with the calprotectin, would you trust it similar?

00:22:10: Pradeep Mundre: Are there any changes during pregnancy?

00:22:12: Pradeep Mundre: Would you trust it the way you would interpret it in a non-pregnant person?

00:22:16: Pradeep Mundre: So are there any physiological changes that affect calprotectin at all?

00:22:19: Mette Julsgaard: Yeah, so I'm really glad you highlight that, Prad, because we know that, as you also indicate here, that CRP and the leucocyte count is increased in pregnancy just as a result of being pregnant because of the physiological changes.

00:22:33: Mette Julsgaard: So having slightly elevated inflammation markers in blood tests might not be due to active disease more as a result of being pregnant.

00:22:43: Mette Julsgaard: Whereas calprotectin, we've shown that beforehand, is not affected by pregnancy.

00:22:49: Mette Julsgaard: So that we can actually use calprotectin to guide clinical decision and using the same cutoff as in the non-pregnant patient.

00:22:57: Pradeep Mundre: So, Mette, I know we've already spoken fairly in depth on medications.

00:23:02: Pradeep Mundre: Use preconception.

00:23:04: Pradeep Mundre: We'll continue the same theme of medications in pregnancy.

00:23:07: Pradeep Mundre: Take us through each class of drugs and just mention whether you would continue them in pregnancy and breastfeeding, or whether you would initiate such class of drugs during pregnancy and breastfeeding, and would you use it in case of active disease.

00:23:19: Pradeep Mundre: If you just go through each class of drugs and mention their safety data.

00:23:23: Mette Julsgaard: Yeah, so first of all, always folic acid supplements in a patient who wants to fall pregnant.

00:23:30: Mette Julsgaard: That's important.

00:23:31: Mette Julsgaard: And also during pregnancy.

00:23:32: Mette Julsgaard: When it comes to amino salicylic acid, it's like 5-ASA.

00:23:37: Mette Julsgaard: That is.

00:23:37: Mette Julsgaard: safe and does not affect fertility, can be continued throughout pregnancy, also at the highest dose, and also during breastfeeding.

00:23:45: Mette Julsgaard: Of course, folic acid supplementation at a higher dose in case of sulfasalazine.

00:23:51: Mette Julsgaard: When it comes to corticosteroids, it can be used prior to during and during pregnancy, and also during breastfeeding.

00:23:59: Mette Julsgaard: Minimize the dose and always imply a steroid-sparing therapy.

00:24:04: Mette Julsgaard: We have seen in a large Taiwanese study, but also in the PIANO registry, prospective registry, that in case of exposure, especially during the second or third trimester, of pregnancy.

00:24:15: Mette Julsgaard: That was the case

00:24:16: Mette Julsgaard: in the PIANO cohort.

00:24:18: Mette Julsgaard: Infants exposed to corticosteroids are at increased risk of infections during the first year of life.

00:24:25: Mette Julsgaard: However, if corticosteroids are needed, they should be used in order to ensure remission, but shortest possible duration.

00:24:34: Mette Julsgaard: Antibiotics, that can be used as well, but in case of infections like fistulas or paroxiditis, again, a short course, both during pregnancy and during lactation as well.

00:24:46: Mette Julsgaard: When it comes to thiopurine, there was an FDA warning, I think in 2024, stating increased risk of intrahepatic cholestasis of pregnancy.

00:24:55: Mette Julsgaard: I actually always mention this to our patients because some.

00:24:58: Mette Julsgaard: of our patients, they look at the internet and they see this warning and they get deeply concerned, and they might stop the treatment.

00:25:04: Mette Julsgaard: So address it and say, like, look, the risk of intrahepatic cholestasis in pregnancy is in general very low, around 1%.

00:25:14: Mette Julsgaard: And these smaller studies indicated increased risk of cholestasis in case of thiopurine exposure.

00:25:21: Mette Julsgaard: The risk is around 6% to 7%, so low.

00:25:24: Mette Julsgaard: So I continue, in case of monotherapy with thiopurines, I continue this during pregnancy, but I recommend control liver enzymes at least every trimester, and you can consider also monitoring metabolites.

00:25:40: Mette Julsgaard: But never increase the dose with increase in weight during pregnancy.

00:25:45: Mette Julsgaard: So keep the pre-pregnancy dosing, that's important.

00:25:49: Mette Julsgaard: And of course, if you have a patient who's on combination therapy, like infliximab and with thiopurine, consider stopping the thiopurine.

00:25:57: Mette Julsgaard: Is it really needed to keep the patient in remission?

00:26:01: Mette Julsgaard: But of course, this discussion would be best prior to pregnancy and not during pregnancy.

00:26:08: Mette Julsgaard: And methotrexate, we discussed that before, that this should be discontinued prior to pregnancy, at least one to three months prior to conception.

00:26:16: Mette Julsgaard: If I rarely have experienced patients falling pregnant with methotrexate, then referral to the obstetric department, extra scan, discontinue the treatment, initiate another type of treatment, another like a biologic, which is perfectly safe during pregnancy.

00:26:33: Mette Julsgaard: So, and that sort of leads on to biologics.

00:26:36: Mette Julsgaard: All of the biologics, the TNF-alpha inhibitors, the anti-integrins, the anti-IL-23, 23, and also the newer anti-IL-23, which we discussed before, like the mirikizumab, risankizumab, guselkumab.

00:26:51: Mette Julsgaard: All of these can be continued throughout pregnancy.

00:26:54: Mette Julsgaard: We have, as I highlighted, excellent data on infants exposed during pregnancy, and they're doing really well and no increased risk of infections.

00:27:02: Mette Julsgaard: So, please

00:27:03: Mette Julsgaard: continue in pregnancy.

00:27:05: Mette Julsgaard: And also whilst breastfeeding.

00:27:09: Mette Julsgaard: And I highlight this both during pregnancy and just after giving birth again, because it seems that our women, they accept they need these drugs during pregnancy, but once they're giving birth and they're breastfeeding their child, they start to get concerned about, is this really safe?

00:27:26: Mette Julsgaard: And yes, these drugs can be continued throughout breastfeeding.

00:27:30: Mette Julsgaard: There is this rule of thumb saying that if a drug can be measured, that the drug measurement in maternal milk is less than 10% of what you can measure in the blood, then.

00:27:41: Mette Julsgaard: you can continue the drug.

00:27:43: Mette Julsgaard: For all of the biologics, what you can measure in the milk is less than 1%.

00:27:49: Mette Julsgaard: So, these biologics penetrate poorly into breast milk, and they are not designed to be absorbed from the GI tract either.

00:27:57: Mette Julsgaard: So, really, the exposure of the infant is extremely low.

00:28:00: Mette Julsgaard: And another key point, sort of just reassuring that these drugs can be safely used whilst breastfeeding is that when look at infants exposed to these drugs during pregnancy, looking at the clearance of these drugs in the infants, breastfeeding did not affect time to clearance.

00:28:20: Mette Julsgaard: So, really, it's safe to use biologics whilst breastfeeding.

00:28:25: Mette Julsgaard: And finally, for the JAK inhibitors, tofacitinib, upa and filgotinib, again, use only, as we discussed, if there's no other viable option to maintain maternal health, keeping the woman in remission during pregnancy.

00:28:39: Mette Julsgaard: I have actually also initiated treatment during the second and third trimester with a JAK inhibitor in pregnancy because we had no other viable option in order to ensure remission in case of severe active disease.

00:28:55: Mette Julsgaard: But when it comes to breastfeeding, we have done extensive investigations for both tofacitinib and for UPA.

00:29:01: Mette Julsgaard: And although the relative infant exposure is around 3% to 4%, there's also all the active metabolites, and we know the absorption from the infant gut is really high.

00:29:14: Mette Julsgaard: And we don't know how these drugs actually affect the developing immune system in the neonate.

00:29:21: Mette Julsgaard: And because there's a great option like bottle feeding the infant, I highly recommend, as we have also stated in the global consensus, that in case of treatment with JAK inhibitors, but also S1Ps during the breastfeeding period, then this woman should not breastfeed.

00:29:40: Mette Julsgaard: Bottle feeding is the best.

00:29:42: Mette Julsgaard: Formula feeding is the best option for those women.

00:29:46: Mette Julsgaard: We have no lactation

00:29:47: Mette Julsgaard: data for other Ozanimod and Etrasimod, so the S1Ps.

00:29:54: Mette Julsgaard: So, until we have data, breastfeeding should be avoided as well.

00:29:58: Pradeep Mundre: Okay.

00:29:59: Pradeep Mundre: So, the take-home, Mette, 5-ASAs continue and safe, thiopurine safe, but monitor more.

00:30:06: Pradeep Mundre: Of course, methotrexate would have stopped.

00:30:08: Pradeep Mundre: Stop if they fall pregnant.

00:30:10: Pradeep Mundre: Avoid JAK inhibitors.

00:30:11: Pradeep Mundre: Avoid S1P receptor modulators.

00:30:13: Pradeep Mundre: But all the other anti-TNFs, vedolizumab, ustekinumab, newer IL-23, which is mirikizumab, present kizumab, continue, and corticosteroids.

00:30:23: Pradeep Mundre: Try to minimize the dose by replacing.

00:30:26: Pradeep Mundre: I'm assuming that instead of continuing low-dose corticosteroids, you'd rather.

00:30:30: Pradeep Mundre: initiate a biological treatment rather than using a low-dose steroid.

00:30:35: Pradeep Mundre: So, you would want to minimize the steroids as much as possible.

00:30:38: Pradeep Mundre: Is that sort of the take-home?

00:30:41: Mette Julsgaard: That's spot on.

00:30:42: Mette Julsgaard: Really, if you have active disease in pregnancy, we have highlighted that in the ECCO guideline and also in the global guideline, you need to treat active disease aggressively, just as in the non-pregnant patients.

00:30:53: Mette Julsgaard: Even more so, I think, in pregnant patients, it's hand-on.

00:30:56: Mette Julsgaard: So, really, initiate new types of treatments in pregnancy.

00:31:00: Mette Julsgaard: That also goes for biologics.

00:31:02: Mette Julsgaard: And, of course, biological naive, infliximab, adalimumab, fast-acting biologics, in order to ensure remission.

00:31:10: Mette Julsgaard: You might then not even need to use steroids.

00:31:13: Mette Julsgaard: Or then, in case of steroids, it's needed as bridging, shortest possible duration.

00:31:18: Mette Julsgaard: What I've done also when it comes to, for instance, vedolizumab, ustekinumab, but also, more recently, risankizumab, mirikizumab, and guselkumab, the anti-IL-23s, that initiate this treatment in pregnancy.

00:31:32: Mette Julsgaard: And then, of course, of budesonide, because that bridging to ensuring remission on a biologic is a great option as well.

00:31:42: Mette Julsgaard: But in case of systemic corticosteroid is needed, then shortest possible duration.

00:31:47: Mette Julsgaard: But again, the main focus should.

00:31:49: Mette Julsgaard: always be ensuring remission.

00:31:52: Mette Julsgaard: So, never use low dose of corticosteroids just to ensure remission.

00:31:56: Mette Julsgaard: Then you need to also the treatment.

00:31:59: Mette Julsgaard: Initiate biologics if needed.

00:32:01: Pradeep Mundre: Okay.

00:32:01: Pradeep Mundre: That's a very good way to put it.

00:32:03: Pradeep Mundre: Well, a couple of miscellaneous things I just want to bring up.

00:32:06: Pradeep Mundre: In preparation, I was just going through your consensus statement.

00:32:09: Pradeep Mundre: Something struck me, which I was totally unaware of.

00:32:12: Pradeep Mundre: It's about aspirin use.

00:32:13: Pradeep Mundre: Can you mention about this, and then why are you talking about it in the consensus statement?

00:32:20: Mette Julsgaard: Yeah, this is new in the consensus statement as well.

00:32:23: Mette Julsgaard: There has been different national recommendation regarding the use of low dose aspirin in women with the IBD.

00:32:30: Mette Julsgaard: And I'm really happy about that.

00:32:31: Mette Julsgaard: We have summarized the data available in the global consensus.

00:32:35: Mette Julsgaard: And we have one global recommendation now.

00:32:37: Mette Julsgaard: And really, women with the IBD should be started on a low dose of aspirin between gestation week 12 and 16.

00:32:46: Mette Julsgaard: So, always initiate low dose of aspirin prior to gestation week 16 in order to reduce risk of preeclampsia.

00:32:55: Mette Julsgaard: Women with IBD, especially women with Crohn's disease, are at increased risk of preterm preeclampsia and early onset preeclampsia.

00:33:05: Mette Julsgaard: And those are.

00:33:06: Mette Julsgaard: really the conditions we need to be aware of.

00:33:09: Mette Julsgaard: Because they are high risk for both mom and infants.

00:33:12: Mette Julsgaard: And by starting a low dose of aspirin, we reduce the risk markedly.

00:33:17: Mette Julsgaard: We have also seen that women with IBD who have active disease, they are at increased risk of preeclampsia.

00:33:25: Mette Julsgaard: Hence, also women with ulcerative colitis needs to be started on a low dose of aspirin.

00:33:30: Mette Julsgaard: So again, to keep it simple, in order to reduce the risk of preeclampsia in women with IBD, you need to start a low dose of aspirin prior to gestation week 16.

00:33:41: Mette Julsgaard: And then, of course, one can discuss discontinuing the treatment around gestation week 37 in order to reduce the risk of bleeding close to term.

00:33:50: Mette Julsgaard: But really, of utmost importance, please do start your patients or the obstetricians who started.

00:33:56: Mette Julsgaard: But either the gastroenterologist or the obstetrician should start a low dose of aspirin in IBD patients.

00:34:04: Pradeep Mundre: Okay, that's a good point, Mette.

00:34:06: Pradeep Mundre: I think it was something that was completely new, I thought.

00:34:08: Pradeep Mundre: Hi, it's Pradeep here from after the recording.

00:34:11: Pradeep Mundre: Unfortunately, or maybe fortunately, our conversation with Mette ran much longer than we planned.

00:34:18: Pradeep Mundre: And rather than cutting it back, we thought we'd release it in two parts.

00:34:23: Pradeep Mundre: So part two will be out on Wednesday, the 2nd of September.

00:34:28: Pradeep Mundre: We continue our conversation, the exciting conversation that we've had so far.

00:34:33: Pradeep Mundre: We delve into some difficult conversations where I discuss with Mette in situations where you ran out of all advanced options and the only option left for a disease flare during pregnancy is JAK inhibitor.

00:34:49: Pradeep Mundre: How would she deal with such a situation?

00:34:52: Pradeep Mundre: Would she use JAK inhibitors in such situation?

00:34:56: Pradeep Mundre: Or would you give low-dose steroids?

00:34:59: Pradeep Mundre: Or would you live with an active disease?

00:35:02: Pradeep Mundre: So these are difficult questions and difficult answers for Mette to discuss.

00:35:06: Pradeep Mundre: But we talk about that.

00:35:08: Pradeep Mundre: We also discuss about surgery and acute severe colitis in the episode.

00:35:13: Pradeep Mundre: So please tune back in on the 2nd of September for continuation of the second part of this episode.

00:35:21: Pradeep Mundre: Until then, why not listen to some of the older episodes?

00:35:24: Pradeep Mundre: Goodbye.