#410 - [Journal Club] - 📌 Does Drying Very Preterm Infants Before Wrapping Improve Normothermia?

In this Journal Club episode, Ben and Daphna review the eye-opening results of the NeoDry Trial recently published in JAMA Network Open. They explore the clinical rationale of whether drying very preterm infants before applying a plastic wrap in the delivery room improves rates of normothermia upon NICU admission. While the intervention did not significantly improve temperatures, it unexpectedly revealed an alarming increased mortality risk for the smallest neonates. Tune in as they break down the study's design, discuss the potential causes for this stark safety signal, and highlight the ongoing challenge of maintaining thermoregulation for our most vulnerable preemies!

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Drying Very Preterm Infants Before Plastic Wrapping at Birth: A Randomized Clinical Trial. Cavallin F, Doglioni N, Risso FM, Monari CB, Aversa S, Troiani S, Battajon N, Moschella S, Villani PE, Vedovato S, Maiorca D, Frezza S, Lista G, Laforgia N, Mondello I, Sibona I, Staffler A, Pratesi S, Paviotti G, De Bernardo G, Lama S, Miselli F, Bua J, Gitto E, Pesce S, Baraldi E, Trevisanuto D; NEODRY Trial Group.JAMA Netw Open. 2026 Mar 2;9(3):e2556902. doi: 10.1001/jamanetworkopen.2025.56902.

Transcript

Ben Courchia MD (00:00.706) Hello everybody, welcome back to the Incubator podcast. We're back. Today is Wednesday. We are here for Journal Club, and I have another paper for you today. Daphna, good morning. How are you?

Daphna Yasova Barbeau MD (00:11.271) Good morning, good morning. What do you have for us this morning?

Ben Courchia MD (00:15.15) I was very excited about this paper for a multitude of reasons. I'm going to tell you it's a paper I found in JAMA Network Open. The article is called "Drying Very Preterm Infants Before Plastic Wrapping at Birth, a Randomized Clinical Trial." This is coming from the NeoDry trial group.

Daphna Yasova Barbeau MD (00:36.797) What a great name.

Ben Courchia MD (00:42.254) The senior author of the paper is none other than Daniele Trevisanotto, who we did a whole series with. I would say a year ago, maybe more than a year ago now.

Daphna Yasova Barbeau MD (00:54.181) It's probably two years. Yeah, November 2023 on thermoregulation of the neonate.

Ben Courchia MD (00:57.292) It feels like it was just yesterday, but it was a really great mini-series. We got a lot of good feedback on the mini-series. On thermoregulation. I know, right? I was going to say last year, but it was a great mini-series because thermoregulation is an important topic. It's an important marker of quality, and it's highly associated with mortality and other morbidities. So we should pay attention to thermoregulation, which is why I think the series was so good. We want to thank GE Healthcare, who helped with the production of that series. We can't do it without the help of our sponsors, so thank you to them.

Daphna Yasova Barbeau MD (01:36.861) For people who are looking, that's episodes 159 through 163, if you want to take a listen.

Ben Courchia MD (01:41.376) Right. And Daniele Trevisanotto, who is coming from Italy, was one of the featured guests on this series. I always enjoy talking to people, especially from abroad, because you can always learn about new ways of doing things. I was very excited to see this paper for that particular reason. I thought the question was very clever. Let's go through the paper.

Ben Courchia MD (02:09.11) The introduction is very important. The maintenance of thermal homeostasis is a critical milestone, as they call it in the paper, in neonatology. We know from extensive research that hypothermia at birth is clearly associated with adverse neonatal outcomes. Despite this awareness, the incidence of hypothermia in very preterm infants at the time of admission to the NICU remains stubbornly high.

Daphna Yasova Barbeau MD (02:28.803) Stubbornly. Who's stubborn? Us or the babies?

Ben Courchia MD (02:31.99) Well, listen to the series. Not you, Daphna. I know you were there. I think we don't realize that we're doing all these efforts to keep babies warm. But we're also doing interventions for neurodevelopment that are increasing the time the baby is not under the warmer, for example. As we delay cord clamping, how are we maintaining homeostasis and thermoregulation during that time?

Daphna Yasova Barbeau MD (02:48.637) That's right.

Daphna Yasova Barbeau MD (02:53.701) Yeah, and temperature is so linked to IVH.

Ben Courchia MD (02:57.166) Yeah, absolutely. I think it's very interesting because it's something that is very difficult, that always falls by the wayside. Again, listen to the series; it's something that is often delegated to the nurses when it really is a team effort, truly. But it's true, when you're doing a minute of delayed cord clamping, how are you setting up your OR? What kind of temperature are we talking about? All these things are very important.

Ben Courchia MD (04:37.976) International guidelines for neonatal resuscitation suggest several standard interventions to prevent thermal loss. They include ensuring adequate room temperature, infant warmers, applying polyethylene bags or wraps, using preheated mattresses, applying caps, and utilizing heated and humidified gases. Interestingly, while drying the infant is a highly recommended procedure for the thermal management of babies born at 32 weeks or greater, this intervention is explicitly not indicated for very preterm infants. Current practice dictates that these tiny vulnerable babies should be put directly into a plastic wrap immediately at birth without any prior drying. The authors point out that this specific recommendation to skip the drying portion is based on prior studies that compared wrapping the baby in the bag without drying against drying the baby without wrapping the baby. I'm going to say that again. The comparison made was whether we should just put the baby straight in the bag or whether we should dry the baby and not put the baby in the bag.

Daphna Yasova Barbeau MD (04:33.382) It's one of those things we've been doing all this time, thinking there was great evidence, when maybe there was a third group that got dried and put in a bag.

Ben Courchia MD (04:42.762) Yeah, right. What they're saying is, what if we combine the interventions? Meaning, what if we dried and put the baby in the bag? They said this had not really been fully explored. To the authors' knowledge, only one prior study had investigated the role of drying before wrapping. While that study found comparable temperatures between the two methods, it did not look at very preterm infants who are at significantly higher risk for heat loss due to evaporation. Based on this gap in the literature, they hypothesized that drying the infant before putting the bag on the baby could limit evaporative heat loss immediately after birth and then improve rates of normothermia at NICU admission.

Ben Courchia MD (07:04.502) Let's talk a little bit about the methods. This was a multicenter, unblinded, randomized clinical trial performed across 21 Italian tertiary hospitals. It was conducted according to the principles of the Declaration of Helsinki. Neonates were eligible to participate if they had an estimated birth weight of less than 1,500 grams, a gestational age of less than or equal to 30 weeks and six days, or both. They had to be inborn, get parental consent, and they excluded neonates with major congenital anomalies, cardiac disease, congenital diaphragmatic hernia, abdominal wall defect, and neural tube defects. Before the trial began, they randomized the babies one-to-one for each participating hospital. They were either going into the intervention arm, which involved drying the baby before wrapping in the delivery room, or the control arm, which involved just putting the baby in the bag without drying. In the delivery room, participants in both arms were managed according to current guidelines for neonatal resuscitation. Standard care included maintaining the room temperature of the delivery suite between 23 and 25 degrees Celsius, employing delayed cord clamping for more than 30 seconds in babies that were uncompromised, or vigorous. Placing the neonates under a radiant warmer set to maximum power, covering the infants with a plastic bag or wrap up to the shoulders, and covering the head with a cap.

Ben Courchia MD (09:35.052) Importantly, pre-warmed mattresses and heated humidified gas were optional based on the clinician's preference. The critical difference was that participants in the treatment arm were intentionally dried with a pre-warmed towel before the plastic wrap was applied. I think it's important to mention that the blanket or towel used was not cold. When did they then measure the temperature? At the end of stabilization and resuscitation, each subject of the study was transferred to the NICU in an incubator set at 37 degrees Celsius. Once in the NICU, the plastic wrap was removed when the infant was placed into its incubator. Axillary temperature was measured using a digital thermometer at three distinct time points: at the end of stabilization in the delivery room, upon NICU admission, and finally one hour after admission. All participants were then followed up until either discharge or death. The primary outcome was the proportion of participants who were in the normothermal range, defined as between 36.5 degrees and 37.5 degrees Celsius at the time of admission. Secondary outcomes included proportions of participants with hypothermia (less than 36.5), moderate to severe hypothermia (less than 36 degrees), or hyperthermia (anything above 37.5). They also tracked some notable clinical morbidities: IVH, RDS, late-onset sepsis, BPD, and in-hospital mortality. Let's talk about the results. From 2023 to 2024, the study screened 458 neonates for eligibility. They were able to randomize 354, including 180 females and 174 males, with a mean gestational age of 28.6 weeks. 177 infants were randomized to the drying arm and 177 assigned to the control arm. When looking at the primary outcome, the intervention did not show an advantage. At NICU admission, normothermia was... Let me just ask you this, Daphna. Are you with me here? I'm gonna put you on the spot. You don't have the paper in front of you. What is the percentage of babies who reach normothermia upon admission to the NICU?

Daphna Yasova Barbeau MD (09:41.085) That's not what I thought you were gonna ask me.

Ben Courchia MD (09:44.174) Just like a Price is Right type of stuff. I would have said something like 70%. Specifically, coming from centers part of this group, they're very intentional about normothermia. Well, there was not a big difference between the two groups. Upon NICU admission, normothermia was reached in 45.8% of neonates who were dried compared to 46.3% of neonates who were not dried.

Daphna Yasova Barbeau MD (09:56.692) Wow. We've got a long way to go. But I did think the drying would help.

Ben Courchia MD (10:20.142) I know. We'll see what it's not. We're not finished with the data, because you're going to see you definitely don't want to dry babies. The proportion was not statistically different between these two arms in the unadjusted and the adjusted analysis. In terms of secondary outcomes, for almost all of them, there was no evidence that the clinical outcome differed between the two arms. Looking at safety metrics, there were a few cases of severe hypothermia, but they were not statistically significant between the arms. There were also no cases of severe hyperthermia. In terms of mortality, there was a stark and unexpected difference. In-hospital mortality was observed in 14.7% of the drying arm.

Daphna Yasova Barbeau MD (11:16.741) I know, it's so disappointing. You wonder what the downward effects of skin integrity are.

Ben Courchia MD (11:28.038) This generated a relative risk of 2.7. As you can expect from a team of rigorous researchers, they went deep into the data and performed a rigorous post-hoc analysis, which confirmed that the drying arm was associated with increased mortality even after adjusting for clinically relevant confounders like sex, gestational age, multiple births, and intrauterine growth restriction.

Daphna Yasova Barbeau MD (11:37.403) You gotta take a look, yeah.

Ben Courchia MD (11:57.454) Or even the temperature upon NICU admission. We'll talk a little bit about that because the discussion becomes very interesting; we have to speculate as to why this happened. In terms of gestational age sub-analyses, they looked closely at 102 participants born between 23 and 27 weeks and six days. In this extremely preterm group, the drying arm had a significantly lower neonatal temperature at one hour of age and an alarming increased relative risk of mortality of 4.71. Conversely, for the 213 participants born between 28 and 31 weeks and six days, the outcomes were not significant between the two arms. In the discussion, the authors confront the surprising mortality head-on. They acknowledged that the higher mortality rate among the dried neonates was unexpected. Particularly given the general safety of the procedure. It's a fairly safe procedure.

Daphna Yasova Barbeau MD (12:53.117) And because it's the mainstay of the initial steps of NRP, right?

Ben Courchia MD (12:58.272) Yeah, but not for these very small preemies. Because this mortality finding remained consistent across more than one sensitivity analysis, they emphasized that it required further clinical attention. They carefully reviewed the clinical records of each neonate that passed away. According to the authors, most of the deaths could be expected due to the "compromised clinical profile" of the neonates, saying that these babies were sick to begin with. Again, relating to the extreme prematurity, severe disease state, and so on. Furthermore, the stratified analysis suggested that the subgroup of the smallest infants was really what contributed to the mortality difference between the study arms. The authors noted that they could not completely exclude the possibility that the physical process of drying the infant immediately after birth could have triggered some degree of cardiovascular instability due to the manipulation of these very small, very fragile infants. But ultimately, they could not find a definitive pathophysiologic explanation related to the trial intervention itself, leading them to suggest that the mortality difference might just simply be a random finding. I don't disagree with their thought process, but if you are learning statistics and research methodology, this is an incredibly interesting topic because you can see an association, but not causation, right? It's difficult to explain. They also highlighted that while drying is formally recommended for the thermal management of older patients born after 32 weeks, their trial suggests...

Ben Courchia MD (14:55.276) ...that the procedure is not actively harmful in babies who are 28 to 32 weeks. Really, we're talking about that much smaller group. Still, they warn that the importance of this critical mortality outcome cannot be understated and warrants further investigation. They also draw attention to the elephant in the room beyond the mortality, which is that less than half of the neonates arrive in the NICU in a normothermal range. This highlights the fact that maintaining normothermia after birth is a major unresolved issue. They explored the potential benefits of trying to make that better, and we just reviewed all the results. To wrap up, I'm going to quote the conclusions from the study: "In this multicenter randomized clinical trial, drying before plastic wrapping provided no benefit to very preterm infants in maintaining normothermia at NICU admission." "Approximately half of the infants were outside the normal thermal range at NICU admission." "Most deaths could be expected due to the compromised profile of the neonates, and we could not reasonably find a pathophysiologic explanation related to the trial intervention." "Thermal management of such vulnerable infants is still a challenge and needs further investigation on suitable improvements of the current thermal intervention."

Daphna Yasova Barbeau MD (16:13.125) Now, I do think maybe they don't have that information, but not all the babies had the same thermal environment, right? They weren't all on thermal mattresses. That was different between babies. This wasn't a randomized trial, obviously.

Ben Courchia MD (16:34.062) You could potentially make the case for the mattress to basically improve the rates of normothermia on admission. But do you think that impacted... I mean, that could have an impact. And then mortality could be a downstream effect of that.

Daphna Yasova Barbeau MD (16:44.945) Maybe. Absolutely. Especially because, as we learned, there are so many ways thermoregulation works, right? Convection, et cetera. All those things that are also frequently tested on the board exams.

Ben Courchia MD (17:00.322) All the things. You're post-call, we're gonna excuse you. Evaporation, radiation, conduction, convection.

Daphna Yasova Barbeau MD (17:10.235) Radiation, convection, conduction! So that would be conduction, right? Direct skin to warmer, transwarmer.

Ben Courchia MD (17:21.078) Yeah, to the transwarmer. Exactly.

Daphna Yasova Barbeau MD (17:24.859) But I also think it highlights some low-hanging fruit where you're like, this is clearly a deficit for a lot of units. Let's work on thermoregulation. And that may look different for every unit, how you're able to tackle that.

Ben Courchia MD (17:44.94) Or just do the thing that they did. Just look at admission temperature, look at mortality. It's always an interesting thing to do when you're doing your stats for your unit. All right, buddy. I'll see you tomorrow.

Daphna Yasova Barbeau MD (17:55.837) All right.