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#154 - [Special Episode] - 🚨Update on FDA warning re: Probiotic in the NICU







Hello Friends 👋

Exciting news! The latest episode of The Incubator Podcast is live!

Join us for an interesting discussion with Dr. Ravi Patel and Dr. Rune Toms, exploring the FDA's recent warning about using probiotics in preterm infants in the NICU. 🚼🚨

Unpack the science, implications, and expert insights to navigate this critical neonatal care topic with us! 🩺👶

🎧 Tune in now on

Enjoy!

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Links to some of the articles mentioned on the show can be found below 👇

Probiotics, Prebiotics, and Lactoferrin-Implications for Preterm Mortality and Morbidity.

Pammi M, Warner BB, Patel RM.JAMA Pediatr. 2023 Oct 2. doi:10.1001/jamapediatrics.2023.3856. Online ahead of print.PMID: 37782507 No abstract available.


Use of Probiotics to Prevent Necrotizing Enterocolitis: Evidence to Clinical Practice.

Razak A, Patel RM, Gautham KS.JAMA Pediatr. 2021 Aug 1;175(8):773-774. doi: 10.1001/jamapediatrics.2021.1077.PMID: 34047767 No abstract available.



Probiotics, Prebiotics, Lactoferrin, and Combination Products for Prevention of Mortality and Morbidity in Preterm Infants: A Systematic Review and Network Meta-Analysis. Wang Y, Florez ID, Morgan RL, Foroutan F, Chang Y, Crandon HN, Zeraatkar D, Bala MM, Mao RQ, Tao B, Shahid S, Wang X, Beyene J, Offringa M, Sherman PM, El Gouhary E, Guyatt GH, Sadeghirad B.JAMA Pediatr. 2023 Oct 2:e233849. doi: 10.1001/jamapediatrics.2023.3849. Online ahead of print.PMID: 37782505 Free PMC article.


Trends and Racial and Geographic Differences in Infant Mortality in the United States Due to Necrotizing Enterocolitis, 1999 to 2020. Wolf MF, Rose AT, Goel R, Canvasser J, Stoll BJ, Patel RM.JAMA Netw Open. 2023 Mar 1;6(3):e231511. doi: 10.1001/jamanetworkopen.2023.1511.PMID: 36867411 Free PMC article.

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Transcript for today's episode can be found below 👇

Ben Courchia MD (00:00.655)

Hello everybody, welcome back to the Incubator Podcast. We are back for a special episode today. We are joined with the usual crew. Daphne, how's it going today?


Daphna Yasova Barbeau, MD (she/her) (00:10.262)

I'm doing great, thanks, Ben.


Ben Courchia MD (00:11.775)

And we have two special guests, Dr. Rooney Toms and Dr. Ravi Patel Rooney Ravi. How are you both doing today?


Ravi Patel (00:19.894)

I'm good. Ben, Daphne, and Rudy, it's good to be here.


Rune (00:22.998)

Yeah. Thanks Ben. Thanks, definitely doing well.


Ben Courchia MD (00:26.267)

Thank you both for making the time to be with us. And the purpose of this update episode is really to try to talk a little bit about what's been happening with probiotics in the NICU world. I think if you've been just glancing at Twitter recently, there's a lot of talk about probiotics and people may wonder, did something happen? Did a big publication come out? And so we wanted to give you an update as to, first of all, what happened? And then maybe share our thoughts.


about what this means for our patients, for the NICU, and for future in general. So the decision to record this episode is mostly driven by a warning sent by the FDA on September 29th, 2003, so a few days ago, where the FDA is basically warning that preterm infants, and I'm quoting from the FDA warning, that preterm infants who are given probiotics are at risk of invasive.


potentially fatal disease caused by the bacteria or the fungi contained in the probiotics. What exactly happens and why this has been published is because they are in the process of investigating the passing of a preterm infant who was receiving probiotics, specifically a single strain of probiotic containing biphedobacterium longum. And the passing of this infant is being investigated because genomic sequencing data


demonstrated that the bacterium that caused sepsis in this baby that died was a genetic match for the bacteria in the probiotic. Now, in the information section of this warning, the FDA is not going easy on the NICU providers saying that the FDA cautions that microorganism contained in probiotics have been reported in the medical literature as causing bacteriumia or fungimia.


sometimes with a severe clinical course in very preterm or very low birth weight infants. They are also referencing the American Academy pediatric statement where they basically quote that sentence from the paper by Dr. Poindexter and colleagues saying that the AP cannot recommend or does not support the routine universal administration of probiotics to preterm infants, particularly those under a thousand grams. And they're attaching a few case reports.


Ben Courchia MD (02:45.227)

about instances of babies who've received probiotics who have unfortunately passed away. So obviously, that's pretty much it when it comes to the FDA warning. We're here to discuss a little bit what does that mean and where is that coming from? Is this really grounded in evidence? So I guess the first thing we should probably do is go around the room and maybe, Ravi, if you want to get us started, share your thoughts on...


what this means and how you felt when this warning came out.


Ravi Patel (03:18.078)

Yeah, thanks, Ben. And nice summary. First, I would say it's great to share this. People should be aware of this. And I think the FDA is doing their job in alerting clinicians and healthcare providers about these risks to make sure people are aware. I don't think this is a new risk. People in the field and even the AP statement have highlighted that there are risks of infection potentially from bacteria that are contained in these probiotic products. And that's been reported before. Unfortunately, it's a very


rare and infrequent risk. And we know from trials and in babies in trials that over 10,000 babies, there were no reported cases of probiotic associated sepsis. I think we can say this is something we should all be aware of, but we have to remember to put it in the context about this being infrequent, rare risk and balance that risk with the benefits that we know of these products.


like we do for many of the things that we do in the NICU on a daily basis.


Daphna Yasova Barbeau, MD (she/her) (04:24.752)

muted, Ben.


Ben Courchia MD (04:27.355)

I'm trying to do good by muting myself so that I don't cause any extras. But Rune, I'm curious to get your perspective. You have a lot of experience. You are Daphnia and I's regional medical director, but you've been the medical director at the University of Alabama. So I think that from a quality standpoint and from seeing this on the more macro scale, what do you think about the FDA coming out with this warning after investigating the death of a single patient?


Daphna Yasova Barbeau, MD (she/her) (04:29.507)

I know.


Rune (04:54.675)

Yeah, well, so I mean, you're right. This has been a discussion for many, many years, right? So at UAB, for example, there was, we've had, I don't know, during my time, in multiple, multiple discussions whether or not we should start probiotics or not. And I think, honestly, to this day, they may actually not uniformly use it, partially because of the evidence. And we can spend an entire, probably,


episode talking about the evidence. But my take would be this, that I agree with Ravi that the FDA, they're doing their job. And I'm happy they're on the field of probiotics discussions right now, because they've been absent in many ways. All the probiotics that we use are not FDA approved. And in the early phases of starting probiotics, there were certain cases where


We were giving probiotics and they were being tested and it turns out that there were actually no bacteria in there. And then the question about liquid form versus powder form, contamination certainly in the powder form. And then the big question about what bacteria is it that we actually want to give or what population or constellation of bacteria do we want to give that can...


positively influence the complex microbiome of a developing intestinal tract in a pre-me. So I feel as though had the FDA not done what they did, they would not be doing their job. So I'm actually happy that they did this. And I see this as an opportunity to bring the microbiome probiotics discussion to the forefront.


hopefully provide even more information based on this bump in the


Ben Courchia MD (06:50.691)

That's an interesting take, obviously, because I think you're seeing it from the perspective of, will this be the spark that initiates the FDA to actually finally look at these products that we want to be using in our infants and maybe consider the evidence that we'll talk about in a little bit to maybe outline a path for us to be able to bring this therapy to the NICU. Daphne, any thoughts on the FDA warning? And you were one of the first few to share this with our group and our division. And I remember you're the one who sent an early email.


I'm curious to get your thoughts on that.


Daphna Yasova Barbeau, MD (she/her) (07:24.318)

Well, I mean, first, of course, any death in the NICU obviously is tragic, right? So, you know, certainly we don't want to diminish what this means for that infant, what that means for this family. And as we discuss the evidence, you know, we'll talk about potentially how many lives have been saved with, you know, the use of probiotics. And so it's always such a balance.


But, you know, I agree with Rooney. I'm trying to be hopeful about it. I think the community is coming out pretty strongly. And I think parents, especially those involved with the next society, are coming out very strongly. And so people are going to have to pay attention to this. And if not probiotics, then what's the alternative? And if not some medicinal alternative, then what are we doing as a society to ensure the procurement of human milk? Which we are just...


not able to do for every infant. So how do we protect them?


Ben Courchia MD (08:28.615)

Absolutely. I think to me, my main takeaway is that for anybody listening to this episode or who have seen the FDA warning is to not substitute the warning for a summary of the evidence. I think people may say this and say, well, the FDA looked at everything and they said that's no good. When in truth, when you look at the references in the warning, it's very sparse kind of data that they publish and there's nothing really


about the many, many trials that have looked at this. So I think that's the first step. And then I think it's a little bit biased in my opinion because there's this quote from Nassim Taleb in the Blacks One where he says that there's no monuments to all the September 11 tragedies that were prevented. So it's hard to, it's always easy to look at the dramatic outcome that is in front of you, but it's rarely easy to.


actually appreciate all the things you've prevented. And I think that's where it's going to get tricky to balance the two. And the reason I think it may be a damaging warning as well from the FDA is I think that for many institutions, looking at this from a medical legal standpoint, at the very least, what we'll have is we'll have a moratorium on probiotics where people will say, well, until we can figure out something, we're going to just stop using it. And...


Ravi Patel (09:42.56)

Thank you.


Ben Courchia MD (09:52.287)

In our institution, that's what is currently happening. And there are many people having discussion. But I'm curious if you have any thoughts on what you think is going to happen based on this warning. And maybe if you, what would be your approach if you had all encompassing power, obviously, because it's a very dynamic and multifaceted process. But what would be your approach in light of this warning?


Ravi Patel (10:17.606)

Well, I think that those are important points. And I would start with saying, the FDA doesn't practice medicine, clinicians do. And we should realize, we have to weigh the risks and benefits of various treatments and discuss that with families and think about the values and preferences of families. They want their babies to have the best health outcomes. And we do that in...


on a daily basis, you know, let's step back maybe and frame it. I was reflecting on kind of this issue and thinking about steroids and then we can come back to the evidence and probiotics. So, you know, steroids have been tested and evaluated as one of the first trials in the new Nail Research Network in the late 80s and widely used. You know, in 2002, the AP had a statement that really was very cautionary about the use of steroids and across the United States, steroid use.


really diminished. You can read their statement last year, they reflect and say, unfortunately, that led to an increase in the incidence and severity of BPD. So more babies were impacted by this disease. Fast forward from 2002 to today, people are using it. If you look at, you know, we don't have any new drugs to prevent BPD that are available. These are the tools we have today to prevent diseases like BPD.


And clinicians are using it, even if there's still not a recommendation for routine use. If you look at the data, 25 to 40 percent of the kind of smallest babies receive systemic steroids. And in that statement, they say that clinicians should really weigh the risks and the benefits. There are clearly risks, but there are also benefits. And discuss it with families. And that is, I think, what we should do in the practice of medicine. Steroids don't have an FDA-approved label for the prevention of BPD or the facilitation of extubation.


but we use it today. What's different about probiotics? Probiotics fall in this different regulatory environment. There are companies pursuing a drug labeled indication or a live biotherapeutic product indication for this product. But it is a tool available today for clinicians. Just like steroids, if you thought 40 years later, where are we? We don't have any other treatments. I worry about, as to your comment about,


Ravi Patel (12:36.558)

the future going to hold or what's the landscape going to be, that what do we have in the pipeline for things we can do today or five years from now to prevent NEC? And I think human milk is incredibly important. And if you look at the data, most we've done a good job with providing access to that, but what else do we have? And that's where this is an important tool. And we know it's one where we have a lot of data.


Ben Courchia MD (12:46.51)

Mm-hmm.


Ravi Patel (13:03.966)

It's not something that's just starting to be studied. There are about a third of NICUs using it, and many, many clinical trials, many studies for routine use, a lot of information we can do to quantify actually pretty well, I think, the benefits that this has.


Ben Courchia MD (13:22.475)

So I think to illustrate this point, because we've been talking about the evidence supporting the use of probiotics, you wrote a very nice, or you were the coauthor of a very nice editorial in JAMAPEDES coming out, that's come out a few days ago, where you're writing an editorial on a paper that conducted a main analysis on the use of probiotics in the NICU. And I just wanted to quote some of the parts of this editorial, because I think it's very interesting.


The mid-analysis ended up including 106 trials involving 25,840 preterm infants and concludes that multiple strain probiotics, which is what they were looking at, are associated with decreased alcohol's mortality compared with placebo with a high certainty evidence. And we know that that's not often the grade that we see with a relative risk reduction of 31%, an absolute risk reduction of 16.7%. And then...


And then you write, among all comparison, this is the only intervention associated with decreased all-cause mortality. You also mentioned how probiotics have been one of the most evaluated interventions with over 50 randomized clinical trials and over 10,000 participants. You also wrote a few months back, a few years back in August 2021 with our friend Abdul Razak, another viewpoint in JAMAPEDS where you had conducted this sort of


fake mid-analysis where you said, well, let's look at all the evidence that we have currently and what would it take for a new study to come and swing the evidence in the opposite direction? And I think that without getting into too much of the detail, the scenario in which the evidence would start swinging completely in the opposite direction would need to involve a trial of 80,000 neonates, I think, and show no beneficial outcomes. So I think...


When we say that there is evidence, we're not talking about like one or two papers. We're talking about a lot of babies, tens of thousands of babies and many, many trials. So I think that's a critical point to start bringing up. Bruni, any thoughts on what this warning means for the future of NICUs or the future of probiotic use in the US specifically? Because obviously the FDA is a US entity.


Rune (15:33.867)

Yeah, absolutely. No. So I mean, you know, that kind of data is important, obviously. I know Ravi's done a tremendous job of kind of sorting through the data and information and the publications. And just for the record, I was an early adapter when it comes to probiotics. For me, it's all about intestinal health, right? My one concern, though, as in this


Rune (16:03.863)

bifidobacterium longum infantilis. We've sat through lectures, they tell us this is a bacteria we should focus on. Even a company has been able to isolate that bacteria and produce it. That's the one we've been giving. This is the one that also caused that one situation of sepsis. Then there are other probiotics which have more of a balanced kind of flora of...


bacteria. And so in many ways the way I see it is that we're given giving all sorts of different types of bacteria. It's not as though we're all only giving say five milligrams of per kilogram of ibuprofen every single time in every single hospital all over the world and we can say hey this is making a difference right. So what I'm hoping is going to come out of this is for us to


embrace the complexity of the microbiome and maybe dive in a little bit deeper in the understanding of are we actually talking about one bacteria? Are we talking about a thousands of bacteria? Are we going to be able to create some? We can measure the colony forming units in the urine, but we don't have that as part of when we gave the Avivo. I have no clue how much bacteria of the


Are we going to start being able to titrate it? Are we going to be able to give different populations to certain weight groups versus another? Are we going to give certain probiotics with mother's milk and certain probiotics with formula, for example? That's what I'm hoping is going to come out of this.


Ben Courchia MD (17:47.099)

Yeah, thank you. Thank you, Runeen. Daphna, before you give your thoughts, I just want to maybe continue to share some of the comments that we are seeing on Twitter. And I think Dr. Suresh Gautam, who's very active and a great educator, posted recently on Twitter that the use of probiotics and neonate in the US is, in his opinion, almost a lost cause. The first nail in the coffin was the 2021 AP.


Coffin Statement and the recent FDA alert sealed the fate for probiotics. In my opinion, we should focus now on reducing intestinal dysbiosis and neonates in other ways. And there's a long discussion involving a lot of very prominent researchers, authors, and clinicians like Nick Ambleton, Jonathan Swanson about that. But I'm just curious, what are your thoughts on what this means for the future?


Ravi Patel (18:34.907)

I can share that. I think we as clinicians should advocate for the tools that we can use today, that we have available today, legally available, to help prevent morbidity. And I think that would be one of the things before just accepting that this is just going to be the fate. I think there's an opportunity to advocate and maybe to really bring in the voices of patients and families who can be impacted by this. Because this is, if every NICU in the US stops using this today, there's going to be an impact.


and the evidence is going to show there's an impact. And it's going to be a real, I think it's going to be a tangible impact. We know on our own data, we've looked at one baby a day dies from neck on average in the United States. So I think we should realize that I would be a little bit more optimistic and hoping there's a path forward for those centers that really would like to use it. We'll have to see of thinking of ways they can inform families. And that would be one of the ways I think to you.


Ben Courchia MD (19:30.523)

That's my question to you next, Ravi. That's exactly what I wanted to ask you, because you posted something that is actually quite impactful on Twitter. But I just wanted to see if Daphna wanted to share her thoughts before we move on to what is going to be the path forward. Because I think, like you said, Ravi, there is a path forward.


Daphna Yasova Barbeau, MD (she/her) (19:46.042)

No, well, I think you guys have touched on this. I think this is a very US-focused discussion, right? Because this is not a discussion being had globally because probiotics have basically been adopted in many other countries. Von put out a study in 2021 looking at probiotic exposure between 2018 and 2020. And


I mean, in European countries, it's nearly 50%. In the Asian and Pacific Rim countries, it's nearly 40%. Here in North America, it's 13%. And our Canadian colleagues are using probiotics in much higher numbers than we are. And I guess my thoughts about the discussion are, we talk a lot about how do we get research to bedside and why does it take more than a decade to do that?


And what are our obligations as clinicians and scientists about pushing the, not just industry, but our regulatory organizations to say, we need recommendations, we need help with this. Why has it taken so long? Why has this kind of last real decade of investigation on probiotics been kind of ignored for the most part?


Ben Courchia MD (21:10.457)

Mm-hmm.


Daphna Yasova Barbeau, MD (she/her) (21:10.834)

And I don't have the answer to that. It's just.


Ben Courchia MD (21:14.751)

Ravi, I wanted to follow up what you were mentioning earlier. You posted something on Twitter a few hours ago saying that looking at a paper published on the JAMA network that from 1999 to 2020, there were 8,951 deaths from necrotizing enterocolitis in the US, which meant that on average one baby died from neck each day in the US. And you said, let that sink in one baby every day. And I think like you said that...


This is not a warning that will be without repercussion. I think there will be direct repercussions if we decide to withhold an intervention that can prevent a mortality associated with neck. And I guess the question that I'm asking you is I think there will be a path for probiotics and this kind of intervention to probably make its way back to the NICU. Do you feel that this is going to be something that will be able to maybe reintroduce in the form of a


a drug that has a parental consent and we can say, hey, we're going to actually end up delivering it as a shared decision-making process with the parents? Or do you think that the voice against this warning from the clinicians is going to be so strong that the FDA will have to come out with a more comprehensive statement that reviews the entire body of evidence? I'm just curious what you think because I know you've been trying to get a hold of the FDA.


Rune (22:14.471)

Thank you.


Ravi Patel (22:33.478)

I think that the kind of comment about the requirements for an IND for clinical use, I think that needs a little bit of clarification as how it impacts science. I do think, and this would be consistent with the recommendations by the AAP, that we should have discussions with families about the benefits and the risks, and this is one of those risks I think it's been known. I'm not sure if there was a drug formulation of a live bacteria that actually this risk would magically disappear.


because even if there was a drug formulation of a probiotic bacteria that you're giving, there's still gonna be risks of sepsis. It's probably gonna be infrequent. It's unclear if a trial could detect that because it's probably gonna be uncommon. But informing families, my hope for the path forward for those centers that really want to use it is that there's gonna be available supplements on the market.


that they can use to supplement these beneficial bacteria and that they can go forward and if they're concerned to have discussions with families and informing them and maybe for some NICUs, that might be a written informed consent process. And for others, they can make decisions and say, this is something that we wanna wait for a drug formulation and there's trials ongoing. And I think that's also very reasonable to say, and we should encourage and.


those companies that are pursuing products to give us more options for those NICUs that don't want to. But that would be where I think there's, the two paths forward, we talked about it in the article a couple of years ago, but I think we shouldn't close one of those paths forward and just stop completely.


Ben Courchia MD (24:11.019)

Yeah. So one of the things you mentioned, you mentioned the term IND. And for people who are not familiar with that acronym, it's investigational new drug. And basically, this is a process that if you want a drug to be used in the United States, you have to submit this application to the FDA and they have to approve it. And obviously, this is something that the probiotics have, do not have. And it surrounds, I guess, the question of is this a supplement? Is this a drug? And I'm curious to hear.


Daphna Yasova Barbeau, MD (she/her) (24:35.9)

Mm-hmm.


Ben Courchia MD (24:38.135)

what you think, because this is a topic of discussion all the time. Even when we were implementing the use of probiotics in our NICU, the question is, well, is this going to be pharmacy who's going to be dispensing this or is this going to be in our milk as part of the nutritional supplements? So, Rooney, any thoughts on that?


Daphna Yasova Barbeau, MD (she/her) (24:47.859)

Mm-hmm.


Rune (24:53.939)

Yeah, and I think this is maybe going to help identify its place in our treatment. And yes, as clinicians, we have to be fully informed about this. But remember, I like the discussion because we're passionate about this and we've all experienced neck. Every neonatologist hates neck. And that's why we're so passionate about trying to prevent it. But preventive medicine within the NICU...


has been on the back burner for many years. So now preventive kind of medicine is being brought to the front burner within neonatology. And I will say, you know, this is not like, you know, Dr. Bartlett putting the first baby on ECMO many, many years ago, that baby had a, you know, 98, 99% chance of not surviving either way. So they attempted ECMO. Here we're attempting to prevent a devastating disease, a deadly disease in a patient.


that maybe has a, you know, depending on your institution, a three to 5% chance of developing that. So that's a discussion. And are we focusing on, is a bacteria the thing, or is there something that the, is it all about inflammation and development of the intestines? And that's what I would love to bring forth as part of this discussion. Maybe we're...


talking about the chicken and the egg, maybe there's something that's part of that biofilm that's being produced that reduces inflammation, optimizes development in the intestine. So that's the discussion I look forward to.


Daphna Yasova Barbeau, MD (she/her) (26:32.714)

Well, I wonder, you know, we talked about how this will affect the use of probiotics, but I'm kind of worried about how to affect just our ability, our research on probiotics. And I wonder what everybody's thought is about that and how we move forward, getting the funding needed to continue to study it, getting the participants needed to continue to study it.


Ben Courchia MD (26:57.463)

I'm going to let Ravi, if you want to take that.


Ravi Patel (26:57.582)

Thanks for watching!


Yeah, that's a great question. You know, the challenge with NAC is it's, fortunately, relatively uncommon, even though it's devastating and tragic when it happens. And so to do trials of prevention strategies, because it's three to 5% incidence, you need a very large number of patients to study for prophylaxis. And that leads to large trials that are quite expensive and a large investment from...


industry to do those trials in a market that you could say is not the same as it would be for an adult, for example, or for children or for healthy infants, because there's a relatively... And that, I think, is a challenge for prevention trials. Now, I strongly believe that for an NEC, that prevention has to be critical to the strategy, because once a baby develops the disease, it's really hard. There needs to be better treatments at the onset, but that's going to be a harder thing to tackle. And so we really have to believe in prevention.


but doing large clinical trials takes, you know, 100 plus million dollar investments. That's not gonna be done, I think, through NIH or through academia. That has to be taken on by industry, and there's an important advocacy point for that. But those are things that are outside of, you know, the control of what clinicians sometimes can achieve. So what did those happen? And, you know, there's trials ongoing. That might provide products that people can...


can use, but I think in the meantime, we should also not take away tools that clinicians have, just like we still have steroids available, even if they're not recommended, even if they're not approved by the FDA for the use in which the way neonatologists use it. Now, steroids are a drug and they're regulated as such, systemic steroids, but probiotics fall into a little bit of a different regulatory.


Ben Courchia MD (28:36.452)

Mm-hmm.


Ravi Patel (28:52.942)

area by the FDA and I think that's part of some of the complications here that are different than the way if we were talking about drugs that are used off label for which most of us are used. Most of us use many of the treatments. So I think that future study is going to be, I think in reality, just a challenge for large, large trials of many of these strains, to at least for the outcome of prevention of NAC. There might be other outcomes that...


clinicians can, you know, studies can look at that feeding and tolerance or days to feeding or other things that might be able to be studied easier.


Ben Courchia MD (29:29.463)

I think we said that we will try to keep this podcast within a half hour. And so as we're getting close to that time point, I think what we're gathering is that this FDA warning is definitely creating a lot of discussion about probiotics in the NICU. And for that, it's definitely positive. It is very concerning that it is pushing the field in a direction that moves away from a tool like in probiotics that we have.


to significantly reduce the incidence of neck. I think if you follow the coverage that we did of the next society symposium, the biggest takeaway is we have to build a world without neck. The goal is not to find the best therapy for neck, but the goal as Ravi was just mentioning is to try to find the best preventive tools that we have to avoid it altogether. I mean, to me, I think we should maybe go around and share our thoughts about this in terms of what we feel this is, what our impressions are.


I think to me, in my opinion, this FDA warning is very damaging because it is putting clinicians in a very difficult position, both from a treatment standpoint at the bedside, but also like Daphne was mentioning, from a research standpoint. And the reason is that the FDA published this warning that's number one, but it got a ton of media traction. I mean, if you Google this, you'll see that this was covered by many very respected media outlet like CBS News, CNN, and so on and so forth.


Daphna Yasova Barbeau, MD (she/her) (30:50.166)

Hmm.


Ben Courchia MD (30:59.127)

And so I think that even though my hope is that we can all sit at the bedside and go over the evidence with the parents, I put myself in the position of a parent that is not the most knowledgeable person on this specific topic. And you see a doctor that, again, they don't know us very well as neonatologist. They've met us for the first time after the birth of their baby. And we're going to try to say, hey, this tool is actually working. And then on the other hand, you have organizations like FDA and then CNN and all these other outlets are saying it's no good.


it's going to make our job very difficult to get to a point where we're going to be able to actually objectively present the evidence and let families make an informed decision. So I think for that alone, to me, it's a big issue. I just hope that the FDA can follow this warning with a more comprehensive statement that puts back, that restores balance and the force if you are a star. But yeah, so these are my takeaways. I'm curious, Rooney, what are...


Rune (31:50.104)

Hehehe


Ben Courchia MD (31:56.035)

your thoughts as we wrap up this episode.


Rune (31:58.911)

Yeah, absolutely. So working, having worked in the quality and safety field for a very, very long time, clinicians hate being told not to do something or not to provide any kind of therapy, which I totally get. So I think what we're in right now is a reactive kind of clinician kind of discussion, which is great. We should see the FDA warning as something invigorating.


we should see it as an opportunity to move the field of necrotizing endocolitis prevention forward, rather than falling back in maybe the old track that we were in. Maybe we had too much trust in the probiotics. Maybe we had too much trust in the industry producing the probiotics. Maybe there was not enough oversight. Who knows? So, in that sense, I'm...


I'm excited about this. I'm excited at looking at new maybe anti-inflammatory aspects of a microbiome, new research that will maybe one day provide us with a drug or a cocktail of bacteria where we can say, hey, we know exactly what we're giving and we have more control over exactly this preventive strategy for this devastating disease.


Daphna Yasova Barbeau, MD (she/her) (33:22.322)

Yeah, I'll go next so Ravi can close us out with expertise. You know, my last kind of thoughts are more of a, let's say a parent than a neonatologist. You know, we're thinking about this in our very specific, very high risk and sick population, but truthfully the use of probiotics in infants has exploded in the well baby sector. And so I think the potential benefit of that is that...


the lay public likes their probiotics. And so I think they're gonna continue to push for that and industry is gonna continue to push for it because it meets a need that families are looking for, especially as the microbiome in general is becoming such a hot topic. And I was disappointed because


We've discussed probiotics almost every journal club, it feels like. The community was not totally convinced, though there's definitely a movement based on this layers and layers and layers of data. I feel like for some people who are on the fence, this is going to be problematic. I am hopeful, like Rudy said, that we will band together and say this is something that we…


need. The discussion has really been focused on NEC, but truthfully, there are so many aspects of optimizing the infant microbiome and other disease pathways that we haven't even explored. So I think cutting that down is a mistake.


Ben Courchia MD (35:09.472)

Ravi.


Ravi Patel (35:11.658)

Well, first, thanks for the opportunity to join and I've enjoyed this discussion. I'm a really passionate believer about evidence-based medicine. My first, I think specifically to the clinicians and the families who might be listening is we really should think about the evidence and don't forget the evidence and considering risks and benefits like we do for all the other things and don't single out probiotics and just take it out of that equation. Keep it in the equation like we do for steroids and for other things. I do hope that there's an opportunity that the FDA...


agrees to engage with the New Deal community, with stakeholders, with patients and their families. I know the next society is very focused on this and hopefully we'll have a statement coming out that they engage and really hear the concerns and maybe provide some clarity about kind of the ways forward. And so that would be my kind of hopeful stance. We'll have to see if that happens. But I would say for the clinicians,


you know, don't forget evidence-based medicine. And there's a lot of evidence out there and that evidence is always balancing risks and benefits, your own personal experience and the kind of preferences and values of families and to really put this within that lens.


Ben Courchia MD (36:20.063)

Love that. Love that. Thank you. Thank you, Ravi. Rune, Ravi, definitely. Thank you. Thank you very much for joining the show today to talk about this. And I'm sure there will be more ongoing discussion. I think we hope that this episode was helpful in bringing you up to speed as to what exactly happened and what is the what is at play and what is the level of evidence and what is the confidence level of the evidence and so on. So you have a balanced perspective.


We will see you all on Sunday for an episode of the Incubator with a great interview with Dr. Page Church. Until then, everybody have a good rest of your day.


Rune (36:57.016)

Thank you guys.


Daphna Yasova Barbeau, MD (she/her) (36:57.386)

Thanks everyone.


Ravi Patel (36:58.766)

Thanks.



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