top of page
Search

#236 - 📑 Journal Club - The Complete Episode from September 1st 2024



Hello Friends 👋

In this episode of Journal Club, hosts Ben and Daphna discuss several recent neonatal studies. They begin with a paper from Pediatrics examining variability in care practices for extremely early deliveries (22-24 weeks gestation), highlighting changes over time and persistent differences between centers. They also review a commentary on important questions raised by these variations in care.

The hosts then analyze a study on the use of inhaled nitric oxide in preterm infants, discussing its effectiveness, costs, and potential overuse. They cover a paper on monocyte count trends as a potential diagnostic tool for necrotizing enterocolitis.

A special segment features Dr. Jane Stremming discussing a New England Journal of Medicine study on nutritional support for moderate to late preterm infants. The hosts also touch on new treatments for hemolytic disease of the fetus and newborn, and surfactant use in infants who develop bronchopulmonary dysplasia.

The episode concludes with an ethical case study about a father's unexpected request to withdraw care for his preterm infant, emphasizing the importance of understanding families' perspectives in complex medical decisions.


----

Don't forget to secure your spot for the upcoming Delphi conference 🤩

----


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





----


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


Ben Courchia MD (00:01.169)

Hello everybody. Good morning. Welcome back to the incubator podcast. We are here this Sunday with a new episode of journal club. Daphna, how are you?

 

Daphna Yasova Barbeau, MD (00:12.622)

I'm doing well, buddy. You know, I was thinking just as we were logging it, people always wonder like, how do we get it all done? And you're post 24, so this is how we get it all done.

 

Ben Courchia MD (00:24.709)

Yeah, I mean, we look... And people think we're idiots, by the way. People say, guys... So it's interesting because there's this admiration that transforms into disdain once we actually... There a people that we actually do talk to and they're like, wait, how do you... And we're like, yeah, this is how we do it. And they're like, you guys are idiots. But yeah, I was on... Yeah. That's absolutely right.

 

Daphna Yasova Barbeau, MD (00:30.316)

Yeah, I don't blame them for those thoughts, you know?

 

Daphna Yasova Barbeau, MD (00:38.339)

That's it.

 

Daphna Yasova Barbeau, MD (00:46.68)

Yeah, well there are days where we feel that way too.

 

Ben Courchia MD (00:52.953)

We have been on service since Monday the 5th. I've been pretty much working every day since in one form or another, either 24s, nights, days, but every day of the week so far. And I'm post call today and I'm going back again tomorrow. So, so it's very tiring. But like I said, the we have.

 

Daphna Yasova Barbeau, MD (00:59.618)

Yeah.

 

Daphna Yasova Barbeau, MD (01:07.896)

That's it.

 

Daphna Yasova Barbeau, MD (01:14.892)

You know, and I don't think that makes us unique. think everybody in our community is kind of right squeezing stuff in between these difficult, complicated clinical shifts, right? But anyways, I hope you'll get to rest after this.

 

Ben Courchia MD (01:24.171)

Absolutely. Yeah. But we got better at doing it. And we are very privileged to work where we work. We have a unit of appropriate size that we get to shape and build together, is very, very exciting. I just dropped something.

 

Daphna Yasova Barbeau, MD (01:34.435)

Yeah.

 

Absolutely.

 

Yeah.

 

Daphna Yasova Barbeau, MD (01:47.946)

Yeah, you know, I think the other unique opportunity we have, a kind of a medium sized unit is that we really know the patients like really well. So like, when they misbehave, you like know they're misbehaving. And when they don't, when they're maybe doing some things, you know, like, you're like, this is what this baby does. I think that changes the clinical practice like significantly personally.

 

Ben Courchia MD (02:10.607)

It does change how we communicate with one another. I got a text from Daphne this weekend that was literally just a number and I was supposed to remember that this was my patient's platelet count. It was literally a number and three question marks. You can guess whether the platelet count was high or low, but that's it. And that's how we, it's a very tight knit family.

 

Daphna Yasova Barbeau, MD (02:26.338)

Yeah, that's true. That's right. We've got close group.

 

Ben Courchia MD (02:32.583)

All right. We have a lot of episodes to go through. We're very excited to have an EB -Neo segment today where we talk to Dr. Jane Stremming, one of the EB -Neo contributors who's going to go over a paper that was reviewed. We reviewed the paper on Journal Club, think some time ago. It was published in New England looking at nutritional support for moderate to late preterm infants.

 

great discussion that we had. It's a paper that despite the fact that it didn't have like earth shattering results, I bring up on rounds many, many times. So I think it's a good review. We're going to have a special episode this week for Delphi. We're going to open virtual registration very soon. So.

 

Daphna Yasova Barbeau, MD (03:17.378)

Yeah, I mean, we're so thrilled by the response that we have, like people asking for virtual registration and saying, like, you know, I wish I could be... It's so hard to get to conferences these days. It really, really is. So we're so grateful for people who are making the trip, for sure. But we just had such a request for this additional component.

 

Ben Courchia MD (03:39.515)

Yeah. And that's another thing where we are not doing things the normal way. So we're not working with a university that sets this all up for us. So thankful to the team of our videographer, Mark Parsons, who's going to set this up for us in terms of having a reliable, high quality. Like I think the stream is going to be a very high quality. No, no, not in your hopes. we were, we're yeah. The budget people know so. and, and so that, that's, that's.

 

Daphna Yasova Barbeau, MD (03:49.272)

Yeah.

 

Daphna Yasova Barbeau, MD (03:56.622)

I hope so, yeah. No, we know so, we know so, we love his work, but.

 

No, so.

 

Ben Courchia MD (04:09.371)

Really outstanding. And so that's something for you to look out for. If you have registered, just know that there's opportunities to register for the workshops. So we're going to have some pretty cool workshops throughout the conference, one on basically writing with Dr. Rachel Fleischman. So if you've always wanted to put pen to paper and really wanted to overcome the inertia, what a better...

 

There's no better way to do it than with a published author, colleague, neonatologist, and really make this connection. think Rachel is so approachable. It's a really rare opportunity. We have a special workshop on artificial intelligence from the team at Neomind .ai and a very exciting workshop with our friend and colleague, Dr. Gabriel Altit, Dr. Lauren Ruoss, who are going to do a Point of Care ultrasound workshop looking at...

 

Daphna Yasova Barbeau, MD (04:56.59)

Hmm?

 

Ben Courchia MD (05:05.479)

various use and giving you tips and tricks. I believe that one of their little module is like the crashing patients. So it's

 

Daphna Yasova Barbeau, MD (05:13.794)

Well, the overarching theme is the crashing patient. So really high yield clinical scenarios for using.

 

Ben Courchia MD (05:19.599)

Yeah. So you get to learn from Gabriel, from Lauren, who are veterans, super smart people. And it's a kind of a cool case because, I mean, I've done some ultrasound stuff and you're like, all right, like that's great. But like, okay, so I can ultrasound the bladder. Great. And now what? It has come in handy, but it's like, I want to use this for the NICU stuff. So anyway, so that's going to be fun.

 

Daphna Yasova Barbeau, MD (05:36.918)

Yeah, which notably has come in handy many times, right?

 

Ben Courchia MD (05:49.031)

So go register. mean, I'm actually happy that tickets are selling out. I would say that, I don't know, at this point, we're like, between 50 and 70 % sold? So.

 

Daphna Yasova Barbeau, MD (06:00.56)

yeah, more than that. You know, we're a small, we're an intimate conference. I think that's part of the draw. Like people really get to network and talk to the speakers. And I mean, that's, that's what we like about the conference.

 

Ben Courchia MD (06:02.374)

Okay.

 

Ben Courchia MD (06:11.879)

Daphna hates me because I pick venues that are, I like venues that are kind of cozy. so it's, so the first thing they told us this year was spaces, like you really cannot like overfill the room. And Daphna was like giving me the, the eyes and I was like, that's great. And so here we are now. So anyway, if you haven't registered, go do so it's going to be a fun conference. And yeah, we're going to have a special episode going over that. And that's pretty much it. think.

 

Daphna Yasova Barbeau, MD (06:18.498)

Yeah, really a struggle.

 

Ben Courchia MD (06:43.643)

I don't really have any other announcements. I think we should get on with a journal club. Does it sound good?

 

Daphna Yasova Barbeau, MD (06:50.968)

Did you want to mention there was a duplicate episode on Sunday, but the new episode is posted, so nobody, I know you're, I can see this look you're giving me, but I want to make sure people go back and hear the episode. That's it.

 

Ben Courchia MD (07:02.215)

So talking about doing things post -call, I released an episode on Sunday that was not the right audio file. And so I did not even notice until someone messaged us. So I apologize profusely. 100 % my fault. But yeah, no, but we record the episodes, they come back from post -production, have them lined up and I clicked on the wrong one anyway. so yeah, I had to take the episode down and I had to re -upload. it's all...

 

Daphna Yasova Barbeau, MD (07:14.094)

See, I didn't say it was your fault. I'm just saying that it happened.

 

Ben Courchia MD (07:31.385)

up and running. Great episode on the neonatal kidney with Dr. David Askenazi and Dr. Tara Beck. Go give it a listen. Again, my apologies. You see, it's not perfect.

 

Daphna Yasova Barbeau, MD (07:33.539)

Yeah.

 

Daphna Yasova Barbeau, MD (07:42.028)

It's not perfect, but we winna make sure people don't miss the opportunity to hear the episode, right? Yeah, that's right.

 

Ben Courchia MD (07:44.005)

The episode is great. They're great. But the logistical stuff is, yeah, you know.

 

Daphna Yasova Barbeau, MD (07:51.938)

Well, buddy, I think that is your first mistake in three and a half years, so.

 

Ben Courchia MD (07:57.349)

I just want to say, when we started this, said we're not going to miss weeks unless we decide to take a week off. So we've done pretty good so far. All right. Okay. So let's begin Journal Club. Daphna, I want to start off with a very optimistic paper that I found in the archives called The Effect of a Live versus Heat Inactivated Probiotic Bifidobacterium

 

Daphna Yasova Barbeau, MD (08:04.972)

done pretty good yeah

 

Ben Courchia MD (08:27.513)

in preterm infancy randomized clinical trial. Very interesting indeed. So obviously the background is quite long, but I'll summarize this for you. We know that probiotics are live microorganism, That when you consume them in the right amount, they offer you, they confer benefits to the host. And we know that the evidence is quite favoring the use of probiotics.

 

Daphna Yasova Barbeau, MD (08:30.062)

Very interesting.

 

Ben Courchia MD (08:54.983)

to reduce the risk of necrotizing enterocolitis stage two or more, all cause mortality, late onset sepsis and feeding intolerance in very preterm infants. Most studies including babies less than 1500 grams. But there are concerns that have been brought up about probiotics, namely sepsis, the development and spread of antibiotic resistance and altered long -term immune responses. Now,

 

In the US, obviously, as you may know, the FDA has really created a situation in which it's halted the release and implementation of probiotic use in the neonatal ICU for the prevention of neck. And the biggest issue that we have in the US right now is that I think the FDA is going to treat each strain of probiotic like a medication.

 

Each, every time somebody wants to come out with a new strain of probiotic, they'll have to go through like the approval of a medication almost. So it's very long, very protracted, which may end up being the safer thing. We have an episode on this. can, you can go take a listen. that's not really what I want to address, but the background mentions this emerging evidence suggesting that heat inactivated probiotics may provide an alternative to probiotics by avoiding their risks while retaining their benefits and looking at systemic reviews.

 

One in particular that included 40 randomized clinical trials reported that modified probiotics were not significantly more or less effective than probiotics in 26 out of 40 preventive trials. that's 86 % of case of trials and 69 % of actual treatment trial. So modified probiotics referred to basically dead bacteria or yeast derived after inactivation thanks to heat or sonification or sonication. Sorry.

 

The modified microbes were compared with placebo, either the same type of probiotics or standard therapies in the trials that we just mentioned. And they found that modified microbes were significantly more effective in 15 % of treatments. The adverse events were comparable. considering our population, really given the potential advantages of this new modality, the team

 

Ben Courchia MD (11:11.591)

that is coming to us out of Australia aimed to assess the safety and efficacy of heated and activated probiotics in preterm infants. The first author of the paper is Dr. Atalai Jape. I forgot to mention the author's name. So this was a double -blind randomized controlled trial of very preterm infants that were born before 32 weeks. The inclusion criteria were based on gestational age,

 

the babies being ready for starting feeds or already on feeds within 12 hours, and obviously parental consent. The intervention, basically one group received this heat -inactivated mixture of Bifidobacterium. I'm going to try Brevi M16V.

 

Bifidobacterium longum subspecies infantis M63 and Bifidobacterium longum subspecies longum BB536. So to give you basically the different strains. The control group received the live probiotic. So it's interesting. think that in the US right now, probably the control group would be a placebo, but it's an interesting case because that's what we want to know. Would this be comparable? So I think it's a great control group for us to look at the live versus the heat inactivated.

 

Daphna Yasova Barbeau, MD (12:26.446)

question.

 

Ben Courchia MD (12:29.063)

They also had a pre -planned subgroup analysis where they said, let's look at the babies that are less than 28 weeks, because we know these are the highest risk for mortality and morbidity. So they wanted to look at that specifically. What kind of outcome did they look at? The primary outcome of this study was to compare the levels of fecal calprotectin, referred to as FCP throughout the paper, at two time points throughout the study. T1, which is basically within the first week.

 

and T2, which is between 21 and 28 days after starting trial supplementation. So the results of the study are as follows. 86 infants that were born between 2018 and 2019 were randomized, which is interesting, right? Because they were randomizing these kids back then. I don't think they suspected this would be such an impactful study later on.

 

Daphna Yasova Barbeau, MD (13:22.38)

Yeah, absolutely critical in our discussion, I think, of what's next for probiotics.

 

Ben Courchia MD (13:25.703)

Yeah. In terms of baseline characteristics, the only real difference is that the mothers of the babies who received the heat -inactivated probiotic were more likely to have completed antenatal steroids. There was no other real difference. In terms of the primary outcome, the total fecal calprotectin, the levels were comparable between the two groups at both time point 2 and time point 1.

 

the median fecal calprotectin levels decreased from the first time point to the second time point in both groups. And there's a very nice graph that's showing you that. So it's really exciting to hear this specifically that maybe an inactivated form of probiotics could potentially be just as beneficial. In terms of, so most people will say, I don't really care about fecal calprotectin, what about neck? So that was actually...

 

part of their secondary outcomes. And I really want to start making sure we've done this very well on Journal Club. Studies are powered for their primary outcomes. So that's what we always will focus on. But let's go through these secondary outcomes because they are of importance. So in terms of clinical outcomes, they were comparable between the two groups. And the Bayesian statistician and some of us will have an issue with this. They said there were no cases of neck stage two or more. Zero. something to aspire to.

 

Daphna Yasova Barbeau, MD (14:46.744)

I mean, that in and of itself is a huge result of the work.

 

Ben Courchia MD (14:51.045)

Yeah, I see it from the standpoint of any difference would have been more noticeable if you really have zero with the regular probiotics. The fact that you still have none with the, yeah. There were four cases of confirmed late onset sepsis, two in each group, the median time to full feeds, the median time of total parenteral nutrition, the length of stay, the and confirmed late onset sepsis were all comparable between the two groups.

 

Daphna Yasova Barbeau, MD (15:00.91)

Mm

 

Ben Courchia MD (15:20.013)

The, in terms of looking at this from an intention to treat standpoint, also no differences and there were no cases of probiotic sepsis. All infants tolerated the trial supplement quite well. They then looked at the richness and diversity of the fecal microbiota and infants in both groups showed significantly increased alpha diversity. The microbial richness and Shannon index was comparable between the two groups at the two times points when they were checking.

 

The better diversity analysis shows that the community structures differed significantly over time, but not between the groups. Finally, we talked about the subgroup analysis, really looking at the most vulnerable babies. In terms of these specific infants, less than 28 weeks maternal neonatal demographics and clinical outcomes and total fecal calprotectin levels were all comparable. The median calprotectin

 

Sorry about that. The median calprotectin level decreased from T1 to T2 in both groups and significantly in the heated inactivated probiotic group. In terms of the conclusion of the study, I think it's quite exciting that heat inactivated probiotics is safe and showed no significant difference in the calprotectin level as compared with the live probiotic and that maybe more adequately power trial are needed to assess the effects of this particular agent on clinically significant outcomes in preterm infants and maybe

 

might, that's what I'm adding now to the conclusion, might make our process to get this approved by the FDA in the US more easier since it's no longer live bacteria.

 

Daphna Yasova Barbeau, MD (16:54.306)

Mm -hmm.

 

Daphna Yasova Barbeau, MD (17:00.97)

Mm -hmm. Mm -hmm. And I mean, we've done this with other products, right? And it has worked excellent for the NICU population. And I mean, I hope people are thinking about doing more work on this because it's exciting, but it's urgent, right? So yeah, very good. I love that paper. Yeah, that's me. I'm sure she's on it. I'm sure she's on it. OK.

 

Ben Courchia MD (17:14.759)

It's exciting.

 

Ben Courchia MD (17:18.34)

Absolutely.

 

I'm emailing Jen Canvasser right now. I'm sure she's on it.

 

Daphna Yasova Barbeau, MD (17:30.848)

My turn. Okay. So I kind of have a cluster of papers, the first of which is this paper in pediatrics. It's entitled variability of care practices for extremely early deliveries. The lead author is Danielle Lo Ray.

 

Ben Courchia MD (17:31.749)

Yeah, go ahead.

 

Daphna Yasova Barbeau, MD (17:51.63)

senior author Dahlia Feldman, they are on behalf of the Investigating Neonatal Decisions for Extremely Early Deliveries study group. This is the Indeed study group. So they're specifically looking at the ethical aspects of decision -making regarding resuscitation at infants in this earliest group, the 22 and zero to 24 and six weeks gestation. So in this specific study, it was a multi -center.

 

Retrospective cohort study, they screened all birthing parents admitted with live fetuses who delivered at a number of institutions, 13 US training centers, and all of the fetuses were between 22 and zero and 24 and six, seven weeks gestation. So the dyads were divided into two epochs. So they were defined by year of delivery to look at changes over time. So they looked at 2011 to 2015.

 

and 2016 to 2020. And so this split actually coincides with this 2015 AEP antenatal counseling guidelines were updated to even kind of include 22 weekers. So, and one of the other important components is one of the most important things they saw looking at survival at that time was that inter -center variability in resuscitation.

 

So two different time courses and across 13 different studies. So they were looking at those newborns who received active resuscitation compared with those newborns who did not receive active resuscitation. So interestingly, newborns not receiving active resuscitation are sometimes recorded as quote unquote stillborn. I think this is an interesting

 

point because obviously, maybe not obviously, but theoretically, if it was stillborn, no heart rated delivery, they wouldn't get active resuscitation. But I think this should be in a totally separate group. But I think sometimes these babies are included. So I think that's something that we need to evaluate.

 

Ben Courchia MD (20:05.947)

mean, this is really the black box of neonatal statistics, right? Because at what point do you say, this was a fetal demise versus this was a baby that was born with maybe a very weak pulse or maybe, but just any sign of potential quote unquote life and was elected to not proceed with active resuscitation?

 

Daphna Yasova Barbeau, MD (20:09.548)

Yeah, that's right.

 

Daphna Yasova Barbeau, MD (20:14.296)

That's right.

 

Daphna Yasova Barbeau, MD (20:18.168)

That's right.

 

Daphna Yasova Barbeau, MD (20:26.606)

Yeah. And so I think babies could be counted in either direction, right? So it's, yeah, it's really problematic. But in terms of active resuscitation, this was defined as receipt of assisted ventilation, either CPAP or other forms of noninvasive positive pressure ventilation or endotracheal intubation in the delivery room. So during these time points, 2011 to 2020, in these 13 units, had 2 ,028

 

Ben Courchia MD (20:30.853)

Absolutely.

 

Daphna Yasova Barbeau, MD (20:55.982)

birthing parents delivering 2 ,327 newborns. It's a reminder how many multiples are born in this early gestation. So they looked again at the two different time points. So first they looked at the 22 -weekers. So rates increased over time for the following. Neonatology consults increased from 37 to 64 % in odds ratio of almost three.

 

Antenatal corticosteroids increased from 11 .4 to 30 % in odds ratio of 3 .26. Live births increased from 66 to 78 .6 % in odds ratio of 1 .88. Active resuscitation did also increase 20 % to 37 % in odds ratio of 2 .32. And survival increased, I'd say marginally, from 3 % to 8 .9.

 

I mean, I guess it tripled, but with an odds ratio of 3 .11. Then they looked at the 23 -weekers. So rates increased for the following. The neonatology consults actually also increased 73 to 80 % odds ratio of 1 .5. Antenatal steroids improved from 63 to 83 % and odds ratios of nearly three. C -sections increased 28 to 44 % and odds ratio of two.

 

live births increased from 88 to 95 percent on an odds ratio of 2 .6 and active resuscitation increased from 67 to 85 percent on odds ratio of 2 .74 as well as survival 28 percent to 42 percent on odds ratio of 1 .76. Now for the 24 -weekers actually, much did not change and I think that speaks to

 

we had, I think, a better consensus at 24 weeks, even in the year of 2011. So those did not change, nothing changed over time between the 24 -weekers. Now among newborns receiving active resuscitation, rates of survival to discharge or transfer did not significantly change between the epochs 15 .4 versus 24 and a half at 22 weeks, 44 versus 49 at 23 weeks, and 67 versus 67.

 

Daphna Yasova Barbeau, MD (23:19.662)

at 24 weeks. Okay. So then they looked at the variability in interventions and the outcomes again by time period. So in the 22 weeks gestation, the variability of corticosteroid administration increased. So there was more variability between centers.

 

That's really the only thing that changed. For the 23 weeks groups, the intercenter variability for neonatal consults actually decreased significantly, which I thought was very interesting. They also looked at corticosteroids and attempted resuscitation. This also decreased in variability, but these were not statistically significant.

 

And then variability between individual centers for live birth and survival to NICU discharge were similar between the groups at each gestational week. So as a reminder, the rates did not decrease, but the variability decreased. So we had a better consensus in the 23rd week. Factors associated with attempted resuscitation were also analyzed. So again, looking at which newborns received or did not receive active resuscitation.

 

In this group, they had 1 ,971 birthing parents, and newborns of 75 % of the birthing parents received active resuscitation in the delivery room, whereas newborns of 25 % of the birthing parents did not. Several factors are significantly associated when they were analyzed individually, but when controlling kind of in a multivariate analysis, only the following remains significant. So black versus white race and odds ratio of 1 .0.

 

Daphna Yasova Barbeau, MD (25:38.158)

5 .8. So the black neonates were more likely to have active resuscitation. Previous delivery of a premature infant, an odds ratio of 1 .54. So if you had previously had a premature neonate, they didn't say what gestational age, but they were more likely to do active resuscitation.

 

And I guess not surprisingly, more advanced gestational age at delivery and odds ratio of 8 .57 and higher neonatal birth weight, odds ratio of 1 .01 were both associated more commonly with active resuscitation. Active resuscitation also varied significantly by delivery center. And these odds ratios were different by center as well. So I think what it shows

 

globally is that we've got better consensus in the 23rd week, still a lot of variability in the 22nd week, which I guess is not surprising.

 

Ben Courchia MD (26:41.767)

It's interesting because, right, we were discussing this a bit earlier about this article that came out in New York Times or the Wall Street Journal, I forget which, discussing almost that exact topic, just trying to understand why some parents were offered resuscitation at 22 weeks, others were not based on different centers. And I think it's an interesting paper to see that it's not a consensus everywhere. And I think...

 

Daphna Yasova Barbeau, MD (26:48.344)

That's right.

 

Daphna Yasova Barbeau, MD (27:08.163)

Right.

 

Ben Courchia MD (27:09.167)

I think there's a lot of factors implicated into this process, resources being one of them, obviously, in order to be able to care for these infants. But I think what's interesting to see, I mean, I think this figure too in the paper is so interesting, this bar graph of the various different variables. But to see the change in neonatal consultation is to me the light at the end of the tunnel, right? Because

 

As we see this increase for 22 -weekers going up from 86 to 146 in terms of between the two epochs, I think that already shows that the discussion is happening. And as over time, these consultations get better, parents will have more information, and then more decisions can be made. Because when you think about it, there are very few consultations prenatally that we do where actually decisions have to be made.

 

Daphna Yasova Barbeau, MD (27:52.238)

Yeah.

 

Daphna Yasova Barbeau, MD (28:05.858)

Mm -hmm.

 

Ben Courchia MD (28:06.055)

A lot of time, it's a lot of counseling, consulting, and just saying, here's what will happen. But 22, 23, and then maybe some places 24, you really have to come up with a plan with these families. yeah, it's already... No, I said, first having to sit down at 22 weeks, it's terrific because having to sit down means you talk about initiating steroids early, which then leads to the increase that we're seeing in parents saying, yes, give me steroids at 22 weeks.

 

Daphna Yasova Barbeau, MD (28:18.274)

Yeah. I agree. And go ahead.

 

Ben Courchia MD (28:35.525)

because if I deliver, I might want active resuscitation. then basically one graph leads to another, which leads to a live birth, which leads to attempted resuscitation, which potentially leads to survival. So I kind of like this path of, it all starts at the consultation and you have some more papers to talk to us about consultation. yeah.

 

Daphna Yasova Barbeau, MD (28:45.262)

Hmm?

 

Daphna Yasova Barbeau, MD (28:53.832)

I do. But I mean, I'm wondering, some people might be wondering since you brought up this article, it's the Wall Street Journal article entitled, doctors can now save very premature babies. Most hospitals don't try. So this has been a point of discussion on neonatal forums. think the gist of the paper, shared some, I'm going to say they shared some stories of babies who had survived in these early gestational ages and

 

Ben Courchia MD (29:13.937)

Careful.

 

Daphna Yasova Barbeau, MD (29:23.096)

The gist was a little negative. That's it. That's it.

 

Ben Courchia MD (29:25.023)

It's a bit of a reduct, it's a bit of a simplified and reductive argument to say, since some babies have survived, why not offer it to everybody because they will all survive? And it's like, that's not, that's more complicated than that. But the idea of offering is, it's an interesting concept because I think it misses the mark a little bit. It's not about offering resuscitation. It's if resuscitation is desired, that may mean you need to set up a transfer, right? Because

 

Daphna Yasova Barbeau, MD (29:36.396)

Right. Yeah, I think that's it. was.

 

Ben Courchia MD (29:54.695)

Centers may not be equipped to take care of a 22 -weeker, and then in which case you have to set up a transfer. And I think that's more of the day -to -day conversation.

 

Daphna Yasova Barbeau, MD (30:00.62)

And I think it speaks to, yeah, and a much bigger situation about perinatal care, right? What does the prenatal care look like? What are we doing to optimize mothers, to optimize deliveries and try to make these situations as successful as possible? It felt a little like, you know, some teams just don't want to or just don't care to, and that's obviously not the, that's right. That's right.

 

Ben Courchia MD (30:10.067)

-huh.

 

Ben Courchia MD (30:24.231)

The doctor was tired at 10 PM and so he didn't offer resuscitation. It's usually most of the time, think, everything I've seen is more of a division slash institution decision of can we offer this service, which is not an simple one.

 

Daphna Yasova Barbeau, MD (30:29.71)

That's really not the case, yeah.

 

Mm

 

Daphna Yasova Barbeau, MD (30:40.91)

Yeah. And the truth is, there are some quote unquote guidelines to this area and this, requires ongoing consultation with the families. And I think that, I think that opportunity was lost in that article to say, people need to understand what is happening. People understand the need to understand what the range of outcomes are and that it's every baby, every diet is a total unique situation.

 

Ben Courchia MD (30:48.294)

Yeah.

 

Ben Courchia MD (31:05.031)

And it's not an RDS patient that you can just sort of stabilize with some CPAP and then wait for someone to pick them up. Like if you mess up the delivery in golden hour and so on, you really could have a pretty damaging effect long term.

 

Ben Courchia MD (00:01.206)

And so today we're very excited to have with us Dr. Jane Stremming from the University of Colorado, where you are a neonatologist, of an assistant professor of pediatrics. Jane, thank you for being on with us for this EB -Neo commentary on this paper.

 

Jane Stremming (00:24.84)

Yeah, thank you so much for having me. I'm really excited to be

 

Ben Courchia MD (00:28.39)

We're very excited to have you on. Daphna is here today. sometimes it's the, yeah, how are you Daphna?

 

Daphna Barbeau (00:34.744)

I'm doing that. Yeah, sometimes we got to split up, but we're all here today.

 

Ben Courchia MD (00:38.707)

But we're all here today and you're and Jane you're talking to us about this paper that really made the rounds a short while ago published in the New England Journal of Medicine. This was the Diamond Trial Group and the paper was called Nutritional Support for Moderate to Late Preterm Infants, a randomized trial. As we were saying a bit off air, this was really the paper that you read about it and you're like, I really want this to work.

 

There's some real, there's some interventions that you're like, I really would like them to be significant. But unfortunately, this did not all planned out as we would have all hoped. But can you can you for the audience who doesn't recall exactly what that paper was all about, can you give us a brief synopsis of what they were trying to do and what did they what did they find?

 

Jane Stremming (01:29.268)

Absolutely. So in this paper, the authors were really looking at sort of different strategies when feeding the moderate to late preterm infant. So they were really looking at infants that were born between 32 weeks gestation, then all the way up to 35 and six weeks gestation. And they actually looked at a lot of different interventions, three different groups to look at some of these feeding practices. in their...

 

three groups and each infant was sort of randomized to one of each of these three different components. In the first group, they looked at infants that were receiving either a amino acid solution, so sort of like a TPN based solution versus just getting a dextrose solution. In the next set of comparisons, they looked at infants that were receiving exclusively mother's milk.

 

or they were looking at infants that were receiving mom's milk plus a supplementation, whether that be donor milk or formula. And then in the third sort of comparative group, they looked at either offering sort of a taste and smell exposure to the infant during their two feedings versus none of those exposures. So each infant was randomized to one of those three components. So there was a lot of groups. There was actually eight groups in this study looking at these different groups.

 

Ben Courchia MD (02:51.652)

And I was really hoping the smell was going to be a big difference maker.

 

Jane Stremming (02:53.787)

Yeah, yeah, yeah, it's a really nice thing to do, but didn't quite pan

 

Daphna Barbeau (02:53.92)

Me too. I really thought so.

 

thank you for setting that up for us because it was a complicated, you know, setup. So that's very helpful.

 

Jane Stremming (03:06.964)

Yes, yes. So in the paper, they actually had a pretty big group. There were 532 patients in one of these groups, which was about 80 or 90 babies per group, per the eight groups. These were all babies that were admitted to a neonatal intensive care unit, and they were all getting intravenous access for some reason or the other. And then these were all, of course, mothers that were intending the breastfeed.

 

Ben Courchia MD (03:36.004)

And so the outcomes they were hoping to test for really had to do with growth and body fat percentage and so on. Can you tell us exactly what were the that might be of interest to us as clinicians and what were some of the results of the study?

 

Jane Stremming (04:00.722)

Yeah, absolutely. their primary outcome, had two different outcomes sort of based on these comparator groups. So looking at the groups that either received the amino acid solution versus the dextrose solution, as well as the maternal breast milk only versus the maternal breast milk plus supplement, they were looking at body fat percentage at four months corrected gestational age.

 

And then for the taste and smell intervention, they were looking at time to full enteral feedings. and that could include, that did include full gavage feeding. And then in terms of secondary outcomes, they looked at a lot of different things. So they looked at time to full enteral feeds for all the groups. And then they looked to what they call time to full suckling feeds. So the time that the baby was taking all feeds by mouth, or alternatively, they were looking at time to discharge.

 

they were looking at length of hospital stay. And then they were also looking at what they said, breastfeeding status at four months corrected age, as well as discharge. So looking at how many infants were getting breast milk at those time points. And then they were also looking at changes in Z score for weight, length and head circumference. And they were comparing birth to both discharge and then four months correct adjust station. And then they also, in addition to their primary outcome, we're looking at body fat composition at four months.

 

Ben Courchia MD (05:02.137)

Mm -hmm.

 

Jane Stremming (05:22.238)

They were also looking at other means of body composition. for example, lean body mass at four months corrected as

 

Jane Stremming (05:33.78)

And then in terms of results, so really they were looking at sort of two groups, they sort of divided the gestational age into two groups, the moderate preterm versus the late preterm. So the moderate preterm babies, they defined as babies who are 32 weeks up to 34 weeks, and then the late preterm was the 34 up to 36 weeks, correct, to gestation.

 

Ben Courchia MD (05:36.101)

Mm -hmm.

 

Jane Stremming (05:59.604)

On average, the babies in this study were just shy of 34 weeks corrected. So a little bit more happily favoring the moderately late preterm, but fairly even. Overall, a little more than half were males. And then the average birth weight was about 2 ,100 grams. And then the other thing was about 11 % of the babies were small for gestational age. Really, when looking at outcomes, they didn't find really any differences in any of the groups.

 

Ben Courchia MD (06:22.436)

Mm -hmm.

 

Jane Stremming (06:28.724)

When looking at the amino acid solution versus the dextrose solution, they didn't find any differences in body composition at four months. And the same was true for the infants that were receiving exclusively mom's milk versus the mom's milk plus supplement. When they were looking at time to enteral feedings and the taste versus the smell group, they also didn't find any difference in the time to full enteral feedings. And then looking at all of their secondary outcomes, they really didn't see any differences among the groups either.

 

So I think there's a lot of, it's a neat study and there's a lot of potential looking at these different feeding methods for these sort of late preterm babies, but unfortunately there really weren't any significant differences at least at this point in

 

Ben Courchia MD (07:15.332)

And so in terms of interpreting these results, I mean, I think there's, to me, there's two ways of looking at this. The first one being, well, is there enough equipoise for changing a practice that clearly is showing to be equivalent to a new practice, whatever practice you're using within your unit? Or there is also this idea of, well,

 

should we try to avoid certain interventions like IV nutrition, IV fluids, IV TPN in favor more enteral feed? So I'm just curious as to how do you personally perceive these results and how they should direct our evolution of bedside care?

 

Jane Stremming (08:01.948)

Yeah, absolutely. think, you know, one thing about these results is it's sort of encouraging that there were actually no differences between any of the groups. And what I mean is that we can sort of, you know, focus on what are the parents sort of expectations and hopes for their baby and really focus on supporting lactation more than anything. you know, if there are families that are really uncomfortable with supplementing the formula or even donor breast milk, that's something

 

I think the study shows us that it might be okay to do at least in these first five days of life, which is when the study actually occurred. After five days, they were able to add supplementation to the maternal only breast milk or things like that. So, I think we can really work with parents to support their preferences and maybe not focus so much on, is the baby receiving a TPN for five days? that really?

 

important versus just getting a little bit of IV fluids in addition to the breast milk. So I think that's encouraging that, you know, whatever strategy we take, at least we don't necessarily see changes in body composition in this early life period, or we're not seeing changes in time to full interval feeding.

 

Daphna Barbeau (09:18.392)

I love this concept that you're using the data and saying like, can actually individualize this, right, for patient scenario, but specifically family scenario. And I guess some of our families are really interested in the data and the literature. So how would you go about introducing this concept to the

 

Jane Stremming (09:40.51)

That's a great question. I think really first introducing lactation support is the most important thing and encouraging these moms to breastfeed and pump as much as possible. And I think we can individualize like each scenario. So, one thing I really wonder about this study is are there subgroups of populations that really some of these interventions may make a difference. So for example, in the baby who's small for gestational age or with growth restriction, are some of these

 

Could some of these interventions be really actually helpful to them in the long run? In the study, only about 11 % of the babies were SGA or small for gestational age. And so I don't think they were powered to necessarily look at that subgroup, but that might be a group where we need to focus on providing more nutrition. Whereas there's other babies that we may not need to. I think introducing this idea as whatever your unit is doing at the time, whatever their sort of protocol is,

 

introduce that to the family and then if the family has concerns about that or specific recommendations, I think we can hopefully try and accommodate some of that within reason for the clinical scenario of whatever their baby is going

 

Ben Courchia MD (10:53.622)

That's very helpful. Jane, thank so much for going over this with us. You seem to be the EB -Neo resident for nutrition papers. You had written the commentary on the early amino acids. So we're looking forward to the next nutrition paper and having you back on to talk about it. Thanks again for this outline and we'll link to the EB -Neo commentary that will be published in Acta Pediatrica.

 

Jane Stremming (11:20.958)

Thank you so much for having

 

Daphna Yasova Barbeau, MD (31:19.694)

Yeah. So back to this pediatrics issue. So there were some other papers related to this paper. So I'll just run through these two pretty quickly. The first was, I don't know, would you call it an op -ed? I'm not sure what I would call it. Anyways, it's called Four Important Questions About Between Hospital Differences in Care at Less Than 25 Weeks Gestation.

 

Ben Courchia MD (31:46.915)

It's officially listed as a commentary.

 

Daphna Yasova Barbeau, MD (31:48.768)

A commentary. Okay, that's perfect. Thank you. The lead author, Matthew Rysavy, senior author Kelly Gibson. But basically, they referred back to this Indeed study group trial and showing that there are at least four important questions that relate to this inter -center variability. So the first, what caused changes in intervention during the past decade?

 

So certainly they talk about the ACOG guidelines. Again, how do we prepare fetuses for preterm delivery? So the ACOG guidelines change significantly to include 22 -weekers at all. And then obviously there has been a number of international papers showing improved survival in these very early births.

 

So with these higher rates of survival, 22 to 23 weeks, our thoughts around survivability need to change also. Okay, the second question, what do families know about between hospital differences in treatments and outcomes? And this relates to what you said about that Wall Street Journal article. Like, I don't think they know anything about in the hospital differences and outcomes.

 

Ben Courchia MD (33:13.88)

Mm -hmm.

 

Daphna Yasova Barbeau, MD (33:14.028)

We know that deliveries at this gestational age are often unplanned. They're often emergent. They often occur shortly after admission by the birthing parent. So a lot of times families show up to a hospital that may not be prepared to manage a baby in this gestational age. So they talk about, should there be public information on hospital level practices or outcomes in this gestational age? They don't make a

 

They don't make a recommendation, but they say, that something that we should do? Something to think about. The third question. Yeah. The third question. Should all hospitals provide intensive interventions for deliveries at 22 to 24 weeks? And so, yeah, that's right. So they mentioned the AAP recommends that all level threes through four NICUs should be equipped for infants born less than 32 weeks.

 

Ben Courchia MD (33:45.645)

you

 

Ben Courchia MD (33:50.267)

Very savvy, very savvy to not...

 

Ben Courchia MD (34:00.167)

That's an easy question.

 

Daphna Yasova Barbeau, MD (34:13.038)

But we know that there's a huge difference in risk resources and expertise in infants between this 22 to 31 weeks. So there's some discussion about centralization of extremely early deliveries, but we really don't have a system for that. But notably, there's a discrepancy, huge range of outcomes.

 

at that gestational age? And fourth, what evidence supports specific interventions for deliveries at 22 to 24 weeks? So we know that there's a positive data for these babies. Like they've been frequently been excluded from research. So that's a big one. We don't have a lot of standardized practices. So it's really hard to study. So that's really, again,

 

Not a lot of answers, but these are the big questions about how can we even improve the way we study these babies so that way we can make recommendations and hopefully one day answer these four questions. So I thought that was interesting. And then finally, I wanted to highlight this Pediatrics Perspectives article, The Value of Parental Judgment in the Ethical Gray Zone of Periviability. Words matter. And the authors are Matthew Drago and Mark Mercurio.

 

Ben Courchia MD (35:23.185)

super interesting.

 

Daphna Yasova Barbeau, MD (35:39.916)

And so I really recommend that everybody take a read. I'm going to, what's the word? I'm going to simplify it, I guess, just for the podcast version. But they really talk about this term we use, what are the parents wishes? And wishes is potentially a complicated terminology to use for a number of reasons.

 

And it works, cuts both ways as they say. So wishes in one perspective makes it seem kind of like whimsical or hopeful, but potentially not based in reality. And that's not necessarily true. So I think that's one component of it. They say, what did they say? I wanted to read this. Other synonyms for wishes include whim, fancy, inclination or hope.

 

There are terms more likely to be used to ask, you prefer cream or sugar in your coffee rather than the life or death of their child? And then on the other side of that, using the word wish might predict even better outcomes saying things like, your wish is my command, right? So using the word wish makes it seem either not strong enough,

 

or potentially too strong all at the same time. So really the point of the article is that we should really change the way we refer to parent communication and parent involvement in decision making. I'm going to read this last paragraph. Simply put, words matter. Neonatology is a field must be mindful of how our language may be interpreted. It not only influences how we partner with parents and share decision making, but communicates far more.

 

about the nature of that partnership to our colleagues, the court of public opinion, and the next generation of clinicians. Clinicians and professional bodies that create and support resuscitation thresholds have a responsibility to use appropriate language to describe the role of parents in perinatal decision -making. When parents are extended the right of parental authority, we should refer to their decisions as parental judgment. Failing to do so risks not just suggesting that we should place less weight on the opinions of parents,

 

Daphna Yasova Barbeau, MD (37:55.106)

but jeopardizes the right of parents to make decisions on behalf of their extremely preterm newborn in the ethical gray zone of variability. So I hope everybody will take a look at that paper. And then I have another paper that relates to parental authority and autonomy, but I'm going to let you do some papers first.

 

Ben Courchia MD (38:07.963)

Yes.

 

Ben Courchia MD (38:11.793)

Sure. it's, no, no, no, it's fine. But I think it's interesting because I was talking to my brother who's an attorney in France, nothing related to medical. He does like a company, whatever, corporate law. Yeah, but he says that when you work with a client as a lawyer, you ask them like, what do you want? And then it's like, what can you live with? It's like, so I have a range. I was talking about this. We were not talking about medicine, but I was thinking about it from what you're just saying about like wishes.

 

Daphna Yasova Barbeau, MD (38:20.491)

Yeah.

 

But where words very much matter, right, in law?

 

Daphna Yasova Barbeau, MD (38:31.512)

Hmm. Hmm.

 

Daphna Yasova Barbeau, MD (38:37.848)

Mmm.

 

Ben Courchia MD (38:41.467)

And it's true, like we never really ask the family, like, what can you live with? Because we say, like you said, we say, what's the best case scenario? And we always aim for the best case scenario, but we know that very often it's not always the best case scenario, but we really, maybe we should, I and again, maybe some people are listening and be like, I ask, I ask, is the family? But I feel like maybe this is an interesting approach to redefine what we call parental wishes. Maybe we can define more of a window in which parents are.

 

Daphna Yasova Barbeau, MD (38:59.468)

Yeah.

 

Ben Courchia MD (39:10.961)

finding outcomes acceptable.

 

Daphna Yasova Barbeau, MD (39:12.502)

And I think that's where it becomes more informed consent, right? Because there is this range and that's the question we need to know from families that maybe that's not the right way for us to say to families, the what can you live with question. Like what is an acceptable quality of life for your family? Yeah. No, no, But the point is well taken, right? Yeah, exactly. Love it.

 

Ben Courchia MD (39:23.409)

Yeah.

 

Ben Courchia MD (39:29.78)

Yeah, maybe the words are not the right, I mean, that's what as a lawyer, asks companies. But in terms of... All right. Keep going. This is very interesting conversation. So you're going to talk to us about...

 

Daphna Yasova Barbeau, MD (39:42.912)

No, you go. My other paper is related, but not totally aligned. So you go, and then I'll go. A totally different.

 

Ben Courchia MD (39:48.807)

because I'm taking you in a way different direction now. All right. So I read a paper about nitric oxide. I love using nitric oxide. It's called retrospective study of preterm infants exposed to inhale nitric oxide in the Kaiser Permanente Southern California morbidity, mortality and follow up. First author is Dr. Bhatt and colleague. It's in the Journal of Perinatology. And I'm going to try to be brief. Really the specific objective of the study

 

Daphna Yasova Barbeau, MD (39:58.348)

You know I love nitric.

 

Ben Courchia MD (40:16.583)

are fourfold. Number one, to identify all the preterm infants born before 34 weeks in the Kaiser system between 2010 and 2020 who received NITREC. They wanted to get an understanding based on individual chart review of their clinical course, their condition, their echo findings when they were at the time they were initiating NITREC, their response to NITREC, and their NITQ outcomes. But interestingly enough, they wanted to test the hypothesis that preterm infants with echographic echocardiographic

 

pH, pulmonary hypertension, at the time of nitric initiation in the first 10 days of life would have better initial oxygenation response and survival compared to infants without evidence of pH. know, because I mean, I think that's always the right. And finally, the other hypothesis they wanted to test was

 

Daphna Yasova Barbeau, MD (41:03.288)

Well, it's interesting, right? Because that's what the insurance companies are looking for. So it's an interesting question.

 

Ben Courchia MD (41:06.823)

Of course. And the other hypothesis they wanted to test was related to rupture of membrane versus babies without rupture of membrane. And I think that for many centers, yeah, obviously, if you're Gabriel, like our colleague Gabriel, and you're a hemodynamics person and you can actually quantify this at 2 a by yourself, it's very helpful and you can actually make much better informed decisions. But for many centers, they won't get an echo in the middle of the night. And that can be hard or the patient may not give you the luxury of obtaining the echo.

 

And because I mean, we are fortunate enough that we could get an echo in the middle of the night, but you still have to have a tech command and you still have to have the image captured and so on and so forth. So I think it's a very interesting question. think the Kaiser system is so renowned, has such a large network that I was very curious to hear what their findings were. This was a retrospective study of all preterm infants born in the Kaiser system before 34 weeks over this course of 10 years who received nitric. They mentioned there's no formal guideline in their system to

 

to administer nitric. So it's really a little bit whatever the clinician decides. The exposure to nitric was identified based on the database that they're collecting. And they're reporting this, obviously, to Vermont Oxford Network. Interestingly enough, they had to decide when they were looking at response to nitric. They said, we have to define what we would call a good response. I mean, to us, it's like you see the SATs come up pretty quickly.

 

They had to quantify that and they said that they arbitrarily define an oxygenation response to nitric as an absolute decrease of 25 % in the FiO2 with an increase in the SpO2 to FiO2 ratio by 30 or greater within two hours of initiation. I'm like, that's quite long. I want nitric to respond like that. I want to see it instantly. But I guess two hours is...

 

Daphna Yasova Barbeau, MD (43:00.686)

And that's what we were all taught, right? That if it doesn't come up in 15 minutes, that it's not going to work, right?

 

Ben Courchia MD (43:06.151)

Right. there's a total, the total and the results of the study show that a total of 418 ,000 infants were born in the system during that time. And 10 ,000 of these babies being before born before 34 weeks, among all of them, 0 .18 % were exposed to nitric in the NICU during this period. And so it's a good reminder that when you're having that really career, you're,

 

pondering the career choices you've made at 2 a when you have to be a nitric on a baby that's really sick and you're like, why do I put myself in this position? It is really, most of our babies do relatively well, which is kind of nice. 36 % of all infants exposed to nitric were less than 34 weeks. The incidence of nitric exposure was 2 .63 % among preterm births before 34 weeks. They included in the analysis anyone who received nitric, including congenital anomalies, chromosomal, aneuploidy,

 

whatever, everybody was included. In terms of baseline characteristics, it was basically showing that one growth restricted infant was born at 26 weeks of gestation with a birth weight of 270 grams. And they mentioned this case and I was like, man, this is quite impressive. They said the baby developed hypoxic respiratory failure following doctor ligation, received nitric oxide and survived. 270 grams. The rest of the characteristics,

 

were fairly benign. I gestational age 26 weeks, birth weight in gram was 780 grams, but the range goes down to 270. So you're like, wait, what? And yeah, and that kid survived. yeah, 97 % inborn, 74 % delivered VSC section and 13 % small for gestational age. These are sort of the baseline characteristic. How crazy, 270 grams. The indications for nitric are pretty much what we know, hypoxic respiratory failure and pulmonary hypertension.

 

and pulmonary hypotension. Majority of patients, 88 % of them, were in hypoxic respiratory failure and required inspired oxygen of 70 % or more. 3 fourths of the infants were on 100 % at the time of nitric initiation. Looking at other factors associated with initiation of nitric, 5 .6 % were receiving less than 50 % and had clinical signs of pulmonary hypertension.

 

Ben Courchia MD (45:33.415)

And that's sort of a theme where you see that the babies who didn't really have the echo findings were usually on much higher settings. And the ones that were on lower settings who received nitric, usually that was sort of guided and educated by the findings on echocardiogram. 59 % of patients were acidotic with a pH of less than 7 .25 at the time of initiation. 12 % had less than a 7 .0 pH at the time of initiation.

 

0 .6 % of 240 infants with sepsis workups had positive blood cultures at the time of nitric initiation. So these are some of the stats. Do with that as you wish. Let's talk about some of the things. We're going to talk about the response. We're going to talk about comorbidities. We're going to talk about cost and survival to discharge. In terms of response to INO, so remember they define this as an arbitrary response with a decrease by 25 % in your FIO2 and an increase

 

by 30 on this ratio of SATs to FiO2 within two hours. So 32 .6 % had a positive oxygenation response to nitric. Responders usually had lower SATs prior to initiation of INO. They also had lower gestational age and higher incidence of pulmonary hypertension on echocardiogram, 49 % versus 35 % compared to the non -responders.

 

Survival to discharge was 72 % among the responders, 58 % among the non -responders. But when you corrected for gestational age sex, this was no longer significant. Looking at comorbidities further down the road, at 36 weeks post menstrual age, 63 .5 % met the Vaughn criteria for BPD. In terms of IVH, it was seen at 36 % of babies who developed grade three.

 

Ben Courchia MD (47:29.638)

So 36 % developed IVH, Grade 3 was seen in 8 % because I was going to say this is kind of a high number for Grade 3 IVH and Grade 4 in 11 .9%. Satyan is on this paper, so you're not surprised to see a cost analysis on there. The total cost of nitric for the Kaiser system for these 270 infants was close to $4 million. A total of 39 ,804 hours of nitric.

 

Daphna Yasova Barbeau, MD (47:52.578)

Dang.

 

Ben Courchia MD (47:57.415)

use in the NICU during the study period among infants born before 34 weeks and the median cost per patient was about $8 ,000 with an interquartile range of about $10 ,000. So quite impressive.

 

Daphna Yasova Barbeau, MD (48:15.04)

Okay, I'm going to say one thing about the cost

 

Ben Courchia MD (48:17.543)

give me let me finish and then I'll let you I'll let you rent. Survival to discharge is about 73 percent when they looked at the babies who had a rupture of membrane at delivery basically seven the rates of survival were 71 percent if you had a rupture of membrane for one to 18 hours 78 if you ruptured from 19 to 120 hours and only 52 if rupture of membrane was more than 120 hours. Now the overall survival

 

Daphna Yasova Barbeau, MD (48:18.902)

Okay.

 

Ben Courchia MD (48:46.663)

to discharge among the infants that had either less or more than 18 hours of rupture was not really statistically significant. So it really depends how you break it down. If you really look at the extremes, and obviously, I mean, if you have more than rupture of memory for more than 120 hours, how much of that really plays a role in your degree of pulmonary hypoplasia, then that's an important component. So they mentioned that 28 infants exposed to nitric had clinical diagnosis of pulmonary hypoplasia, of which 50 % died.

 

I think this is really much, they're very much interconnected. When they adjusted for gestational age, growth status at birth, female sex, that was associated with improved survival. What else can I tell you? I'm almost done. In terms of timing of initiation, initiation of nitric in the first 72 hours after birth was associated with a mortality rate of 44%.

 

In the first week of life, was associated with a mortality of 33%, one to four weeks, 21%. And yeah, so this was obviously much lower compared to babies who were started on nitric oxide after four weeks of life with mortality rates of 84%.

 

In terms of follow up at 12 months, I'm just going to finish with that. 63 % of preterm infants who receive NITREC were discharged alive from the NICU. The discharged survivors experienced frequent rehospitalization in 35 % of cases, use of supplemental oxygen, sildenafil, diuretics, bronchodilators, and steroids. Four infants had persistent pulmonary hypertension and five infants died after NICU discharge. The conclusion of the group is that data from their regional healthcare system shows that infants who are treated with NITREC,

 

have relatively high NICU mortality and readmission rate after NICU discharge. Though two thirds of the NICU survivors were on room air without any evidence of pH by one year of age. Inhaled nitric oxide treatment was primarily associated with hypoxic respiratory failure rather than pulmonary hypertension. And in their cohort, pulmonary hypertension was not associated with risk -adjusted two -hour oxygenation response or improved survival. It really was what we said earlier, that clinical presentation that made such a difference.

 

Ben Courchia MD (51:02.097)

This suggests that nitric oxide therapy may be an indicator of disease severity rather than an indicator of a process where clinically meaningful outcomes can be modified by nitric oxide. I think that's a very important sentence. And really the fact that how we use nitric oxide really changes the picture completely. So yeah, I it was an interesting paper.

 

Daphna Yasova Barbeau, MD (51:22.478)

Mm -hmm.

 

Daphna Yasova Barbeau, MD (51:26.158)

I don't have much to say. mean, think this paper speaks for itself. I wanted to say something about cost, just so let me think about cost for like an admission and a baby in this early age, very small just like $8 ,000. I know it's a lot of money. Okay. In my household, $8 ,000 would be no joke, but when we think about what a NICU admission costs, I don't know. I thought it would be worse than that.

 

Ben Courchia MD (51:28.667)

You were going to say something on the cost.

 

Ben Courchia MD (51:52.623)

Yeah, I think

 

You're taking it as a positive. think that's very interesting you're saying that because I think also for people who are listening from abroad, we have a lot of listeners from outside the US. You have to realize that parents as they go home and get the bill for their hospitalization, get a bill for several million dollars sometimes. So what you're saying is an interesting point where you're saying, yeah, ten thousand dollars and a two million dollar bill. I'll take it.

 

Daphna Yasova Barbeau, MD (52:14.04)

For sure.

 

Daphna Yasova Barbeau, MD (52:24.13)

That's right. And I wonder for our international colleagues, maybe nitric doesn't cost so much in the other, in other countries.

 

Ben Courchia MD (52:25.262)

Yeah.

 

Ben Courchia MD (52:33.763)

Yeah, but I think to me what's, and people have to understand too, like if you're a resident, by the way, just know that the reason people are so touchy about nitric is that there's a meter on the tank. So for however long the tank is open, you pay per hour. that's why the cost is so exorbitant. But I think it's an interesting paper to me just because it really puts things back into a frame of reference where

 

Daphna Yasova Barbeau, MD (52:44.387)

Mm -hmm.

 

Ben Courchia MD (53:02.245)

Yes, if I know that there's pulmonary hypertension, nitric is a valid option. But in babies that I see clinically behaving as hypoxic respiratory failure with potentially some clinical signs of pulmonary hypertension, I think we should, I mean, should we be a bit trigger happy with the nitric oxide? You see what I'm saying? I think sometimes there's been a bit of a pendulum swing where people use nitric oxide a lot. Then there was, we were getting a bit chastised by saying maybe we should just use it for babies that have documented pulmonary hypertension. And

 

Daphna Yasova Barbeau, MD (53:04.174)

Mm -hmm. Mm -hmm.

 

Ben Courchia MD (53:31.717)

And this is maybe showing, the babies that have low SATs and who have oxygenation index that are quite high will respond pretty significantly. And I think that it's also important to remember that nitric oxide, it's the only FDA approved pulmonary vasodilator in neonate. So yeah, we don't have a lot of other options as well.

 

Daphna Yasova Barbeau, MD (53:55.394)

We ain't got nothing else. No, there are some other options, but I mean, nitric is the fast acting one for sure. It's interesting. I mean, I think it's like so many other things we use in the NICU. Okay. If you turn it on and it doesn't work, you should turn it off. That's really, I think the problem we see with nitric is once somebody starts it, like we see with so many things, reflux medications, stuff like that. Once somebody starts it.

 

Ben Courchia MD (54:02.917)

Yeah, yeah. Okay.

 

Daphna Yasova Barbeau, MD (54:23.924)

It's very hard for people to take it away. So that's the problem.

 

Ben Courchia MD (54:28.69)

Especially if you have a response.

 

Daphna Yasova Barbeau, MD (54:31.804)

yeah, totally.

 

Ben Courchia MD (54:34.117)

Yeah. All right. I'm going to go over, I have two more papers that I would like to mention. I guess I'll be brief. be three more papers, but I'll be brief. The first one I wanted to mention is in the Journal of Perinatology. called, so this paper is called Blood Absolute Monocyte Count Trends in Preterm Infants with Suspected Necrotizing Enterocolitis and Adjunct Tool for Diagnosis. First author is Dr. Moroze, and this is a study out of the US.

 

And this study really wanted to look at the trends in absolute monocyte counts deviation from baseline over 72 hours after the onset of clinical suspicion for neck and preterm infants and explore its utilization as an adjunct tool to rule out neck. This is a retrospective study. So take that with a grain of salt, less than 32 weeks babies in the first 30 days of life. They exclude the babies with congenital anomalies. And they basically looked at

 

trends in their CBCs in the degrees of absolute monocyte counts. So this was interesting. I would suggest you look at figure one, but the results show that they had 130 infants and the AMC decreased in patients with next stage two or three. Stage two or three next experience a drop in absolute monocyte count.

 

compared to an increase in the patients with no neck, possible neck, or just with a positive blood culture. Absolut monocyte count increase 24 % or less can differentiate NEC stage two or three from possible neck with an area under the curve of 0 .78, while decrease of more than 32 % can differentiate stage two, three versus possible or no neck with an AUC of 0 .71.

 

So I think we're always looking for tools. I mean, I've heard about looking at monocytes since I've been a resident. it seems like there's always a paper coming out every couple of years making a case for it. this has always been an interesting subject for me. But yeah.

 

Daphna Yasova Barbeau, MD (56:53.9)

Well, and I mean, as usual, the truth is we don't have we don't we don't have much else. We're not created predicting that we're not created predicting sepsis. Even I think this is any additional data for making those decisions, I think is an important one.

 

Ben Courchia MD (57:14.14)

Yeah. I'm going to mention this other paper that came out in the New England Journal of Medicine. I'm not sure if people took a look at that. It's called Nipocalimab in early onset severe hemolytic disease of the fetus and the newborn. It's a paper that it's not very much for us. It's probably more for the obese, but it basically looks at the administration. It's a phase two trial. It's industry sponsored, but it looks

 

at the administration of this agent, an anti -neonatal Fc receptor blocker, which basically inhibits the transplacental IgG transfer. And so basically looking at whether for babies that have hemolytic disease of the fetus or the newborn, if we administer this during the pregnancy, could we reduce the complications during pregnancy and after birth?

 

It's showing very promising results. In the intervention group, they showed no cases of fetal high drops that occurred. 46 % did not receive any antenatal or neonatal transfusion. Six fetuses in the study group received intrauterine transfusion, five fetuses at 24 weeks or later, and one fetus before fetal loss at 22 and five. Live birth occurred in 12. Pregnancy, the median gestational average delivery 36 and.

 

and it's concluding that nipocalimab treatment delayed or prevented fetal anemia or intrauterine transfusion as compared with the historical benchmark in pregnancies at high risk for HDFN. yeah, mean, so it's kind of exciting to see that maybe we won't, maybe we might not be in those positions anymore with babies with severe...

 

Daphna Yasova Barbeau, MD (58:57.506)

Hmm?

 

Ben Courchia MD (59:04.677)

get the word that I'm looking for but that's okay. Yeah.

 

Daphna Yasova Barbeau, MD (59:08.618)

Isoimmune, hemolytic disease. Yeah.

 

Ben Courchia MD (59:10.959)

Yeah. can't find the word. Anyway, it will be fine. Okay. And then the last, the last paper that I wanted to mention is a paper that's coming to us from our friends in the BPD collaborative. It's called surfactant treatment at birth in the contemporary cohort of preterm infants with bronchopulmonary dysplasia. First author is Clifford Muller, Mueller, Journal of Perinatology. And it's basically going back to this idea about what does it mean

 

repeated doses of surfactant. So first of all, if you're a trainee, let me just remind you of this because I was reading this and I was like, man, this is quite impressive. Exogenous surfactant therapy has been FDA approved for use in preemies with RDS since the early 1990s. It's really like it's not that long ago. I mean, this is kind of crazy. Although surfactant has clearly been shown to improve outcomes with babies with RDS, it does not, is not associated with a reduction in the incidence of BPD.

 

Daphna Yasova Barbeau, MD (59:42.475)

Mm.

 

Ben Courchia MD (01:00:08.711)

If you're studying for the boards, that's a question. They love that question because you might be tempted to think yes, but no. The one drug that's been associated with reduction of BPD is usually like they like to ask you about caffeine because that's been documented. So the BPD collaborative wanted to say, and I love the aim of this study, said, given our interest in patients with established BPD and since surfactant does not appear to prevent BPD,

 

So they said, we wondered if surfactant use in the first 72 hours of life in preterm infants who went on to develop BPD might be associated with the severity of BPD at the time of diagnosis at 36 weeks. And then they say, in other words, in this study, we're not asking if surfactant therapy has a role in decreasing the incidence of BPD. Rather, our question is, in a cohort of patients with BPD, did surfactant therapy impact the severity of the disease? And they utilized data from their registry.

 

This was observational data. looked at their BPD database. They're using the Jensen criteria. They had 971 BPD infants included in the cohort. The vast majority received surfactant. 89 % did, 11 % did not. Of the infants in the surfactant group, 45 % received a dose of surfactant in the delivery room. We rarely, I mean, you and I rarely give those in the delivery room. We're pretty quick to go to the unit, but...

 

Yeah. Of the infants in the surfactant group, most received either one dose in 47 % of cases or two doses, 37 % of cases, while 14 % of infants received three doses and only 2 % received more than three doses. So if you're a trainee, remember, some docs do give more than two doses, because I didn't know this was a thing until I became an attending.

 

Daphna Yasova Barbeau, MD (01:01:59.308)

Mm -hmm. Mm -hmm.

 

Ben Courchia MD (01:02:01.391)

I thought it was forbidden by religious law to give us...

 

Daphna Yasova Barbeau, MD (01:02:04.578)

That's right. Like you can't even pull it from the pixis, right? No.

 

Ben Courchia MD (01:02:08.615)

Yeah, no, that's right. So in terms of the breakdown, terms of BPD, 18 % of their cohort had grade 1. BPD, 57 % had grade 2, and 25 % had grade 3. And there was an evidence of an association of surfactant therapy and the BPD grade. So when you're looking at the figure, I think it's quite interesting. And I'm going to...

 

spare you the long breakdown of the different results. I just lost my notes. me one second.

 

Ben Courchia MD (01:02:55.013)

Okay, so what's interesting is that they found an association between surfactant and BPD grade. And they found that this association had a greater likelihood of, there was a greater likelihood of grade three BPD in infants who received surfactant in the delivery room or the babies who had two or more doses. So they have this very nice graph in figure two where basically you can see

 

the adjusted odds ratio on the x -axis, if you would like, but looking at this plot of what is the odds ratio if you have one dose of surfactant, two doses, and three doses. And it's really almost like a staircase shape where the more doses you get, the higher the grade of BPD. Also, interestingly enough, there's a lot of overlap, but receiving surfactant delivery room is not too good of a sign prognostically for the development of

 

grade 3 BPD. The group then concludes that in this cohort, surfactant treatment is associated with a higher risk for grade 3 BPD compared to those that did not receive surfactant, particularly in infants who received delivery room surfactant or two or more doses of surfactant. And they say that this leads them to postulate.

 

that in this era where most infants with established BPD received surfactant therapy via endotracheal tube, those that didn't get surfactant therapy likely had more mild initial respiratory disease severity. And not really trying to create an association between surfactant and BPD, but just saying, is surfactant a marker of how sick your patients are? They're saying our data does not demonstrate a cause and effect relationship, as we just said, between the receipt of surfactant and the development of more severe BPD. The data does.

 

does not suggest that any changes should be made in how we administer surfactant, but they are wondering as less invasive methods of surfactant therapy are developed and widely adopted, what the impact will be on the development of grade 3 BPD. Will these will help mitigate that in terms of if you received more than one dose, but it was through a less invasive form like mist or something, will that reduce your risk of developing grade 3 BPD?

 

Ben Courchia MD (01:05:07.476)

The last thing is that they're saying is that however we suggest that surfactant treatment in the current cohorts of patients with established BPD may be a clinical marker of greater risk of developing severe BPD and that future studies should be done. So a very interesting paper because yeah, I think it's important how we counsel families I feel like. If you're going to give that second, third dose, maybe you should start priming families about long -term chronic disease and so on and so forth. I think that's what I would do.

 

Daphna Yasova Barbeau, MD (01:05:26.946)

Mm -hmm.

 

Ben Courchia MD (01:05:37.049)

advice.

 

Daphna Yasova Barbeau, MD (01:05:37.166)

Yeah, it's interesting because sometimes it feels like in those early days to weeks, you're like, we don't know which babies are going to develop BPD, but we do know some things about the babies that are highest risk for developing BPD. Okay. I have one more that I wanted to share. I told you it was adjacent to my previous questions about communication with families, but this was called Beyond the Question.

 

Ben Courchia MD (01:05:52.41)

Absolutely.

 

Daphna Yasova Barbeau, MD (01:06:05.57)

re -examining appearance unusual request, lead author, Catherine Callahan, senior author, Fiester. And this is part of the pediatrics ethics rounds. but it is a neonatal case. So I thought it was really interesting. So what I am going to do is I'm going to tell you what the case was and kind of what the discussion was. So the case.

 

Baby Daniel was born in the United States at 23 and two days gestation mother had troubled from Ethiopian preterm labor Daniel's course was marked by numerous complications as is common at this extreme of prematurity During one episode of sepsis Daniel became critically ill requiring pressers for blood pressure support and the medical team and family discussed the possibility of redirecting care and in that meeting the infants mother met in person with the clinical team and the infants father participated from over the phone from Ethiopia

 

The mother and father both agreed on continuing life sustaining interventions. Daniel recovers and at three months chronological age, he is now weaning on the ventilator with an optimistic prognosis. Daniel's clinical status is past the point at which a neonatologist would typically consider redirection of care. Yet one morning, Daniel's father unexpectedly calls the NICU requesting the removal of Daniel's breathing tube and a transition to comfort only care. So.

 

They talk about like, what do we do? Ben's grimacing, you can't see. But I think this is such an important case to talk about, like for a number of reasons. The first that I'm going to discuss is actually not explicitly talked about in their discussion, but sometimes we introduce comfort care and we don't put any time limits on that. Right? And so it's not totally surprising when

 

Ben Courchia MD (01:07:34.33)

Wow.

 

Daphna Yasova Barbeau, MD (01:08:00.512)

It feels surprising when three months later, a parent says, you know what? I don't want to do this anymore. I don't think this is right for my baby anymore, but we never explained to them what the, what the time frame, what we are looking for when we have this discussion about withdrawal of intensive care, moving into comfort care. And that if babies get better, potentially that's not, that's potentially not an option anymore. So I thought that was a brilliant.

 

point of this case. But I think what's really, I think useful, they have three people discuss the case, Katherine Press Callahan, a neonatologist and an ethicist. They have Eliza Narva, a clinical ethicist, nurse and lawyer, and they have Autumn Fiester, conflict mediator. So they each have a different perspective on the case. But I think the overarching framework is

 

that we tackle these questions a lot of times as the clinical team from an ethical perspective. Like, is it right or wrong to do this? And we miss this opportunity to connect with the family and say, like, why now? Why you bring up a request? What are your concerns? What are, you know, the worries that you have that are having you bring up this request?

 

that totally, I think, can change the discussion when we understand what's happening for families and the backgrounds. And this is true in the prenatal realm. This is true postnatally when parents come to us with questions and concerns or requests. We're so focused on the request that we don't say, this is what my dad always says, what's the question behind the question? So, you know, what are you worried about? Like, why are you bringing this up to me? And if we can start from a place of curiosity,

 

and talk to families in this way, then we may be surprised by the request. We may be able to discuss their concerns and the requests may be different. So I really recommend people to take a look, read these different perspectives and comments, but I especially liked this from coming from the perspective of the conflict mediator.

 

Daphna Yasova Barbeau, MD (01:10:27.232)

and saying, we don't necessarily have to jump right into the ethics. We have this gut reaction to this request, but we should understand the background of the request and why the parents are coming to us. And I'm going to tell you the resolution of the case, which is probably not what anybody expected. But basically, so they did.

 

plan to meet with this family. They asked the social worker to arrange a family meeting and they received news that the father was actually going to get a visa to come quickly to the United States. So they planned to hold a family meeting in person, but as often happens, the visa took quite a long time. So what they thought were going to be days became weeks, became only almost a month. And in that month, the baby did clinically much better.

 

And by the time the father presented to the NICU, the baby was basically ready for extubation and was extubated in the subsequent few days. So they never really had to have this discussion because the clinical situation progressed in a positive direction and the family was there caring for the infant. The team never brought it up and neither did the family. So they never had to come up to really tackle the case. So we don't know how this would have gone in a different scenario.

 

Ben Courchia MD (01:11:45.127)

unfortunate.

 

Daphna Yasova Barbeau, MD (01:11:51.502)

But I think it does elucidate some of what was happening. The father had never seen the child, didn't really understand was there suffering or what was the amount of suffering? What did the day -to -day care look like? What were the long -term outcomes? So if we have a very scary conversation with families and then we don't readdress how the outcomes are changing, we can't anticipate that they would know. So I thought this was a really interesting case, even though

 

They didn't have to have this contentious conversation with the family. Thoughts?

 

Ben Courchia MD (01:12:25.583)

Well, I have a question. If you knew from, let's say, I'm ignoring the case a little bit for now, just assume this case presents itself again. You have a family that's traveling from Ethiopia who plans to go back to Ethiopia. I'm not super familiar with the amount of resources they would have available at home to care for a baby that leaves the NICU after. Yeah. But if you have someone who is delivering in a...

 

Daphna Yasova Barbeau, MD (01:12:27.746)

Daphna Yasova Barbeau, MD (01:12:34.009)

-huh. -huh.

 

Daphna Yasova Barbeau, MD (01:12:40.29)

Mmm.

 

Daphna Yasova Barbeau, MD (01:12:47.15)

But there are many places, right, where caring for medically complex baby is complicated.

 

Ben Courchia MD (01:12:56.959)

a country that has high resources, high level of resources, but plans to go back to a low resource country. Do you change your counseling at birth?

 

Daphna Yasova Barbeau, MD (01:13:07.47)

Well, that's a tough one. That's a tough one. That's, mean, I think this case shows too that we don't know what decisions families will make, right? That they may be planning to go back home. We've had a bunch of families, because we're in Florida, right? So we have lots of families coming on vacation from overseas and they deliver, right? All the time. And they make the choice to move, to relocate to the States when they have a medically complex child.

 

Ben Courchia MD (01:13:08.816)

Ha!

 

Ben Courchia MD (01:13:28.017)

Yeah.

 

Daphna Yasova Barbeau, MD (01:13:37.144)

I don't think so. I wouldn't personally, because I think that parents, social situations might change. I don't know.

 

Ben Courchia MD (01:13:39.431)

That's interesting,

 

Ben Courchia MD (01:13:47.845)

Yeah, because I mean, just without saying that the recommendation should be different, I think the way you present caring for a medically complex child in the US would be very different than if you said, hey, let's how do you care for a medically complex child in sub -Saharan Africa? It's like, my God. And yeah, may not be possible at all. so, I mean, it almost feels like reading through the case that the father had like a little panic moment.

 

Daphna Yasova Barbeau, MD (01:13:59.342)

Mm -hmm.

 

Daphna Yasova Barbeau, MD (01:14:05.022)

Yeah, it may not be possible at all, right? Yeah.

 

Daphna Yasova Barbeau, MD (01:14:17.326)

financially, yeah.

 

Ben Courchia MD (01:14:17.872)

potentially, maybe having this realization saying how we're going to make this work. But it's a very fortunate scenario in which the baby ended up doing well and the scenario ends the way it ends. yeah, fascinating story, fascinating story. yeah, dilemma.

 

Daphna Yasova Barbeau, MD (01:14:27.896)

Mm -hmm.

 

Daphna Yasova Barbeau, MD (01:14:38.112)

Yeah, I think that the lesson is just because we have this like gut feeling and we know we don't want to go into this meeting. We don't want to have to have this quote unquote fight that we can't let our biases and our perceptions of the situation temper. Like what's getting to the root of the issue and finding out why the parents are bringing this?

 

Ben Courchia MD (01:15:00.433)

Yeah.

 

Can you imagine if you're the attending on service on Monday and that's what you're presented with?

 

Daphna Yasova Barbeau, MD (01:15:06.776)

You're like, I know, we'll have a family meeting next Monday, right? No. Just kidding.

 

In our unit, we fight about the family meetings, right? We'll do it on my service.

 

Ben Courchia MD (01:15:15.523)

Alright.

 

yeah. Yeah, we try to make them not too crowded. Everybody wants to be on the family meetings.

 

Daphna Yasova Barbeau, MD (01:15:22.09)

for.

 

That's right, that's right, we've got a good team. Okay buddy, we made it.

 

Ben Courchia MD (01:15:27.461)

All right. Well, that was fun. We made it. Thank you for everything. Thank you, everybody, for listening and have a good Sunday.

 

Daphna Yasova Barbeau, MD (01:15:37.646)

everyone.

 

Comments

bottom of page