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#196 - 📑 Journal Club - The latest research in neonatology (March 22 2024)

Hello Friends 👋

This week Ben & Daphna dive into the latest neonatal research and welcome a special guest in this insightful episode. They kick things off by discussing a study on the implementation of the 2022 AAP guidelines for neonatal hyperbilirubinemia, highlighting the reduced rates of phototherapy utilization and bilirubin measurements.

Next, they explore a fascinating trial on optimistic versus pessimistic message framing when communicating prognoses to parents of preterm infants, shedding light on the impact on parental anxiety, recall, and decision-making.

The episode then delves into a multi-center study on endotracheal tube sizing during neonatal intubations, raising questions about potential adjustments to the current weight-based recommendations.

In a sobering segment, Ben and Daphna review a study on intimate partner violence and depression screening among mothers with infants in the NICU, revealing alarming rates of abuse and depression that often go undetected.

They also examine research on predictors of two-year outcomes in neonates with congenital CMV infection, highlighting potential markers that could guide personalized care pathways.

Additionally, the hosts welcome back James Roberts, the founder of the innovative MOM Incubator system, who provides an exciting update on the progress and impact of his mobile incubator technology across multiple countries.


Find out more about MOM Incubators here


The articles covered on today’s episode of the podcast can be found here 👇

Sarathy L, Chou JH, Romano-Clarke G, Darci KA, Lerou PH.Pediatrics. 2024 Mar 14:e2023063323. doi: 10.1542/peds.2023-063323. Online ahead of print.PMID: 38482582


Forth FA, Hammerle F, König J, Urschitz MS, Neuweiler P, Mildenberger E, Kidszun A.JAMA Netw Open. 2024 Feb 5;7(2):e240105. doi: 10.1001/jamanetworkopen.2024.0105.PMID: 38393728 Free PMC article. Clinical Trial.


Peebles PJ, Jensen EA, Herrick HM, Wildenhain PJ, Rumpel J, Moussa A, Singh N, Abou Mehrem A, Quek BH, Wagner M, Pouppirt NR, Glass KM, Tingay DG, Hodgson KA, O'Shea JE, Sawyer T, Brei BK, Jung P, Unrau J, Kim JH, Barry J, DeMeo S, Johnston LC, Nishisaki A, Foglia EE.Pediatrics. 2024 Mar 12:e2023062925. doi: 10.1542/peds.2023-062925. Online ahead of print.PMID: 38469643


Desai S, Stanzo K, Benskin B, Cardenas K, Gilkey TW, Chiruvolu A.Am J Perinatol. 2024 Feb 29. doi: 10.1055/s-0044-1781423. Online ahead of print.PMID: 38423031


Lee CC, Chiang MC, Chu SM, Wu WC, Ho MM, Lien R.J Pediatr. 2024 Jan 11:113913. doi: 10.1016/j.jpeds.2024.113913. Online ahead of print.PMID: 38218371


Fourgeaud J, Magny JF, Couderc S, Garcia P, Maillotte AM, Benard M, Pinquier D, Minodier P, Astruc D, Patural H, Parat S, Guillois B, Garenne A, Guilleminot T, Parodi M, Bussières L, Ghout I, Ville Y, Leruez-Ville M.Pediatrics. 2024 Mar 15:e2023063531. doi: 10.1542/peds.2023-063531. Online ahead of print.PMID: 38487823


The video from the COPE trial reviewed by Daphna can be found below:


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

Ben Courchia MD (00:00.562)

Hello everybody, welcome back to the incubator podcast. It is Sunday, journal club is back. That's fun.

Daphna Barbeau (00:05.511)

I know, it's been a long time.

Ben Courchia MD (00:07.946)

I know, but we had this, so we are very, we are humbly busy. We have so many people that we wanna bring on the podcast and it's unfortunate, but there's, since we're releasing interviews every two weeks, there's only 26 interviews a year. And yeah, so the calendar is full. We're starting to think of 2025.

Daphna Barbeau (00:18.166)

That's right.

Daphna Barbeau (00:29.511)

I know, they fill up real fast.

Daphna Barbeau (00:35.427)

I'm sorry.

Ben Courchia MD (00:35.826)

And we had this great series of three interviews, I mean actually four, on probiotics that we've been meaning to release. And we're like, when are we? And so we thought, you know what? We didn't want to boot any of our other guests off the lineup. And we said, okay, we'll just dedicate a week that was supposed to be journal club for that. It's also very good review of the evidence. So we felt like it was...

Daphna Barbeau (00:42.717)


Daphna Barbeau (00:56.611)

That's what I was going to say. Yeah, I felt like it was Journal Club, but I'm probiotics.

Ben Courchia MD (01:01.43)

It's exactly right. And then it coincided nicely with the fact that we were both out of the country. So we decided to, so we're very happy. And this was, if you haven't listened to it, it is so good. I think the people that were on were so great. Dr. Blau walks you through some of the evidence that's been published already very nicely. Dr. Swanson is extremely clear and eloquent in how he...

Daphna Barbeau (01:07.223)

That's right.

Ben Courchia MD (01:30.47)

He walked us through some of the ways to think of NEC and prevention. And Dr. Kaufman, who was on this, one of the authors of the AAP recommendations on probiotics, it was great to have him on and to get his thoughts as well on this. So go check these interviews out and let us know if you have any comments. Let us know how you're feeling about the new content that we're providing. I'm thinking specifically about our new series on global health.

I'm thinking of our At the Bench episodes, which will be coming out with new episodes. I think there was one this week and there'll be another one next month. And we're very excited that hopefully this week we'll release our first special episodes that's going to be on a monthly basis of parents talking to other parents from the NICU. So let us know what your thoughts are. Feel free to share feedback. I have to say that we don't just...

rest on our laurels. We look at every feedback that we receive, suggestion, we take that very seriously. So it's very helpful for us.

Daphna Barbeau (02:33.779)

Yeah, I totally agree. I mean, we, one, we thrive on it, right? It's really helpful when we hear positive things. It's helpful when we hear things that we, you know, could be doing differently and requests as always. We like requests.

Ben Courchia MD (02:44.938)

Yeah, everything that is coming out this year at the bench, the Global Neonatal Podcast, the Parents Podcast, which by the way, yeah, so the Beyond the Beeps series, all that is coming from the brain of the community. It's feedback that we received who are saying, can we hear more about this? Can we hear more about that? And we're working very hard to make these wishes come true. So yeah.

Daphna Barbeau (02:48.994)


Daphna Barbeau (03:01.085)


Ben Courchia MD (03:12.246)

We will be presenting Grand Rounds at Nationwide Children's Hospital this week, March 27th, no, 27th. 27th, correct. So we'll be in Columbus, Ohio, and we're very excited about that. And I think after that, probably we'll be at CHOP and then PAS. So taking the show on the road, if you are in these areas, and make sure to come join us for these will be interesting conferences and discussions.

Daphna Barbeau (03:16.06)


Daphna Barbeau (03:19.383)

That's right. Yeah. That's right.

Daphna Barbeau (03:27.198)


Ben Courchia MD (03:43.619)

I digress and Journal Club does not wait for anyone.

Daphna Barbeau (03:48.842)

Let's do it.

Ben Courchia MD (03:50.022)

Okay. All right. I'm going to start us off with a topic that is always very popular on the podcast. And that is Biller Rubin. Everybody loves when we talk about Biller Rubin.

Daphna Barbeau (03:57.987)

Mm-hmm. I was very glad that you picked this paper to review.

Ben Courchia MD (04:02.27)

Yeah, the paper is published in pediatrics. It's coming from the US. The first author is Lila Sarati and the title is bilirubin measurement and phototherapy use after the AAP 2022 newborn hyper bilirubinemia guideline. Let's learn my speech a little bit there. After the 2022 newborn hyper bilirubinemia guideline. So if you need a refresher on the new bilirubin guidelines,

you can go back, we have a journal club that I think may be our most popular journal club ever. And let me see. Yeah, I forget the number, but I can find it. You'll find it for us? All right, very good. So in this paper, really, we know that there has been new guidelines. We know that the new guidelines kind of raised the threshold for phototherapy significantly. And we also know...

Daphna Barbeau (04:41.811)

It was. I'll find it for you. You continue, yeah.

Daphna Barbeau (04:58.051)


Ben Courchia MD (05:01.046)

that the threshold for exchange transfusions and IVIG and so on moved as well but not very much which created a very narrow window for us to work within when it comes to phototherapy and other treatments. And the goal of the paper was really trying to measure the rates of clinical interventions and unintended adverse outcomes before and after the publications of the guideline. So trying to see exactly what has changed since the guidelines were published.

And this was a retrospective cohort study that included data collected across eight hospitals within one healthcare system between January 2022 and June 2023. Basically, the inclusion of, and by the way, the healthcare system we are talking about is the one of...

Mass General in Boston. So a fairly robust health system that has kind of a good catchment area. They included babies who were born 35 weeks of gestation or more. Obviously this coincided with the inclusion of the babies in the actual guidelines. The outcomes that they were looking at were rates of phototherapy, total serum bilirubin measurements before and after the

as well as some clinical outcomes, including length of stay, readmission, and duration of phototherapy. So they were able to abstract 22,500 newborns, maybe a bit less than that, but more rounding up, within their network between 2022 and 2023. Obviously, the big question is, was there a difference between these two cohorts, specifically when it comes to babies that have ABO incompatibility?

And it was reassuring to see that infant direct CUMPS tests were typically checked only when there was some blood typing compatibility, and that the rate of detected direct CUMPS positivity in infants did not really differ between the two periods. So at least from that standpoint. Because if suddenly in 2023 they had so many more CUMPS positive babies, then it would have been an issue. So let's look at the rates of phototherapy utilization.

Ben Courchia MD (07:23.618)

And not surprising, they observed a 46.7% reduction in phototherapy utilization during the hospitalization at birth. And it was demonstrated by a decrease from about 4% of all newborns in the pre-guideline period needing phototherapy to about 2% after the guidelines were published. Obviously, this was a statistically significant change.

As of June, 2023, only 30% of phototherapy administered was initiated at or above the threshold. And I think that was very interesting. Meaning, even though we are seeing a decrease, we are still not really following the guideline as well as we could, potentially meaning that maybe even less babies could be needing phototherapy.

Daphna Barbeau (08:18.7)


Ben Courchia MD (08:22.766)

near threshold initiation of phototherapy had increased to 77%. I think this is fascinating both from a human behavior and maybe the fact that we're not all super comfortable with these very high levels.

Daphna Barbeau (08:32.703)

I think it makes sense though.

That's right. I mean, personally, it felt quite drastic, the change. And we've been, our unit has was early, early adopters, right? We committed to the new guidelines, but it still felt like, oh, surely this kid qualifies for the therapy, but they didn't.

Ben Courchia MD (08:47.254)

that same week.

Ben Courchia MD (08:55.79)

And if you remember correctly from the guidelines, there's obviously the curve. So you have the level itself. But then they tell you, oh, if you're within 2 milligrams per deciliter, but you see that it's rising and you're like, rather just start phototherapy before allowing it to cross the threshold, then you should. But yeah, that's what they, yeah.

Daphna Barbeau (09:17.095)

Especially like you mentioned, that then the window until exchange became a little bit more narrow, you know?

Ben Courchia MD (09:23.098)

Mm-hmm. That's right. So I think that's very interesting, and I'm not going to comment more on that, because obviously it doesn't mention the motivation or what was the reason behind all that. But I think it's interesting, because I felt that we all felt the same way. I mean, I did residency where 48 hours, Billy of 10 was something you should look into. And it's interesting to see Biller-Rubin levels rise to like 15 and just not do anything. Now, when it comes to total serum Biller-Rubin measurements,

In the post-guideline period, the percentage of newborns undergoing any CRM-Beli measurement decreased by 20% from 35% to 28%. This was significant. And the rate of TESB measurements decreased by 22.6% from 712 to 551 per 1000 infant. So again, the difference there was that the first one was a reduction by 20%

in any measurement needed versus the rate of measurements decreasing. That could be a little bit confusing. The outpatient serum belly measurements remain stable. Obviously, the caveat here is that it's unclear whether their catchment area is so good that they're actually not missing any of these measurements, but they're very upfront about this in the limitations. And it's obviously a limitation of the study that maybe patient X went to a different institution that didn't really capture that data in their health electronic medical records.

Some other outcomes that were interesting, they said they were gonna look at the length of stay, but the guideline didn't really impact length of stay. And I think the change was maybe one hour. And post-guideline, the length of stay was longer by one hour, statistically significant probably, but not really clinically significant. The duration of phototherapy remained stable and the mean was about 35 hours. There was no significant change in the rate of overall inpatient readmission during the first 28 days after birth.

or readmission receiving phototherapy. So again, dependent on their healthcare systems catchment area, but no change that they could observe. Interestingly, they reported some rare outcomes. And what they saw was that they saw a slight increase pre to post guideline in newborns with bilirubin values exceeding the escalation of care threshold. And that's all, that's what we were talking about before.

Ben Courchia MD (11:47.282)

escalation of care threshold is when you're like, you're going to have to escalate care beyond phototherapy, but that was not really significant. And the numbers were like four versus six. So to me, um, yeah, they, they were very transparent in reporting this, but not, not statistically significant by no means. And the newborns who received IVIG in the setting of hyperpigmentary rubinemia, one versus five during the birth hospitalization. Interestingly enough, um, all these babies were, um,

treated already during their initial admission. So this was babies that didn't fall through the cracks or anything, but it did lead to a little bit more escalation of care. Similar changes were observed in newborns readmitted for phototherapy. So in the post-guideline epoch, three had bilirubin exceeding the escalation of care threshold and one received IVIG compared with zero in the pre-guideline epoch. So something to...

consider. The conclusion are that the authors write that the 2022 AAP guidelines on neonatal hyperbola ergonemia represent an opportunity to significantly reduce the overtreatment of a common newborn condition and that their study reveals that the implementation of these recommendations can yield a significant reduction in the interventions that future work studying which intervention proves most successful in the guideline implementation will help achieve more widespread improvement and that further population level work is needed to confirm safety and ongoing

But a very interesting paper. Any other thoughts on?

Daphna Barbeau (13:17.923)

A necessary paper. No, I mean, I think it was good to see where is the community at and how did the babies fare and so I think it was good. And just to close the loop, episode 82 in August of 2022, doesn't it feel like a long time? Doesn't it feel like that? Is when we cover the new Billy Rubin management guidelines.

Ben Courchia MD (13:36.69)

It feels like a long time ago. Absolutely.

Ben Courchia MD (13:42.334)

Yeah, but it's very interesting to see that it was reassuring to me to see that other people as well feel like, man, it's like you end up, yeah, you end up treating a little bit before. So anyway, where are you taking us next? Yeah.

Daphna Barbeau (13:50.007)


Daphna Barbeau (13:59.543)

Sounds good. Well, I had some interesting papers this go around. I really like this paper, Optimistic versus Pessimistic Message Framing in Communicating Prognosis to Parents of Very Preterm Infants, the COPE trial. Lead author Fiona Forth, senior author Andre Kidzon. This was in JAMA Network Open and it's coming to us from Germany. It was a single center randomized controlled

crossover trial where they wanted to see if you provided parents with the same content, but you phrased it either pessimistically or optimistically, and I'll get into that, how is it received by parents? So I thought that was interesting. The cohort were parents of surviving preterm infants who had long been discharged from the NICU. They had a

The preterm infants had a birth weight under 1,500 grams and were treated at this institution between January 2010 and December 2019. They were excluded, the families were excluded if they reported acute mental illness or persistent distress from the prematurity experience. This was all by self-report. So basically what they did is participants were randomized to alternate exposure of

a two video sequence. Okay, so they either got the optimistic framing video first, followed by the pessimistic framing video or the opposite. They got the pessimistic framing video first, followed by the optimistic framing video. And what did that look like? So they were experimental video vignettes. They were portrayed by professional actors and it depicted a conversation between a neonatologist and the parents of this.

hypothetical very preterm infant. And the content of the conversation was a recent, a new diagnosis of an acute severe intraventricular hemorrhaging the infant and the associated prognosis. So many aspects of the two videos were standardized, the setting, the actors, the flow of the conversation, the camera work, the duration, and the messages were equivalent, but different in presentation. So.

Daphna Barbeau (16:19.011)

The statistical outcome estimates were a 50% survival and impairment in 50% in the case of survival. But that was either framed either as a probability of survival and a probability of non-impaired. So you had a chance of being 50% non-impaired. That was the optimistic framing. Or a risk of death and impaired survival. So you had a risk of 50% of having impairment if you survived.

That was a pessimistic framing. The priming outcome was really the parent preference for what type of video they received. It was assessed once after the second video in response to the question of whether they preferred the first or the second video. And in addition, at the baseline and after each video, they used the

Gosh, I should have gotten that. It's the state, it's a state trait anxiety index, I think, STAI, but they basically looked as anxiety as a transient response to a stimulus. So they got that at baseline and then after each video.

Ben Courchia MD (17:32.702)

And then the supplemental material, you actually, so there's a YouTube video explaining the trial, but then on the supplemental material, you have the script of the videos, both the optimistic and pessimistic. Are you gonna go into that, or should we give them like one answer so that they get a feel for what that sounds like?

Daphna Barbeau (17:36.148)


Daphna Barbeau (17:42.475)

the videos. Yeah.

Daphna Barbeau (17:52.319)

Um, I, you can go ahead. If you haven't pulled up there, that would be great.

Ben Courchia MD (17:56.602)

So like for example, obviously talking about a head bleed, I'm giving you one of the last answers which should convey the difference. Like the mother asks, what will happen now to Louisa, which is the name of the fictional baby there? What should Shawl can we do? And in the optimistic video, the physician says, nobody knows what the future might hold. Lots of children do not survive situations like this. Most of them.

Those who do only with severe impairments retain severe impairments. I do, however, no children who after severe bleeding of this kind have developed normally. So when the same question is asked and the answer is framed in a more pessimistic manner, the beginning is sort of the same. The physician responds, nobody know what the future might hold. Lots of children do not survive situations like this. Most of them slash those who do only with severe impairments.

Daphna Barbeau (18:40.087)


Ben Courchia MD (18:50.698)

retain severe impairments. I wish the prognosis were different. So very subtle, but still, yeah. And then in the supplemental material, you have the various videos that you have the pessimistic and the optimistic.

Daphna Barbeau (18:55.227)

Mm-hmm. Very subtle.

Daphna Barbeau (19:04.608)


Daphna Barbeau (19:11.139)

Perfect, thank you. The other secondary outcomes they wanted to look at was how did the participants rate the physician's overall impression, the professionalism and physician compassion. So I thought that was interesting as well. 220 parents were included in the final analysis. Some of them did include, you know, like couples or parents of the same former NICU infant.

They had 64% female participants, 92% limited to parent household. Most participants had two children and their preterm infant had been in the NICU a mean of 5.9 years ago. So range from 2 to 11. So pretty remote from their admission. No participant discontinued.

for elevated part psychological distress. So the results, the two groups appear pretty similar, but the statistical significance isn't indicated there. But the end, the punchline is that participants vastly preferred optimistic over pessimistic framing. This was 89.1% preferred the optimistic framing.

And the preference probability for optimistic framing was estimated to be 92% after the model-based adjustment for presentation order. And this is a preference odds of 11. And the preference for optimistic framing was more pronounced when it was presented second than when it was presented first. In terms of the anxiety scores, the baseline state anxiety scores were similar in both groups. So before they saw the videos.

And in response to the first video, with both optimistic and pessimistic framing, interestingly, the participants' state anxiety scores increased equally from baseline. But when pessimistic framing followed optimistic framing, the state anxiety scores stayed stable, high. But in contrast, when the optimistic framing video came after the pessimistic framing video, the state anxiety scores decreased. And...

Daphna Barbeau (21:25.239)

When comparing optimistic versus pessimistic framing, participants who received the optimistic framing rated their overall impression of the physician as more positive, more professional, and more compassionate. All of these were statistically significant. With optimistic framing, the participants were more satisfied with the prognostic communication style. They felt better informed about the prognosis and better prepared to make decisions, shared decision-making.

and act as surrogates for their child. Participants also prove... Go ahead. Hold on, I'll get there. They were more optimistic about the infant's survival and non-imperament, and more hopeful for the infant's future. You want me to talk about the recall?

Ben Courchia MD (21:57.794)

talk about the, what about the recall?

Ben Courchia MD (22:15.35)

The recall, I think, to me was the key of the paper. Because, listen, I think you might say, oh, if I'm too optimistic, I'm gonna give a false impression of what the data really is. They're gonna leave thinking that everything is great and I'd rather be pessimistic and surpass expectations rather than give too hopeful of a message and then people feel disappointed. But what they found in terms of what parents recalled, whether it was from the pessimistic or the optimistic framing, is fascinating because, I mean, you're gonna tell us.

Daphna Barbeau (22:18.38)


Daphna Barbeau (22:46.739)

Exactly. So when they had with both framing variants, the recall survival estimates was more likely to be pessimistic than optimistic. With pessimistic framing, however, this trend was more pronounced, although the result was not statistically significant. In contrast, when the recall of impairment estimates was rather optimistic than pessimistic with both framing variants. So I...

Ben Courchia MD (23:14.018)

So what was interesting is that if figure three, I think, tells a nice picture, because you have the recall of the parents estimates of survival. And what you find is that the participants who recalled the pessimist, who recalled the appropriate survival metric was about 20 percent in the pessimistic group versus what, like five percent in the optimistic group.

Daphna Barbeau (23:18.431)


Ben Courchia MD (23:42.262)

But when we were talking about recall of impairment estimates, I think the optimist recalls were quite high, which I think is interesting.

Daphna Barbeau (23:53.863)

Yeah, I mean, in both scenarios, both of survival estimate and recall of impairment estimates, the people who were framed optimistically had better recall, better correct recall. So they understood or retained the information more often than those with the pessimistic framing.

Ben Courchia MD (24:12.546)

Yeah. And that's what they wrote in the results as well. That with optimistic framing, the odds of correct recall of conveyed estimates were higher for survival. So I think that was interesting. And that for the impairment odds, it was similar trend, but not statistically significant.

Daphna Barbeau (24:19.611)

Yeah. And I think, go ahead.

Daphna Barbeau (24:29.843)

And in the discussion, I think they had a really nice paragraph here about exactly what you're saying is that I think people fear if I'm too optimistic, then, you know, the parents will be disappointed when the baby doesn't do well, or you may have a bias to what decision you think the parents should make. And they may not make that decision if, you know, you're optimistic. But I thought.

They did a great job of discussing that. A potentially overly optimistic view the infant's neurodevelopment with the preferred optimistic framing may be addressed by specific strategies. These might include the repetition of prognostic information in the course or explicitly supplementing the potential positive outcomes conveyed with risks and potential negative outcomes in the sense of a mixed framing. Additional written visual or audio visual materials could be an appropriate measure to reinforce verbal information and enhance parental understanding.

However, it should be recognized that optimizing prognostic recall, especially of impairment estimates, may not be necessary. Impairment estimates appear to be less meaningful outcomes to NICU parents than survival estimates. Moreover, parents generally tend to be more positive about the child's prognosis than physicians. A hopeful and optimistic view of the child's future by parents can be realistic even when the prognosis is poor.

Many studies demonstrate that hope and realism are not mutually exclusive in the context of understanding essential information in the NICU. And I think that's a really important takeaway.

Ben Courchia MD (25:52.279)

It's an important point. It's hard, but it's not impossible. Exactly. Very cool. Very nice paper. Thank you for sharing that with us.

Daphna Barbeau (25:54.911)

Yeah. That's right.

Alright? Sure?

Ben Courchia MD (26:03.122)

Okay, we're going to take a quick break. And when we come back, we're actually quite excited to welcome back a former guest of the podcast on the show who's gonna give us like a little update. So this was a Tech Tuesday episode, and we're trying to do, as we said, more newsy type of segments. And this is like the Shark Tank version of Where Are They Now? So we'll have James Roberts who comes back on the show and tell us, give us a little bit of an update on the MAM incubators. So we're gonna mark this here.

Daphna Barbeau (26:12.159)


Daphna Barbeau (26:23.81)

That's right.

Ben Courchia MD (00:03.226)

So we're very excited to have with us today back on the podcast, James Roberts, who is a designer and an entrepreneur from the UK and who is the founder of the Mom Incubator, which we presented on the podcast in the past. Right. James had come on the podcast. I forget which I forget the year, but it was episode 91.

Daphna Barbeau (00:24.312)


Ben Courchia MD (00:30.326)

And so if you're interested in finding out more about James and the mom incubator, then please go back and listen to episode 91 of the podcast. But, James, thank you for coming back on the show and giving us an update on mom incubator.

Daphna Barbeau (00:30.56)


James (00:44.498)

Firstly, thank you for having me back. A lot has happened since I last spoke to you. And it's great to kind of bring your listeners up to speed. I think when we last spoke, we were just about to get a regulatory approval or we were close to that point. Since then, we've gone on to make, you know, in the small time, a lot of impact in the world. The team's done amazing things. We think we've impacted between three and four thousand babies now with our system. We've got about probably a hundred.

Ben Courchia MD (00:58.453)


Ben Courchia MD (01:10.703)


Daphna Barbeau (01:12.099)

That's amazing.

James (01:13.698)

100 in the field. We're in we're in four countries now as well. So that that's gone. You know, that's been pretty exciting. That's been inbound kind of interest in what we're doing. And we just received well, we're in the NHS now too. So they're using the mom system to stop babies actually being transferred to NICU, or potentially bring them out sooner into what we call transitional care. And ultimately keeping the baby

close to the parents trying to increase that bond and we're exploring how we can increase that use within our own kind of home care place.

Ben Courchia MD (01:51.663)

That's truly amazing because basically you're leveraging the mobility of the mom incubator, the fact that it really is very nimble, able to be set up quickly to basically reduce separation between mother and baby and the potential for the NHS, which is the National Health Service in the UK, really makes the potential for the mom incubator tremendous. So congratulations for that.

Daphna Barbeau (01:56.067)


James (02:15.11)

Yeah, thank you. I mean we develop the first system is truly mobile can go over a parent's bed It's something you can bring the system to the parent of the child rather than the other way around and we're the first ones To be able to do that and that's what's getting people excited Especially when we speak to US clinicians who sometimes face similar problems, maybe something different But our system provides in that flexibility they need to do what they want And that's where we're getting a lot of a lot of interest for what we're doing

Ben Courchia MD (02:43.246)

And your devices, as you said, potentially have impacted already thousands of newborns. And I think if I remember when we discussed this affair correctly, mostly in four countries and not necessarily in close geographical location, you've been all over both in Europe, in Ukraine and even in Africa. Correct?

Daphna Barbeau (03:01.943)


James (03:03.788)


James (03:08.394)

Yeah, we're those kind of well, Sub-Saharan African countries, Eastern Europe, NHS as well, we're proving the system's really versatile, robust, can be used in kind of multiple use cases. So it's being used for anything from standard of care in some countries. So that is the system they have to care for the child. And others like here in the UK, it's to provide flexibility of healthcare in places like labour and delivery, transitional care where you traditionally don't see these types of systems, but now it's possible.

Ben Courchia MD (03:27.642)


James (03:38.43)

Um, so that that's, that's really exciting. Actually, um, is trying to take something, you know, that hasn't been thought about since the seventies or eighties really, and really, and think about, well, where else could you actually use a system like this? If we think about the design of it properly, if we really understand collisions and what they want, um, you can kind of come up with devices like this.

Ben Courchia MD (03:50.76)


Ben Courchia MD (03:59.234)

That's amazing. And congratulations, by the way. I think Mom Incubator won the Princess Royal Silver Medal from the Royal Academy of Engineering. I must say that I'm not familiar with all the engineering awards, but this sounds fancy and this sounds prestigious. So congratulations. I wanted to maybe ask you one more thing before we part ways. And that is, any plans for the Mom Incubator to make a foray in the United States? Have you?

Daphna Barbeau (04:11.607)


James (04:14.99)

Thank you.

Ben Courchia MD (04:28.382)

Are you working on that? Is there any discussions with the FDA by chance around trying to make that available for hospitals and healthcare services here in the US for us?

James (04:39.626)

are about to actually go well, we're making our first submission to the FDA as we speak. So that's already in our plans. I'm coming to the US three or four times this year, visiting some hospital sites. And what I really want to do actually is getting in touch with some KOLs, people who want to think about neonatology or healthcare in a different way, people who are innovative in their mindset and thinking, and people who can help a system like this get to the patients that really need them.

Ben Courchia MD (04:43.49)

That's exciting.

James (05:06.403)

in the US. If there's anybody listening who thinks they can do that and wants to be involved in some great studies then let me know.

Ben Courchia MD (05:12.278)

Yeah, we had a very nice mini series on the podcast not too long ago, looking at thermal regulation of the newborn, where we really talked about trying to prevent hypothermia and how really there's a lot of technical challenges to really maintaining normal temperature, especially in and around the time of birth. I think the mom incubator lends itself quite nicely to that problem. So if anybody listening is interested in that, we'll, we'll have ways to reach out to you in the episode show notes and.

Daphna Barbeau (05:29.067)


Ben Courchia MD (05:38.706)

And I think this is a great opportunity for quality improvement initiatives, research projects, and so on. So thank you for putting this out there. James, it's been a pleasure to have you back on the show. Congratulations on all the success. We're very excited about the future steps for M And we're looking forward to hearing from you again very soon.

James (05:58.806)

Thank you for having me on and watch this space. We've got lots coming up soon as well. So quite some quite exciting stuff. Amazing. Thank you.

Ben Courchia MD (06:04.01)

Awesome. See you then. Bye.

Ben Courchia MD (26:31.662)

Okay, that was great.

Daphna Barbeau (26:41.975)

They've come a long way in a few short years. I think that's really cool.

Ben Courchia MD (26:46.154)

Yeah, and we really try to do our research on the people that we bring on to make sure that what they have to offer is of value, is compelling. And so it's exciting to see that this resonates with the community. So very, very good stuff. All right, I have a few more papers that I wanna review. And the first one is again in pediatrics. I was very lucky to find so many good articles in pediatrics this month. The first one, the second one I'm reviewing today is called endotracheal tube size adjustment.

Daphna Barbeau (26:50.581)


Ben Courchia MD (27:12.822)

within seven days of neonatal intubation. First author is Patrick Peebles, and this comes from the US. It's basically the near for NEOs group. So the background is interesting, right? So ET tubes that are sized too small, we know is not good. You get airway leak, you can get incorrect ventilator measurements, you can get auto triggering or increased an ET tube resistance. Now an ET tube that's too large is also not good. Like if you can fit it in,

You might lead to airway injury. It might lead to intubation failure because you might not be able to get it in and potential for long-term damage to the airways such as subglottal stenosis. And so when we're looking at the recommendations of the NRP, which is the National Resource Station Program here in the US, it provides very clear recommendations as to which tube should you use. And it's fairly easy to remember. Basically you have a 2.5 millimeter tube, which basically when we're talking about the 2.5, the 3, it's like the internal diameter of the tube.

So if you're above two kilos, it's a 3.5. If you're between one and two kilos, it's a 3.0. If you're less than a kilo, it's 2.5. That's the recommendation. Fairly straightforward. I think easy to remember when you're in the crunch of the situation. And yeah, so good. But now the question the team is asking is, how do data-driven weight-based endotracheal tube size threshold for infants undergoing intubation compare to the NRP recommendation?

And so this was a retrospective multi-center cohort study using prospectively collected data on tracheal intubation practice and outcome from the neonatal emergency airway registry for neonate to the near foreign neos, which by the way, definitely we're going to have to bring on the show so that people can start getting reaching out to them. Yeah, they're super popular, but I'm sure some people who are interested in this field have not heard of them and it's a shame because they're amazing. They have an amazing database. They are collecting amazing data.

Daphna Barbeau (28:59.189)

Yeah, I was just thinking about that. Yeah.

Daphna Barbeau (29:07.723)


Ben Courchia MD (29:10.91)

And their quality improvement stuff is terrific. So they included babies who had their first tracheal intubation encounter recorded in their registry between 2016 and 2022. And only infants with a first intubation encounter performed via the oral or nasal route using exclusively uncoffed TT tubes were evaluated. They excluded a bunch of babies. I'm not going to get into the details, like if it was not a neonatology provider that was doing it.

if the ET tube was larger than a 4.0, because then again, how do you compare it with the NRP? Because they don't really make that recommendation. Or if they were missing data or anyway, so anyway, a bunch of exclusion criteria. Then they looked at the need for downsizing the tube versus upsizing the tube. I think that was interesting. So downsizing the tube meant that you had an intubation in which the final successful attempt was completed using a smaller

Daphna Barbeau (30:06.768)


Ben Courchia MD (30:10.186)

And then they did something very clever with the upsizing because that was the tricky part, right? Technically, you could always get a smaller tube in if you're not successful, right? So give me a 2.0 and I can put it into a baby that's maybe more difficult to intimate, but how successful is that? And in order to look for that, what they did is that they looked at upsizing and they said, let's see if upsizing was needed. And that was defined as needing to change the tube size to a higher size within seven days. Because they said, if you really use

Daphna Barbeau (30:17.543)


Daphna Barbeau (30:31.094)


Ben Courchia MD (30:37.902)

too low of a tube, you're not gonna be able to ventilate the baby well. You're gonna have to change it. And so that's why the upsizing window was a bit longer, because you could get away with a smaller tube for like a couple of hours. But I think seven days was a smart way of looking at this. And basically, they looked at that. The primary outcome was any associated tracheal intubation event. And then they had secondary outcomes that included

Daphna Barbeau (30:40.051)

Yeah, you'll get in trouble, yeah.

Ben Courchia MD (31:07.87)

uh events they had a definition for severe events non-severe events i'm not going to go through them they're there they make sense um i'm going to go to the results so uh 7293 patients eligible for inclusion in the cohort the et tube size for the first intubation attempt was consistent with nrp recommendation in 78.9 percent of cases so in 80 percent of cases people follow the nrp recommendation

If you're writing protocols and guidelines, 80% adherence. It's not bad at all. And then interestingly enough, then they had to mention the bad apples. Site level adherence from the NRP recommendation did range from 46% to 100%. So some were very good at following NRP recommendation. Some felt like they didn't need any help picking the right size tube. But the...

Daphna Barbeau (31:55.806)

Wow. That's right.

Daphna Barbeau (32:01.899)


Ben Courchia MD (32:05.95)

interesting thing is that saying, well, if there is variability, then where are we seeing the variability? And that was more pronounced in the weight groups of 1000 to 1200 grams, and the 2000 to 2200 grams, both of which are immediately above the NRP recommended threshold cut points for both one kilo and two kilo. And so they identified these two windows as places where there was the most variability. Clinicians selected an initial ET

instead of the recommended three, in 38% of infants weighing 1,000 to 1,200 grams. And a 3.0 size, while the NRP recommended a 3.5, in 63% of infants between 2,000 and 2,200 grams. And I think it's interesting because while the recommendation is clearly easy to remember, sometimes you look at these babies and they're small and you're like,

Daphna Barbeau (32:53.707)


Daphna Barbeau (33:01.483)


Ben Courchia MD (33:01.974)

that feels like this tube is, you don't feel so good about shoving a tube sometimes that feels quite big into these airways. And so that resonated with me a little bit. When they assessed the full study cohort, the ET tube size was downsized from the first selected size in 5% of encounters and was upsized in only 1.5% of encounters. So very little, right? I mean, we're talking about like 98 to 95, 95 to 98% of cases where

Daphna Barbeau (33:26.593)


Ben Courchia MD (33:32.234)

You don't need either downsizing or upsizing. The ET tube was downsized from a 3.0 to a smaller ET tube in 13% of infants weighing 1,000 to 1,200 grams. Interestingly enough, this is exactly the window where we said that a lot of people go with a 2.5. So I think that's interesting that even the ones who got a 3.0 ended up downsizing. And from a 3.5 in 17% of...

and from a 3.5 to a 3.0 in 17% of cases for the babies weighing 2,200 grams. A few more interesting results across the cohort. Procedural adverse outcomes were more common in TI procedures where downsizing occurred compared with procedures without dine sizing. Any tracheal intubation adverse events and severe oxygenation desaturations were seen. So for the adverse event in 33% versus 17%

when the downsizing versus no downsizing. And for the severe oxygen desaturation, 60% versus 40%. Among infants weighing 1,000 to 1,200 grams, the initial use of a 2.5 versus the NRP-recommended 3.0 was associated with lower adjusted odds of any adverse event and severe oxygen desaturation. So might make for a smoother ride. And then in the weight subgroups of

2000 grams to 2200 grams, the use of a 3-0 ET tube versus the NRP recommended 3-5 was associated with lower adjusted odds of severe oxygen desaturations. So the conclusions, as the authors state them, are that for infants between 1000 grams and 1200 grams and for babies between 2000 grams and 2200 grams, the recommended ET tube size of 3-0 and 3-5 respectively were commonly downsized during the procedure.

and 0.5 millimeter smaller ET tube size were commonly selected, rarely upsized within seven days, and independently associated with reduced odds of procedural adverse outcomes. These results may inform evidence-based recommendations for ET tube size selection during neonatal intubations. And I guess it's very interesting. Not sure what, these are not new guidelines, so you have to take that with a grain of salt, but will it be in

Daphna Barbeau (35:49.577)


Ben Courchia MD (35:53.042)

and will be integrated in future recommendations. I don't know. What?

Daphna Barbeau (35:57.867)

You know, it's complicated because they didn't really talk about the thresholds for upsizing a tube, right? And in my experience, people wait to swap out a tube to a bigger size. I think people tolerate a lot of, potentially a lot before they upsize a tube, especially if maybe the baby was thought to be difficult to debate before, or they needed to put in a smaller tube.

Ben Courchia MD (36:15.616)


Daphna Barbeau (36:24.127)

So, I mean, I actually, yeah, I was quite reassured by the one percent, but what do we tolerate, you know, in the interim? So, but it's an interesting concept for sure.

Ben Courchia MD (36:32.11)

That's true.

Ben Courchia MD (36:36.178)

Yeah, very, very interesting. And no, I think, and this was cleverly done. And I think to me, what this highlights is the difficulty in outlining a guideline that will be readily easy to remember during the time of intubation. So like you can remember very quickly which one am I supposed to pick versus

Daphna Barbeau (36:42.275)


Daphna Barbeau (36:52.981)


Daphna Barbeau (36:56.475)

And I do think the current guidelines are like as simple as they can be, right?

Ben Courchia MD (36:59.55)

Yeah, exactly. I mean, it's not very hard to remember more than two kilos, three, five, one to two, three, less than one, 2.5. But then, yeah, you're trading off a little bit of sophistication and like maybe picking a more appropriately sized tube, but how do you weigh the pros and the cons of a more sophisticated guideline versus something that's super easy to remember for anyone, that's where the challenge lies. And these are centers that are

Daphna Barbeau (37:05.323)


Ben Courchia MD (37:26.562)

very experienced, they have large volumes and they have lots of staff. So yeah, an interesting, interesting paper.

Daphna Barbeau (37:27.848)


Daphna Barbeau (37:33.091)

Totally agree. You want me to go?

Ben Courchia MD (37:36.75)

I mean, you can go, I have more to go.

Daphna Barbeau (37:38.163)

Okay, I know you're following me. I thought this was an interesting paper where you're looking to do a lot more screening in the NICU, this is becoming a big point of discussion in the community. And so this one was actually about intimate partner violence. So intimate partner violence and depression screening of mothers with infants in the neonatal intensive care unit. And this is the one thing that I actually care a lot about and I was still shocked by the results.

I'll tell you. So the lead author, Sujata Desai, senior author, are Pitha Chiruvulu. This is in the Journal of Perinatology.

Ben Courchia MD (38:18.43)

So, no, Chiruvulu is someone that we've referenced on the podcast before. If I remember correctly, I think she even, she was, she even, I'll check, but I think we'll be, I'll check. I think she is at Baylor. I think we talked about her work when it comes to probiotics. Anyway, like in the probiotic series that we just released.

Daphna Barbeau (38:24.138)


Daphna Barbeau (38:35.191)

That's correct, Bailey.

You'll tell us where. So what they wanted to do in this study was to really determine the prevalence of partner violence and depression, but also what was the effect of partner violence on depression in neonatal intensive care unit mothers, or mothers who had an infant admitted to the NICU. So.

At their institution, the mothers are actually currently screened by a labor and delivery nurse for violence and psychological distress upon admission. And this is true for most labor delivery units across the country. So the two intake questions are, do you feel safe at home and have you felt sad? So it's a quick two question screener. And this is not unlike what we do at our institution and at many other institutions. And then...

Parents who, mothers who were enrolled were screened in a safe room away from their partner. So they were screened individually with the Edinburgh Postnatal Depression Scale, which has been validated in mothers with NICU infants and the Abuse Assessment Screen Tool, the AAS, within two days of the newborn's admission. Now, mothers were excluded if they weren't able to get the mother alone, which I thought.

was interesting. So they administered the AAS, so the parents got the screening and labor and delivery, that was the intake questionnaire. The AAS was administered at the first screening, and then the Edinburgh scale was administered up to three times to obtain kind of the most accurate score and trying to look at the ideal time of measurement. So the first time was within 48 hours.

Ben Courchia MD (39:58.082)


Daphna Barbeau (40:23.547)

of infant admission to the NICU for the baseline measurement, and that was done at the same time as the abuse screening. The second one was given at infant discharge if discharge was more than 48 hours post admission, and otherwise was given two weeks after the infant admission. And then the third was given at discharge if the infant had remained in the NICU for more than two weeks. They also inquired about the mother's and maternal grandmother's history of postpartum depression.

and a bunch of maternal demographics and medical history to look at were certain pregnancy characteristics associated with these findings. Okay. So during the study period, May 2021 to May 2022, 170 mothers had infants admitted to the NICU. Of these, 65% were approached for enrollment and 69% of those approached were consented to participate.

Daphna Barbeau (41:23.055)

mothers 31% were either ineligible, either they were part of a CPS, Child Protective Services or DCF case, or the steady team members were unable to speak with the mother alone, or the mother's declined to participate. So I think this is super interesting.

Ben Courchia MD (41:40.277)

Can you tell for our international audience what CPS and DCF? I'm sure this is a...

Daphna Barbeau (41:44.599)

Yeah, sure. So we call DCF here, Department of Children and Families. So this means that potentially there's been a flag in the record for a number of reasons where they're bringing in social services to ensure that this is a safe place for this baby to go home. But potentially during that time period, the parent doesn't have, you know, isn't able to come see the baby, may not be going home with the baby.

but some concern about the social situation in the home. So it's interesting, because that's a 30% that's potentially very high risk. So I just want people to keep that in mind. Interestingly, all mothers responded no, 100% of them, to the abuse question in labor and delivery, which was, do you feel safe? 17% reported a history of depression.

And 10 mothers, 13% reported at baseline that their mother, grandmother, or both had experienced postpartum depression. And I'll just tell you, again, the punchline is that the first screening, which is done to 24 to 48 hours, 31% of parents of mothers flagged.

um for clinical depression so a score of greater than or equal to 10 um and yeah that's incredible

Ben Courchia MD (43:13.89)

Let that sink in a little bit.

One in three basically. You go around your unit one in three, screen positive for depression. That's nuts.

Daphna Barbeau (43:19.563)

That's right.

Daphna Barbeau (43:24.771)

That's right. And then even more so at the 14 day or discharge, 100% of the parents and the mothers of this cohort scored greater than 10. And then at discharge, if the babies had stayed longer than two weeks, it persisted 100% of those remaining moms all screened higher than for clinical depression. Okay. And then of those that had a clinical depression,

at 24 to 48 hours. 50% of them scored greater than or equal to 13, which is a severe clinical depression. 84.3% at the 14-day mark, 68% at discharge. This is consistent with other literature, just so people know. There seems to be a peak at about two weeks, and then usually by discharge, or eventually in the first one to two years, that number comes down, but it never goes back to baseline.

Ben Courchia MD (44:22.893)


Daphna Barbeau (44:23.551)

So that's really interesting. Two factors, maternal age and assisted reproductive technology were significantly correlated with EPDF scores. However, no other significant correlations emerged with kind of the pregnancy history. And unfortunately, the AAS, that abuse screening tool, identified that 33% of mothers had experienced some type of abuse in their lifetime. Past year, physical and sexual abuse was reported by nearly 20% of mothers.

while 17% were still afraid of their current abuser. In addition,

Ben Courchia MD (44:55.298)

So, so nearly 20% of the mothers reported that they had experienced physical abuse since the beginning of pregnancy. This is stacked.

Daphna Barbeau (44:59.167)

Yeah, during pregnancy.

Daphna Barbeau (45:08.227)

Yeah, so 20% experienced physical abuse since the start of their pregnancy. Staggering. Terrifying. And like I mentioned, that doesn't include the 30% that didn't agree to participate, they couldn't get them away from a partner or had a DCI film.

Ben Courchia MD (45:14.87)

This is staggering.


Ben Courchia MD (45:26.878)

Yeah, I guess that's the theme of this paper, which is that all the numbers we're hearing, if anything, are quite under reporting. Yeah.

Daphna Barbeau (45:32.547)

Correct. And I just have one last thing to include, but they even noted, the most critical finding, however, was that none of the mothers reported any abuse at intake. Do you feel safe at home? So they all answered, they all flagged negatively for that question. So even though lots of our institutions are getting questions on labor and delivery, we're not picking up a lot of parents.

Ben Courchia MD (45:49.658)

No. Yeah.

Daphna Barbeau (46:02.272)

very interesting.

Ben Courchia MD (46:04.394)

Well, when the healthcare system puts demands on the providers, nurses, physicians, to do so many things, the question that deserve a little bit of our time so that we could sit down, ask them properly, give space to the patient to open up are completely closed, and we just check it off the list and be like, no, nope, and moving on, not realizing that we're missing opportunities so that we could continue with our...

Daphna Barbeau (46:05.589)


Ben Courchia MD (46:33.67)

very important documentation that trumps all these. We will be addressing that.

Daphna Barbeau (46:36.803)

That's right.

Yeah, sorry, the only other feature I wanted to say is that there was a significant correlation between abuse and baseline depression, which is not surprising, obviously. And we know that those moms who come in with baseline depression are much more likely to have depressive symptoms during the

Ben Courchia MD (46:51.522)


Ben Courchia MD (46:55.782)

Yeah, I mean, I think I read through in the abstract, it was said, right, a significant relationship emerged between depression and the past year partner violence with 100% experiencing abuse in the past after in the past year after pregnancy. 100%

Ben Courchia MD (47:16.218)


Daphna Barbeau (47:16.535)

So I think that's just a reminder for all of us about what people and families have going on for sure. But these numbers were even higher than I had anticipated.

Ben Courchia MD (47:27.082)

Yeah, the prototypical, oh mom doesn't show up.

Ben Courchia MD (47:33.233)


Daphna Barbeau (47:34.84)

Mm-hmm. Or, you know, they need a ride. They can only come when so-and-so's off of work, or, you know, well, maybe, maybe because they can't come without that person. So, a lot to think about. Are you gonna take us somewhere more positive? No.

Ben Courchia MD (47:40.078)

Mm-hmm. Yeah.

Ben Courchia MD (47:48.326)

Okay, a lot to think about a lot. Uh, more positive. Okay. I have two. No, no, I mean, definitely. I mean, it's not, you're not giving me a tough task. I mean, anything can be more positive than that. Um, but the first thing I want to talk about because we're running out of time. I don't know if I'm going to get time for the next one is a paper I saw in the journal of pediatrics called the clinical risk factors for retinopathy of

Daphna Barbeau (47:58.836)

Okay, thanks.

Daphna Barbeau (48:13.707)

Love to this.

Ben Courchia MD (48:14.514)

Intravitreal Antivascular Endothelial Growth Factor Injection. First author is Qiancheng Li, and this is from a group in Taiwan. So we all know that in the 90s, we used to use laser photocoagulation as a primary treatment for ROP, right? And then in recent years, we've seen that intravitreal injection of

as we say, right, antivascular endothelial growth factor. I'm not gonna say this every single time. I'm gonna say anti-VHF has become increasingly popular in the treatment of ROP due to its comparable efficacy and as shown in multiple studies. Now, what we've seen recently, and if you're not aware of this, you should look this up because it's becoming a trend. We're seeing a lot of ROP reactivation, and it's quite scary.

that the babies who are treated with anti-VHFs are coming back with reactivation. And we're seeing a return. You hope it's never. We were talking with Gabriel Altat on the French podcast about this, where there's data showing, like the most concerning part is we don't know when it comes back. And some ophthalmologists have reported they're seeing reactivation like a year or two down the road and go do an eye exam on a one-year-old.

Daphna Barbeau (49:18.655)

Yeah, you hope it's never, right? You do this invasive procedure and...

Daphna Barbeau (49:37.539)

Wow. That's right, a toddler.

Ben Courchia MD (49:40.958)

Now thrashing around, it's very difficult. So it's very, very scary. The question this group out of Taiwan is asking is, what is the rate of retinopathy of prematurity reactivation? And what are some of the risk factors assessed through the analysis of both ROP and patient clinical variables? This is a retrospective cohort study between January, 2017 and December, 2022. The inclusion criteria are,

Daphna Barbeau (49:44.089)


Ben Courchia MD (50:09.074)

infants in their unit who received intravitriol injection with anti-VEGF for ROP. They basically divided the patients into two groups. One group that had ROP reactivation after anti-VEGF and required retreatment, while a control group had no ROP reactivation. Now, during the study period, the anti-VEGF of choice, they had options basically. So, their ophthalmologists could use one of three. They had bivacizumab, they had aflebersept,

and ranibizumab. And basically the decision to choose was made by the ophthalmologist and there was informed consent from the parents. So yeah, not much more information on that, but that's actually where their study is really interesting. Now they defined ROP reactivation as the presence of new lines or ridges that had reached stage three with plus disease or recurrent vascular dilation and or tortuosity or the presence of new extra retinal vessels.

according to international classification of ROP. If you want to learn more about ROP on the neonatology review podcast, we have a whole week where we talk about ROP, so go check that out. Let's talk about some of the results. And I'm going to try to do this quick so that I can get to my last paper afterwards. There was a total of 114 infants, which added up to 223 eyes that were enrolled in the study.

and the ROP reactivation rate was 11.4%. So not something negligible. And the duration, the mean duration of reactivation was about 84 days, plus minus 45 days. So like four to six months after basically, that's what we're looking at. Now among the 223 eyes treated with intravitreal injection, reactivation rates were very different based on the medication that was used. So for

Bivacizumab, it was only 6%. For Aflibercept, it was 14%. And for Ranibizumab, it was 22.2%. It's huge. They did a multivariable regression model that showed that Ranibizumab, the one that had 22% reactivation, was an independent risk factor for reactivation. Other risk factors included things that are associated with increased

Daphna Barbeau (52:13.559)

That's huge.

Ben Courchia MD (52:33.202)

severity of illness for these babies. These include periventricular leukomalacia, having undergone a PDA ligation and requiring invasive mechanical ventilation on the day of intravitreal injection. I'm going to go then to the conclusion. They're showing how all the anti-VEGF agents do carry a risk of reactivation, with the risk being higher for

Daphna Barbeau (52:45.143)


Ben Courchia MD (53:01.078)

compared to the 0.625 milligram of Bivacizumab, and that reactivation of ROPs should be assessed vigilantly, especially in those infants with increased risks, and that future research should look at optimal dosage and optimal medication selection, going back again to maybe studying more of these agents before we make any... They're basically saying, don't make anything conclusive out of this paper. This highlights the need for further studies.

quite interesting.

Daphna Barbeau (53:33.931)

Very interesting. I don't like the data. I don't like the data. But it's good for us to know, especially as we're counseling families, you know, and talking to our colleagues and asking them what they're using, things like that.

Ben Courchia MD (53:37.363)

No, that is scary.

Ben Courchia MD (53:45.536)


Ben Courchia MD (53:51.13)

Mm-hmm. Can I squeeze in one more before we wrap up? Yeah, because I mean, I keep doing this and there's still one more from, and there's always more. But this was something that was quite interesting because it's a very interesting topic of conversation here where we're talking about CMV. And in pediatrics, there's this study out of France called Predictors of the Outcome at Two Years in Neonates with Congenital CMV.

Daphna Barbeau (53:53.815)

Alright, do it.

Daphna Barbeau (53:59.779)

I know.

Ben Courchia MD (54:20.446)

infection. First author is Jacques Fourgeau. This one I can pronounce. So interestingly enough, the aim of the study is to establish a sort of neonatal score basically. They want to be able to assess the likelihood of and identify infected neonates with no or low risk of long-term sequelae from congenital CMV. That would then be helpful

for parental counseling and establishing personalized care pathways. So the methods is that they looked at infants, neonates, who were diagnosed with congenital CMV in 13 hospitals across France from 2013 to 2017. And they evaluated them for at least two years with thorough clinical audiology, imaging, and obviously cycle motor developmental tests.

they were able to enroll 253 neonates. Three of these were later excluded. But I mean, when you think about it and the fact that the incidence of congenital CMV is about like what, less than a percent worldwide, it's quite nice to be able to get like a cohort of 250 kids. Yeah, so they were able to follow 227 infants up to two years. And of those, 82%...

Daphna Barbeau (55:31.379)

Yeah, necessary.

Ben Courchia MD (55:43.79)

were infected after a maternal primary infection, 15% non-primary infection. 40% of these infants that were followed up until two years were symptomatic at birth. 19% developed CMV sequelae, congenital CMV sequelae. Now maternal primary infection in the first trimester was the strongest prognostic factor for long-term sequelae. And then interestingly enough, when they looked at

trying to create a predictive model to look at whether there could be a scenario in which there's really no risk of sequelae at two years. What they found was that the variables that were significant were number one, normal hearing at birth, normal cerebral ultrasound, and normal platelet count.

These three things had a 98% specificity, 69% sensitivity, and an area under the curve of 0.89. And so the conclusions are that in the studied population, children with normal hearing at birth, a normal platelet count, and a normal cranial ultrasound had no risk of neurological sequelae and a low risk of delayed unilateral sensory neural hearing loss. And that the use of this model, based on readily available neonatal markers, should help clinicians maybe personalize the care pathways.

for each congenital CMV neonate. Obviously, I wrote down more stuff. I went through the abstract, but it's quite a long paper. A lot of data is reported. They have some brain MRI findings and so on and so forth. But anyway, I thought I would just mention it.

Daphna Barbeau (57:19.503)

But I think that's super helpful, especially in terms of counseling.

Ben Courchia MD (57:24.318)

Yeah, I never know. Never know what to tell the parents.

Daphna Barbeau (57:28.127)

I mean, it felt like we always had to tell them like, there's still a chance that things are, you know, going to continue to progress, right? And then have poor outcomes. So I think this was really reassuring things that we can offer families.

Ben Courchia MD (57:39.073)


Ben Courchia MD (57:45.706)

Okay. All right, everybody. This is the end of Journal Club. We have more episodes coming for you this coming week. Please check out the program at Delphi. If you are a fellowship program, there's a very cool competition, the Neonatal Brainiacs, where we're putting on stage three members of a fellowship program to compete against other fellowship programs in a trivia competition. The winners will get a cup and a grant award for educational activities within your program sponsored.

Daphna Barbeau (57:46.871)


Ben Courchia MD (58:15.402)

by Dr. Brodsky and Martin and the Neonatology Review Podcast. We're very excited about that. We've already opened applications, so feel free to submit. And as you can see, the conference will be taking place in a beautiful location in the Nova Southeastern University Museum of Art. It has a beautiful auditorium. The one issue with that place is that we only have certain number of seats. And so if you're planning on coming,

Daphna Barbeau (58:27.122)


Daphna Barbeau (58:42.623)


Ben Courchia MD (58:45.83)

register soon and feel free to reach out to us if you have any questions, any specific requests, and we're all very excited about the upcoming Delphi conference and the second edition of our TEDx conference as well. So lots of fun stuff happening. Stay tuned and yeah, let us know if we can help.

Daphna Barbeau (58:58.719)


Daphna Barbeau (59:05.227)

Well, and I think to your point, actually, I mean, Delphi, we hope will always kind of be this kind of intimate kind of setting. So definitely, if you've got questions about the conference, let us know. We'll email you back right away.

Ben Courchia MD (59:16.53)

Okay. All right, everybody. See you next week.


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