Thermoregulation of the Neonate with Dr. Daniel Trevisanuto

Ben Courchia, MD: Hello, everybody. Welcome back to the Incubator podcast. We are back with another episode of our mini-series on thermal regulation of the newborn infant. And today, we are joined by Dr. Daniele Trevisanuto, who's an associate professor of pediatrics in the Department of Women's and Children's Health at the University of Padova in Italy. Daniele, thank you for making the time to be with us. And I think you are our first Italian guest on the podcast.

Dr. Daniele Trevisanuto: Thank you. I am honored to be the first Italian invited person for this opportunity. So thanks for this invitation.

Ben Courchia, MD:  Yeah. I'm sorry. No, of course, of course. You've done a lot of work on thermal regulation, and you've done a lot of studies. You're extensively published. You've done work both in Italy and both in a more global health setting. And I'm just curious about what keeps bringing you back to this topic. It seems to be a topic of interest to you that seems to be fascinating you. And I'm just curious about what is it about thermal regulation that you find so interesting.

Dr. Daniele Trevisanuto:  Probably the most important thing is that as I've been working in low resource setting, I had many projects in Asia, in Africa in particular, and as hypothermia is a real killer in this country, for two reasons, I was very interested in how to try to solve such a, how to say, it seems a very simple problem to solve.

We don't need too much, probably we don't need too much. We need technology, but probably we need other aspects that are low cost, and we can try to solve this problem. And so probably this was my first interest, because I was interested in improving in such a low resource setting this aspect. And of course, it's probably, I discovered it is also important probably in high resource setting.

Ben Courchia, MD:  Yeah, yeah, I think it's interesting how in the first, if we want to call this in the developed world, how we are being reminded of the importance of temperature regulation by all the work being done in, like you said, low resource settings, where we tend to see the effect that not maintaining temperature can have on the baby. And it reminds us in the developed world, my God, like we're doing all these little interventions that are supposed to increase outcome by a few percent point, and then we sometimes forget how just maintaining temperature can have such a dramatic impact on so many variables, survival, comorbidities. Is that something you've noticed as well, where this is something that as the care of the newborn in the first world country has become so sophisticated, we can often forget about thermoregulation?

Dr. Daniele Trevisanuto:  Yes, I agree because we think that sometimes we think that temperature is allowed to say a minor problem or it's a nurse problem, is not a doctor problem. But I think that is a great error, a great mistake to have such an approach because to make attention to the temperature means really to improve.

Ben Courchia, MD: Mm-hmm.

Dr. Daniele Trevisanuto:  a clinical critical outcome such as mortality, such as intraventricular hemorrhage. And so there are many studies that have confirmed the association or the relationship between hypothermia, ethnic transmission, and we play the match during the first 20 minutes of life. And you can make the difference. And so I think that is very important to come back to the basic management of the patient in addition to the

Ben Courchia, MD:  Mm.

Dr. Daniele Trevisanuto: New advanced technology, of course.

Ben Courchia, MD:  When I was speaking to people about this and saying, what do you think about thermal regulation? Many people said to me, you know, I don't think about it too much because I have the warmer or I have the isolate. So like the baby's temperature is automatically taken care of. And I was never thinking about this from a clinician standpoint where we've delegated the thermal regulation task to the machine. And I'm wondering if you can, is that something you've noticed as well, where we assume that the machine is gonna do the work and that it's gonna maintain normothermia for us?

Dr. Daniele Trevisanuto:  I think that technology is very important, but human behavior is very important, the approach of the team. Just to give an example, we published, I think, two years ago, a multi-center randomized control trial on the use of servo control versus no servo control in delivery room.

Ben Courchia, MD:  Mm-hmm.

Dr. Daniele Trevisanuto:  I don't remember more than 400 patients, very low, but in Italy. We had 15 centers and the primary outcome was normal thermal range, ethnic transmission. What we found was that we didn't find any difference between the two approaches. But what was the most important result, in my opinion, was that

Ben Courchia, MD:  Yeah.

Dr. Daniele Trevisanuto: only 40% of very low-birth term infants arrive normothermic in Italy. And we have all of these hospitals are level 3 hospitals. All these hospitals have the same, more or less the same equipment, more or less, of course. But there was a very large range in normothermia. And the range was between

Ben Courchia, MD:  Of course.

Dr. Daniele Trevisanuto:  3% in one hospital, and the best hospital had 75%, 78% of normal thermo and NICU admission. And so it is just to confirm you that the intervention, in addition to the technology, also the organization, the small aspects are very important to prevent hypothermia at NICU admission, also in our setting.

Ben Courchia, MD:  Yeah, this was a paper that your team published in the archives of disease and childhood in the fetal and neonatal edition. In I think 2021, you had 450 infants in the study, as you mentioned. And it was very shocking to see what you just said, how despite the use of servo controlled system, the amount of babies that arrived with no more thermia was, I think, 39.6% in one group, 42.2% in another. And so technology alone cannot do it alone, basically. That there are many aspects of the care of the newborn that is involved in the time of transition after birth, and that we need to pay attention, because I was expecting to see higher numbers. Can you tell us a little bit, what does that mean, servo-controlled? I think I know, but I'm sure that there are some people listening to this podcast who said, I've always heard servo-controlled, temperature, whatever. But what is that?

Dr. Daniele Trevisanuto:  Yeah.

Ben Courchia, MD: What does that mean practically speaking?

Dr. Daniele Trevisanuto:  Practically speaking, is a several control means that you give the organization or the management of the thermal control to the machine, fully to the machine. So you put a sensor on the skin of the baby, and the machine decides the power of the temperature that has given to the baby according to the temperature of the baby. So the machine understands what is the temperature and what is the power that it has to give to the patient. While no servo control means that you set, the clinician set the temperature, the temperature, the entity of the temperature, the magnitude of the temperature that has to give to the patient.

Ben Courchia, MD:  The intensity, yeah.

Dr. Daniele Trevisanuto:  In that study, we found no differences. We set the temperature that the machine had to give to the patient was 37. We discussed this also with the reviewer if it was the case to increase the goal, to say to the machine to set the machine to 37.5, for example. According to the result of the study, if I could or we would do another study, I suggest, OK, we increase the goal because there is a large thermal dispersion in the room or there are other aspects that has to be considered. And so the machine work well, but probably we have to increase the set of the temperature that has to achieve being achieved by the machine.

Ben Courchia, MD:  Mm-hmm. And you have an extensive, many years of experience in this field. I'm just wondering that when you are working in the clinical setting, what to you are some of the biggest challenges we are facing today in trying to be performing at a level that is sufficiently high to maintain temperature? What are the pitfalls that you see where we lose opportunities to keep normothermia and we fall into hypothermia.

Dr. Daniele Trevisanuto:  We have said that the team is strategic. I think the education of the team is probably one of the most important. When a baby arrives hypothermic at our NICU, we discuss with the team, we have a pediatric resident that they are the team leader. Why this patient, and with the nurses of course, why this patient arrives hypothermic at the delivery room? Where we can improve for the next patient. And so this is rare, because we have a good normotermia rate. But sometimes we have this problem. And it depends, maybe the temperature of the room and so on. Try to answer to your question in a more specific way.

I think that we don't know where we have the drop of the temperature. It is immediately after there. We spent more or less 30 minutes from the birth to the admission to the NICU, and 25, 30 minutes, at least in our hospital. So the question is, where is the drop of the temperature? It is already in the womb of the mother because the mother is hypothermic, is immediately after birth because you have a acute drop. It's during the minutes where you do the resuscitation. We know from some study that patients who receive intubation, for example, or some maneuvers, resuscitative maneuvers, they have a higher risk to be hypothermic during the transfer to the NICU, when we put them in the incubator. And so I tried to do a study. I would like to do a study. We received some devices from GE and Europe. They were very kind. Just to try to monitor, strictly monitor, minute by minute, what happened. And if you are able to find that, a specific point, we can work on that point or that reason. 

Ben Courchia, MD:  So, on that moment of when that drop happens. And so it's more, it's very common for all of us to deal with patients who are after birth, not normothermic, right? I mean, as we spoke, it's achieving normothermia is a high standard and we may achieve it for many patients, but there are still some that may find themselves not within that range. I think there's a lot of beliefs around

Dr. Daniele Trevisanuto: Yeah, yeah, that is.

Ben Courchia, MD:  How am I supposed to handle the baby that is not normothermic? And should I just rewarm them pretty quickly? Should I take it slow? I think there are a lot of people who still think like HIE, where I have to warm. If I rewarm a baby, I have to do it slow. But in your experience, what is the right approach when the target is not met and now I have a baby that needs to be brought back to the normal range? How do you approach that?

Dr. Daniele Trevisanuto:  This is another great question. And really, we don't know. There are two, I think, two very old randomized control trials with very low patient, conducted in low-resource setting but I think 30 or 40 years ago. And so a patient with normal weight, so full-term newborns. And so I think that is not, we cannot use that studies. There are some, there is one physiological study that say that we can, we have to avoid to go too fast, higher than 1.5 grade per hour, degree per hour, because we increase the oxygen consumption. But these are all studies, so I don't know if it is correct. 

Now we have some observational study, retrospective study. One was conducted in our hospital, we had 400 extremely low-built weight patients, extremely low-built weight infants, less than one kilo. We compared retrospectively what happened to the patient who had hypothermia, who had re-wormed faster compared to the patient who had re-wormed in a short, in a slowly, slower, yes, sorry. And what we find is interesting because this is, this study has many limitation because it's not a randomized controlled trial. But what we found was that not if the cutoff was, as the cutoff was 0.5 degrees per hour, okay, as we do for the rewarming in during,

Ben Courchia, MD:  Slower, yeah. That's okay.

Dr. Daniele Trevisanuto:  …therapeutic hypothermia. We know that when we do therapeutic hypothermia, in full term, in fact, we have to use 0.5 as a rate. But what we found was no differences in the main important outcomes, such as hypoglycemia, IVH, mortality, and so on. The only difference that we found was the incidence of RDS. Patients who were re-warming slowly RDS. And so it is consistent because when we give surfactant, we warm the surfactant. And so the surfactant in hypothermia or hypothermia increased RDS because you have an inhibition of surfactant in the lungs. And so I enjoy it.

I was very happy for this for what we found for the result. Another study that we conducted was in low resource setting, including preterm and full term newborns. And also in this case, I think that the study was published one or two years ago in children. And also in that study, we did not find any different because faster or slower rewarming rate. 

One of the peak questions in the ERCOR task force is, what is the best way to reward the baby, but also the conclusion of this review and meta-analysis that included our study. And only observation study is that we don't know, really, if it is better to go fast or to go slow. 

Ben Courchia, MD:  And yeah, it's interesting. You would think that with how bad we are at maintaining normothermia that we would have figured out if we should correct fast or slow. But yeah, we'll put all the links to the articles that you are referencing, by the way, in the episode's show notes so that if people are interested in reading these papers, which are very interesting. I think the other paper you mentioned was published in the Journal of Pediatrics. We will put all that in the episode show notes. As we're talking about rewarming and we're talking about normothermia, I think that there are many products that have come out as a result of our initiatives to maintain normothermia after delivery, whether they are, we talked about the warmer, but they are blankets, they are hats, they are polyethylene bags. And you've done a lot of studies to look at different things, whether it was the wool hats, or I've seen a study that you looked at maybe like almost like a shower hat, like the plastic shower hats on babies. Can you tell us a little bit about some of these and how the different material, different products, how does that play a role in maintaining the thermoregulation?

Dr. Daniele Trevisanuto:  OK, yes, it seems that by based on the study that we conducted, I think a few years ago, many years ago, we published it in, I think, Journal of Pediatrics. We were interested in covering the head of the baby with a shower cap. Because of course, the head, the surface of the head 0.8% of the entire body surface. And so it's a very large part of our body. When you are newborn, when you become adult, you become micro-safety. And so now you have an example here. And so the baby has a very large surface in the head. And so in that study, it was a randomized controlled trial. We were interested in covering the head with a plastic bag or with a shower cap was effective. And really, we found it was effective. And so I think that is effective as well as I think a woolen cap. We know that cotton cap does not work. We know the woolen cap are effective in preventing hypothermia. And our study, I think that is the only study. And so it should be nice to repeat. Or another group could repeat it.

Ben Courchia, MD:  Mm-hmm.

Dr. Daniele Trevisanuto:  To cover the death of a baby with a plastic cap it could be reasonable to avoid thermodispation. We are referring to extremely low-bit-to-weight-infra, very low-bit-to-weight-infra. With regard to the material, there is one bank study that has been published, I think, two years ago in archives of disease in childhood.

Ben Courchia, MD:  Yeah.

Dr. Daniele Trevisanuto:  that show that polyethylene bag is more effective than polyurethane bag. And so also the material is make the difference of counts. So please be sure that you have the polyurethane. Yes, the right one, the right material.

Ben Courchia, MD:  The right, yeah, the right material. I think we did review that study from the archives on the podcast. I forget when it came out not too long ago, you're right. And we did review it because it was a very interesting one. In terms of maintaining temperature, I think there's been this question that we've, we're curious to hear from our various guests about. We've set the standard of normal thermia, especially in, in preterm infants, I think the importance of maintaining normal thermia in extremely low birth weight infancy is so important. But we've also set the standard for golden hour where we're hoping to get all the admissions sort of complete within the hour. And I am just wondering, what are your thoughts on sometimes how normal thermia and golden hour can become competing entities where we're trying to finish everything, uh, like the lines and everything, but sometimes it can happen at the expense of the temperature of the baby. How has been your experience in managing all this in your NICU?

Dr. Daniele Trevisanuto:  In my NICU, the baby is managed in an incubator. The incubator is we use it depends if you have extremely low B2H-infinity, the temperature and also in particular the humidity is very high, 90% during the first hour. And we try to give warm fluid.

Ben Courchia, MD:  Mm.

Dr. Daniele Trevisanuto:  And yes, and we try to do a lot of attention. The temperature is continuous monitoring. And this is the way. One of the most important risk is when you do a procedure when the patient arrive. During some time, we found that the patient arrived normothermic at NICU admission.

Ben Courchia, MD:  Mm-hmm.

Dr. Daniele Trevisanuto:  But during the first hour, when you try to put the umbilical catheter, or you do some, for example, you give surfactant and so on, there, there is a risk that you can, after one hour, you can have a drop of the temperature. Not so important, but you can lose 0.5, 0.3 degrees compared to the temperature admission.

And yes, this is important to be careful during the admission in the NICU. And if I can move to low-resource setting, we conducted a very nice study in Beira. Beira is the second city in Mozambique.

Ben Courchia, MD:  Yes, please.

Dr. Daniele Trevisanuto:  And there we have a great collaboration with our, because our PDH residents have the opportunity to spend six a month in that hospital. They have a tutor, a local, but also an Italian tutor. And we work with NGO. The name is QAM Doctor with Africa. It's a NGO from Padua, but there is a strong relationship with our university and NGO. And one of the questions in this low-resource setting was, okay, 65% of babies arrive hypothermic in the NICU. Okay, but what happened the first day of life? Okay, we know that we lose the match during the first 30 minutes of life, or one hour of life, but what happened during the fifth day? And what we find was very interesting because, okay, if you have money, if you have dollar or euro, you put your euro in the first 13 minutes of life. But what we found was that if you arrive hypothermic and you become normothermic in the fifth day of life, your rate of mortality is 40%. But if you arrive hypothermic, and you remain hypothermic during the first 24 hours of life, your mortality rate is 75%. And so it's terrible. And so, of course, we have to take care of hypothermic baby to avoid hypothermia during the first one hour.

Ben Courchia, MD:  Wow, 40%.

Dr. Daniele Trevisanuto:  of life, but also during the fifth day, really, it counts. It has an important impact on the survival of this patient. So the conclusion of this study that we published, I remember, I think, one, two years ago, was, OK, please, be careful during the, make attention during the fifth hour, but also during the fifth day, because the fifth day could be, could add an important risk to your possibility to survive if you remain hypothermic. And so this is, I think, the first study they tried to put to see the temperature, to look at the temperature over time, not only one point, but also after 24 hours from admission. It was interesting information for me.

Ben Courchia, MD:  Yeah, I think that's a very interesting because it's right. We talk a lot about termoregulation in the immediately postnatally, but we rarely think about this beyond that point. So I think that's an interesting point. What has been the drive for you to continue looking at termoregulation on a, always comparing the global health aspect versus what you're doing in Italy, which is a developed country, obviously, but that you seem to be very interested in comparing what we're doing in both places because your papers are not solely studies taking place in low and middle income countries, but there's always a mix. And I'm just curious as to, is this just because the opportunity is there or is there something beyond that you wanna compare all the time?

Dr. Daniele Trevisanuto:  I think that a small thing can change more life in low resource settings. So we try to save 400 grand babies. At least I can understand the family is asking to do everything and so on. But with small, how to say, changes, you can save more life in low resource settings. And I can't say you how to say an anecdote, just to give the idea of what happened in some setting. Last January, I was in a hospital, the only hospital with the CPAP, the availability of CPAP in the NICU in Burkina Faso, in the capital we were there. And the nurses are very expert in the use of the CPAP machine. And we arrive in the morning, 8 a.m., to do the ground round. And we were in the NICU, in the room. And what I saw was this patient was dying. He was a preternuble. The built weight of this patient was 1.5 kilogram. And we put him in the CPAP because we treated him with the CPAP because he was some apnoic episodies. And so it was the reason. But the FIO2 was always 21%. OK. We arrive in the morning, the second day of life, and the baby was dying. And the nurses said, oh my god, this patient is dying for prematurity.

Ben Courchia, MD:  Okay.

Dr. Daniele Trevisanuto:  And so we decided to look at the chart of the night. And what we found was that this patient, the temperature of this patient was 35 at midnight, or 35 at 3 AM, was 35 at 6 AM, and was 35 at 8 AM. And so this nurse was able to measure the temperature in this patient. And so he was not interested. 

She was able to register the temperature. But the point was that she didn't did an action to improve this problem. I would say, and also there was another problem because the weight was 1.2 kilogram. So there was 20% of weight loss. And so just to give you some example of what we discussed with them. OK, no, this patient was the reason of the death of this patient was not prematurity, but was severe hypothermia, was hypothermic collapse. And so it is very important to help this group, these our colleagues, in knowing this aspect. 

They do everything, but also if they register the problem in this case, and so probably they don't believe that the action or they don't believe that the hypothermia is so important because everything was correct. The SIPA machine was set correctly. The nasal canal where is in the right place. So it was not a technical problem. It was a, I would like to say cultural problem, probably. And so just to give you some ideas of how we can impact. And so the technology is important, but yes, the education, yes, the education is make the difference, is the same in our setting. Because, for example, if you look at the last radio

Ben Courchia, MD:  The education.

Dr. Daniele Trevisanuto:  one month ago with the HILCOL group, how to prevent hypothermia in preternum bones. There are many things that we can do. For example, pre-warmer mattresses. Is it important or not? For example, in my NICU, we don't use pre-warmer matrices, but we have less hypothermia than some article that have published this approach. And there is a study, for example, for Colmodone, they show that exothermic matrices can increase the rate of hypothermia. There are some studies that show that, for example, the use of heat and warmer gases, there is also metanalysis.

The short is, but it depends when you work, when you work, what is your setting. For example, in this moment, we don't use pre-warmed and humidified gases in our delivery room, but we have really a very low incidence of hypothermia, lower than, for example, some study from Australia, from, for example, Holland, Netherlands. And so it is interesting. So all the treatment recommendations, for example, from this document, if you go to, you can read them in the Ilkor website, is that when the resources are low and when you think that rate of hypothermia in your setting is important, you can consider the use of gases, ether gases.

Ben Courchia, MD:  Yeah.

Dr. Daniele Trevisanuto:  You can use the exothermic mattress and so on. And so I think that all these measures are important, but they have arranged according to your situation, according to your delivery room setting. If you have hypothermic, for example, if you have 22 degrees in your delivery room, yes, in that case, it could be reasonable to have the pre-warmer mattresses.

Ben Courchia, MD:  Yeah, that's so interesting. As we're getting close to the end of this conversation, I'm just curious about, based on all the work you've done, what are the things you are currently working on or the current studies you have in the works? And where do you think is the future of that area of study going to be?

Dr. Daniele Trevisanuto:  OK, thanks for this last question. Now we are an ongoing randomized control trial, multi-center. We have involved 20 hospitals, level 3 hospitals in Italy. And the question is in the PICO question is in very better infants or less than 30 weeks gestation is the drying of the patient before putting him or her in the plastic bag or not drying the baby. This is the dry trial. The name is the dry trial. And so we are interested because in the big patient or large patient is important to dry. But we don't know if it is important for the small patient. We put them in the plastic bag. 

This is that we are now have enrolled 110, 8, 10 patients. We are in the one-third of the enrollment. We are planning to enroll 360 patients. And we have to give another answer to this, I think, very practical question. I like clinical question and clinical study, because most things can make, I don't want to change important thing, but can change the technical practice, yes. This is relevant to me.

Ben Courchia, MD: What's your hypothesis on this study on the dry trial? What do you think is the right way?

Dr. Daniele Trevisanuto:  No, the hypothesis is that if we dry the baby, we can increase the rate of normothermia. The primary outcome is normothermia. That is important. More important than hypothermia because we want to avoid hyper and hypothermia. Yes, the hypothesis, I don't know if this will be confirmed. We are very curious, but yes, let's see what happens.

Ben Courchia, MD:  Of course. I don't know, we will have to see.

Let's see what we'll be looking out for this publication. Daniel, thank you. Thank you so much for making the time to chat with us this morning. I think it was a very instructive conversation. And congratulations on the body of work that you've been able to publish on this topic. Because all the papers you mentioned and many more that we haven't touched on are so well written. And they're such nice studies that we'll try to link even more of these on the website. And they're super interesting. So congratulations for that. And again, thank you. Thank you for making the time to be with us today.

Dr. Daniele Trevisanuto:  Thank you very much, Ben. I appreciated his invitation. I was happy to be involved. Thank you.

Ben Courchia, MD:  Yeah, we were very happy to have you. Thank you.