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#224 - 📑 Journal Club - The complete episode (July 7 2024)



Hello friends 👋

In this packed episode of Journal Club, Ben and Daphna review eleven recent papers covering a range of neonatology topics. They discuss a study on CRP use in early-onset sepsis evaluations, finding that high CRP use was associated with increased antibiotic administration. Another paper examined iron supplementation in healthy breastfed infants, showing no significant developmental benefits at 12-36 months.

They review a JAMA Network Open study on the long term outcomes of infants enrolled in the umbilical cord milking study MINVI. They also cover a paper on cannabis use in pregnancy, noting a significantly increased risk of fetal death associated with maternal cannabis use.

Other topics include antibiotic exposure and BPD risk in very preterm infants, comparisons of different BPD definitions, and the effects of phototherapy on plasma metabolites in preterm infants with hyperbilirubinemia.

The episode features a special segment with Dr. James Sotiropoulos discussing his recent paper on initial oxygen concentrations for resuscitating extremely preterm infants. The study found a potential mortality benefit with higher initial FiO2, though more research is needed.

Ben and Daphna also review papers on improving NICU communication and antenatal consultation practices. They close by welcoming new trainees starting in July and reminding listeners about The Incubator's board review resources for neonatology fellows.

Overall, this comprehensive episode provides an excellent overview of recent impactful research across multiple areas of neonatology and perinatal medicine.


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


Barboza AZ, Flannery DD, Shu D, Galloway M, Dhudasia MB, Bonafide CP, Benitz WE, Gerber JS, Mukhopadhyay S.J Pediatr. 2024 Jun 18:114153. doi: 10.1016/j.jpeds.2024.114153. Online ahead of print.PMID: 38901777

 

Svensson L, Chmielewski G, Czyzewska E, Domellöf M, Konarska Z, Piescik-Lech M, Späth C, Szajewska H, Chmielewska A.JAMA Pediatr. 2024 Jul 1;178(7):649-656. doi: 10.1001/jamapediatrics.2024.1095.PMID: 38739382 Clinical Trial.

 

Shah S, Myers P, Enciso JM, Davis AS, Crouch EE, Scheurer AM, Song C, Lakshminrusimha S.J Perinatol. 2024 Jun 8. doi: 10.1038/s41372-024-02020-3. Online ahead of print.PMID: 38851854 Review.

 

Sotiropoulos JX, Oei JL, Schmölzer GM, Libesman S, Hunter KE, Williams JG, Webster AC, Vento M, Kapadia V, Rabi Y, Dekker J, Vermeulen MJ, Sundaram V, Kumar P, Kaban RK, Rohsiswatmo R, Saugstad OD, Seidler AL.JAMA Pediatr. 2024 Jun 24:e241848. doi: 10.1001/jamapediatrics.2024.1848. Online ahead of print.PMID: 38913382

 

Habersham LL, Hurd YL, Nomura Y.J Perinatol. 2024 Jun 18. doi: 10.1038/s41372-024-02027-w. Online ahead of print.PMID: 38890400

 

Satrom KM, Wang J, Lock EF, Snook K, Lund TC, Rao RB.J Pediatr. 2024 Jun 28:114175. doi: 10.1016/j.jpeds.2024.114175. Online ahead of print.PMID: 38945444

 

Katz TA, van Kaam AH, Zuithoff NPA, Mugie SM, Beuger S, Blok GJ, van Kempen AAMW, van Laerhoven H, Lutterman CAM, Rijpert M, Schiering IA, Ran NC, Visser F, van Straaten E, Aarnoudse-Moens CSH, van Wassenaer-Leemhuis AG, Onland W.Arch Dis Child Fetal Neonatal Ed. 2024 Jun 19:fetalneonatal-2024-326931. doi: 10.1136/archdischild-2024-326931. Online ahead of print.PMID: 38897634

 

Haward MF, Lorenz JM, Fischhoff B.J Pediatr. 2024 Jun 26:114173. doi: 10.1016/j.jpeds.2024.114173. Online ahead of print.PMID: 38942356 No abstract available.

 

Osborne AD, Worsley D, Cullen C, Martin A, Christ L.Pediatrics. 2024 Jun 1;153(6):e2023064419. doi: 10.1542/peds.2023-064419.PMID: 38716568

 

Shi W, Chen Z, Shi L, Jiang S, Zhou J, Gu X, Lei X, Xiao T, Zhu Y, Qian A, Zhou W, Lee SK, Du L, Yang J, Ma X, Hu L; Chinese Neonatal Network.JAMA Netw Open. 2024 Jun 3;7(6):e2418831. doi: 10.1001/jamanetworkopen.2024.18831.PMID: 38935376 Free PMC article.

 

Katheria AC, El Ghormli L, Clark E, Yoder B, Schmölzer GM, Law BHY, El-Naggar W, Rittenberg D, Sheth S, Martin C, Vora F, Lakshminrusimha S, Underwood M, Mazela J, Kaempf J, Tomlinson M, Gollin Y, Rich W, Morales A, Varner M, Poeltler D, Vaucher Y, Mercer J, Finer N, Rice MM.JAMA Netw Open. 2024 Jul 1;7(7):e2416870. doi: 10.1001/jamanetworkopen.2024.16870.PMID: 38949814 Free PMC article. Clinical Trial.


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


Ben Courchia MD (00:00)

Hello everybody, welcome back to the Incubator podcast. It is Sunday. We are back with another episode of Journal Club. I'm excited about this week's episode. Daphne, how are you?

 

Daphna Barbeau (00:10)

I know, I see you've got a lot of lung papers today. I noted. That's kind of true. It's summertime. This is how you coast. You just pick lung papers, which there was a lot. It was not actually coasting because there's a ton of lung papers to sift through right now.

 

Ben Courchia MD (00:14)

do I? Yeah, that's kind of true. That is kind of true.

 

It was a lot of long papers actually.

 

I realized also that there were a lot of long papers, but there were also many that I left behind. So I ended up picking two, but I have a lot of papers to review today.

 

Daphna Barbeau (00:44)

I mean, it seems our colleagues have been very prolific at the end of this last semester before the summer break. It is, there's a lot of papers. We can't review them all.

 

Ben Courchia MD (00:50)

Mm -hmm. Yeah. Absolutely.

 

And we can't review them all. We're going to do some announcements first. We officially are going to close the three year anniversary survey slash giveaway. So literally, if you're listening to this, we will close it out at the end of today. This episode is airing on Sunday. It is going to be when we're going to say it's July 7th.

 

Daphna Barbeau (01:23)

Mm -hmm.

 

Ben Courchia MD (01:24)

So when you're listening to this, it's July 7th, and we're going to close this at midnight tonight. So you still have Sunday today to submit if you want to participate in the giveaway. And then, no, it doesn't take very long. And at some point, we do have to close it. I feel like in the past, we've been very demanding with our giveaways where you had only like a week. And we've realized that sometimes, like,

 

Daphna Barbeau (01:38)

and it doesn't take very long.

 

Ben Courchia MD (01:54)

I'm giving you an example. I had a trip to France that was a disaster flying back. I'm supposed to submit a letter of complaint because our flight got delayed, canceled. It cost us like, I would say a good thousand dollars to make it back. I still haven't had a chance to do that. Like it's been so busy. So whether the podcast has a giveaway to give me a week to submit the survey, I don't think I would have time. So we gave people plenty of time. We gave people more than a month, but at some point we just have to close so that we can actually give.

 

Daphna Barbeau (02:08)

I know.

 

Ben Courchia MD (02:23)

the winners their prizes. So that has, yeah.

 

Daphna Barbeau (02:26)

Can I say something about the survey? Because you haven't peaked at the results so far. And I can't help myself. I just want people to know, and we've gotten a lot of responses, which everybody's still a potential winner. So just don't let that make you shy away from submitting a response. But we really value that information. Like it really, some of the questions are like,

 

Ben Courchia MD (02:32)

I've peaked.

 

-huh.

 

Daphna Barbeau (02:53)

a little bit demographic, you don't have to answer them if you don't want to, but that really helps us learn more about the community, how we can help more. And we've got some really great feedback. Some of which is like super positive, which is like really, I don't think people recognize how powerful that is for us to keep doing what we're doing. And some really good suggestions that we are going to roll out, you know, as soon as possible. So we really do value the information that comes through those surveys.

 

Ben Courchia MD (03:20)

Mm -hmm. Yeah. I think people need to understand that we're not making money from this endeavor and it's a full -time job. It's really now a full -time job.

 

Daphna Barbeau (03:33)

So we really value your words of affirmation for what we're doing here.

 

Ben Courchia MD (03:35)

Absolutely. Absolutely.

 

The Delphi conference is ramping up. We've had a little inflection point in registration. So it's an auditorium with limited seating this year. Just please make sure to reserve your seats. Look at the faculty list. There's a lot of very cool people you're going to get to interact with. So that's pretty much it for the announcement. I think we should get into Journal Club.

 

Daphna Barbeau (03:43)

Mmm.

 

Ben Courchia MD (04:09)

I have like six papers I want to go over. It's going to be tough. But yeah.

 

Daphna Barbeau (04:12)

Mm -hmm.

 

Let's see what we can do.

 

Ben Courchia MD (04:17)

Let's see what we can do. All right, I'm going to start with an easy one. It's in the Journal of Pediatrics and it's called Trends in C -Reactive Protein in Early -Onset Sepsis Evaluations and Associated Antibiotic Use. First author is...

 

Daphna Barbeau (04:28)

I know you stole it from the folder before I could take it. Actually, there are a handful of papers that I really wanted to review. So I'm looking forward to it.

 

Ben Courchia MD (04:39)

So the first author is Alvaro Zivalos Barbosa. And it's very cool. I always like the papers on CRP because it's a love -hate relationship with CRP. We love to get them. We know it's not great, but we still love to get them. And it showed in the background that a 2016 survey of 81 centers

 

Daphna Barbeau (04:54)

For sure.

 

Ben Courchia MD (05:03)

in the US showed that 35 % of centers incorporated CRP in early onset substance evaluation and 65 % did not. So this is where we are. The objective of that study was to determine the prevalence of CRP use in early onset substance evaluation in the US and estimate changes over time and look at how does that affect antibiotic use. So this was retrospective cohort study of centers contributing data to the premier healthcare database.

 

comparing centers with low to high CRP use in EOS evaluation. This went from 2009 to 2021. 735 NICUs contributed to that database. They included centers with at least 50 annual inborn NICU admissions in the first three days after birth. And they excluded centers without any infant with a blood culture charge on day one to three or more study years. Now...

 

For each year of participation, NICUs were categorized in four levels of their quote -unquote use rates based on this proportion. So they had the low CRP user, the less than 25 % of infants with a blood culture. Then they had the medium to low users. These were 25 to 50%, the medium to high 50 to 75, and then the high user 75 % or more. The primary outcome was to look at the frequency of antibiotic initiation on day one to three after birth.

 

The antibiotic administration for more than three continuous days when initiated on day one to three and the mortality within seven days of birth. Some secondary outcomes, frequency of EOS evaluations, the use of antibiotics other than AMP, GENT or penicillin, antibiotic initiation on day four to seven after birth, length of NICU stay mortality during hospitalization and transfer within seven days after birth. So, ta -da -da, the results are in 572 NICUs.

 

1 ,300 ,000 and more infants were included. And in each study year, most centers basically, it's basically like a religion, they were either low use centers or they were high use centers, right? Either you were on board or not. The majority of centers, that's important to know, are

 

Daphna Barbeau (07:12)

I mean that makes sense I think.

 

Ben Courchia MD (07:22)

categorized as low use centers. So 55 % would be categorized as using it less than 25 % of the time. High use centers are 26%. And so what you write, so then you start getting a sense, right? And then you had 10 % for the medium to low and 10 % for the medium to high. Compared with 2009, the proportion of centers categorized as high CRP users significantly decreased.

 

looking at 2021 going from 25 % to 17 % began showing that maybe this the evidence on the use of CRPs other modalities to evaluate for early onset sepsis new algorithms and so on trend pushed people towards a lower use.

 

Among these centers, 50 % of the centers that were high medium CRP users shifted to low as well. So compared with low use centers, a greater proportion of centers who used CRP very frequently obtained blood cultures and initiated antibiotics in infants on day one to three. The proportion of infants administered prolonged early antibiotics was also greater in high CRP use centers compared with low CRP use centers, 25 % versus only.

 

Infants with prolonged antibiotic administration had a higher number of CRP tests done in the first seven days after birth compared with infants who did not receive prolonged antibiotics. This finding held true on multivariable analysis and in the multivariable infant -level analysis, the adjusted probability for an infant to receive prolonged early antibiotics was two -fold greater in these high -use centers compared to the ones that were considered low -use.

 

The indications for antibiotic prolongation and microbiology results, they were not available for the cohort. So it really cannot be truly determined. That's a big caveat that the authors do disclose in the paper if there were appropriate indication for this prolonged antibiotic duration. So they can tell you that they were prolonged, but they cannot really tell you whether that was. Absolutely, that's. However, the incidence of culture confirmed EOS was relatively constant in the US during the study period. So the more.

 

Daphna Barbeau (09:25)

Hmm.

 

I think that would have been really valuable.

 

Ben Courchia MD (09:41)

the broad, broad, broad epidemiologic data doesn't seem to show that it would be justified, but it's always the trade -off when you have databases with millions of babies, you're going to lose some of that granularity, as we always say. The other outcomes, including median rates of mortality and transfer to another hospital within the first week of life and mortality during the hospitalization, it was not really different between the different groups. And so,

 

In secondary analysis of the 27 centers where CRP use changed from high or medium high to low use, the study outcomes changed significantly. There was a significant reduction in the median proportion of admitted infants started on antibiotics, and there was a reduction in the number of babies administered prolonged antibiotics. Median mortality rate did not change. And so in conclusion, they found that

 

decreasing use of CRP in EOS evaluations in centers in the US over the last decades and that NICUs with high CRP use were associated with higher rates of prolonged antibiotic use among infants undergoing evaluation and that the de -implementing CRP testing as part of EOS evaluation may be really a valuable approach and effective approach to reduce variation in antibiotic use in a NICU.

 

While replacement of CRP with a different inflammatory marker, such as poor calcitonin or interleukin 6, maybe another reason for reduced use, they found that charges for these markers in less than 1%. So it's really not that people have traded the CRP for another marker. It really is that the practice evolved. And I think, I mean, Dustin Finery is the second author on this paper, I believe. And I think the new EOS algorithms, which

 

Daphna Barbeau (11:16)

Mm -hmm.

 

Mm -hmm.

 

Ben Courchia MD (11:28)

do not rely on CRP values are a huge added benefit to not having to get these markers early on for early onset sepsis. And that maybe explains why the rates of ProCal and Interleukin -6 have not really gone up. So I thought this was an interesting paper. I think this is still relevant. 35 % of centers still use CRP for US evaluations. So I think this is interesting.

 

Daphna Barbeau (11:30)

Mm -hmm.

 

Yeah, I think it's totally fascinating. I think the hope is always like, okay, let's use CRPs and maybe it will reduce our antibiotic use, right? Like let's just trend serial low CRPs, right? But it doesn't look like that is the case, unfortunately. I do think though there's this gestalt in practice of like, am I going to rely on my lab values or I'm just going to rely on like the baby's clinical picture, right?

 

So I think that makes sense. There are some units who are more likely to be more conservative and use more antibiotics. And then there's some who say, I'm going to wait until the baby shows me that they need it, I think. That's not what the paper said, but this is my sense.

 

Ben Courchia MD (12:25)

Yeah, I think...

 

Yeah. Yeah, I think we don't, with these term infants, we don't get a lot of time with them. I think there's a fear of saying, am I going to get enough data points in my exams and my serial evaluations to give me a good indication of what I should be doing? And so adding the CRP to the mix feels like, I have one more data point, but it doesn't seem like it's the right.

 

Daphna Barbeau (12:45)

That's right.

 

Mm -hmm.

 

I certainly think, though, that the Kaiser calculator has been very helpful. It's changed our practice significantly, but not everybody has adopted it, right?

 

Ben Courchia MD (13:10)

And I think the Kaiser calculator is so good because it gives you sort of flexibility on the outcome saying, well, if you perceive this baby to be an equivocal clinical case, then do X. It's not really giving you. Yeah, because I think if it gives you like a very definitive answer and be like, don't do it, then you'd be like, I don't agree. Like, I think this kid has something, but it gives you more options. And I think that's critical.

 

Daphna Barbeau (13:17)

Hmm.

 

Or it gives you this four -hour observation period, right?

 

I also think as a learner, as a trainee, because we started using the calculator, I think early adapters in my residency program, but it helped me understand the risk factors a little bit better because you can make that rupture of membranes go very long and it doesn't change the situation, but that height of maternal fever certainly changes the output.

 

So I thought that was super valuable as a trainee to just make some hypothetical cases in my mind and see how changing the variables changed the outcome. I thought that was valuable.

 

Ben Courchia MD (14:04)

Mm -hmm.

 

Where are you taking us next? I can go next. You want me to keep going?

 

Daphna Barbeau (14:19)

you want me to go next?

 

No, I'm going to go. I've got some quick papers, I think. So I'm going to do this one first. Yeah, then we're just going to turn through here. This was in JAMA Pediatrics. It's effective low dose iron supplementation on early development in breastfed infants, a randomized clinical trial. And I will set this up with saying this is in healthy term infants.

 

Ben Courchia MD (14:23)

Ha.

 

We have a lot of papers to review, so might as well be quick today.

 

Daphna Barbeau (14:51)

But I think it's still valuable. We are having this discussion about iron in our unit. And anyway, so anytime there's an article on iron, I love to see what they're saying. So lead author Ludwig Svensson, and this was a quadruple blind study. And notably, the medications are given by the parents. So the parents are blinded, the researchers are blinded.

 

And it was done in Poland and Sweden between December, 2015 and May, 2020 with follow -up through May, 2023. So what they were looking at is basically in this cohort of healthy singleton term infants born between 37 to 42 weeks gestation. They had to have a birth weight greater than 2 ,500 grams and who were exclusively or predominantly breastfed greater than 50 % of daily feedings and did not have anemia.

 

at age four months when the study was really initiated. So anemia meant less than 10 .5 grams per deciliter of hemoglobin. They did exclude major illness, congenital anomaly, food allergy, or difficulty communicating with caregivers. So basically what they did is they had two arms. Infants in the iron supplementation group received single daily dose

 

sachets with hat, which had iron and malted maltodextrin. So you either were in the cohort that got iron with the mix with the maltodextrin or the sachets, just had maltodextrin in the control group. So the sachets were identical. The mixing instructions were identical and they were supposed to use whatever medication they got in 10 mls of lukewarm water.

 

or breast milk to feed. And so basically what they did is they gave the medication from four to nine months and then they were looking at follow -up. So what were the outcome measures? They looked at the Bailey at 12 months was the primary outcome. Secondary outcomes were motor development at 24 and 36 months. The cognitive and language scores at 12, 24 and 36 months. And then they wanted to look at the rates of iron deficiency.

 

Ben Courchia MD (16:46)

Mm -hmm.

 

Daphna Barbeau (17:12)

and iron deficiency anemia at 12 months. So they had 221 participants. 111 were randomized to receive iron, 110 to receive the placebo. And the baseline characteristics were actually pretty similar and compliance to intervention was 66 % for whole population, which actually I think is better than most. I remember having to give the iron drops and we did not have a 66%.

 

science. And in total, they had about 65 % of participants complete all three Bayley assessments. Okay. So the gist of the study is not as hopeful as I would have dreamed. There was no apparent effect of iron supplementation on cycle motor development assessed by the motor score of the Bayley 3 at 12 months, both in the unadjusted and the adjusted model. So they adjusted for sex, gestational age, maternal education.

 

And there was no difference between the groups for the cognitive scores or the language scores at 12 months. They also wanted to look at the effects of supplementation on development depending on the initial iron status. So they did a post -hoc analysis looking at the initial starting ferritins, which like splitting the groups to the ferritin below or above the median. And unfortunately, no significant findings there either.

 

Then on the other things, they found no statistically significant effect of iron supplementation on scores at 24 and 36 months. At age 12 months, iron deficiency was present in 6 % in the iron group and 13 % in the placebo group. The relative risk crossed once, not statistically significant. One child in the iron group and one in the placebo group developed iron deficiency anemia.

 

And they did not detect a significant effect of the iron intervention compared to placebo on hemoglobin and serum ferritin levels at 12 months in either the intention to treat or the per protocol analysis. I was also interested in the adverse events. So they had this data for GI symptoms during the intervention period. This is something we're talking about in our unit, iron in the...

 

premature population, but they had this GI symptoms recorded for close to 70 % and most experienced no adverse events. However, in total, any diarrhea was reported in 30%, vomiting in 31 % and constipation in 22 % of infants. But there were no differences between the study groups.

 

They did have two serious adverse events occurring, a brain tumor and acute leukemia, unfortunately. And they were both in the iron supplementation group, but they were considered to not be related to the intervention. So I was hopeful that all this work giving iron supplementation in the exclusively breastfed infant would have some improvements in developmental outcomes, but that's not what this paper showed.

 

Ben Courchia MD (20:25)

Yeah, I mean, it's hard to say. They had incredible Bayley 3 scores. These were smart kids. Even the placebo group with scores consistently above 100 on the mean. So I think that's interesting. And then the rates of iron deficiency anemia were low.

 

Daphna Barbeau (20:36)

Yeah. Yeah.

 

Yeah.

 

Super love.

 

Ben Courchia MD (20:55)

So I mean, it's, I mean, yeah, they have to tell us.

 

Daphna Barbeau (20:59)

Yeah, I was most interested in this kind of post hoc analysis about, okay, maybe it's the kids who are iron deficient that will have an improvement, but that didn't turn out to be true either. Yeah. Your turn.

 

Ben Courchia MD (21:11)

No, that's what was interesting.

 

Okay. I'm going to take us to a big paper that came out in JAMA Network Open called the two -year outcomes of umbilical cord milking in non -vigorous infant, a secondary analysis of the MINV randomized clinical trial. First author is Anup Katheria, which we had on the podcast. Go listen to his interview. He's a very bright guy. Basically, optimal umbilical cord management in non -vigorous infants who may need resuscitation after birth is something that had not been very clear.

 

Daphna Barbeau (21:23)

Mm -hmm.

 

Ben Courchia MD (21:44)

This group performed this trial called the MINV trial, the milking in non -vigorous infant trial, which basically was a large randomized clinical trial of non -vigorous infant at near term and full term, comparing the umbilical cord milking to early cord clamping. So either you milk or you cut. And this included almost 2000 kids. Now in that study, after a brief assessment of the baby's color, tone, and breathing for about, I would say 15 seconds,

 

Infants who were deemed to be non -vigorous received umbilical cord milking, which is milking of 20 centimeter of cord over two seconds, a total of four times, or they were randomized to early cord clamping, which is clamp within 60 seconds of birth, which for many, clamping within 60 seconds might be considered delayed cord clamping. You can take your issues about that with the original paper, which is not what we're here for. The primary outcome was admission to the NICU.

 

And what it showed is that it was not significantly different between the two groups. The secondary outcomes of delivery room, cardiorespiratory support, HIE diagnoses and therapeutic hypothermia were however lower in the randomized groups to the milking strategy. Umbilical Cord milking is believed to enhance blood volume similarly to delayed

 

cord clamping, but has the advantage of allowing resuscitation to begin much sooner. So you can quickly do this milking and really get to work. I don't know if you remember, we reviewed the other aspect of this paper where they did this exact study, but on preemies. And this was one of these trials, the papers with the preliminary results were published in pediatrics. And this was one where in babies that were, I think, less than 28 weeks, there was higher rates of IVH, and so they had to stop.

 

really making the case for a milk accord milking being something that's appropriate for more mature infants, but not so much for micro-premies. So I feel like a lot of stuff is being published, which is why I'm mentioning this, because you could be like, wait, which paper was that? So the MENVI trial that we're talking about, which really talks about near -term or full -term infants, is a paper that, if I remember correctly, was published in an OB journal. It was not even in...

 

Daphna Barbeau (23:56)

That's right.

 

Ben Courchia MD (24:11)

We talk about this at many of our talks, Daphne and I, where you can be following all the right papers and yet these will escape you. It was in the American, let me see, it was published in the American Journal of Obstetrics and Gynecology. So if you are not an avid reader of the American Journal of Obstetrics and Gynecology, you may have missed this paper. All right, so the study design is that this is a pre -planned secondary analysis of the MINVI trial done between 2021, 2023.

 

And the objective was really to evaluate the rates of abnormal development on the ASQ, the ages and stages questionnaire, and the rates of medium to high risk scores on the MCHAT, the Modified Checklist for Autism in Toddlers with the revised follow -up, the MCHAT -RF at two years of age. And really try to compare these two outcomes between the two groups. As we said, this is an inclusion criteria that are these eligible infants in the non -vigorous group of babies born at

 

term slash near term. Exclusions are usually are typical stuff, major congenital anomalies, monochorionic multiples, chord abnormalities, et cetera, et cetera. I'm not going to go too much more into the methods I think we understand. The results are that at the age of two years, 81 % of the infants had an ASQ3 scores completed or had passed away before that could be achieved. Among the

 

1 ,730 non -vigorous newborns enrolled in the primary trial. 1 ,206 were discharged alive and the parents provided consent for long -term follow -up. Four infants died in the hospital and three infants died after discharge. So of the 1 ,730 newborns enrolled, the 971 infants included in the analysis were more likely to have been born by C -section.

 

they were more likely to have older mothers and had a higher maternal educational level compared with the 759 infants who were not evaluated for neurodevelopment. Again, typical issues of follow -up studies where the attrition rate is not just the problem of how many you're losing, but who are the ones you are losing in the analysis. So in terms of the median ages and stages questionnaire three, the total scores

 

in any of the five subdomains and the medium to high risk MCHAT scores were all similar between the treatment groups. So really no differences across the five subdomains. Four to 11 % of the children were identified to have severe delay with no significant difference between the treatment group. And overall, 78 % of the milking group compared to 83 % of the early clamping group had normal scores in each of the five developmental subdomain. Again,

 

It's not something that's statistically significant. The sex interaction was conducted but did not change the primary outcome. And so the conclusion of this analysis is that in non -vigorous infants born between 35 and 42 weeks, the parental assessment of neurodevelopmental outcomes at two years were not different when we're comparing the babies who underwent cord milking versus the ones that had early cord clamping within 60 seconds.

 

Considering the important previously reported short -term benefits of early chord milking to enhance placental transfusion, this study adds further support to the safe facile zero -cost intervention as a preferable practice compared with early chord clamping. So, very cool stuff.

 

Daphna Barbeau (27:47)

Yeah, I love it. I mean, I think what I think is most, I mean, the work itself is very, very valuable, right? What are we supposed to do with this cord? But I think what's just so fascinating, and I hope it opens up the discussion for lots of other things that we do in the NICU, is that like, we cannot treat every baby the same, right? And I think that's what the more and more data is, vigorous, non -vigorous term, preterm. So.

 

Ben Courchia MD (28:07)

Mm.

 

Daphna Barbeau (28:15)

I think it's super cool. I think it's a discussion we have to have for basically every intervention that we do.

 

Ben Courchia MD (28:22)

Very cool. We're going to take a short break and then when we come back, we're going to have a special segment with Dr. James Sotiropoulos, who is the first author of this JAMA PEDS article. And so we had this rare opportunity to actually review the paper with the first author. So we took that on.

 

This is a paper that's called Initial Oxygen Concentration for the Resuscitation of Infants Born at Less Than 32 Weeks of Gestation, a Systematic Review, an Individual Participant Data Network Mid -Analysis. It's a very important paper that maybe makes the case that we should use higher oxygen, a fraction of oxygen during resuscitation of preemies. And it's a paper that has all the big names on it, which I think

 

is why it carries so much weight. Ola Saugstad, who we recently interviewed in episode two or three of the podcast, is one of the authors. So we're very excited to bring to you this special segment. So we'll take a short break and come back with James in a few seconds.

 

Daphna Barbeau (00:02.606)

So we've got the pleasure of having a special article review today, hot off the presses. I have with me James Sotiropoulos, a junior doctor and PhD candidate at the University of Sydney. And we're talking about the long title, the NETWORK Meta Analysis of Trials of Initial Oxygen in Preterm Newborns, NETMOTION. This is a systematic review and individual participant data network.

 

Meta analysis. James, welcome.

 

James Sotiropoulos (00:34.883)

Thanks for having me and yes, the title is definitely a bit of a tongue twister.

 

Daphna Barbeau (00:38.67)

Well, I think you got to say everything you wanted to say there in there, so that's good. Well, tell us a little bit about Netmotion and what were your goals with the paper.

 

James Sotiropoulos (00:41.091)

Yeah.

 

James Sotiropoulos (00:50.723)

Yeah, so the aim of Netmotion was to really drill down into the question of what initial oxygen concentration we should be using for preterm infant resuscitation. Lots is known about this question in term infants, but much less is known in preterm infants. So we focused on randomized controlled trials in the population of preterm infants less than 32 weeks gestation. And we systematically searched for all of those studies and used individual participant data network meta -analysis.

 

to look more into this question. Now, for those that aren't aware, individual participant data meta -analysis refers to going back to the original trial authors and collating the raw line -by -line data. And we did this as it offers certain advantages, particularly for gathering unpublished evidence, reducing problems with outcome harmonization, and et cetera.

 

With network meta -analysis, this is an emerging methodology where multiple different interventions can be compared and ranked simultaneously. So we did this by breaking oxygen into low oxygen, less than 30%, intermediate oxygen around 60%, and high oxygen, which was 90 to 100%. So we found 11 eligible RCTs, which had 1 ,055 participants.

 

And we actually found that using high initial FIO2, so 90 % or greater, conferred a mortality benefit compared to low initial FIO2. And the odds ratio attached to that was about, was 0 .45. Now, the certainty of evidence had to be downgraded for a number of reasons that I'm sure we'll discuss later, but the certainty of evidence with that finding was low certainty. So we concluded that high initial FIO2 possibly confers a mortality benefit.

 

compared to low initial FiO2.

 

Daphna Barbeau (02:47.182)

Okay, and will you tell us a little bit more about those parameters, high, low, what exactly were you looking at?

 

James Sotiropoulos (02:53.859)

Yeah, so previous systematic reviews and meta -analyses and trials have kind of clumped, always looked at just high versus low. And the low has usually been the room air to 30 % oxygen group, and the high has usually been 50 % or greater. So we tried to look at whether there was a difference essentially between that intermediate group, the 50 to 65%, and the much higher groups, and so 90 to 100%.

 

Because when we're thinking about oxygen, it is really a spectrum between room air and 100%. And we've previously just categorized it into less than 50 or greater than 50. So with the network matter analysis, we tried to break it up into a few more groups.

 

Daphna Barbeau (03:36.014)

I love that. I think that's been the question all along. We knew that potentially preterm infants might need more, but we didn't know how much more. Can you tell us a little bit, maybe more of the specifics then about your results and findings?

 

James Sotiropoulos (03:46.147)

Yes.

 

James Sotiropoulos (03:53.571)

Yeah, so for the comparison, so the primary outcome was all cause mortality to hospital discharge. And the main finding was that resuscitation with high initial FIO2 significantly reduced mortality compared to low initial FIO2. So the odds ratio was 0 .45 and the credibility interval of the 95 % credibility interval around that was 0 .23 to 0 .86. There was...

 

For the primary outcome as well, we had a very low certainty finding that intermediate FIO2 was inferior to high initial FIO2 as well, but the credibility intervals of that were very marginal going up to 0 .99. So we interpret that finding with a lot of caution.

 

For the secondary outcomes, which included morbidities of prematurity and oxygen saturation, we had inconclusive effects and the certainty of evidence was very low or low for all of those outcomes.

 

Daphna Barbeau (04:54.478)

Okay. And I am interested in some of your other findings, which I think goes along with another recent paper that you had, the air oxygen for infant resuscitation. And really about, we have these markers for when we anticipate babies to meet certain target saturations, but they're not always doing it. So maybe you can tell us a little bit about that.

 

James Sotiropoulos (05:07.395)

yes.

 

James Sotiropoulos (05:22.595)

Yeah, so we knew from a previous collation of this IPD that very few of these pre -term infants, particularly those less than 32 weeks gestation, hit that 80 to 85 percent at five minutes, SpO2 that's recommended in some guidelines such as NRP, which I think is used in North America. It's slightly different. It's got a different name in Australia.

 

And we found in this study that unsurprisingly, most of them undershot it, so less than 80, and a few of them overshot it, so more than 85, and very few were in that target of 80 to 85%. And I think that starts getting into the question of, well, we don't know where to start, but we also don't know how to adjust the oxygen over the first couple of minutes and even beyond there to reach these oxygen saturation targets. So I guess that's one question.

 

The other question is, what do the oxygen saturation targets mean? There's some evidence that not reaching 80, 85 % is bad, but we're not really sure. So we're titrating based off evidence mainly in term infants rather than preterm infants.

 

Daphna Barbeau (06:29.358)

Perfect, perfect. And I'm sure people are listening, are thinking, okay, now you guys are telling me high initial FIO2 had this significantly reduced mortality compared to the low oxygen group. And again, that high oxygen is greater than 90 % or 0 .9. And...

 

James Sotiropoulos (06:41.219)

Hmm.

 

James Sotiropoulos (06:50.147)

Yeah.

 

Daphna Barbeau (06:53.166)

People are saying, well, I'm remembering the ILCOR guidelines. And here, like you said, the NRP guidelines are saying we should resuscitate with 21%. That's for term infants. That's not the group you were studying. You're studying these preterm infants where the guidelines say we should probably start with 30. But truthfully, we didn't get a lot of information after that. So how do you think this falls into those guidelines?

 

James Sotiropoulos (07:18.947)

So I think this evidence is a step in the right direction to getting a conclusive answer, but unfortunately, it isn't the conclusive answer that everyone's hoping for. The certainty of evidence being low really limits our ability to comment what we should do in practice. So the answer is that we still don't know. I think what this study really adds is that potentially we should be less scared of using a little bit of high initial oxygen in this population. But...

 

The caveat to that is that titration is really key to reduce the oxygen load. So although that we found high initial FiO2 is beneficial, in the supplement there's quite a nice graph that shows that by about four or five minutes, most of the infants were getting around 40%, regardless of what group they started in. So titration is going to be really key moving forward as well. So I think we need some evidence for that.

 

So I guess just to summarize and come back to the main point of the question, the answer is that we, I guess we still really don't know in this population, but perhaps using high, we should have more confidence going back to high oxygen as an option to, to reinvestigate and do some more good trials on.

 

Daphna Barbeau (08:31.758)

and in the preterm population specifically.

 

James Sotiropoulos (08:33.251)

in the preterm population and specifically that less than 32 weeks.

 

Daphna Barbeau (08:37.902)

Okay. And so I agree with you. We're hammering down to the right answer. So what do you think are the next steps as left to be done?

 

James Sotiropoulos (08:50.019)

Yeah, so there's a couple of ongoing studies that are really important. So there's the HILO trial run by Prof. Mulzar in North America and the Torpedo 3060 trial run by Prof. Uy in Australia and some other international sites. So we're planning to synthesize those in a prospective meta -analysis. So that's one similar to the NEOPROM meta -analysis that some people might be aware of where the results of the, where the eligible studies are identified before the results are known.

 

and that confers a number of benefits. So we'll take those two studies plus some other smaller ones happening in America and India, and we'll bring those all together prospectively with IPD as well and try to update these results to get a better answer. So that might give us a clearer picture. But one knowledge gap that still remains, no ongoing study is investigating this intermediate, so the 60 % group versus the high, so the 90 to 100 % group.

 

So although we had that potential marginal effect that high was better than intermediate, it was very low certainty evidence. So we do really need some good trials to compare perhaps 60 versus 100 % initial FIO2 in the less than 32 weeks population. That will also enable us to have better strength in the network meta -analysis if we were to update it, as then we'd have direct evidence compared with all the different comparisons at once.

 

I guess, apart from initial oxygen, as I alluded to before, titration is going to be key as well. And I think there's a study being planned in the early phases of being started up at UT Southwestern by Vishal Kapadia, called OptiSTART. And that will look at the outcomes associated with different titration strategies. So that will be important as well.

 

Daphna Barbeau (10:36.014)

And so this question has been ongoing for really decades, right? People have dedicated their entire careers to studying what is the right oxygen use for resuscitation. Why do you think it's so hard to study?

 

James Sotiropoulos (10:51.203)

I think that's a really good question. And I think perhaps we've been trying to, in the past, group large groups of infants together when it's not necessarily possible. And I think this starts getting to the point of individualized and personalized medicine. We have to really carefully look at the infant that we're treating in front of us and try to picture their whole situation when prescribing the right amount of oxygen, as well as other interventions.

 

We started trying to look at that with some of the subgroup analysis we did, but we were limited in that. But hopefully in future updates, we'll start being able to see more into that. But I think that's probably one big reason why it's so hard to study is that different infants with different characteristics need different treatment.

 

Daphna Barbeau (11:40.11)

I love that. I think that's a great take home message. And I love that you've talked a lot about the missing link of what to do once the baby gets where we want them to be in this titration of oxygen. So tell me a little bit, you know, we feel the struggle in the delivery room. We don't know how fast to titrate, where we're, what is our target? So what are your long -term goals around that?

 

James Sotiropoulos (12:07.907)

Yeah, so I think once we've got some more trials, we'll be able to look at it a bit more specifically. We attempted to, in this study, break it into fast and slow titration, so adjusting more than I think we arbitrarily set it at 0 .1 of FiO2 per 30 seconds or so. But the studies just did it so heterogeneously that we weren't able to do anything meaningful.

 

So I think in future, if we could look at different titration strategies as an intervention in themselves, that would be really important. The other thing that I think is slowly creeping its way into the delivery room is automated oxygen control, which is becoming much more popular in the NICU environment. And there are some early studies, I think there's a group in Hobart Australia that's looking into it as well as others internationally in Europe that are trying to apply that technology to the delivery room.

 

And I think just from an ergonomic perspective, removing that cognitive load of having to adjust the oxygen and letting the computer do it for you, although that might have its limitations, is a good avenue to pursue, I think. So it'll be interesting to see what evidence comes out around automatic oxygen control in the delivery room in the next few years as well.

 

Daphna Barbeau (13:22.414)

Okay, and probably my last question for you today is how did you get interested? You're early in your career. How did you get interested in resuscitation work?

 

James Sotiropoulos (13:29.443)

Yeah.

 

James Sotiropoulos (13:33.667)

Yeah, so this whole journey for me started as a medical student. My university, University of New South Wales, where I did my medical studies makes us do an honours research year. So I did that with Prof Uyi at the Royal Hospital for Women in Sydney.

 

And that study you mentioned before, the air oxygen cohort study for the moderate to late preterm infants got me on this track. And I then got in touch with Lena Seidler's group at the University of Sydney who've worked on projects like NeoProm and the ICONF meta analysis that was published in the Lancet last year. And this project kind of was born out of that collaboration between Prof Uyi and that group there.

 

And I've just kind of luckily fallen into a series of these opportunities and it's led me down this path.

 

Daphna Barbeau (14:23.406)

Well, I appreciate you joining us today. I hope people learned a little bit. I think you are a rising star here. You're quite prolific in your early career. So I hope people will take notice. Some of the other articles I really appreciated reading your review, The Quest for Optimum Oxygenation During Newborn Delivery Room Resuscitation. Is it the baby or is it us?

 

So I think we'll be seeing a lot more from you and we're looking forward to reviewing more of your papers on the podcast.

 

James Sotiropoulos (14:56.387)

Hope so. Thanks so much for having me. It's been a pleasure.

 

 

Ben Courchia MD (44:11)

okay. Thank you, Daphna, for interviewing James and going over this paper with us. This was super interesting and reassures me that I always wanted to do this and start up with high FIO2 and titrate down instead of the opposite. So I feel vindicated.

 

Daphna Barbeau (44:28)

you

 

Ben Courchia MD (44:30)

Okay, the next paper is a paper that I wanted to review. It's not really medical, but it is related to medical education and it's called Should Neonatal Perinatal Medicine Fellowship Move to Two Years?

 

Daphna Barbeau (44:42)

This is where you had to put one of those sound effects in. Yeah.

 

Ben Courchia MD (44:46)

First author is Shetal Shah. It's in the Journal of Perinatology and it's a very cool paper. It's basically a discussion about whether we should keep NICU fellowship as a three -year program or move to a two -year program. And the paper is organized with various questions and then you have pros and cons being defended, almost like it's a trial, almost like the fellowship, yeah, almost like a debate.

 

Daphna Barbeau (44:52)

Yeah.

 

A debate. A debate.

 

Ben Courchia MD (45:14)

And Dr. Satyan Lakshminrusimha is on the paper as well. And our very own Betsy Crouch is also one of the authors. She is one of the hosts of At the Bench on the Incubator podcast. So kudos to Betsy for being involved in this paper. And so I'm going to try to go over it and we'll see what we think, Daphna. Okay. So it has some general overview of fellowship duration and there's a lot of interesting

 

Daphna Barbeau (45:23)

Mm -hmm.

 

Ben Courchia MD (45:44)

arguments being made about, well, how long should a fellowship be? And we're comparing that with adult subspecialties. And then there are arguments being made about how much money is earned by people in the field of pediatrics compared to adult specialties. And the arguments are starting really to burgeon at that point about, can we even compare ourselves to adult specialties saying, hey, they do three years, we should do three years or the opposite, when really the pay scale is very, very different.

 

after we finish these fellowships. And I think this is an argument that Satyan has made many times where for many of the prospective trainees, there is concerns about, hey, is this financially valuable for me considering the amount of debt that I have to carry to pursue these relatively long fellowships? So I think that really sets the stage for a lot of the discussion that's happening. So I'm just going to go over some of the questions that are being brought up. Obviously, it's a long paper that

 

very entertaining read. This is the kind of paper you print on Friday and you read over the weekend. It's actually fun to read. But the first argument that is being discussed is one about clinically focused careers versus scholarly activity requirement. And so in favor of the two -year fellowship, they're saying that most neonatologists do not really pursue research careers, right? That a lot of people are just doing clinical work, making the current research requirements irrelevant in their career paths.

 

and that clinical care and quality improvement really are probably more essential for that specific targeted population. And so considering that, maybe we don't need that additional year where we can do a lot of research work. Now, the counter to that is that eliminating scholarly activity really undermines critical thinking skills that everyone, no matter where you're practicing, needs for analyzing research and really to analyze the research and move forward with developments in the field.

 

And so the three -year model does provide time for in -depth research and really advanced training. So I think that's kind of an interesting argument. There's also a question being brought up about how do we support the neonatology workforce and saying that really are we seeing a dwindling down of our ranks and that maybe we need more people and we need to be able to support the workforce? The argument for a two -year fellowship is that shorter training can help maintain a robust workforce, especially given

 

an aging population of current neonatologists and the expanding duties within an IQ. I have my notes here, but I believe that at some point in the paper, they mentioned that we have the oldest workforce in pediatric subspecialties. And I think I did not realize that. The ABP report

 

Daphna Barbeau (48:33)

Which is kind of baffling if you think about it.

 

Ben Courchia MD (48:35)

The ABP reports, and I'm quoting from the paper, that about 45 % of board -certified neonatology workforce is over the age of 60, with an average age of 51, the oldest of all subspecialties. Dang, I did not realize that. There's nothing.

 

Daphna Barbeau (48:50)

me that generation really loves what they do, right? They've seen neonatology come so far. I also think it means, and that's what you're going to go into today, some young people are like, is it worth it? The nights, the weekends, the stress, is it worth it? I don't know.

 

Ben Courchia MD (49:05)

Right. Now the argument against that is saying that the current training model has remained stable over the years and that reducing fellowship duration is not necessary to support the pipeline and that the recent decreases in NICU exposure during residency training may actually require us to do more clinical time in fellowship. As we are really limiting the amount of exposure to procedures and intensive care rotations in pediatric residency, maybe that's something that would reinforce a three -year fellowship.

 

Another argument that is being brought up is the economic implications of shortening fellowships. And so people are saying that it may be better to go to a two -year fellowship because shorter training can alleviate the financial burden of educational debt by allowing earlier entry into attending level positions. And that financial supports like the NIH pediatric loan repayment program can still facilitate research opportunities. So you would be incentivized to remain in academia because you would be able to have some help.

 

with loan repayment. The argument against that is that neonatology is already one of the highest paid pediatric subspecialties and that shortening training does not substantially impact educational debt and may not attract more trainees. I don't know if I don't disagree with that, but it would have. One year of attending salary is always nice when it comes to these 6%, 7 % interest rate loans that we all have to carry year over year. In terms of

 

And so by the way, in each of these arguments, you have the initials of the people making the for and counter arguments. So it's kind of nice. So you know who's, they're putting their names behind the arguments. They are not shying away from that. The shortening of fellowship and expertise. The argument for a shorter fellowship is that increasing the workforce through shorter training can help meet the demands of 24 seven in -house coverage models and prevent burnout among neonatologists by having

 

more people to work with. Now, however, the counter to that is that reducing residency exposure has already led to a first year fellows being much less prepared than we would like them to be. Shortening fellowships further may exacerbate this trend requiring longer clinical service commitments to achieve competence. In terms of research and research scholarship, many people are saying that a two year program with accelerated training models such as the accelerated

 

research pathway can reduce overall training duration without compromising research opportunities, and that we can redesign medical curricula to reduce financial burden. Saying something to the effect of could we even dissociate your clinical training from your research endeavors so that you could do this almost on an attending salary. The argument against that is that the current three -year model is essential for preserving the physician scientist workforce and that it provides unique opportunities for in -depth research, the amount of

 

quote unquote, protected time you have during fellowship is nothing you can make up anywhere else. And it is crucial for driving discoveries and maintaining an academic neonatology. I think that's interesting too, because they're saying if we're not doing this, how are we, what kind of quality of research are we going to have in the future? Really posing that question, which is a tough one to actually read about. And then finally, they talk about the health of the field.

 

saying that a shorter training can help address the decline in general pediatrician capable of attending deliveries and stabilizing critically ill infants, and that this is crucial for maintaining neonatal care in rural areas. They're mentioning how in rural areas, there's many instances where entire divisions and departments are closing down because they do not have the right staff to resuscitate critically ill newborns, and that maybe moving to a two -year fellowship would be beneficial. They mention...

 

maybe even a potential for creating like mini fellowship or rural track residencies of six to 12 months to create quote unquote neonatal pediatricians comfortable in covering deliveries in rural areas. I cannot go through my highlights right now, but they are talking about a specific example where a place closed their division because of lack of support. Now the argument is that

 

for the health of the field is mentioning increasing the number of neonatologists may threaten long -term compensation. So it's like if there's more of us, it's going to be less money to go around and create a surplus and reducing overall financial incentives and potentially undermining the quality of overall neonatal care. I think that's kind of a stretch. But the other thing too that was interesting is I forget where I wrote this down, but mentioning the mix of

 

male to female ratio in medicine and saying how neonatologist is really a specialty where in recent years, a lot of female physicians have entered the field and they're entering the field at a childbearing age and they might be interested in building a family. And so how do we accommodate this important part of our workforce and maybe moving to a two -year fellowship would provide more people in the pool to actually provide easier coverage models so that

 

so that we can address that. It's obviously a very interesting paper. The conclusions actually are significant. They are making a commitment, and they're saying that based on the pros and cons being presented, they're saying everything should remain three years. They're saying that there's not enough arguments to move to a two -year fellowship. Figure two is an interesting schematic representation of the arguments for and against with basically

 

the different things that we talked about. It's a very interesting paper. It does bring up at some point the idea of saying, can we just look at this from a pediatric neonatal thing where we could just maybe do a combined five years like some other specialties are doing where do we need a full six years? I would be inclined to doing that, but granted when I started fellowship, I had no idea I wanted to, when I started residency, I had no idea I wanted to do NICU. So yeah.

 

I'm curious to get your thoughts. I really don't know how I stand if I'm pro or against, but...

 

Daphna Barbeau (55:22)

I don't know. I don't know. The problem is in a perfect world, three years would easily be the right answer, right? But we don't live in a perfect world and this, we live in this, you know, we're not on an island where we have this so, you know, economic push, social push, family push, you know? So, so I don't know. I, I, I don't know. I don't think

 

Ben Courchia MD (55:44)

Thank you.

 

Daphna Barbeau (55:50)

the two years are going to be easier. I think if we did it in two years, I think those two years are going to be harder potentially. Yeah. And I mean, there are people like me who took a chief year, right? So we delayed our earning potential even more. And I don't regret that. I don't regret that. I learned a lot. So I don't know. My bank account is definitely a ripple. I've made a few decisions in my life.

 

Ben Courchia MD (55:57)

So hard. Yep.

 

Your banker might be regretful.

 

Daphna Barbeau (56:19)

that were regretful on the financial front. Yeah, no, I mean, you will never make that year up for me two years.

 

Ben Courchia MD (56:19)

Yeah.

 

I had like, I had a, Patrick Myers is also on this paper, Clara's song, like all the people that we're good friends with. I spoke for 45 minutes with Shadow over the phone about this, about this. And he was saying how he was, he was for the argument of staying for three years. I think he makes the argument obviously that like, we need to, we need to be well -trained. Like this is, this is a hard specialty and we're being shortchanged in residency as it is.

 

Daphna Barbeau (56:32)

Yeah.

 

Mm -hmm.

 

See ya.

 

Yeah, I think that's an interesting thought though. Like if you know, if you know what you want to do when you hit residency, could it be five years, right?

 

Ben Courchia MD (57:00)

I mean, we just had an email from a listener who's in high school who says that she's interested in neonatal medicine. I don't know how that's even like in high school, I was an idiot. I don't even know that all these things were possible. So kudos to her. But like you said, there are some people who know very early on, so maybe that's an option for them. Cheryl was also mentioning that Satyan was very much the pro argument for a two -year fellowship.

 

Daphna Barbeau (57:03)

That's right. She knows what she wants.

 

Yeah.

 

Ben Courchia MD (57:28)

And Satyan has made this point before, especially from an economic standpoint where the NICU quote unquote floats other departments because it generates so much money for these children's hospital that it really funds a lot of other specialty sometimes that are not as lucrative. And so his point is we need to, we need to be like, whatever happens in neonatology will have dramatic impact on these other specialties and we should not forget about that. And I think that's an interesting point. So

 

Daphna Barbeau (57:31)

Mm -hmm.

 

Mm -hmm.

 

Mm -hmm.

 

Ben Courchia MD (57:56)

This is in Journal of Perinatology. I think it's open access. And it's a good read. It's a good read. It has a little graph about the salaries of pediatric subspecialists compared to adult. It's depressing. It does feel like we're taking care of little adults because it's little pay, but...

 

Daphna Barbeau (58:14)

No, if it was little adults, we'd probably get paid more. That's right.

 

Ben Courchia MD (58:18)

Well, that's such a such an argument is that they're smaller. So the complexity should is higher. So the pay should be higher, but it does feel like we're taking care of a 50 % size adult. So our pay is 50 % of the adults pay.

 

Daphna Barbeau (58:31)

my gosh. But you're right about those interest rates. This is my thought, okay, for anybody who's going out there to advocate for a loan repayment, okay? I'm happy to pay back my loans, but they'll have to pay back so much interest, okay? That's all. I think they should just remove the interest is what they should do.

 

Ben Courchia MD (58:36)

Woo! My god.

 

When you talk to people in finance and you say, yeah, 6%, 8 % interest, they're like, what? They are shocked at how much money we spend in interest. So anyway, and I think many people don't know how to calculate interest rates. So you don't understand how you're... I mean, I'm saying...

 

Daphna Barbeau (58:58)

I know.

 

I know that all I've paid back is interest. That much I know.

 

Ben Courchia MD (59:14)

I'm saying this because my brother who recently graduated from grad school, I sat down with him and I'm like, here's how your monthly payments affect how much you end up paying at the end. And you see that like, if you take the attractive low monthly payment, the amount of money you paid for school at the end of all, it's double, triple sometimes. And it's like, boy, like, do you really want that? And so I think it's, use these online calculators and make the most of them.

 

Daphna Barbeau (59:20)

It works.

 

And I'm going to disclose on your behalf, people should listen to you because you have been very fruitful at paying back your loans, so. Aggressively.

 

Ben Courchia MD (59:46)

Yeah, I mean, I am not, yeah, I'm paid off, which is a big deal for my wife and I, but I'm going to give the credit to, I guess, you as well, because you introduced me to Jimmy Turner, who has great resources, and the White Coat Investor has, I mean, I read, that's the book I read as soon as I finished fellowship and followed it to a T and it worked. So yeah. Okay. What I wear, I guess.

 

Daphna Barbeau (59:58)

Mm.

 

Okay, is it my turn or is it your turn?

 

Ben Courchia MD (1:00:15)

I can always go, so you go.

 

Daphna Barbeau (1:00:17)

I'm going to go, okay, this is another short one. It's journal of perinatology, the longitudinal assessment of prenatal cannabis use on neonatal outcomes. Something else that's come up many times during this last service block. Lead author, Leah Habersham. So basically it was a retrospective cohort study. They were using data collected from the SIP, the stress and pregnancy longitudinal study.

 

they were looking to evaluate the association between cannabis use and several neonatal outcomes. So these were the neonatal outcomes they looked at. Fetal death, so spontaneous abortion, fetal demise in utero and stillbirth, low birth weight, preterm delivery, and NICU admission. They were also looking at a number of pregnancy outcomes. So basically the SIPP study was done in New York.

 

between 2009 and 2013. And I'll just get you to the results. They had 791 pregnant individuals meet the inclusion and exclusion criteria, and then definitely had documentation either for documenting their cannabis use. Either they used or they didn't. 104 had prenatal cannabis use, 687 did not.

 

The only substances reported to be used during pregnancy within this particular cohort were cannabis, nicotine, and alcohol. And there were some differences between the two groups. So I think those are important to look at right out the gate. The mean age for cannabis users was younger. So that group of cannabis, the group of cannabis exposure during pregnancy, the mean age was 25 .9 compared to non -users was 27 .9. This was significant.

 

Black participants were overrepresented among cannabis users, 37 .5, as compared to non -users, 22 .7. In contrast, Asian participants were underrepresented among cannabis users, 1 .9%, compared to non -users, 9%. Half of the participants identified as Hispanic with similar proportions between cannabis users and non -users. A significant majority of unmarried individuals, 85 .6%, reported cannabis use.

 

contrasting sharply, they said, with 14 .4 among those married, and this was significant. Cannabis users also reported a higher prevalence of nicotine use. So, unadjusted models did not show a significant elevation in risks tied to maternal cannabis use for factors such as low birth weight, NICU admission, or preterm birth.

 

But after adjustments were made for various risk factors in the model, there was a marked increase in risk for low birth weight and adjusted odds ratio of 1 .67. And there were also, they wanted to look at in the adjusted model risks associated with the preterm birth or NICU admission did not reach a level of significance. But they really found this striking data about fetal death.

 

So there was a seven -fold increase in the risk of fetal death linked to maternal cannabis use in the unadjusted model. And this risk persisted with significance to an adjusted odds ratio of 6 .31, even after counting for variables such as maternal nicotine use, marital status, age, and race. Interestingly, in this cohort, alcohol use showed no association with neonatal outcomes. So I thought it was interesting. We're having a discussion about...

 

cannabis all the time, but, and it's becoming more and more and more popular nationally, obviously. So I thought this was interesting.

 

Ben Courchia MD (1:04:10)

Absolutely. And I mean, I think most of the cannabis discussion has been about providing appropriate counseling to families. And so that data is always helpful because parents want data to say, hey, what are the risks? What are the numbers? And I think this is kind of good and it's presented in a way that's easy to understand. Yeah, absolutely. Okay. I have maybe two other papers that I quickly want to mention. The first one is an interesting paper coming out.

 

of China. It's called early antibiotic exposure and bronchopulmonary dysplasia in very preterm infants at low risk of early onset sepsis. First author is Wei Shi from the Chinese neonatal network. We are actively trying to make a Sunday episode happen where we interview a neonatologist from China, which is not easy. We would love to get a look at what their practice looks like, some of the things they deal with on a day -to -day basis. There's a lot of

 

paperwork and a lot of red tape, no pun intended, that we need to go through. But it's been something we're very excited about, so stay tuned for that. The Chinese Neonatal Network published this in JAMA Network Open, and it really wants to examine the association of duration and types of early life antibiotic exposure with the incidence of mortality or BPD in very preterm infants at low risk.

 

of early onset sepsis. They included babies that are less than 32 weeks or who had a weight less than 1500 grams. And they were categorized at low risk if they exhibited the following delivery via C -section, no rupture of membrane at a time of delivery, absence of any clinical features of chorio from the obstetric history. They excluded infants with congenital anomalies, those on inotropes, those who passed away discharged within seven days after birth.

 

the infants with culture proven sepsis, urea, plasma infection, next SIP, all within the first seven days. The exposure was really defined as the administration of antibiotics within the first seven days. The duration of exposure was looked at for the duration. It didn't matter if it was consecutive, not consecutive, they just added everything up. And they looked at whether you were given broad spectrum or narrow spectrum. Broad spectrum was really extended spectrum penicillin with beta -lactamase inhibitors, third generation cephalosporins.

 

fourth generation cephalosporins, carbapenems, linezolid, and vancomycin. Narrow spectrum was basically all other antibiotics except antifungal drugs and these with unknown classification. The primary outcome was a composite outcome of moderate to severe BPD or mortality at 36 weeks. They used the 2001 BPD definition and they had a long list of secondary outcomes. They had basically 6 ,510 infants. 24 % were categorized as low risk.

 

The 20 % received no antibiotics, 17 % were treated for antibiotics between one to four days, and 62 % received antibiotics between five and seven days. The baseline characteristics were not similar between the two groups, the prolonged antibiotic treatment group, the ones who received it for five to seven days, really included neonates with lower gestational age, lower birth weight, decreased incidence of small for gestational age status, and lower ABGAR scores.

 

These infants were more likely to require intubation at birth, mechanical ventilation during the first week of life, needing surfactant, nitric oxide, as well as medical treatment for PDA. Moreover, the mothers of these infants tended to be older, less likely to have received antenatal steroids or magnesium sulfate prior to delivery. So take that into account as we analyze this results for the primary outcome after adjusting for these infant demographic characteristics, because obviously the raw data probably will not be very helpful.

 

Within seven days of life, the prolonged antibiotic exposure group, five to seven days of antibiotics, showed a significantly higher risk of moderate to severe BPD or death compared with those who either did not receive antibiotics or who had short -term exposure. The association remained significant even after incorporating additional confounding variables in a second adjusted model when comparing early exposure to none and comparing the early exposure of five to seven days.

 

to the ones for one to four days. In the kids who survived to 36 weeks, prolonged antibiotic exposure was consistently associated with a high risk of moderate to severe BPD in all the different models that they used. An analysis of antibiotic exposure as a continuous variables revealed that each additional day of antibiotic use within the first week of life was associated with a 10 % increase odds of the primary composite outcome.

 

Compared with infants without early antibiotic exposures, the babies who received a broad spectrum for one to seven days had an increased risk of moderate to severe BPD or death at 36 weeks. And so in terms of conclusions, the findings highlight a concerning overuse of early antibiotic among very preterm infants at low risk of early onset sepsis in China. I think this probably is something that can be applicable, I feel, to a lot of other units around the world.

 

Prolonged treatment with broad spectrum antibiotics in these inferences associated with a high risk of developing moderate to severe VPD or mortality. And it underscores, they're saying that the findings underscored the importance of cautious antibiotic use, especially in the early stages of life for this vulnerable population. So an interesting paper, yeah, an interesting paper from a country that we rarely represent. So happy to review that.

 

Daphna Barbeau (1:09:44)

Mm -hmm.

 

Ben Courchia MD (1:09:45)

I have, we're very much behind schedule. So.

 

Daphna Barbeau (1:09:50)

And I had two more papers, but I just don't know if we're going to get to them.

 

Ben Courchia MD (1:09:54)

So I wanted to mention one more that's published in the archives of disease and childhood that looks basically at the association between BPD severity and its risk factors for long -term outcomes in three definition, a historical cohort. And it's basically a paper that looked at the three possible definitions of BPD, the 2001, 2018 NIH and then the 2019 Jensen definition. And they looked at the, and this was a single center historical cohort. So they looked at single center,

 

in the Emma Children's Hospital in Amsterdam University between 2009 and 2015. And what they did is that they looked at the composite outcome of neurodevelopmental impairment or late death and respiratory morbidity at two to five years. And it's a long paper, but it's showing some things that are quite interesting, which is that these definitions do not do a great job.

 

when you're looking at how they predict no developmental impairment or respiratory morbidity at either two years or five years. I think the conclusions are quite strongly worded. They're saying the historical cohort study with retrospective data collection shows that the 2001 NIH, 2018 NIH, and 2019 Jensen definition show similar but low accuracy of probability forecast for no developmental impairment and respiratory outcomes at two and five years.

 

the three BPD definitions, so similar association with perinatal characteristic and respiratory interventions. And they're basically saying they're all equally bad. I don't know if I would go this far, but table two is an interesting table where you can actually look at the odds ratio for the different grades of different BPD. So you can see what you want to see basically is that for these outcomes, you expect the odds ratio to progressively increase as the severity of BPD does go up.

 

And for some, it doesn't work. So if you're looking at the neurodevelopmental impairment for the 2018 NIH definition and you're looking at NDI, the odds ratio is 1 .51 for grade one, 1 .61 for grade two, 3 .94 for grade three. And this incremental increase is not something you see consistently throughout, especially when you're looking way down the road. So we take the same definition in 2018 and now we look at five years.

 

The odds ratio is now 1 .71 for grade one, 1 .87 for grade two, and 2 .78 for grade three. And so there's this again, I'm using the wrong example. I realize this now. But in terms of how this works is that you have to look at the 95 % confidence interval basically. But they're not doing such a good job at discriminating between these patients based on their grades of BPD.

 

most of the papers that had been published tend to complement the 2019 Jensen definition, but even then, these confidence intervals are not so great in this particular paper, considering it's a retrospective study from a single center, but it's kind of a nice table and you can take a look at that. So that was one of the papers that was published in the archives that could be a good review.

 

And my final paper for today is a very quick paper in the Journal of Pediatrics called Phototherapy alters the plasma metabolite profiles in infant born preterm with hyperbilirubinemia. First author, Catherine Satram, basically looking at the effects of gestational age and phototherapy on the plasma metabolite profile of preterm infants with hyperbilirubinemia. I really like this paper. We give phototherapy to preemies and we have no clue what we're doing. So they looked prospectively enrolled infants born preterm. They looked at their plasma sample.

 

Whether they were very preterm, moderate to late preterm, and they collected these plasma sample before the initiation of phototherapy and 24 hours after starting phototherapy. The metabolic profiles were determined using ultra -performance liquid chromatography, tandem mass spectroscopy. What they found is not surprising. Phototherapy is initiated at much lower total serum bilirubin levels in very preterm infants. No surprise there. 664 metabolites were significant for a phototherapy effect.

 

191 metabolites significant for gestational age effect and 46 had this gestational age and phototherapy interaction. Longer duration of phototherapy had a larger mean effect size. The pathways affect top pathways affected by phototherapy include membrane lipid metabolism, one carbon metabolism, creatine biosynthesis and oligodendrocyte differentiation. I think it's a

 

article to show that phototherapy is not benign. We shrug it off and we say, one more day, a few more. And we really have no grounds as to what constitutes the appropriate initiation of this therapy for hyperbilirubinemia. And it does have some effects. So the authors conclude that phototherapy alters the plasma metabolite profile more than gestational age in preterm infants with neonatal hyperbilirubinemia affecting pathways related to lipid and one carbon metabolism, energy biosynthesis, and oligodendrocyte differentiation. Yeah. Yeah, I went fast. But I mean, these are, I'm not going to get to them next time.

 

Daphna Barbeau (1:15:10)

Yeah, it's important. Yeah. It takes you back to our biochemistry days. Those papers. Do we have time for me just to mention these two papers? Okay. I think if you are a new trainee, it's July. We didn't even welcome the new trainees who might be listening and joining us. Welcome. New trainees. But if you're new or you're teaching new trainees and you're like,

 

Ben Courchia MD (1:15:15)

Mm -hmm. Absolutely.

 

Absolutely.

 

Welcome, attorneys.

 

Daphna Barbeau (1:15:39)

You know, how do we teach this communication thing? I just gave a lecture on perinatal palliative care and just a little bit of the prenatal consult. And I just think this paper did such a nice job. It's in the Journal of Pediatrics, Antenatal Consultation Research and Practices through the Lens of Decision Science. Lead author is Marlise Howard. So basically, Hayward. They took its...

 

almost like a meta -analysis of three review papers on how parents and clinicians engage in decision -making during kind of prenatal consultation. And I would read the paper. It's one of those papers that's easy to read, but I think you'll learn a lot. And I think they highlight some major points, and then they talk about each one specifically. I'm just going to run through the major points.

 

This is exactly what I said in this lecture I gave, so I think it's beautiful. All parties to a decision must be proactively engaged. We forget that sometime. Our goals for a meeting are different than the family's goals for a meeting. Decisional preferences should be sought early, so we really have to understand family's values so that we can give them decision choices that are in line with those values. Emotions are an inevitable part of the process with both positive and negative effects. I think this is...

 

should be starred. We cannot forget to respond to emotions in the prenatal consultation. Clinicians face challenges, understanding parents' perspectives. Underline, underline, underline. We just come at a clinical case differently than the parent and family does. And I think it's just important for us to recognize those biases. Parents need facts critical to their decisions and they need to be delivered effectively. Yep, totally agree.

 

and how choices and information are presented matters. And they talk a little bit about a review about how we can present those choices in different ways. And decision support should continue after medical care concludes. This is something that as a community, we're not really good at because we don't tend to have a lot of opportunities to engage with our families after our medical care concludes. In particular, those

 

who may have made choices, say, for comfort care. So the baby has passed away. But that we should continue to support parents and families in their decisions even after the fact. So I thought that was very, this is very valuable. I hope people will take a look at it. I also wanted to highlight this paper, Enhancing NICU Care and Communication Perspectives of the Moderately Preterm Infant Parents. Lead author, Ashley Osborne.

 

and they basically did these semi -structured, qualitative interviews for, 16 birth parents, whose infants were born between 32 and 34 weeks gestation. And I think this is a particularly vulnerable population because they spent quite a bit of time in our NICU. And I'm just going to say my perspective. I think sometimes we tuck those babies in their relatively straightforward admissions and.

 

They're not the sickest patients in the units most of the time. And so sometimes the days and weeks can pass without a lot of engagement of these families. So I thought this was a particularly interesting group to study. And they really came across four themes, which I think are pertinent for all of our families. The first thing, medical team inclusion and connection. So parents overall felt well supported in the NICU, mostly because

 

of how the nurses supported them. But they still report mixed feelings about connectedness and inclusion with their care teams. They think, you know, parents of any NICU child, being a parent of a NICU child is really scary. I wish doctors would take more time and just sit with you. The second theme, confusion regarding NICU care. I wish I received more support when it came down to the medical aspects of it. This...

 

I still really don't know why he was admitted. So I think that's really important, you know? The third theme, discharge readiness. Parents felt prepared for discharge. They wanted to be discharged. However, time and time again, they reported wanting more lead time about the anticipated discharge date. Many of them spoke about, you know, I kept asking about the discharge date and then all of a sudden it was the next day. People said, your baby's going home tomorrow.

 

Ben Courchia MD (1:20:05)

god.

 

Daphna Barbeau (1:20:28)

So certainly we can do better at that. And then methods of communication. I think this is when we talk about AI and how it can help, I think it will not replace what we do at the bedside, but certainly there's a place I think for it. Parents currently use and desire a mix of in -person and electronic methods. So emails, texting, apps for routine information and communication. So they needed to talk with us at the bedside, but...

 

They liked having that written documentation that they could look up at a later time, maybe when they left the NICU or especially when they were discharged home from the NICU and couldn't remember all the things that they had been taught. So I hope people will take a look at those two papers. Thank you for letting me squeeze them in.

 

Ben Courchia MD (1:21:08)

Yeah, my, I want to credit my attending Dr. Daniel Rauch, who as residents told us that for every patient that's admitted, we had every day to explain to the families, here's why your patient, your baby or your family member is admitted. And here's why they'll remain admitted for now. Exactly. Because it's like, here are the problems we still need to solve before we can actually get to clearance for discharge. And then that goes a long way because parents understand it's like, Hey, until your baby feeds completely by mouth.

 

Daphna Barbeau (1:21:13)

Hmm.

 

Mm -hmm. Why they're still admitted. Yeah. Yeah.

 

Mm -hmm.

 

Ben Courchia MD (1:21:38)

we are going to stay in the NICU.

 

Daphna Barbeau (1:21:41)

And it's a good reminder for the team sometime. Why is this baby still here? What are we doing? Can we be moving forward on anything here? So cool.

 

Ben Courchia MD (1:21:46)

I know.

 

Absolutely.

 

All right. This was a great Journal Club. I think we went through nine papers. I had a hard time keeping up, but yeah, but we did it. It was definitely a loaded week. We're very excited about all these different papers. Thank you to everybody who is supporting us. Please, to the new fellows, feel free to reach out to the Incubator Podcast. We are very responsive and happy to help in any way we can.

 

Daphna Barbeau (1:21:58)

Yeah, keeping track. We did it.

 

Mm -hmm.

 

Maybe it's a good reminder we've got good for the board review for fellowship programs. We just had gotten a bunch of emails about that. Remind people. So if you are a fellowship program or you are a fellow in a fellowship program, if you want your fellowship to support the board review subscription, we have a discount for kind of multiple fellows in a program. So you can find that on our website. I don't know. You tell them where to find it.

 

Ben Courchia MD (1:22:29)

Yeah, please remind people then.

 

Yeah, so you can find all the information on our website. You actually on the incubator podcast website, which is the dash incubator dot org. There's a section called podcast in there. You will find the neonatology review podcast section. So you will get all the information you need there. Once you're there, there's a few tabs, there's how to listen and you have different ways to subscribe. We even have like a little explanatory video, but you can click.

 

Daphna Barbeau (1:23:05)

Mm -hmm.

 

Ben Courchia MD (1:23:18)

There's a little banner called Click to Subscribe and then you'll be directed step by step over there. And on that page, there's link to the Brodsky and Martin Review Books, which we're collaborating with for this particular series. There's access to some of the show notes and there's a way to contact us if you need any technical support. So.

 

Daphna Barbeau (1:23:38)

Yeah, and about midway through, there's that institution subscription, if anybody's interested in that.

 

Ben Courchia MD (1:23:43)

Yeah, so there's institution substitution, but when you click on that banner to click to subscribe, you should end up in a page with the three different formats and that should make it fairly straightforward. We've really worked so hard to make this easy for people because Apple and Spotify are not the best when it comes to helping us help our listeners, but we've made it work.

 

Daphna Barbeau (1:23:45)

Mm -hmm.

 

People can also reach our incubator shop there if they want to welcome new trainees, new fellows to the fellowship with NICU Swag. So that's another thing to look at if you're on the website.

 

Ben Courchia MD (1:24:08)

That's true.

 

That's right.

 

I think we've done everything we needed to do. Daphne, this was fun. I'll see you later this week. Have a good one. Bye.

 

Daphna Barbeau (1:24:20)

That's it, buddy.

 

Sounds good. Bye everyone.

 

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