We'll invite the next speaker. It's a pleasure to invite Dr. Susie Cain, who's actually a professor of medicine at Mayo Clinic Rochester, and she's one of the experts in management of IBD during pregnancy. And we asked her to talk on the role of diagnosing therapeutic endoscopy fibro during pregnancy, indications and precautions. Welcome, Dr. Cain. Thank you for inviting me to do this. Endoscopy in the IBD patient during pregnancy, well, just as we heard from the last speaker that there's not a lot of specific data in this area, I'm going to show you basically what the evidence is. So if there are trainees or fellows out there or young faculty who need another niche, this is right for study. So I thought what I would do is because not necessarily a lot of people think about scoping the pregnant patient that we're going to just talk a little bit about in general, and then I'll show you the actual data. So I just want to make sure that you guys all understand the background of the FDA categories and what the context is for medications as we talk about that. And so the FDA categories, I will tell you, are no longer used formally, but we all seem to go back to them because we're so comfortable. And it's going to take another seven years or so to understand that we have to use data. But a Category A means that controlled studies in animals and women have shown no risk in the first trimester, so that possible fetal harm is remote. There are very few Category A therapies, which is why the FDA realized that it really needs to change their vernacular. A B means that either animal studies have not demonstrated a fetal risk, but there are no controlled studies in pregnant women, or that animal studies have shown an adverse effect, but has not been confirmed in humans. So that's a lot of rigamarole that basically means that animal studies are considered safe and that there's lack of data to show harm in women. So that's a B. C means no controlled studies in humans, but that in animals, there have been adverse events, but that if you need the medication to treat mom, you do it. D is that there is evidence of fetal risk, but again, the benefits may outweigh the risks. And then X is where the medication is absolutely contraindicated. So having said that, the Federal Register in 2008, so that was a long time ago, said, hey, this system is antiquated and not appropriate, and that every prescribing insert now has to have separate categories for pregnancy, labor and delivery, and nursing for every medicine that's out there. And that this label is to include a summary of the risk and the discussion of any data supporting that summary. So that we've eliminated these A through X categories, and that if you notice any new therapies that are coming or have recently been FDA approved, that they just have these paragraphs and summaries now, and they don't give you a pregnancy rating or category. So it's up to you to decide what to do in terms of using that therapy. So that comes into context when we start talking about therapies and medications that we use during endoscopy, because you were wondering where I was going with all of this, and that's where I was going. So as we talk about the medications used during endoscopy, what do we know about their safety? So let's just stop a minute and talk about, I don't need to necessarily tell this advanced group the indications for endoscopy, but the indications for endoscopy during pregnancy is significant or continued GI bleeding, severe or refractory nausea, vomiting to where there is metabolic derangement, dysphagia or odoniphagia, and again, all of these indications are for when there is going to be a change in management based on endoscopic findings. A strong suspicion for colon neoplasm, again, because you can give chemotherapy during pregnancy, so if there is a strong suspicion because of family history or a genetic disorder, then you can scope them. Severe diarrhea with an otherwise negative non-invasive workup, again, because management is going to change if you have biopsies. Now again, you want to do an ERCP only if it's going to be interventional, not just necessarily diagnostic, so that would be for biliary pancreatitis, symptomatic choledocholithiasis or cholangitis, or biliary or pancreatic duct injury. So in pregnancy, the principles of endoscopy, I will refer you to an excellent guide, which is the ASGE Guidelines for Endoscopy During Pregnancy, published in now very outdated January of 2012, but believe me, this is the most recent updated guideline that's out there, so again, if you are looking for a project, this might be an area, but unfortunately, there's not a lot of updates, just because we haven't added necessarily any kind of new significant techniques or medications to our armamentarium. The endoscopy is safe if the appropriate reason for performing the procedure exists, that monitoring the fetus is recommended if the patient is in her second or third trimester, it goes without saying really that you want to use as little sedation as possible, and that a full colonoscopy is rarely indicated, unless again, you are suspecting a right-sided colonic lesion. So in terms of general principles, that pre-procedure consultation with an obstetrician is necessary regardless of the fetal age, that again, and I'll say this and stress it multiple times, that you always need to have a strong indication that i.e. it will change your management so that you want it to be very diagnostic or else actually therapeutic, but having said that, you know, do not endanger maternal health by delaying what is an appropriate procedure. So I'm saying, well, maybe we don't really need to do this, don't put it off if it's actually going to endanger maternal health. Defer endoscopy to the second trimester whenever possible, but again, if a patient is having a significant GI bleed, you do not defer that endoscopy. You want to position the patient in the left pelvic tilt or left lateral position to avoid the vena cava or aortic compression. So some more general principles is that if the pregnancy is before 24 weeks of gestation, it is sufficient to confirm the presence of fetal heart tones by Doppler before sedation and then after the procedure. However, if you are doing this procedure after 24 weeks gestation, that's simultaneous monitoring of fetal heart rates and uterine contractions before and after the and then ideally throughout the procedure. So then this obviously means that you need an obstetrician with you in the room. So even more general principles that I think are important to keep in mind is that amniotic fluid can conduct electrical current. So be mindful where you are putting that pad if you have to do cautery and that you should use bipolar electrocautery to minimize the risk of that I should say stray current going through the fetus. And then endoscopy and lactating women is not different from non-pregnant women, although care about certain medications, particularly the antibiotics that are transferred to breast milk. All right, so what are contraindications to endoscopy during pregnancy? Placental abruption, imminent delivery, ruptured membranes, or uncontrolled eclampsia. These are all considered obstetric emergencies where delivery is utmost importance and that you need to put off an endoscopy until there has been a delivery. All right, so let's get back to our endoscopic medications discussion. That if you need to give antibiotics beforehand, use ampicillin and gentamicin. That propofol is preferred sedation if available, otherwise midazolam and meparidine. So that's the M&M for mothers to be. If you are going to do a colonoscopy or even an extended flexible sigmoidoscopy, a one-time use of polyethylene glycol is fine. And again, if the patient is lactating or nursing, that you need to pump and dump if certain antibiotics are used and we're going to talk about those. All right, so here is the entire list. Well, not necessarily the entire, but a list of the common therapies that we use during endoscopy. And then I just finished telling you that we don't use the FDA scores anymore or the grades, but I think again, most of us are in that mindset and that it's going to take education to get us out. So I do put those in here just to help you. So ampicillin is what I told you, you should use for antibiotic use. It is safe for both endoscopy and for nursing. Diazepam is not to be used. Midazolam, which has a shorter half-life. So the M&M for mom is what's preferred. Again, electricity is okay to use if you need to. Bipolar electrocautery is preferred. Epinephrine should be avoided unless there is frank bleeding that you need to use this as your intervention. Fentanyl you can use in low doses. Flumazenil is obviously okay if you need to treat for a benzodiazepine overdose. And both of those are okay for nursing. Gentamicin is the other antibiotic that you're going to use as opposed to the ampicillin. Glucagon is okay to use for ERCP. We do not necessarily know the effect on nursing. Lidocaine is okay if you want to use it for an upper endoscopy. Gargle and spit it out. Meparidine is the other M that you can use for sedation if you are not using propofol. Midazolam is better than diazepam, but you want to try to use as little as possible for that procedure. Obviously, nonaxone is appropriate for severe overdoses. Polyethylene glycol, again, as I said, is to be used for the prep. It's interesting that there are no human data during pregnancy. Again, because, and I'll tell you that what I do during pregnancy is that most of the time you can get away with an unprepped flexig as opposed to a full prepped colonoscopy. Propofol is actually to be avoided in the first trimester if at all possible. And that if you're going to use glycol electrolyte solutions, again, a one-time use is fine. All right. So what are the data for the safety of endoscopy during pregnancy? So this is an updated paper out of the Swedish Medical Birth Registry. This was Jonas Lugvisson who put this together. And it was published in Gastro in 2017. So it's the only paper that is more updated than the guideline of 2012, but I think it's an important paper. And thus, perhaps the practice parameters group at ASGE should think about updating their endoscopy guidelines. So this was a nationwide population-based study, 3,000 pregnancies exposed to endoscopy. And most of those were upper endoscopies, 1,100 lower endoscopies, 58 ERCPs compared to 1.5 million unexposed. So what they did was they examined pregnancy outcomes in terms of preterm birth, stillbirth, small for gestational age or congenital malformations in endoscopy just before or after pregnancy. And again, not necessarily looking at as much during pregnancy as we would have hoped. But what they did look at during pregnancy was the exposure to endoscopy as their primary risk factor and that there was an increased adjusted relative risk for preterm birth, for small for gestational age, not for congenital malformations and not for stillbirth. And none of the 15 stillbirths into women with endoscopy occurred within less than two weeks after that endoscopy. And these adjusted relative risks were independent of trimester. So what are the takeaway points here is that preterm birth and small for gestational age appear to be associated with having an endoscopy during pregnancy. And the authors I think very reasonably concluded that the reason that we saw that is because of the underlying condition of the mom that necessitated an endoscopy during her pregnancy. So congenital malformations and stillbirths, which have to do with the health of the fetus itself, was not affected by having an endoscopy during pregnancy. All right, so here we go. What do we know about safety of colonoscopy and IBD? These are data published by the Dilema Group and this is from 2015. There are no other more updated papers. This was a case control of pregnant IBD patients matched to age, medications of use and disease activity. 42 women underwent 47 lower GI procedures over a time span of about seven to eight years. The median birth weight was lower in cases, but there was no difference in spontaneous abortions, gestational age, birth defects or APGAR scores in the women with IBD who needed to undergo a procedure during their pregnancy. So what do these very limited data tell us? That if you need to do an endoscopy during pregnancy in an IBD patient, that you should do it, again, if your indication is strong. So what do I do for a pregnant IBD patient? I try to get away with an unprepped flex sig without sedation. So I will schedule it so that I am doing it so the mom knows that it's me. I'll use an upper scope and when am I doing this? I am doing this in refractory ulcerative colitis where tissue acquisition is important to rule out CMV. I've already done my stool studies to make sure that this isn't an enteric pathogen or to look why a patient with a history of IBD is having unexplained rectal bleeding. And I will give you a true story case about a patient that I saw who has a history of ulcerative colitis and it was maintained. She maintained a remission throughout pregnancy. She did very well and when she was nursing, she called me and said, Dr. Cain, I'm having rectal bleeding. She was not having urgency. She was not having diarrhea, no cramps, just bleeding. And she said this isn't like a normal flare. So we brought her in, did an unprepped flex sig and it was just that her distal rectum just sort of looked sort of edematous and boggy and was sort of oozing blood. But it did not look like what you would expect ulcerative colitis to look like. It didn't have a granular pattern and biopsies were actually totally nonspecific and showed quiescent ulcerative colitis. And so what did it turn out to be? That she was nursing. She was taking fenugreek as a supplement to help with her lactation and milk production. And it turns out that fenugreek actually contains a warfarin-like component and can lead to bleeding. So this is a favorite supplement of lactation consultants, but if your patient has IBD, you want to make sure that they understand that if they take this, that they are at risk for bleeding, not from their IBD, but from this agent. So it was a lesson that I learned the hard way, but I share this anecdote for others who may freak out because their patient, they think they are flaring when they are not. For a patient who has a pouch that tap water enemas as a prep, and then again, no sedation for pouchoscopy. And why would I do a pouchoscopy during pregnancy? That I want to perhaps make sure that exposure to antibiotics is appropriate. Again, that metronidazole and ciprofloxacin are sort of our go-to for pouchitis, which are not appropriate for a patient who is pregnant, particularly in the first trimester. And so ampicillin and the brand name Augmentin are what I use as sort of second or third line for pouchitis during pregnancy. So I will do an enema prepped, unsedated pouchoscopy to try to tell what's going on if needed during pregnancy. So speaking about pregnancy and also the indications for endoscopy during pregnancy in IBD, it turns out that Sonja Friedman and her group have done some very nice work to show that you can actually use fecal calprotectin as a non-invasive way to assess disease activity. So this was a Danish study, 219 singleton pregnancies of patients with a history of moderate to severe disease. And that during their pregnancy, if they had no symptoms and that were considered clinically inactive, their fecal calprotectin ranged from 80 to 120. If they were having mild symptoms, that their fecal calprotectin ranged from 260 basically to 350. And that if they were having moderate to severe symptoms, as well as other objective markers like a CRP was vastly elevated, that their fecal calprotectin was upwards of 1,200 or even 1,300. So during pregnancy, they found that the test characteristics were that there was a sensitivity upwards of 80%, a specificity of about 74%, positive predictive value up to 74% when a cutoff of 200 is used. So I use fecal calprotectin during pregnancy to try to help me understand whether there is really an indication of active disease and do I really need to do any kind of endoscopy or give that any thought. So with that, I'm going to stop again. This just goes to show how limited the data really are for this particular niche category. I want to thank the organizers for asking me to come. Hopefully that you've learned just a few important takeaways as you think about your next pregnant patient that you may need to scope. I know that David Rubin yesterday gave a talk on medical management of IBD. It's obviously a completely different ballgame during pregnancy to consider what you should and should not do. And I do see a question here. Is budesonide an option for treating ulcerative colitis during pregnancy for patients who need steroids? So excellent question. And the answer is that budesonide MMX is actually taken up more readily by the placenta than prednisolone is. So prednisolone is actually metabolized by the placenta. We actually know the enzymes that can do that. So ironically during pregnancy that you'd actually want to use prednisolone over budesonide because there's actually less exposure to steroid of that fetus. Now if there is a contraindication to using corticosteroids and you want to use budesonide, that's okay. Dawn Beaulieu at Vanderbilt showed, actually she did the work when she was in Milwaukee still, she looked at budesonide for Crohn's disease and her N of 12 showed that it was low risk. And so I would say that you can, but if there's a pregnant patient who needs, you think needs steroids, give them prednisolone, get the disease under control, minimize that fetal exposure, and then get them off the steroids. If you need to start a biologic during pregnancy, you should do it.

Dr. Susie Cain

therapeutic endoscopy fibro

pregnancy

medication safety

performing endoscopy

fecal calprotectin