#378 - 💡 Rethinking Phototherapy – Considerations for Preterm Infants

Hello friends 👋

What happens when we challenge our long-standing assumptions about phototherapy in the NICU? In this special installment of our Rethinking Phototherapy series, Ben and Daphna are joined by Dr. Deepak Manhas to examine one of the most complex questions: how should we manage hyperbilirubinemia in preterm infants?

Unlike term babies, preemies face unique risks—shorter red blood cell lifespan, immature bilirubin conjugation, lower albumin binding, and increased blood-brain barrier permeability—all of which make them more vulnerable to bilirubin-induced neurologic dysfunction. This conversation explores why traditional guidelines cannot simply be applied to preterm infants and why clinicians often initiate phototherapy earlier.

Dr. Manhas discusses the creation of gestation-specific treatment charts, the challenges and dangers of exchange transfusion in this fragile population, and the uncertain role of therapies such as IVIG, albumin, and phenobarbital. The team also unpacks practical issues: what “double phototherapy” should really mean, how to order irradiance and body surface area coverage with precision, and the role of bili blankets in promoting family bonding.

By situating this discussion in the broader Rethinking Phototherapy series, the episode highlights both the progress and the unanswered questions in caring for preterm infants.

📖 Reference: Pathogenesis and Management of Indirect Hyperbilirubinemia in Preterm Neonates Less Than 35 Weeks: Moving Toward a Standardized Approach (NeoReviews)

Link to episode on youtube: https://youtu.be/xY6BWliZ_x8

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Short Bio: Dr. Deepak Manhas is a Clinical Associate Professor with the Department of Pediatrics and a clinical neonatologist with the Division of Neonatology. He completed his Pediatric Residency and Neonatal-Perinatal Medicine Sub-Specialty at the University of British Columbia and his Masters of Medical Education with Maastricht University.  His Masters Thesis was on the use of Telesimulation to provide Outreach Education for Community Hospitals.  After his fellowship, he completed his training in Neonatal Resuscitation at the Oregon Health & Science University.  He is the Program Director for the UBC Neonatal-Perinatal Medicine fellowship program and chairs the Neonatal Resuscitation Committee.  He chairs the ACoRN Education Committee for the Canadian Pediatric Society and is a member of the Canadian Pediatric Society’s Fetus and Newborn Committee.  He currently chairs the Canadian Neonatal OSCE Committee.  His recent work has been improving parental-neonatal bonds and time-sensitive neonatal care with his work with the Neonatal Golden Hour.  He is currently evaluating methods of improving Teamwork and Communication in our clinical settings.

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The transcript of today's episode can be found below 👇

Ben Courchia (00:01.752)

Deepak, my first question for you is that term infants are often managed for their hyperbilirubinemia with well-validated bilirubin guidelines. Why is extrapolating these same thresholds to preterm infants problematic?

Deepak Manhas (00:17.411)

So these are problematic for a couple of reasons, which we can go into in a little bit more detail. But really, the level of bilirubin is often higher in preterm babies. Secondly, the amount of free bilirubin is also affected by factors in the preterm baby. The bilirubin is more likely to cross the blood-brain barrier. And lastly, there's more susceptibility of the neurons themselves in a preterm baby.

And there's a couple of things that are going to be affecting all four of those factors. For example, for the bilirubin levels, the preterm babies' red blood cells have a shorter lifespan. And so they're going to turn over more. They're going to release more bilirubin. The preterm baby is going to have impaired conjugation. So those levels will stay higher for a longer period of time. They're often feeding less. There's less going through their gut. And so their enterohepatic circulation is decreased. And they're often susceptible to other infections like sepsis and other infections, which we know for all babies is a risk factor. In terms of the free bilirubin level that's circulating, they have lower albumin levels and bilirubin binding capacities. And they're often on multiple medications that can affect bilirubin. So antibiotics and things like that. And so when that bilirubin arrives to the brain or that blood-brain barrier, lower gestational age makes it so that there's more permeability so the bilirubin can cross over into the brain easier.

And there are more often those states that occur in term babies as well that can increase this, such as acidosis, high CO2 levels or inflammation. And all of that are making the preterm baby more likely to get bilirubin going into the brain. And then once that's in the brain itself, the neurons are proliferating. That preterm baby's brain is different than a term baby's brain. They're more actively dividing. They're trying to have their synaptogenesis. They're going through correct locations. And so they're more susceptible to injury. There's also other comorbid problems happening in the preterm brain. And there's immature transporters trying to get bilirubin out. So lots of factors that are affecting the preterm baby compared to a term baby.

Ben Courchia (02:25.038)

And it's not making things simpler. And I think that this creates a lot of, I think, anxiety for me, at least as a clinician. We have so many pathologies that we're trying to account for with our preemies that the concept of any form of bilirubin-induced neurologic dysfunction is something that we do not want to add on top of everything else. And so I think that for that reason, we are...

Daphna Barbeau (02:27.291)

No.

Ben Courchia (02:54.538)

more likely, in my opinion, to intervene. Can you tell us a little bit currently what is, in your opinion, the most common way people approach the management of hyperbilirubinemia for preemies? Assuming people understand a lot of the concepts you've already outlined in the first question.

Deepak Manhas (03:16.035)

Yeah, I think one of the things that we saw with term babies is that, you know, having a standardized approach to something like this really takes a lot of that cognitive load off of physicians. You know, being able to have it and it's automatically graphed in many systems with electronic medical records, you just see right where it is. Is it above the line? Is it below the line? Do I start phototherapy? It just takes a lot of that extra load off of having to be able to do that for a term baby. And we know that the preterm babies are at a higher risk and we don't have those same graphs.

So we're having to sit there and think, "Oh, should I start phototherapy or do I not start phototherapy?" And so a lot of people are starting phototherapy at lower levels because they're trying to prevent injury. And when we had the introduction of a standardized approach for term babies, with people following guidelines, there was a huge reduction, like a 70% reduction in severe cases or poor outcomes because of that. So massive reduction for term babies. And so we probably will see a similar thing or hopefully we'll see a similar thing for preterm babies. We are seeing people be more happy, I guess, to start phototherapy earlier and at lower levels. It's just that all interventions, even though this is just light, all interventions have side effects that we know about or don't know about yet. So trying to minimize risks from the phototherapy itself as well as for anything that we're doing.

Daphna Barbeau (04:31.218)

Hmm.

Deepak Manhas (04:37.794)

Yeah.

Daphna Barbeau (04:40.562)

We talked—and thank you for that overview. We talked on another episode about how actually difficult it was even to come up with the consensus in the full-term infant. What do you think has kept people, has kept the community from creating a kind of standardized nomogram for the preterm infant?

Deepak Manhas (05:02.881)

I think like many things that we see in pediatrics, we see data that kind of comes through adults first and then trickles down to the smaller children. I think similarly, we're seeing that there's just a lot more term babies. You know, when you look at cases, the majority of cases of severe hyperbilirubinemia were with term babies because that was the largest population. And so they were easier to study, they were easier to get nomograms, to graph, to generate predictions.

And so we have Bhutani's curves, which we use. And that took a long time for it to come into effect and people to actually consistently be using them. Our preterm population is 10% of our babies. And the younger you go, the less likely you'll see them. So just getting the data on that was difficult. You know, when they did autopsies on premature babies, when they weren't surviving as much, a lot of them had kernicterus changes. So we knew that it was affecting them. But it's just been harder to get that data to get that standardization.

The thing with the nomograms is, yeah, it's preterm and term babies, but it's generally, you know, 35 to 42 weeks we're talking about, like a smaller gestational age range in there. When we're talking about babies less than 35 weeks, we're talking about babies who are 22, 25, 28 weeks. So there's a lot of variability there. So it's a little bit harder to standardize that. And even when you look at the new curves that have come out, they are stratified by 35, 36, 37, then greater than 38 or 40. And so these ones will have to have a lot more stratification and the gaps between each of those is likely a bit more variable than it is once you get to the higher ranges. So I think these are all factors that have contributed to it. And I think we just haven't had as much data to know and say confidently like this is a better spot to change that. We have two, like our two main data points come from Maisels or the National Institute of Health, and they are two graphs and they're similar, but they are different. And so having to kind of figure out which piece you're going to be taking from each of them has been important. And I think almost everybody has been using one of those two data sets.

Daphna Barbeau (07:18.216)

Very interesting. You also highlighted another thing that we see in the NICU all the time. Even if babies are maybe not at light level, and these very small babies, there's a tendency to start sooner, start at lower levels, like you said. I've also seen this phenomenon where people are like, "Well, they're gonna just be on and off phototherapy all the time. Let's just leave them on for the first three to five days instead of checking and rechecking." And you talk, I mean, of course you alluded to the fact that all treatments have risk, some risks we haven't fully elucidated yet. But what do you say to the people who are like, "Let's just leave it on for a little while"?

Deepak Manhas (08:01.165)

So, I think the thing is we've seen with oxygen the problems that we have with doing treatments like that, right? So let's just leave the oxygen on, let's keep their saturations higher and it's just oxygen, it's in the air, right? And we've seen so many effects of oxygen free radicals and retinopathy of prematurity and changes that we're seeing. So it's not as simple as that. Leaving it on might prevent some of your spikes in bilirubin or surges, but it also might expose your baby to longer amounts of phototherapy. So, and we have side effects of that too. We know that phototherapy, we've seen it associated with PDA requiring treatment, increased intraventricular hemorrhage, higher respiratory support needs, poor feeding, temperature instability, and also rashes, loose stools. And there's likely so many things that we don't know about. We also see a separation of baby from mom. The baby gets assessed less because people don't want to disturb the baby, whether that's the assessments or the parents getting to see them. And so I think there are definitely effects from having a baby on phototherapy. And there are side effects that we are going to see. I think that if you feel that the baby is going to be having a rising bilirubin such that they're going to need it, yeah, I think that you want to start earlier, but I don't think that we should be just leaving a baby under phototherapy unless there is a true need for that. So are they hemolysing? Do they have ABO incompatibility? So they have a G6PD deficiency? Do they have a cephalohematoma? All of these things may lead you to say, "I think I'm going to keep you on a little bit longer." But I don't think that that should be the standard. The standard should be when do I need to turn it on and when do I need to turn it off? And I think I would think of it.

In a similar way to how we think about oxygen or antibiotics or other treatments that we do that we should weigh the benefits against the risks and make the decision at that time.

Ben Courchia (10:30.272)

And I think that that's one of the most important points you've been making, which is that when you're dealing with the preterm infant and you're thinking about the benefits and harms of phototherapy, these harms also need to be balanced against the fact that, as you mentioned, a preemie is working against so many more challenges. And one of the effects you mentioned was PDA.

And so can you, before we move to talking about the article itself, can you expand a little bit on the potential mechanisms of what can phototherapy be doing that increases the risk of PDA?

Deepak Manhas (11:03.221)

Yeah, so when we think about PDA itself, so we see, and a lot of the mechanisms that we're going to talk about come from data done in preterm monkeys. So preterm monkeys were put under phototherapy and the control group was not. And so they saw a lot of these effects happen in these animals. And one of the big ones was higher oxygen-free radical presence. So in general, we know that preterm babies have lower antioxidant levels and higher oxygen-free radical levels. And we're seeing that just exposing them to light, because they don't have those protective mechanisms that exist in term babies, is leading to that higher, just overall higher level of oxygen-free radicals.

The other thing is that when we look at PDA, PDA we've seen a lot associated with this nitric oxide. We know that there are mutations that can lead to that. And we know that phototherapy at the wavelengths and frequencies that it's currently administered at will convert nitric oxide to nitrogen dioxide and then ultimately to nitrates. And all of those, when we have nitrates and nitrogen dioxide, can lead to those problems of vasoconstriction and higher PAH, which are leading to PDA. And so we're seeing that that reduction in that nitric oxide may be associated with it.

And also we know that the bilirubin itself actually helps scavenge for some of those oxygen-free radicals. And so it is antioxidant. So by reducing it, we're also reducing that defense.

Ben Courchia (12:32.696)

Yeah. And I think if we're talking about antioxidants in bilirubin, a question that I've had in my mind that I think may also be on the lips of some people in the audience may be, if you're telling me that bilirubin can be an antioxidant, have there been any studies and...

Daphna Barbeau (12:33.82)

Right.

Ben Courchia (12:50.99)

What was the outcome of these studies looking at whether maybe we shouldn't treat? Or have there been any studies that we should mention looking at the potential upside to having elevated bilirubin, especially in preterm infants?

Deepak Manhas (13:05.377)

Yeah, so this is looking at the U-shape. So typically we see kind of a straight line going up. The higher your bilirubin levels, the more toxicity you're going to see. But some people have said, "No, maybe there is a U-shape. So really low levels are not good and really high levels are not good." So is there a sweet spot that we want to be in for bilirubin? And there was two studies that kind of have showed two different things. One study that Dr. Wachko has done has shown that maybe there is no adverse effect from low bilirubin.

Daphna Barbeau (13:10.878)

Mm-hmm.

Deepak Manhas (13:36.111)

And the other study that did come out of Europe, I believe, which did show that they were seeing some higher death and BPD with babies that were not having higher bilirubin levels. But it is a tricky one because many of the babies that would have very, very low bilirubin levels at one to two days of life are also babies that are sicker. So is it because they're getting less enteral feeds, is it because they're on antibiotics, they're more septic? So.

Daphna Barbeau (13:59.655)

Mm.

Deepak Manhas (14:04.835)

Can we attribute low bilirubin on day one of life? Can we say that that's what happened? Or is this just another marker of sickness? So it is tricky to tease out these pieces and that's still something that I think is an active area of study.

Daphna Barbeau (14:18.27)

Interesting. I want us to talk a little bit more about that nomogram that you published, so you alluded to it. There's a couple of nomograms floating around the US, Canada. You mentioned Maisels and the NIH. But let's talk about kind of your approach to this, which is to say standardization. So what were kind of the big key points that were important, I think, to getting better...

care for preemies when you're thinking about hyperbilirubinemia.

Deepak Manhas (14:58.979)

Yeah, so when we were looking to create our graph, we knew that there were these two graphs or two sets of data published already. And I think the big thing is we wanted to choose one. So we wanted to have one at our institution that everyone was following. Having two is confusing. It creates more cognitive load. And so what we did is we compared the two to see, are they similar? Are they different? Where are the similarities and where are the differences? And then we used those, the Maisels curve, primarily for the data that we had created this from. But we also used the data from the National Institute of Health. So we used both to create our final curve. And I think one of the things that we did is we said, "Where are the differences?" And then we chose the more conservative approach in what we're doing. So if one of the graphs were different than the other, we tried to choose the one that was lower, the threshold that was lower. And I think that was one of our big things. And the second thing is we wanted to make sure that we had a stepwise approach. So it's one thing to have this graph, but how are you using this graph? When do you start phototherapy? When do you stop phototherapy? And if you're not having a hemolytic disease, I think the problem is we had a lot of tables and there wasn't a lot of visual prompts, is what I would say. And I think having a graph that you can just plot on and see this is what I'm supposed to do.

automatically makes that cognitive load go way, way down. And I think it makes it easier for bedside nurses who are seeing, "Hey, this doesn't look like I expected." It makes it easier for the fellows and the residents and anyone who's on to seeing it and saying, "Oh, this is where they're falling." So I think that was a big piece and what we wanted to have done.

Ben Courchia (16:38.956)

I was curious about your position on hemolysis, because I think one of the, I feel like maybe some clinicians are sometimes doing the bilirubin fractions, and sometimes I sense that maybe they're looking for the direct fraction to help them in their management. And I think that we know that there's some dissociation between maybe the direct fraction and what we do for our preemies, but hemolysis is a common etiology. And there's the kind of visible hemolysis with the blood type incompatibility and things like that. But...

Is there actually a way that you can figure out the degree of hemolysis in the preemie to know whether you're going to be dealing with somebody who's got a higher likelihood of really spiking in the bilirubin that would make you intervene sooner?

Deepak Manhas (17:28.759)

So I think the first thing is you made such a good point about the fractions. So direct hyperbilirubinemia, that's a whole separate discussion. That's a whole thing.

Daphna Barbeau (17:28.798)

Thank you.

Ben Courchia (17:36.664)

Yes.

Deepak Manhas (17:39.187)

It's not gonna be what phototherapy is doing anything for. Direct is conjugated. We've already done it. It's already been changed. It's not gonna cross into the brain as long as things are doing well. And so phototherapy's not gonna be doing anything for that. In our institution, our lab automatically gives us back conjugated and unconjugated. And then we try to use the unconjugated, even though that total serum bilirubin we use for our graphs just because...

Daphna Barbeau (17:42.164)

Correct.

Deepak Manhas (18:08.419)

even conjugated can revert back, and so we just use the total. And I think for hemolysis, if you are seeing ABO incompatibility, you're seeing G6PD deficiency, you're seeing those type things or you have a family history like in Greece of some of the beta thalassemia or things like that, I think you treat more aggressively. And you actually put those babies in a separate category based on their coom status. And so if they're positive, they're going into a group that you're going to be looking at differently in the first 24 hours of life and they're going to be on phototherapy a lot earlier than anybody else.

Ben Courchia (18:45.954)

But beyond that, there's not really a way that you can, I guess, assess degree of hemolysis or somehow.

Deepak Manhas (18:52.301)

So there are other things that you can use. Like you can see if they have anemia. You can look at reticulocytes. You can look at other markers like that. But I think, generally, we see...

Ben Courchia (19:01.89)

Yeah.

Deepak Manhas (19:02.231)

some earlier work done about looking at end tidal CO, which is your baby's exhaling and expiring out and looking at what you're getting from there. But I think in general, most places aren't doing those types of tests on a baby unless they're suspecting that specific type of disease. Otherwise we're just using the markers that we have of reticulocytes, CBC and kind of standard workups and I don't think that there is a clearly defined way that we can say you are or are not hemolyzing but we try to use the markers that we have.

Ben Courchia (19:32.568)

Yeah. We're getting into the end of the interview. Daphna, we're running out of time. Well, there's tons of stuff that we want to cover. So we always do this in the end where we ask, "How do we balance what's urgent and important?" And I think one of the things that we were trying to understand from the paper was this concept that currently in Canada, for the phototherapy of preterm infants, you have these recommended thresholds. However, you don't have exchange transfusion recommendations yet for babies less than 35 weeks. That's correct?

Deepak Manhas (20:08.279)

Yeah, that's correct. So we have graphs that go up to 35 weeks, but we don't have any exchange transfusion thresholds for the Canadian Pediatric Society recommendations yet. And I think that was an intentional piece that was looking at the data that they have and saying, "We don't know for sure. So we're not going to say this is going to be the threshold." And unfortunately, it does lead to some ambiguity. And when it comes to doing the exchange transfusion, or even earlier than that, just calling for a consult from your pediatric hematologists because at many sites it requires...

getting that group involved when you get closer to those exchange levels. So I think they were trying to be open and actually more cautious about stating what those were because of the limited data.

Daphna Barbeau (20:58.078)

What do people do while we're waiting for good data?

Deepak Manhas (21:03.005)

Yeah, so I think most people are using the numbers from the NIH paper or the Maisels paper. Those had suggested levels for all the different gestational ages that they had. And so I think most of the time people are defaulting to those and talking with their consultants and doing that. There is, like you said, Ben, there is a lot of questions around like, what do I do with these babies? And I don't think that there's a ton of exchange transfusions happening. But when they have happened, I think that most people have used...

one of the graphs that exist.

Ben Courchia (21:39.468)

Yeah. I mean, do you think that there is the data to support establishing an exchange transfusion threshold for preterm infants or, I mean, are we, is that something that you think we're going to see or it's just not possible? Like, what do you think?

Deepak Manhas (21:56.781)

I think that we have in the graphs that exist, the NIH and Maisels data does have suggestions. And I think I wouldn't be opposed to standardizing on those. It's a rare event. And so I think as long as we are taking them and standardizing them, I think that we'll likely be able to see that it's better for a site to have the same graphs for both phototherapy and exchange transfusion. And if you're following that, you're probably going to be okay for those. So I think standardization is still a huge piece of it and would make it better for those sites to be able to do something.

Ben Courchia (22:32.622)

Yeah, I think it's interesting because you're touching on a concept that came up in prior episodes that these thresholds, they're not obviously set in stone and there is quite a bit of flexibility. And I do think that having a reference to something is better than having nothing. And so I think that that's a helpful direction. We are coming to the close. I wanted to ask you, and this is going to require you to channel your inner hematologist, which you're probably well equipped to do, but we get...

quite a few babies who are getting screened in utero and found to have blood type in the antibody testing and so on. And I'm curious with the fetus that has known hemolytic disease, what is your approach in terms of bilirubin management? Do you wait for the baby to be born? Do you set up the phototherapy lights even before the baby comes out of mom?

Deepak Manhas (23:24.855)

Yeah, so actually there's a separate pathway for those. And I think you do treat those babies differently. I think that having that, so we have two graphs that we created. One of them is a positive DATS, positive Coomb status. So if you're having an ABO or Rh isoimmunization, you're actually, we start earlier. And if you have any bilirubin in the first 24 hours of life, we're starting phototherapy right away. A lot of the recommendations and things that we'll do actually is having everything ready and being prepped for it. And so having the Coomb status sent at birth, having the DATS ready to go and having it actually tested right away. And we also will get a CBC. And when we do that, we often do a bilirubin without blood work anyway. So while we're getting, while we might be thinking of some other disease process being higher on our list, we're often getting the blood work for this. So I think that we're probably treating many of them, but I think the trigger happens to be sometimes might be later than what some of us are always comfortable with. That's something that comes up in reviews and things like that in many sites. So...

Daphna Barbeau (31:43.741)

And then I want to take you all the way to the other end of the spectrum of the babies, spectrum, no pun intended, of the babies we're talking about today. And I think that we sometimes get into this clinical dilemma with the 34-weeker who becomes a 35-weeker and the nomograms don't overlap such that they have a common crossing point. And so I think there's this group of babies that we just don't know which nomogram to follow. Any recommendations for the upper limit of your nomograms here?

Deepak Manhas (32:21.193)

Yeah, that's a tricky one. Usually when we're talking about bilirubin, we're seeing that increase that goes over the first week, right? Like it peaks in that three to five day period for preterm babies and things like that. So really we're looking at that first week. And so what we say is that once you've been plotted on a graph for your weight, that you do follow that same gestation for that first week at least. And so we don't change our nomograms because you've changed gestational ages.

And so you just see it going in. So in our electronic medical records, we have the one graph for them and it continues to be plotted on that one graph. I think also, I think that's important because it's not just the level that we're talking about, but we're also talking about like rate of rise for many instances, right? And so if you're changing which graph you're on, it is a higher likelihood that you'll miss something of like, "Hey, this looks like a significant rise." Rate of rise, we've been able to define better in term babies.

And so if the next question is going to be what is the rate of rise that we're looking for in preterm babies, I don't know. But we talked about a rate of rise in the first 24 hours of five in Canadian units at three and a half after 24 hours, dividing that by 17.1 to get our American units. They're not metric. So no worries.

Ben Courchia (33:39.81)

Thank you.

So what is the rate of rise we're looking for? I'm kidding. The time is flying by and this is all very informative. So thank you for that. I think that what I would like to focus on for the remaining few minutes that we have is really, what is your thought on where we are versus where we're going? It feels like, I don't know, maybe I'm wrong, but it feels like we've been a little bit in stasis when it comes to the development of management and even pathophysiologic understanding of hyperbilirubinemia, specifically in preemies. So do you think that something is coming down the pike? If yes, what is that? Or maybe not? I'm just curious to get your opinion as to where the field is and where we're moving towards in the next few years.

Deepak Manhas (34:36.759)

I think that there are still groups that are looking at alternative treatments other than phototherapy for our term and our preterm babies. So I think that that's really great. I think that more and more studies are including preterm babies in what they're doing. And so I think we'll be able to get a bit more data on that. And hopefully we continue to get more than our NIH and our Maisels data for what we have.

I think one of the things that we talked about, that we touched on earlier was just the standardization and what the Bhutani curves have done for term babies. And so we had published this years ago now. And, you know, some places have adopted similar type curves and standardized that process for their site. Some are using tables, some are using graphs. One of the nice things that the Canadian Pediatric Society has agreed to this year is that they're going to standardize the preterm graph. So the American Academy of Pediatrics a few years back had their 35 weeks and above graphs come out. The Canadian Pediatric Society, that happened in the past year or so. And so they're in line with the AAP ones. And once the greater than 35 weeks graphs were released, they did agree to try to put together a national proposal for babies less than 35 weeks. So that can be standardized across Canada. And I think having a national guideline will help sites just not have to develop their own and have a process that they think will be safe. And I think that as we see that in countries, it will expand beyond. And that's one of the things that I would love to see happen is having like the AAP as well have a national guideline for maybe less than 35 weeks, for example. That's a huge population that we're able to get. And then other places around the world will have access to resources that we've put out there. So I think that we can affect and benefit the children in our groups and then have that effects go more globally.

Ben Courchia (36:30.35)

So you're saying stay hopeful. That's the message. That things, okay.

Deepak Manhas (36:32.693)

I think so. I think the thing is that these babies, the preterm babies, have so many factors that they're having to fight against and we're seeing that they're doing so much better than they were years ago. And I think the standardization of protocols, whether that's small baby bundles and things like that, I think have been what our newest wave of improvements are showing.

Ben Courchia (36:53.74)

Very interesting, very interesting. Well, Dr. Manhas, thank you so much for taking the time to share what we know and also what we don't know about hyperbilirubinemia in preterm infants. I think this was very informative. I'm going to refer people back to the article that our conversation was based on. It's a paper in the NeoReviews, "Pathogenesis and Management of Indirect Hyperbilirubinemia in Preterm Neonates Less Than 35 Weeks, Moving Toward a Standardized Approach." I think the title is so good because it was the first point you made in one of the first answers. That just maybe the first step is standardization. And I think that the paper commits significantly to offering a standardized approach. And that's what made us reach out to you. So thank you. Thank you for the work and thank you for your candid answers. We had a fantastic time.

Deepak Manhas (37:42.403)

Thanks, Ben and Daphna, for having me. It's been a pleasure.

Ben Courchia (37:45.998)

It's been a pleasure.