Pregnancy while living with inflammatory bowel disease (IBD) feels scary. But thanks to the groundbreaking Pregnancy Inflammatory bowel disease And Neonatal Outcomes (PIANO) study, there is now so much more data and information to help moms and their doctors make decisions. Dr Mahadevan began the PIANO registry in 2007, which followed women and their babies through pregnancy and after. What was learned from this registry was how IBD medications, and especially biologics, affected pregnancy, birth, and infants. Learn how Dr Mahadevan has grown PIANO over the years, the most important findings so far, and how pregnant women can join the study and help the next generation of moms with IBD and their babies.
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Episode transcript and more information at:https://bit.ly/AIBD136
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[Music: IBD Dance Party]
Amber Tresca 0:05
I’m Amber Tresca and this is About IBD.
Amber Tresca 0:07
I’m a medical writer and patient educator who lives with a j-pouch due to ulcerative colitis. It’s my mission to educate people living with Crohn’s disease or ulcerative colitis about their disease and to bring awareness to the patient journey.
Amber Tresca 0:19
Welcome to Episode 136.
Amber Tresca 0:21
One of the many aspects of IBD for which we can use more information is pregnancy. Just 15 years ago when I wanted to have a baby, there were still a lot of unknowns.
Amber Tresca 0:31
Today we have much more information about how to approach pregnancy for people with IBD, and much of it is thanks to my guest for this episode, Dr Uma Mahadevan. Dr Mahadevan began the PIANO registry in 2007, which followed women and their babies through pregnancy and after. What was learned from this registry was how IBD medications, and especially biologics, affected pregnancy, birth, and infants.
Amber Tresca 0:50
The results led to several articles and the creation of a clinical care pathway for pregnancy and IBD. This is a roadmap for healthcare providers to follow as they advise pregnant women who live with an IBD.
And Dr Mahadevan isn’t finished yet! PIANO is leveling up and moving onto a new phase, which is really important because several new medications have become available in recent years.
Amber Tresca 1:12
Dr Mahadevan tells me how PIANO has changed over the years, some of the most important findings so far, and how pregnant women can join the study and help the next generation of moms with IBD and their babies.
Amber Tresca 1:26
Dr. Mahadevan, thank you so much for coming on about IBD.
Uma Mahadevan, MD 1:30
My pleasure. Thank you for having me.
Amber Tresca 1:33
Oh, absolutely. I would like to get started first with some introductions before I start firing away. And you can tell us all about the PIANO Study. Would you please just let the listeners know who you are?
Uma Mahadevan, MD 1:42
Sure. My name is Dr. Uma Mahadevan. I’m a gastroenterologist at The University of California, San Francisco. I’m the director for the Center for Colitis and Crohn’s disease there. I specialize in inflammatory bowel disease, in particular pregnancy, and Drug Safety among women with IBD.
Amber Tresca 2:02
Right, which is a topic that is very near and dear to my heart as well. So I’m really excited because today our topic is the piano study. And piano stands for pregnancy, inflammatory bowel disease and neonatal outcomes. I have to write it out every time because I do not remember. So this research has told us so much already. But there’s always more to learn, especially because there are new drugs coming, which is wonderful for the IBD community. But I would really like to start at the beginning and just have you give us a level set and tell us what is the PIANO study? And then how how did you come up with the name?
Uma Mahadevan, MD 2:41
So the name actually, we were looking for a good acronym for the study and Peter Higgins, I still remember, Crohn’s Colitis Research Alliance meeting came up with it. So this really goes to the credit goes to Peter Higgins at the University of Michigan. And the study started in 2007.
Uma Mahadevan, MD 3:01
It was a confluence of two important things. One was the Crohn’s Colitis Foundation started the Clinical Research Alliance. And this is a group of over 30 IBD centers across the United States that came together to pool our resources and our patient numbers to try to answer important questions. And the alliance was looking for good studies to do and safety of medications and pregnancy was one of the big questions and this was back in 2007. So infliximab was only then starting to be used regularly among all patients.
Uma Mahadevan, MD 3:39
And the default for women had always been stop all your medications when you get pregnant. And we now know how bad that can be because women can flare and so to be able to continue your medication you needed to know safety. So through the Crohn’s and Colitis Foundation, I received several senior research awards, and then now we’re funded through the Helmsley Foundation.
Uma Mahadevan, MD 4:04
So this has always been pharmaceutical company free. So it’s been Foundation research. And we have sites across the country that enroll pregnant women with IBD. Patients can contact us directly. Physicians can contact us directly, even if they’re not an enrollment site. And we enroll patients remotely. And we have followed women throughout pregnancy through the first year of the child’s life, then through the first four years. And now we’re following people out to 18 years of age to understand short term and long term impact of these medications and exposure in the uterus.
Amber Tresca 4:44
Wow. So that was a lot of information that actually I did not know so I’m so glad that I asked that very, very basic question. I’m wondering though, what was your interest in pregnancy and IBD? What made you pick this niche I mean, I’m super grateful that you did, but I’m just wondering if there’s anything behind it.
Uma Mahadevan, MD 5:04
So I think the first thing was knowing that I loved IBD. So I trained at Mount Sinai, which is where burl Chrome was from, and they have a long legacy of taking care of patients with inflammatory bowel disease. And I did my advanced IBD fellowship at the Mayo Clinic in Rochester with Bill Sanborn. And one day, as all good mentors do, we sat down and said, Okay, what are you interested in? Where are the big holes in the data and pregnancy and IBD was one of those areas where there really was no information.
Uma Mahadevan, MD 5:38
And it being a woman, I saw a lot of patients come to see me who were women, they wanted a woman gastroenterologists. And this was a question that came up all the time. And that’s really what drove this interest. And then of course, personally, wanting to be a mom and becoming a mom and understanding how hard that whole process can be, has really helped fuel my interest and passion for this area.
Amber Tresca 6:04
So the registry the study, rather, I think previously, we called it registry. And now we can say study, I’m a little…
Uma Mahadevan, MD 6:13
I mean, we enroll patients prospective. Okay, we look at all different outcomes. I think either name is okay.
Amber Tresca 6:19
That’s, that’s good, because sometimes I would correct myself. And then I wasn’t really sure, because I think the study has grown and changed over the year, as you were saying a little bit. But I’m wondering now because now you’re kind of in a you’re in a 2.0 situation. So can you tell us how the registry has leveled up and you know what you’re doing now?
Uma Mahadevan, MD 6:40
Yeah, so we were very excited a year ago to receive funding from the Helmsley Charitable Foundation. And what we were able to do with their generosity. PIANO was really run on a shoestring there was very, very little funding for it. And with the Helmsley, we were able to get substantial increase in funding that allowed us to expand the website to ask more questions, get more coordinator support, be able to make it develop a patient portal. So now instead of the coordinator calling and going over all these questions, patients can just directly entered into a patient portal.
Uma Mahadevan, MD 7:23
So there have been a lot of upgrades to the process that makes it more user friendly. We have more support, we were able to develop this beautiful website and answer more questions and gave us funding to continue to follow patients already in the study, continue to learn about existing drugs, and then enrolling patients on newer medications. So your risankizumab, Skyrizi, Rinvoq, which is upacitinib, Xeljanz, which is tofacitinib, Zeposia, which is Ozanimod. And we have really no data on those medications. And because it is up and running, and we have the infrastructure as soon as someone gets pregnant on it and contacts us. They’re in and we have our first data points.
Amber Tresca 8:08
Yeah, you got you know, you’ve got this up this website up and running, you have this, this cool new logo, like it’s been really great to watch the evolution of, of the project. So I’m wondering, alright, somebody is pregnant, they live with an IBD. What can they expect when they enroll because it does sound like it has changed that it used to be someone would call you? How is that different now.
Uma Mahadevan, MD 8:32
So it’s still the same patients can contact us through our website, which is pianostudy.org, they can email us at email@example.com. The traditional way people get enrolled as they see their doctor, their doctor is a PIANO site, and their doctor enrolls them in the study.
Uma Mahadevan, MD 8:52
But even if you are not at a PIANO site, you can directly enroll through UCSF through the website. And that allows us to capture people from all over the country and have more diversity in the kind of patients that we enrolled, which is all very important to answering these questions.
Uma Mahadevan, MD 9:11
So once you reach out to us, or you’re referred to us and we reach out to you, you sign a consent form, which the coordinators go through. And the consent form can be overwhelming because it has to be in the ethics committees always want us to put all these things in. And what we essentially want is a questionnaire every trimester, the questionnaire delivery, and that month’s for nine and 12 of the baby’s life and then once a year thereafter until they’re 18 you can drop out at any time so when you sign that it’s overwhelming to think I’m committing to this for 18 years you’re not you can drop out at any time.
Uma Mahadevan, MD 9:51
And the most important part is really through pregnancy and through delivery in the first year of the baby’s life. That’s those are the key details when we would see The birth defects when we will see other issues. The long term study looks at impact on immune system on risk of malignancy on the baby developing IBD other questions that you really can’t get within a year. So you’ll do these questionnaires. And as noted, you can do them on the portal, you can do them with the coordinator. There’s also a separate questionnaire called the Ages and Stages Questionnaire, which is something whenever you go to the pediatrician, they ask you, can your baby turn their head? Can they clap their hands. So for the first four years, we do ask that as well.
Uma Mahadevan, MD 10:36
At the time of birth, we collect samples of blood from the mother, and the cord blood, and the baby and the baby’s optional, because cord blood and baby blood are fairly similar. And what that information gives us is the amount of blood being sent to the amount of drug that transfers to the baby. And that’s where and it was through piano that we had all the levels. And we understood that biologics are present in the baby through at least the first six months of life. And we showed that there was no impact on development and infection rate based on that. We check levels in breast milk in the past. The that part we’re not doing any longer, but we’re checking blood, we’re doing the questionnaires. And if you’re at UCSF, we will also collect your placenta.
Amber Tresca 11:23
Oh, wow. Okay. I was kind of thinking to myself, signing up for 18 years of questionnaires, but you also just signed up for 18 years of motherhood, so maybe it’s not — this might be one of the easiest parts of motherhood.
[MUSIC: About IBD Transition]
Amber Tresca 12:05
All right, this is a huge question that I’m gonna ask you here. I’m going to ask you, what are some of the most important outcomes that you have gotten through the PIANO study? So far? What do we know?
Uma Mahadevan, MD 12:17
So I think one of the biggest things that came out of PIANO is that we found that women with ulcerative colitis are more likely to flare and have complications during pregnancy than women with Crohn’s disease. And this was a surprise to everyone. And this data has been replicated now in European datasets. And the surprise was we always worried about Crohn’s disease, because often they were sicker, they had more complications. And women posted quite as can be doing just fine. And they go into pregnancy, and they have serious flares. And even if they don’t have a significant flare, they’re more likely to have pre tremors and low birth weight. And so I think that was a surprising finding and pregnancy of the PIANO registry.
Uma Mahadevan, MD 13:00
And because of that, we’ve really monitor all women, but women with ulcerative colitis more closely, I will do a flex SIG, or a calprotectin, or now and intestinal ultrasound to confirm they’re in remission before they can see. We follow them during pregnancy. And if there’s any suggestion of a flare, were more careful. And we also really emphasize the importance of continuing safe medication.
Uma Mahadevan, MD 13:25
We looked at response to vaccines, and we saw that infants exposed to IBD medications when they’re in the womb, still have good response to vaccine. We showed that biologics do cross into breast milk, but this does not impact the outcomes of the babies. And we found that babies exposed to anti TNF had better outcomes on ages and stages questionnaires and the general population. And that was not surprising in that if you’re at an IBD center, you have health insurance. And you know, social determinants of health are important for milestones.
Uma Mahadevan, MD 14:02
But even when you compare within PIANO of the different drug exposures, the anti TNF always did the best. And whether that was better control of inflammation or something specific to anti TNF, not clear. You know,
Amber Tresca 14:16
One of the first times I think I saw you present, I believe it was at digestive disease week and presenting some of these results. I’ll never forget what you said was very funny. You said, I’m not going to say that an anti TNF makes your baby smarter. But it might make your baby smarter.
Uma Mahadevan, MD 14:37
It does and there probably is related to much tighter control of inflammation, because inflammation really impacts how the baby’s neural pathways in the brain are formed. So one additional thing is that for many women, the process of going through pregnancy can be very confusing. And so one important document is that the American Gastroenterology Association and the Society for Maternal Fetal Medicine came together.
Uma Mahadevan, MD 15:07
Now, it’s 2017, but came out with a care pathway for the management of pregnant women. So if your OB says, oh, no, you have to stop all your medication, you can point to this article that is in their own literature that supports what we’re doing. And so I would encourage all women with IBD, who are pregnant, to consider seeing a maternal fetal medicine specialist, all my patients see maternal fetal medicine specialist, they won’t be the person to deliver you, necessarily, but they should at least be involved so that your OB feels safe with what you’re doing, and that you’re being adequately monitored for complications.
Amber Tresca 15:47
So PIANO is for US residents, is that is that right?
Uma Mahadevan, MD 15:54
Amber Tresca 15:54
Is there anything equivalent in other places in the world?
Uma Mahadevan, MD 15:59
There are. So they’re in Australia, I believe they have the PICO registry in Spain, they have the Dumbo registry. The European groups have gotten together and put published joint results in Denmark Mette Julsgaard, as following her cohort. So every country has their group. I think in the US, we were such a big country, we’ve been lucky to be able to consolidate all of these patients in one study.
Amber Tresca 16:29
Alright, so I just want to make sure that I have that correct. So that when people want to get involved, if they’re at an IBD center, or they’re at a center, where PIANO already has a presence, they will probably work with their physician, but if they’re not at an IBD center, they can go to pianostudy.org and connect with you there.
Uma Mahadevan, MD 16:51
Okay, all right. Or they can email us at firstname.lastname@example.org.
Amber Tresca 16:57
Okay, great. Okay, so you’ve got this next iteration that you’re going through now? Do you have any more plans? That might be a dumb question, you probably always have more plans. Is there something else that you’re hoping that you can study or look into?
Uma Mahadevan, MD 17:14
Yeah, so one of the things I mentioned is the placenta study, we’re collecting placentas exposed to different medications. And this really comes from concern that women with IBD have higher rates of pre eclampsia and gestational hypertensive disorders. And so is it…
Uma Mahadevan, MD 17:32
And remember that pregnancy is such an immune state, your immune system is depressed during pregnancy, there are all these cytokines and the placenta is one of the biggest immune organs. And so when your immune system isn’t, is dysfunctional, as people with immune mediated disease can be that can affect the placenta. And so we want to look at the percent of women with IBD and see if we can find something that helps explain why there is that risk. Also, women who are at increased risk of preeclampsia, which is all women with IBD, should be on low dose aspirin during pregnancy. And there’s a concern among women with IBD, whether aspirin leads to flares. And so we looked at that, and we’ll, we’ll submit those results to American College of Gastroenterology. But so far, it doesn’t look like it causes a flare.
Uma Mahadevan, MD 18:22
And the biggest thing is that today for World IBD day, we announced a global consensus conference. And this is really important. This is the first time it’s ever been done in inflammatory bowel disease. You mentioned that different countries, you know what the other countries do. Other countries also follow their patients, and other countries and regions have their own guidelines. But this is going to be one guideline for the entire world. And so we have the people who wrote the guidelines from Australia and Canada and South America and Europe and Africa and Asia. And we’re all getting together and starting this process, it’s going to be a great guideline, which doctor really long will lead the great process.
Uma Mahadevan, MD 19:08
We have patient ambassadors, we have a multidisciplinary, team with the teratology list and NFM and surgeon, etc. We’re gonna start going through the questions at DDW 2024 We’re gonna get together to vote and then write the paper. And, again, never before done. All the major GI journals have agreed to review with intent to publish
Amber Tresca 19:32
This is incredible. Okay, we’re recording on world IBD Day, May 19. This was just the time that we found to be able to do it. So just coincidentally, and then you announced this initiative today, because there are differences and I only know this from talking with other pregnant people or mothers in the IBD community between for instance, let’s say the UK and the United States. And so there’s usually a little back and forth when you get folks together, and they say, Well, I was advised to, you know, stop my medication at x weeks or, you know, something like that. And it just seems like everybody, everybody’s doing it differently. And maybe that’s just part of IBD, because everyone is so individualized. But then you get people because of social media around the world talking. And we’re realizing that it’s very different. There’s definitely no, no consensus. So this is really, really exciting.
Uma Mahadevan, MD 20:28
Yeah, it’s a big deal to get everybody even to agree to be in the same room and come out with one product. Because there have been like, in Europe for a long time, they were stopping at 22 weeks, and we just continue. But I think there’s been a change in thinking, a greater acceptance of the safety of biologics and a greater understanding of the extreme risks, you’re putting the mother by stopping the medication.
Amber Tresca 20:54
Well, I’m definitely in awe of this initiative, because it’s going to be wonderful. But I feel as though you might be herding cats for a little while here. And then the website is pianostudy.org.
Uma Mahadevan, MD 21:12
Amber Tresca 21:14
Okay. Great, perfect.
Uma Mahadevan, MD 21:15
And there. And also on the on the piano website, there is a box where you as a patient can submit an important question that you feel hasn’t been answered. And we will look at. So if there’s something that you feel is not out there that you can’t find an answer for. And that’s an important question, you can submit it to as a patient.
Amber Tresca 21:38
Oh, my gosh, that’s incredible. That’s just music to my ears, maybe piano music to my ears. You are so busy. I’ve always been in awe of everything that you’re doing. I’ve seen you present many times. It’s always a pleasure. I’m wondering, do you have any self care strategies that you care to share with us that you keep yourself sane with?
Uma Mahadevan, MD 22:03
So you know, I think I’m also a mom have an eight year old. There’s very, very little, I would say, but I think I really, I really enjoy what I do. And I think I always tell people, if you if you if you love what you do for 50% of the time, you’re not gonna burn out. And I definitely think the research, the mentoring and development of junior faculty and fellows hanging out with my eight year old and my family husband, those are all fun things. And so I’m very lucky i in terms of self care, I, I schedule time to exercise during the week, because if I don’t, it doesn’t happen. I also I love to read and I read junk. I don’t read anything serious at night. I read archaeological fiction I read, you know, whatever. Nothing sad nothing or anything bad happens to children can’t stand those books. And so that is my night, I need to relax and escape a little.
Amber Tresca 23:07
Oh my gosh, I love hearing that. I’m the same. I don’t want anything ever. If something happens to a kid in the story or in the movie, I’m out.
Uma Mahadevan, MD 23:18
I can’t I can’t handle that. I cannot I can’t do it.
[Music: IBD Dance Party]
Amber Tresca 23:20
Yeah. Well, thank you so much. I mean, it’s truly what you’ve done for women and their babies in IBD is incredible. I had my first in 2007 when you guys were just getting started. And it wasn’t great, you know, trying to figure out what to do and trying to get all my physicians to be on one page and to agree about what to do. So thank you so much for all of the work that you have done over the years and everything that is to come and for talking to me today on World IBD day. Thank you so much.
Uma Mahadevan, MD 23:53
Thank you for having me.
Amber Tresca 23:58
Hey super listener!
Amber Tresca 23:59
Thanks to Dr. Uma Mahadevan for all her work and being a champion for pregnant women with IBD and for taking the time to talk with me about it.
Amber Tresca 24:08
If you live with IBD and are pregnant, or you know someone who is you can take part in the study by talking to your doctor, or by getting in touch with the piano team at pianostudy.org
Amber Tresca 24:19
As a mother of two who entered into pregnancy with a lot of support, but without a lot of information. I am so excited that new mothers and their doctors have good information to guide their decisions, links to a written transcript.
Amber Tresca 24:33
Everyone’s social media handles and more information on the topics we discussed is in the show notes. And on my episode 136 page on aboutibd.com
Amber Tresca 24:43
You can follow me Amber Tresca across all social media as about IBD
Amber Tresca 24:48
Thanks for listening.
Amber Tresca 24:50
And remember until next time, I want you to know more about IBD
Amber Tresca 24:57