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#120 - 📑 Journal Club 47

Hello Friends 👋

We hope you are having a nice weekend. A new episode of journal club is ready for you! This week we review a series of interesting papers, notably the effect of azithromycin to prevent maternal and neonatal sepsis/death, screening and management of hemodynamically significant PDA from the amazing folks at the University of Iowa, and much more. We hope you enjoy this episode. Happy Sunday!


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

Tita ATN, Carlo WA, McClure EM, Mwenechanya M, Chomba E, Hemingway-Foday JJ, Kavi A, Metgud MC, Goudar SS, Derman R, Lokangaka A, Tshefu A, Bauserman M, Bose C, Shivkumar P, Waikar M, Patel A, Hibberd PL, Nyongesa P, Esamai F, Ekhaguere OA, Bucher S, Jessani S, Tikmani SS, Saleem S, Goldenberg RL, Billah SM, Lennox R, Haque R, Petri W, Figueroa L, Mazariegos M, Krebs NF, Moore JL, Nolen TL, Koso-Thomas M; A-PLUS Trial Group.N Engl J Med. 2023 Mar 30;388(13):1161-1170. doi: 10.1056/NEJMoa2212111. Epub 2023 Feb 9.PMID: 36757318 Clinical Trial.

Beltempo M, Sargi E, Patel S, Lacroix G, Lapointe A, Taylor-Ducharme S, Morin S, Bizgu V, Piedboeuf B; Quebec investigators of the Canadian Neonatal Network.J Perinatol. 2023 Apr;43(4):490-495. doi: 10.1038/s41372-022-01596-y. Epub 2023 Jan 6.PMID: 36609482

Giesinger RE, Hobson AA, Bischoff AR, Klein JM, McNamara PJ.Semin Perinatol. 2023 Mar;47(2):151721. doi: 10.1016/j.semperi.2023.151721. Epub 2023 Mar 5.PMID: 36882362

El Rafei R, Maier RF, Jarreau PH, Norman M, Barros H, Van Reempts P, Van Heijst A, Pedersen P, Cuttini M, Johnson S, Costa R, Zemlin M, Draper ES, Zeitlin J; SHIPS Research Group.Arch Dis Child Fetal Neonatal Ed. 2023 Sep;108(5):492-498. doi: 10.1136/archdischild-2022-324988. Epub 2023 Mar 3.PMID: 36868809

Bahr TM, Christensen TR, Henry E, Astin M, Ilstrup SJ, Ohls RK, Christensen RD.J Pediatr. 2023 Jun;257:113388. doi: 10.1016/j.jpeds.2023.03.003. Epub 2023 Mar 16.


Find some of our notes here 👇

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

Ben 1:04

Hello, everybody, welcome back to the incubator podcast. It is Sunday. We are back with Journal Club. We share our Yeah. After what would some people say a well deserved break? Some others we would say a too short of a break.

Unknown Speaker 1:21

Yeah, flew by didn't it?

Ben 1:24

It did fly by? Definitely. What do we have for updates for our audience today?

Daphna 1:30

Oh, I something I wanted you to tell the audience. Obviously, they're listening to us. They found us already. But about the Patreon account for maybe people they know and who aren't able to access.

Ben 1:43

I need to Yeah, I need to give people so we have our second podcast aboard review podcast we is available on Apple podcast, Spotify, and to people who may be surprised when it comes to subscription podcasts on Apple or Spotify. These guys are terrible. Like they have. They have no portal for us to manage our subscribers like people are emailing us with questions about hey, I'm subscribed

Unknown Speaker 2:08

fairly good questions, right? Simple problem.

Ben 2:11

I turn around and I go to Apple or Spotify and I say hey, this person can I can I just fix their their subscription that like no, we can give you access, they have to do it on their end. And I'm like, that's not good customer service. So anyway, so that's number one. Then we have people from other countries who are saying we can't listen in our country. So then I turn around to Apple and I say why can people in Turkey listen. And they're like, oh, because they have to like change their settings on their computer to listen to, to things that are not suited for work. And I'm like, In what world is our Board reviewed podcast? There's no swearing, there's nothing. And then I go no, that's like our I was like, Okay, so in the end, we decided to just provide more more ways to subscribe. So we have now a ways you can subscribe to Patreon. The cool thing about the Patreon, which is what I'm excited about is that all the episodes are sort of tagged by specialty. So you can technically like say I just want the GI episodes and just room you can just like listen one after another. But there's also opportunities through a partner that that's called member for. And that's actually quite cool. Because you can subscribe for the month by month, you can subscribe for the year. But I've also had program directors who reached out to me and they said, hey, I want my fellows to listen to the podcast. But because it is a subscription, I can't really force them to because they have to pay. Can I just buy them the subscription? I asked apple and Spotify? They said no, nobody can. So now you can. So if you're a program director and you want to buy like three to four or five subscription for you fellows, you can you can even make that like six 710. Obviously, as you as you purchase either the yearly subscription or you purchase like the institutional there's like significant discounts, obviously. But yeah, and if you have an if it still doesn't, if it still doesn't meet your needs, let us know, we'll find a way to make it work. And as we've said, from the beginning of that podcast, the reason it's a subscription is because it's intellectual property from the neuro review books that we are basing this from Dr. Brodsky and Martin. And also there's a lot of costs associated with that pencast. However, if for any reason, the cost is prohibiting you from subscribing, you shoot us an email, and we will make it work for you. I hope everybody understand what that means.

Unknown Speaker 4:26

We will find a way.

Ben 4:28

Yeah. But now the ways are much easier. Yeah. So for example, some guy emailed me saying I can subscribe to initial subscribing. I'm not gonna go into the details. And so I was like, I'll give you the episodes I literally will send so I was saying to, I asked Apple, can I give this guy a free subscription? They're like, No, no. I'm like, they're like, No, I'm like, What the fuck? No. So I ended up doing it like on the Google Drive. I ended up putting like the episodes on the Google Drive which for the guy was imposters like it's it's very inconvenient for me to listen to an audio podcast on Google Drive. I'm like, Are you telling me But yeah, they were like, you can give him a free trial. I'm like, I don't want to give him a free trial. I want to, I want to give it to him. Anyway, it was just just fun. All right now that I've vented, we're, we're making some changes to our website. There is now a hub for all the different podcasts that we offer in different languages, which is kind of cool, because now we have we have a Spanish podcast, we have a Portuguese podcast, we have a French podcast, and our latest edition. Our latest edition is the podcast in Farsi from two physicians from Iran, I'm so proud of the fact that we're giving that our platform is able to give a voice to these physicians. This is phenomenal. Their first episode, like literally, like so many downloads, which was so cool. And then. So that's, that's actually quite exciting. We are finalizing the last edits on the videos from the Delphi conference. So if you didn't get a chance to attend, there will be an opportunity to watch those videos. And finally, we are working on the merch store. So look out for that on the website. It's not ready yet. But

Daphna 6:11

you know, it's funny, we had talked about a merch store and they were like, well, what are we really gonna do a merch store? But people keep asking us for merch. So we will. And if you if you've got a saying you want to see on your merch that's Nikki related, then you just send it to us.

Ben 6:28

Yeah, it's gonna be like, just like the you're not going to buy a t shirt with our faces on it. Let's

Speaker 1 6:36

I don't think so. We don't have that in the plans.

Ben 6:39

No, it's not in the plan. But it would be cool to have like, T shirts about like NICU related stuff. I remember, I won't steal this from my former residency program. But they had made coffee mugs with the words on it saying baby's fine. Because that's like you go to a delivery. And then when you come back, the CO fellows are like so and you're like baby's fine. That was very funny. Anyway, so that will be and then we're we can submit ideas, obviously. So that will be quite cool. All right. We've now spent six minutes should What

Daphna 7:13

do you think? What do you think if somebody submits an idea that we use? We'll give them a free? Yeah. A free merch?

Ben 7:22

Yeah, for sure.

Unknown Speaker 7:26

All right. That's a little incentive, I guess.

Ben 7:29

I mean, the goal is always the same. We build the platform, people use it. And then that's it. That's just Yeah. All right. Let's do journal club, you should I start or should you start? You start? You always start every time I keep asking. Okay, so I'm going to start with, I'm going to ease us into Journal Club today. This is a paper that I thought that was very interesting. So it's a paper published in the Journal of pain intelligence from the Canadian neonatal network. It is called Neonatal Intensive Care Unit occupancy rate, and probability of discharge of very preterm infants. first author is Dr. Bell tempo and colleagues. And again, like I said, it's the CNN, Canadian neonatal network. So the background is not very earth shattering, but it does, it does highlight a lot of the things that are important to understand before we delve into the paper, there's a lot of variability when you're looking at Interstate between NICUs and countries, and that variability has not really gone away. With with time now, there's many factors that contribute to the variation of NICU length of stay. And that could be the ability to transfer a baby to like a step down unit, the ability to provide adequate family teaching, we all know how time consuming it can be to make sure a family is properly ready to go home. And if you don't have the staff to give this teaching, adequate teaching, it can it can really jeopardize not only the discharge, but all the work you did during the admission. And obviously, organization of post discharge follow up. Now they're saying what about occupancy? Now they're talking about they're referencing a study done in the US of infants born between 30 and 34 weeks, that had highlighted the fact that maybe babies are discharged home, or more likely to be discharged home on days of hierarchy potency, suggesting that it may have a role. Now, what they're saying is, what about more premature infants? What about complex patients? That's the questions that they're trying to raise. So the paper really is asking what's the association between NICU occupancy and the probability of discharge and then they'll stay in either level three or level four NICUs in infants were born below 33 weeks of gestation. So this is a multicenter retrospective cohort study that include infants born between 23 weeks and 32 and six weeks, they're admitted to five level three slash for NICUs in the province of Quebec, between January 2014. And December 2018. The study included, as I said, Five NICUs. And this was for level fours and one, level three, which babies were included. Basically, let's start with the exclusion criteria, I think there'll be better. So they excluded infants that were either moribund on admission or admitted for palliative care. Babies who had major congenital anomalies died before NICU discharge, obviously, or who had like a missing discharge date in their in their record, the primary exposure was the unit occupancy before discharge of each patient. There's more obviously, to the study design, but you sort of get the idea. And let's get into the results, because the results are quite interesting. So there's a total of 3820 infants, about 4000 infants that were born between 23 and 32 weeks of gestation, that were admitted to these NICUs during the study period. Now, they applied all their exclusion criteria, and they were able to, they were removing that 500 babies, so they were left with 33,388 infants that were included in this study. Now, let's get to some of the key results among included infants. 37%, were born before 29 weeks. And 10% were considered small for gestational age, and 28%. Were part of the multiple jurisdictions. So that gives you a sense of the population that we're dealing with. So they were not. But yeah, but I think it's quite representative. To be honest, the median length of stay was 51 days, the median corrected gestational age at discharge was 37 weeks. That's something that made me chuckle. The median NICU occupancy prior to an infant discharge, which was done using the mean of the set of the seven shifts was 90%. And it sort of goes back to something we've talked about, which is, are we busy, because we're busy, or are we busy? Because we have beds? You know? That's a big question anyway. That's not what the paper is addressing the unit occupancy quintiles correlated with probability of discharge with the Spearman rank correlation coefficient of point six, nine. And when the unit occupancy was in the lowest quintiles, infants were respectively 12% and 11% less likely to be discharged than expected. I think that's interesting. When the unit occupancy was in the highest quintile IQ five infants were 20% more likely to be discharged. They did a subgroup analysis by gestational age, which showed similar results for infants born between 29 and 32 weeks. But the discharge for babies that were less than 29 weeks occurred within expected rates for all occupancy, quintile among these infants. So obviously, the smaller ones were less subjected to this pressure of the census.

Unknown Speaker 13:17

And that makes sense, right? In fact, that might be thank God,

Ben 13:20

thank God.

Daphna 13:22

Right? That might be a baby who stays longer because you're busy, right? Because you got you got too many things to organize for them, I don't know,

Ben 13:31

the pressure to make sure the discharge happens correctly, that is safely higher. A few more results in the subgroup of infants discharged to a another unit occupancy in the highest quintile was associated with a higher probability of discharge with comparable effect among infants discharged home now, they also looked at the nurse to patient ratio. And I was very happy to see that median nurse to patient ratio prior to discharge was about 1.03 discharges occurred within expected rates for all nurse patient ratio quintile suggesting no association between nurse patient ratio and probability of discharge. Thank God because obviously, you don't want that to be interesting now. Yeah, that's very interesting. And you don't want I mean, which I think also maybe reflect the I didn't know, I mean, it was I was happy to see this from the standpoint of not it being a factor, but it also reflects maybe the robust nature of the health care system in Canada where somehow that doesn't become an issue. Because yeah,

Daphna 14:40

or I mean, I think, you know, it was credit to our nursing colleagues, they just get it done one way or another.

Ben 14:48

But but the fact that the nurse patient ratio really was like, like the median nurse patient ratio was still like around one. I thought that was very interesting, because that was nice. Like, that's exactly right. That's what I'm saying. That's what I'm saying. During the robustness of the health care system in Canada, because I mean, it, it seems like shortage is not an issue. I mean, I don't know. This is like one piece of research anyway. Finally, multivariable analysis of all infants born less than 33 weeks showed that higher occupancy prior to discharge was associated with a 4.7 day reduction in length of stay compared to like the lowest quintile. So that was interesting that even on the multivariable, that's what they were able to see. Now, the graph will post on Twitter, it's kind of interesting because they have the different quintiles and you can see sort of how the length of stages start shifting as the quintile Go, go down. And the conclusion is that higher NICU occupancy was associated with higher probability of discharge from Level Three for NICUs, a very preterm infants born before 33 weeks gestation, suggesting that providers integrate organizational variables in their clinical decision making for discharge planning. This decision was mainly attributable to the subgroup of the 29 to 32 weeks, as we've mentioned, and obviously more research is required to identify strategies to harmonize discharge planning, and reduce length of stay. Right, now's a good way to ease us into Journal Club today.

Unknown Speaker 16:16

That's right. And what a lovely way to to harmonize anything that you would like that.

Daphna 16:24

All right, well, thank you, buddy. I have one that I didn't get to review last time. So I'm going to start with that one. And this is in the New England Journal of Medicine and entitled azithromycin to prevent sepsis or death and women planning a vaginal birth. Lead author. Let's see last name, Tita. And this is for the eight plus Trial Group. This is coming to us out of the University of Alabama, Birmingham. And so the question was

Ben 16:55

published in the New England Journal of Medicine. Yes. That's what I said first, did you say that? Oh, mister. I'm sorry.

Daphna 17:03

So, so big, a big article, right. And the reason it's an important article is because there has been studies done on azithromycin reducing maternal infection in in pregnancies for unplanned cesarean delivery, but it had not been well studied and planned vaginal delivery. So this question was does an intrapartum oral dose of azithromycin reduce maternal and or offspring sepsis or death? So an interesting question, we know that preterm labor is frequently associated with a typical colonization. So study design, it's a multi country double blind, placebo controlled, randomized trial. It was conducted in eight states, eight sites in seven low to middle income countries, using the global network for women and children's health, part of the NIC HD. So pregnant people were assigned, so in labor at 28 weeks gestation or more and who are planning a vaginal delivery to receive either a two gram oral dose to visit for Meissen or placebo. They used a one to one randomization schedule for zithromax and placebo, and it was stratified according to site using block randomization. So the inclusion criteria, pregnant people who had been admitted to health facilities for spontaneous or induced vaginal delivery were eligible and they included Singleton's and multiple gestations of at least 28 weeks with informed written consent, the exclusion criteria, so pregnancies with known infection warranting the use of antibiotics, arrhythmia, cardiomyopathy, allergy, Tirza, through myosin or other macrolide antibiotics, planned cesarean delivery, because obviously, they wanted to study the effects on vaginal delivery, advanced stages of labor, and any medical condition that was quote unquote, considered to be a contraindication by the site investigator. Oh, and I'll know advanced labor was defined as complete cervical dilation or dilation of more than six centimeters. So ready to basically the primary outcomes that they were looking at were a composite of maternal sepsis or death within six weeks after delivery, and a composite of stillbirth or needle neonatal death of sepsis within four weeks. Maternal sepsis was defined according to the WHO criteria. I won't review those. Now. neonatal sepsis was defined as a proven or possible serious bacterial infection on the basis of, again, the WHO criteria, but I'll mentioned severe chest drawing fever, hypothermia, no movement or movement only on stimulation, poor or no feeding, convulsions, pneumonia or meningitis. So they had a list of secondary outcomes as well. Secondary maternal outcomes were specific infections including chorioamnionitis. And then we trade as wound infections, abdominal or pelvic abscesses, mastitis and ammonia pyelonephritis. therapeutic use of antibiotics duration of hospital stay readmission admission to the special care unit, unscheduled health care visits, this neonatal outcomes that they looked at secondarily were, again components of the primary outcome other infections, duration of hospital stay readmission admission to a special care unit, unscheduled health care visits and safety outcomes. So we had about 44,000 Women who underwent screening and about 29,000 who underwent randomization so they had 14,590 women. This included 14,687 neonates or stillbirth to deliveries to the azithromycin group, and 14,688 women, which comprise 14,782 deliveries to the placebo group. Advanced labor and planned cesarean delivery were the most common reasons for exclusion and the characteristics of the two groups were pretty similar at baseline, the majority of patients were enrolled in Asia 55%. And at randomization, 18% had induced labor about 9% were quote unquote high risk for infection. The groups are also pretty well balanced with respect to labor and delivery characteristics frequencies of prophylactic on antibiotic use. And to Syrian delivery did vary according to site with interestingly, higher occurrences is not that it's just not that surprising, with higher occurrences at non African sites. So, for the primary outcome, maternal sepsis or death, occurred in 227 of the 14,526 patients so 1.6% in the azithromycin group, and occurred in 344 of 14,637 or 2.4%. In the placebo group. This is an adjust adjusted relative risk of point six seven so statistically significant maternal sepsis occurred in 1.5% in the azithromycin group 2.3% in the placebo group relative risk 2.65 deaths from sepsis occurred in less than point 1% of the women in each group. Now for the neonatal outcomes, stillbirth or neonatal death, or sepsis within four weeks after delivery occurred in 10.5% in the azithromycin group, and then 10.3% in the placebo group, so relative risk of one not not significant, significantly different. neonatal sepsis occurred in 9.8% in the azithromycin group and 9.6% in the placebo group relative risk one so not different. The findings in the suburbs are generally consistent with the overall results with the exception that there appear to be greater maternal benefit with the azithromycin use in Africa than in Asia. And then in regards to the secondary outcomes, and in the treatise occurred in 1.3%, in the azithromycin group and a 2%, and placebo relative risk of point six, six wound infections in 1.6, in the azithromycin, 2.2%, and placebo relative risk point seven one and other infections in 1%, azithromycin 1.5% of the placebo group respectively. And overall chorioamnionitis was rare and the two groups and the other interesting results since we're using a lot of azithromycin Pyloric stenosis was diagnosed in eat infants Niza through Meissen group, and then three in the placebo group. Yeah, interesting, right. So the state, the takeaways are really that among planned vaginal deliveries, a single oral dose of azithromycin resulted in significantly lower risk of maternal sepsis or death than placebo, but had little effect on newborn sepsis or death. So this is consistent with the use of azithromycin in C section deliveries. I think it's especially interesting, you know, in in, for example, where places where it neonatal mortality is high like in in some of these regions in Africa that had an even bigger effect of azithromycin. I think this is a pretty important study.

Ben 24:36

No, it's I think it's a Yeah, no, I'm saying I think it's I think it's a huge study. I do think it's a huge study, and I think there's several things that I'm taking away number one, the mortality rates, it's interesting, because in the discussion, they mentioned how their maternal mortality rates are low at baseline, right. And, and it's, it's true in the placebo I think it's 2.4%. But I think we should not shrug this off. Because in low and middle income countries, even I don't know if there's a number that's tolerable, because we know the importance of the mother in the household. I've done a lot of work in some work in global health and losing a household that loses a mother is a catastrophic, it's catastrophic for not only the household for potentially the generations that are coming after that. So I think any reduction in maternal mortality is very well taken, they do mention the risk of obviously, starting antibiotics, and the risk of resistance. But I do think that the it is worthwhile, especially since the issue of multidrug resistant organism is really a first I don't like the term first world, but you know, what I mean, like a developed world problem. And we can hopefully, mitigate that. Now what the question that's interesting is, obviously, the maternal mortality rates have been in the news recently, especially in the US, because of how bad I

Daphna 26:13

was gonna say, I mean, we are not without our own mortality, maternal mortality, right. It's exactly

Ben 26:17

right. They're still, they're still, I mean, thankfully, they are lower than what the paper presents, thankfully, based on the resources that are available in the US, for example. But I think that's where it gets really interesting, because it seems to me that if you can, I mean, in this case, they had about, like, let's say, 15,000 patients in each group, and they had a reduction by about 100 100 less deaths, right? Or sepsis, in terms of deaths from any cause. They had about two less deaths in either groups. And then And then, but anyway, I think those numbers, I mean, if it were me, I would want my my significant other to get azithromycin. But it becomes an interesting question as to whether this will permeate into practice in developed country. I don't know what your your thoughts are on that, because we've been talking about the zero context of ureaplasma and all that stuff. So I mean, it's interesting that it had no If not no real effect on the neonates, because there was a big discussion about should impingement also include or, yeah, include ZipGrow.

Daphna 27:27

I think we're, I think we're gonna keep learning more and more about atypicals and their role on for example, preterm labor, so I think we will move in that direction, but we will review those papers when they as they come out as they come

Ben 27:40

out. Interesting. It's such a fodder for discussion for sure. This episode is proudly sponsored by racket meat Johnson. Recommend Johnson is dedicated to the research and development of nutrition products that help support baby development at every stage, including an extensive Enfamil portfolio for premature and low birth weight infants learn more at HCP dot meet Okay, oh, boy, already, I have a big paper that I need to review. It's a big paper. It's published in the seminars in Perinatology. It's called Impact of early screening echocardiography and targeted pediatric mental neonatal outcomes in 22 to 23 weeks, and 24 to 26 week infants. The it's a it's a huge paper, and I had to almost at some points, scroll back up to the beginning of the paper to see if it wasn't a review paper because it was such a sweeping summary of a lot of things that were being done. The first author is Reagan, Gisiger from Iowa to who we send our kindest regards. Obviously, the rest of the team from Iowa is on that paper flast author is Patrick McNamara. So if Patrick is listening hello to you as well. But I'm going to get into it because there's a lot to cover, I usually do a one page summary of these papers. And this is like a two pager. So the background is is is fairly straightforward, right? We know that there's wide variation in the approach to the management of PDA both on the evaluation side on the management side, they highlight the fact that that 60 randomized trials have failed to demonstrate improved outcomes with medical treatment. But we all know that each of these trials has significant methodological limitations. Not because the authors were careless, but because it's just such a difficult subject to discuss. Most trials have randomized few, if any preterm infants born between 22 and 23 weeks. These are the babies that we are now actively resuscitating. These are the babies that are giving us probably the most trouble in terms of their complexity. We know that the PDA is associated with long term term morbidities, especially BPD. And so, they're saying that it's as it is biologically plausible, as suggested by a recent postdoc analysis of a pilot randomized trial, that successful early elimination of hemodynamically significant PDAs shunt may be associated with a reduced risk of BPD, among extremely preterm neonates. And I think the question the primary aim of this study is to evaluate the impact of early hemodynamically significant PDA management based on targeted neonatal echoes in extremely preterm infants born at 22, to 23, and six, as compared to a historical epoch during which exclusively clinically symptomatic treatment after postnatal day seven in the presence of echo confirm PDA, on the composite outcome of death, and Atlas, that before 36 weeks, or severe BPD. I think what's very interesting is that we know that Iowa is the University of Iowa is probably one of the world's leader in their approach to extremely low birth weight infants, especially on the edges of viability are 20 to 23 weeks. They're also pioneers in the in through their hemodynamics program and their approach to hemodynamics evaluation. And so it's very interesting for them, and very generous of them to actually do this study where they're looking at their current approach to the evaluation and management of PDA and comparing it to what they were doing in the past, which as we'll see sounds like what we're still most of us doing in our units. So the study design is that this is a cohort of neonates that were born before 27 weeks of gestation, who were either in born or admitted within 24 hours to their to the University of Iowa NICU. All neonates during the study period were considered eligible unless they had major anomalies congenital heart disease. Obviously, that doesn't include PDA, let's Okay, fine, fine, small VSDs, or atrial defect. So we're talking about like structural, really large structural anomalies, or resuscitation that was either incomplete or not provided. Now patients were recruited in two distinct epochs. So they have the hemodynamic screening epoch, which is taking place from like, October 2018, to April 2022. And then they have a historical cohort, which goes from 2010 to 2017. Now all patients were included, if they were diagnosed with a hemodynamically, significant PDA or if they died in the first postnatal week. Now the inclusion of these babies who died in the first postnatal week in the historical epoch was to account for an unknown hemodynamically significant PDA status, particularly among historical patients who routinely had echo on approximately postnatal day seven, due to the strong association of early mortality and the presence of a PDA on day three. So already, you'll start seeing glimpses of how having a hemodynamics team can really help you get more information early on, on these PDAs. Now, the hemodynamically, significant PDA was defined based on the IOA PDA score, and they had to have a PDA score of six or more. Now, the paper has tons of tables. It's amazing. So in this case, if you want a quick review of the Iowa PDA score, I know that Gabriel Altet on your Korea Lab probably has it as well. But basically it's a it's a list of measurements. So we have about, I want to say six, seven, we have seven measurements, which I'm not going to get into their seven measurements from that you can get on echocardiography, and based on the value that you're getting, you can either assign it a score of 01 or two. And then you basically compute that and you get your PDA score. Now, this is also very valuable information because if you've reviewed the literature like we have, having standardized way of defining a hemodynamically significant PDA is something that's very difficult. They collected a ton of clinical variables. I'm not gonna get into that. The duration of hemodynamically significant PDA was defined from the first echo demonstrating these findings until interventional closure or the first echo demonstrating the hemodynamic non significance, after which no real manifestation occurred. If the first echo demonstrated the hemodynamically significant PDA D zero was designated as the start of PDA exposure. Now, what I want to highlight in this part of the paper is that we can see that they're not just talking about the presence or absence of a PDA right? It's really the presence of a hemodynamically significant PDM making A concerted effort here to make sure that I don't just say PDA because if the PDA is not hemodynamically significant, then it's it's really neither here nor there. So I think that's, that's already something that's very important in their in their approach.

Daphna 35:13

Well, unlike you like, I mean, like you've said, and we've discussed before, what what is he would be significant. So we have to pick something, right. So it would be helpful if the, if the community could just agree on something so that we could study it right, just like we said with BPD. And just like, with Yeah,

Ben 35:32

and I think that's where that that's where it gets interesting is because we've always defined hemodynamically significant PDA based on clinical findings, right, whether you have hypertension, so on and so forth. But as you see in their PDA score, the doctors diameter is only one of the parameters. All the other parameters are very objective echo findings, the aortic to peripheral Doppler, for reversal, the isovolumetric relaxation time, all these things, I think, are are showing another approach that's not always clinical, because what permeates to the surface of clinical evaluation may not always be the most reliable. So what is the approach to the evaluation and management of hemodynamically significant PDA in the new epoch in the hemodynamic screening epoch. So if you're interested in starting a hemodynamics, program, man read that paper, they outline everything. I've taken screenshots of that paper left and right. So during the hemodynamic screening epoch, all neonates undergo comprehensive echo between 12 and 18 hours postnatal age, followed by physiologic guided therapy. Each echo consists of 80 to 110 clips, and include a comprehensive appraisal of systemic and pulmonary hemodynamics objective measurement of by ventricular cardiac function and characterization of shunts, they're done by neonatologist using warmed gel, that's something I was like, Man, I never thought of warming the gel. What? That's a good idea. Of course, it's a great idea. I was like man ever

Daphna 37:05

said to the to our echo or ultrasound techs, you're using the warm gel right on my very tiny baby here.

Ben 37:11

You knew about that? Of course. Clearly, you've

Daphna 37:14

never had an ultrasound done. That's exactly right. That's right. And we wouldn't do ultrasounds on say pregnant people without warmed gels. We don't do that. So why would we do it to babies with

Ben 37:26

Yeah, my wife and friends didn't get the benefit of warm gel.

Daphna 37:30

Okay, I guess we do do it sometimes, but we shouldn't most vulnerable babies.

Ben 37:37

And another interesting aspect was that the usual duration of these echoes were 20 minutes. And that's something that I've had an issue with sometimes when we want to order a necklace like hey, don't don't spend 45 minutes because these babies are cannot probably cannot handle 20 minutes. The usual approach to a hemodynamic hemodynamics hemodynamically significant PDA this is going to kill me before the end of this review was to administer acetaminophen so first line treatment is Tylenol 15. Mix procure lo que six for three days IV. A further four days of therapy with Acetaminophen is provided if response was demonstrated. So if you see that, on the on the follow up echoes, there's improvement you can continue that for another four days. indomethacin at point two milligram per kilo followed by two doses of point one mg per kilo at 12 hour intervals was used as a second line therapy. Other shunt modulation strategies including avoidance of anemia with the transfusion threshold with a defined transfusion threshold avoidance of hypo cap anemia and tolerance of lower targets situation were also commonly used. So to give you a glimpse, we're not doing any of that document. Like this is not our approach. But I'm wondering like I think for us, right, definitely correct me if I'm wrong. We don't have a protocol ICD approach. But I think our first line is ibuprofen, which correct I think most people still use ibuprofen as a first line. So I was and it's interesting considering the paper that shuba Shauvik wrote that we presented last time how you are no better city Munificent. Like I'm so struck to see that this is like first line treatment anyway. or medical treatment was followed by a reappraisal within 24 hours at the end of therapy. Since 2019, percutaneous device closure in the pediatric cath lab has been the standard of care or surgical ligation has been was performed if contraindication to percutaneous closure were present. So when they did fail medical treatment and they decided to go forward with with with with closure, then that was done in the cath lab. Okay, so now, now that we all feel bad about ourselves, let's go back to the historical epoch and see how they used to manage these babies before the advent of their hemodynamic program. So during the historical cohort, echocardiograms are performed by pediatrics and ographers and interpreted by Pediatric Cardiologist that's how we do it. It was standard of care for some clinicians to perform and echo on postnatal day six or seven to screen for PDA, whereas others relied exclusively on the appearance of clinical signs of hemodynamic significance as we spoke before, the first Echo was a complete anatomic study of sufficient quality to rule out congenital heart disease. Thereafter, a focus study was typically performed to evaluate for ductal patency follow up evaluations were performed at the request of the clinical team when signs of hemodynamically significance were judged to be present. They had no standardized echo definition of hemodynamic significance. echocardiograms were routinely performed within 24 hours of the completion of a course of therapy. The management of hemocyte hemodynamically significant PDA in that historical cohort, included up to three doses of indomethacin followed by surgical ligation of the ductus remains significant. So very, I mean, very different from what they're currently doing. Right. In terms of standard neonatal care, I thought it was very important to mention this, the approach to care of extremely preterm infants include active obstetric management with antenatal steroids beginning at 21, and five. That's something that we're advocating for as well see section for fetal indications starting at 23 weeks. Magnesium sulfate for ivh prophylaxis standard latency, antibiotics for preterm prolonged rupture of membranes and routine delayed cord clamping for 30 seconds. The approach to neonatal respiratory care includes the utilization of two Oh endotracheal tubes as needed. First intention, high frequency jet ventilation, surfactant prophylaxis to 24 weeks no early excavations, universal caffeine administration vitamin A prophylaxis and midline positioning for the first 14 days. So, again, this is yeah.

Daphna 41:54

I'd like to hear more about that. You know, I, obviously, we want to review more papers out of Iowa, obviously, right. We all want to know what they're doing. But

Ben 42:04

I'm already amazed that, I mean, I feel like I get to browse through their protocol. It feels like it's so detailed. It's such a well outlined, it's really, and it's sort of to be very honest, I have never met Dr. Kissinger, but knowing Patrick, now for a bit of time. It's such in mind with his generosity of like, yeah, like, like, yeah, we are happy to show

Unknown Speaker 42:23


Ben 42:29

Okay, no, then I'll keep going. Okay, so what were their outcomes? The primary outcome was a composite of death before 36 weeks or severe BPD defined by the Jensen criterias. secondary outcomes included death and severe BPD as individual outcomes survival free of morbidity, pulmonary hemorrhage, pneumothorax, PDA therapy, medical orient have entered interventional intestinal complications and retinopathy of prematurity treatment. Okay, so now let's get into the results. 189 infants were included in the 22 to 23, and six group, they had 73 in the hemodynamics screening group 116 in the historical cohort, and then they had 312 infants included in the 24 to 26 and six group one weight in the hemodynamic screening group 204 in the historical cohort. So some pretty large numbers there. Obviously, okay, fine, I'm going to skip this doesn't matter. The babies who were born at 22 and 2223, and six were in the historical cohort had lower birth weights significantly, and were more likely to be female. But well, we'll get to that in a second. So the first areas of results is the influence of hemodynamic screening on hemodynamically significant PDA exposure. So, in the in the most recent epoch, the first Echo was conducted on postnatal day zero for all neonates in the 2223 and six cohort, as compared to a median of the seven in the historical cohort. I think that's, that's, that's something that, yeah, I write up now we never get an echo on day zero. This is a luxury that's a luxury that currently we do not have.

Speaker 1 44:15

But it is in line with what we learned about in Japanese units. Right? That is that is that conference. That's

Ben 44:21

exactly right. And then listen to this, the use of vasopressors in the first postnatal week was lower in the in the in the ones the hemodynamics team was screening these babies and restricted to the group of patients who had an earlier pre screening echo, all of whom had either sepsis or perinatal hypoxic ischemic injury.

Daphna 44:42

And this makes sense, right? So we treat all hypotension. We just throw on the pressors and we don't even know which presser to use, but by using you know targeted echo you can say like, what's the problem and how can I fix it and I think obviously this will show an improvement in outcomes because we're using the right tool for the right problem.

Ben 45:06

And depressor may not be the right approach like you could, regardless right to titrate fluids and the rate of medical therapy for PDA was higher too, in the hemodynamic screening epoch, the rate of interventional closure was 33%. Compared to 47%. In the historical cohort, there was no difference in the rate of hypokalemia major fluctuation in co2 in the first 24 hours, or the incidence of thrombocytopenia. Now, looking at the more mature group, the 24 to 26 and six, there was a reduced need for indomethacin and the rydoo and a reduction in interventional closure by approximately 50%. That's less. Yeah. So clearly, those more mature babies are benefiting tremendously from this this sort of close follow up. Yeah. What is the effect of acetaminophen therapy on the duct in the hemodynamics screening cohort? So of the 64 patients, born at 22 to 23 weeks who received medical therapy 50% responded with resolution of the hemodynamic significance, right? Listen carefully to what I quoted from the paper 50% had resolution of the hemodynamic significance, meaning it doesn't really tell you whether the PDA fully closed or not. But all the parameters that they used to define significance were abated. 63% really manifest stated re manifested later, and therefore required second line therapy. Now in the more mature group and the 24 to 26, and six group 70% had a positive response with resolution of hemodynamic significance, with only 44% This time who re manifested and then needed more treatment, so a higher response and also less relapse. There's however, no difference in either a cinnamon with acetaminophen response or PDA recurrence between the gestational age subgroups. Now in comparison to the historical epoch, in which 85% of the infants born between 22 and 23 weeks, and 71% of the kids in the 24 to 26 weeks had hemodynamically significant PDA at day seven in the hemodynamic screening epoch, only 53% and 41% respectively, continue to have hemodynamically significant PD at a similar time point. So what we're trying to show here is because the historical cohort usually didn't get screened until like the seventh, they said, Alright, let's look at the seven and they said in the historical cohort, about like 85% and 71% of the kids had hemodynamically significant PTSD seven, but thanks to the hemodynamics team that they had implemented in the new epoch, they were able to get these numbers down from 85% to 53%. And from 71% in the 2014. Season to 41%. So they were already well ahead by day seven compared to the older the older cohort. What is the impact of hemodynamic screening on acute illness severity? Well, the echocardiography findings included acute pulmonary hypertension alone in one case, acute pulmonary hypertension, with right ventricular dysfunction in seven cases by ventricular dysfunction in three cases hemodynamics significant obviously, in six cases transitional circulation, in one case and vaso dilator shock in two cases, trees treatment was prescribed based on physiology. And physiologic guided therapy was associated with a lower rate of nitric oxide use lower respiratory requirements, fewer sodium bicarbonate boluses and the snap to score was also lower in the hemodynamic screening epoch. hydrocortisone use in the first week was frequent, but similar in both epoch, specifically in the 22 and 23, weak infants, whereas in the older cohort, the administration of hydrocortisone was more frequent in the hemodynamic screening epoch, then compared to the control. So interestingly, while the hemodynamic screening has helped reduce a lot of the use of various medication, the use of hydrocortisone remained more frequent in the 24 to 26 in the 24 week patients in the in the new epoch a few more results and then we can conclude on this paper. What is the impact of hemodynamic screening on neonatal morbidities sort of what we were sort of aiming to test to begin with, there's a 50% reduction in the primary composite outcome of death before 36 weeks or grade three BPD in the 22 to 23 and six week patients. I mean, 50% Show me. I mean, these are these are. The problem with this paper is that the findings up until this point have been so incredible that you're sort of almost jaded by this point. But I mean, that's right. I mean, I had to reread this several times. And I actually, truth be told, I was reading it on a PDF. So I went back to the website and looked at the full text in the browser to make sure that it was not a typo. Because that was like 50% Man 50%. This was accompanied by an increase in survival free of severe morbidity to 73% and the reduction of a variety of other important neonatal outcomes. Of note the reduction in the rate of severe, there were reductions in the rates of severe ivh and NEC in both subgroup. Last few things in the hemodynamic screening epoch, fewer of the 22 and three infants died, in addition, that occurred at an older median age, and was less likely in the force in the first postnatal week, which to be honest with you is when I mean, when these babies pass away, they very frequently die in the first the first week. There were no cases of pulmonary hemorrhage, or non significant but relevant trends of an already very low rate. If you look at their numbers, they were quite low to begin with. So could they I'm not sure what to make of that. In terms of multivariate model after adjustment for co founders in the 22 and 23, week cohort, year of birth, and the hemodynamic screening era, they were both the your birth and the hemodynamic screening era were independently associated with survival without severe BPD. After adjustment for both the screening, the hemodynamic screening and the year of birth, only hemodynamic screening predicted a higher likelihood of survival from severe BPD with an odds ratio of 5.1. The conclusion is that among neonates born between 22 and 23 weeks early hemodynamic screening, PDA diagnosis, and physiologic physiology targeted treatment was associated with a reduced risk of the composite primary outcome of death before 36 weeks or severe BPD as compared to a historical cohort of patients. These extremely immature neonates may present with a variety of cardiovascular pathologies in the first 24 hours, of which he most dynamically significant PDA is one of the most frequently given the extreme paucity of literature on hemodynamically. Significant PD in the in the less than 24 weeks gestation population, it is important that developmental and physiological first principles are considered these, which I think this paper just outlines very clearly, these neonates may be particularly disadvantaged due to extreme immaturity. This magnifying the impact of shunt physiology on pulmonary and other systemic outcomes. It is important for readers to recognize that effects seen in our center may not be easily generalizable to other centers, further study in this population is warranted, and it will be increasingly possible as these extremely preterm infants are more widely resuscitated. I don't I kind of agree with that last statement. I also think that as soon as another center reproduces these outcomes that said, then the race is on, because they are not, I think the only obstacle for people to reproduce these results are for Iowa to be very opaque about what they do, which they are not. And so I think somebody is going to implement some of these interventions in their centers, they're going to find similar outcomes, I hope for them, and then everybody is going to be looking to, to do that. So. Okay, I told you was going to be a long one, but what a paper?

Daphna 53:29

Yeah, very important. I mean, I think it really underscores the use of point of care ultrasound, right. So I mean, that's really was my major takeaway, right. And delineating, in particular, the causes of hypotension in neonates, I think or this, like they say the shunting physiology we all say, oh, it's the PDA, but that can be so many things. So very interesting. Well, it's hard to follow that up, obviously. But I'll reach out to you by paper.

Ben 54:04

I didn't write that paper.

Daphna 54:05

You didn't write the you did a very nice job. You did a very nice job reviewing it. Okay. This is coming to us from France. This paper your neck of the woods, so postnatal growth restriction and neurodevelopment at five years of age, a European Extremely preterm birth cohort study. I told you is coming to France. It was published in the Archives of disease. Lead author written L. Rafi.

Ben 54:37

I have you know what I'm actually sadly okay. This is like a behind the scenes. I'm looking for the paper on our shared drive.

Unknown Speaker 54:43

It's in my folder. Is it in your folder? Yeah.

Ben 54:46

I only see the information in

Unknown Speaker 54:48

your folder. Okay. It's so funny because I don't see anything in your folder.

Ben 54:51

No, I didn't put anything in my folder today. So that's my fault. Alright, I'm gonna I'm gonna find that paper again. One second man. All right, backbone four. It's in your folder. Oh, yeah, I see it. Okay. Hold on, is it? Is it the rough a paper? Okay, RIM al Hafi. It doesn't sound like it sounds like Middle Eastern name. So I don't want to meet even if I pronounce it the French way. I'm afraid I'm still going to butcher it. Yeah, we have. We have a very diverse population in France. So I wouldn't be surprised, but a female half is how we would pronounce it in French.

Daphna 55:32

Okay. For the ship's research group, and I'll tell you about that. So what's the question, they wanted to investigate whether extra uterine growth restriction during the neonatal hospitalization among extremely preterm infants is associated with neurodevelopmental outcomes like cerebral palsy, and COVID cognitive and motor abilities at five years of age. So, the study design, this is a chord of extremely preterm infants. And basically, this is data from the I'm not actually sure how you say it, but the the epi CE cohort of births less than 32 weeks of gestational age from 19 regions in 11 European countries with follow up in the screening to improve health and very preterm infants in Europe. That's the ship's study. So perinatal, and neonatal characteristics until hospital discharge were abstracted from medical records follow up data on the children's health and development healthcare, socio demographic circumstances are collected using parental questions at two and five years. And when possible, standardized clinical assessments were performed at five years of age on the extremely preterm infants in the group. So I

Ben 56:45

don't know if they intended to do that. But the effective perinatal intensive care in Europe is pronounced in French, a piece, which stands for spice. So it's like spices, so it's kind of cool. So if on the French podcast we will rate this acronym pretty highly, I think it doesn't translate very well on the English one, but I'm sure Gabriel and flora are gonna are gonna like that one.

Daphna 57:08

Okay, so basically, they took this, this is like a secondary analysis of this cohort of extremely preterm infants. They identified which infants had postnatal extra uterine growth restriction. And they did this in two ways. They first calculated the change in weight Z scores between birth and discharge, according to the Fenton growth chart the Fenton delta z score, and classifying its EGR extrauterine growth restriction as severe and moderate, when the delta z scores were less than minus two standard deviations for severe and moderate between minus one and minus two standard deviations. They use the second measure Patel's weight gain velocity, which computes average gain in grams per kilogram per day from birth and discharge weight using an exponential models. So then they have cut offs for severe moderate, whether they're below the first quartile in the sample, or between the first and the median, respectively. And then this group of children were evaluated at five years of age for neurodevelopmental outcomes, the exclusion criteria were. So interestingly, this is of note they excluded children with severe nerve sensory impairments, IQ less than or equal to 54, or severe hearing or visual impairments, which is 27 infants, because the clinical assessments are really not designed for these children, right to be able to participate in them. But we did lose this coat, you know, this little group of severely impaired children. So the study had three primary outcomes cerebral palsy, cognitive and motor function. Sorry, cerebral palsy is one and then cognitive function and motor function among children without cerebral palsy. Cerebral Palsy was determined by a clinical diagnosis reported by parents except in France, where it was ascertained during a medical visit. So a lot of survey data, cognitive and motor functions evaluated by trained psychologist or physiotherapist five years of age, and local routine follow up programs when available. When not available again, using a lot of parent data, cognitive abilities were measured using the wipsy the Wechsler Preschool and Primary skills of intelligent and they evaluated motor function using the m back the movement of M A BC movement accessory battery for children based on characteristics and mean gestational age for the group was 25.9 weeks and the mean birth weight was 873 grams 13.5% of children were SGA less than third percentile and 34% had been EPD 24.6% had severe non respiratory neonatal morbidity. On average, the needle hospitalizations lasted 91 days with children discharged at on an average of 39.4 weeks of postmenstrual age, weighing an average of 2692 grams. So the results using the Fentons delta z score 40.1% of children were classified with moderate extra uterine growth restriction, and 33.9% with severe extra uterine growth restriction, that's a lot of growth restriction. But tells measure was distributed according to the median and to the quartile values. And the risk factors for severe extruder and growth restriction as defined by both measures included severe neonatal morbidity BPD and later discharge. Overall, 9.1% of children had a diagnosis of cerebral palsy, and cerebral palsy risks were related to severe extra uterine growth restriction among boys in unadjusted models using Patel's weight gain velocity with this significant interaction by sex, but the confidence intervals for adjusted risk ratios included one something to note, key value point one seven similar patterns were observed for Fentons delta z scores so that is in children with cerebral palsy. Among children without cerebral palsy, those with severe extra uterine growth restriction had the lowest IQ scores. After adjustment severe extra uterine growth restriction was associated with an IQ reduction of 3.9 points. And five points depending on whether you use the Fenton Delta score 3.9 points, or the Patel's weight gain velocity five points respectively with no interaction bisects the risk of an IQ less than 70 were much higher among children with severe extreme mood and growth restriction a risk ratio of 1.7. And if you used Patel's weight gain velocity, this adjusted risk ratio is even higher 2.8. For movement difficulties, there was no associations with extra uterine growth restriction and no interaction with sex. The reason they were looking at sex specifically is because this study had been done previously and they did find interaction between sexes. So study takeaways are really, among very preterm infants at five years of age severe postnatal extrauterine growth restriction was associated with lower IQ, but not with movement difficulties, or cerebral palsy. The association with cognition was similar for boys and girls contrasting with previous reports at two years finding an association only for boys. And then the they quote, better nutrition to reduce extra uterine growth restriction may be a lever for improving long term cognition among children born extremely preterm. So I don't think this is earth shattering information, like we know that nutrition is linked to cognitive outcomes. But it's a good reminder. And I thought, especially interesting, that of the group, only 13% were small for gestational age. So it's not that they had this, like small growth potential, or they were coming, you know, from behind. This was something that happened in the neonatal unit that they had growth failure. Yeah,

Ben 1:03:30

I mean, it keeps adding to the, to the, to the pressure that they have of optimizing nature, optimizing nutrition, because I think you're I mean, for people who think that our job is stressful. Think about it, like you have a kid who you're doing the growth curve, and you're seeing that there's growth restriction, and you're like, Oh, my God, like, if I don't, if I don't correct this, this kid at five years will have impaired it's like, ah, the stress.

Daphna 1:03:54

Yeah. And I think our ability to prognosticate neurodevelopmental outcomes is so complicated because we use like ivh, but it's not just IV H right. It's IBH and steroid use and nutrition and sepsis. And it's we don't have a calculator for it.

Ben 1:04:10

That's right. That's right. But no, I mean, again, it's just where we're not going to be able to escape this. It needs to be well addressed, this needs to be it needs to be well thought through and cannot be cannot say, Oh, I'll catch up on the growth later. Right. I'll fix some other things today. Yeah, no. Okay. I guess you're me. I can do one more. Okay, it's it's an easy, it's an easy one. It's an easy, we're already over time. I know we're already over time. It's a quick one. It's interesting because it follows up on something we've presented. It's called platelet transfusion in a multinational healthcare organization before and after publication of the planet to clinical trial. first author is Dr. Barr and colleagues. It's from It's from the journal. It's in the Journal of Pediatrics. And I want to say that Dr. Christensen is on this paper as well. Yeah, Robert Christensen is on this paper as well have had a lot of big names today. I know, I know, star studded. So the background really goes over some of the things that we've discussed that liberal platelet transfusion practices for preterm neonates have been associated with worse outcome. The group of Dr. Christensen, obviously out of Utah is called Intermountain Health. So they're talking about Intermountain Health has basically changed their transfusion guideline after the publication of the planet to trial. And it's very interesting, right? Because many people are saying how long we've asked this question at Delphi in terms of delivery of health care. And we said, what is the rate of adoption of new evidence? And how likely are you to implement new evidence. So this is clearly a team that that that that valued the findings and change their protocols right away. And they were very honest, in the paper that they're writing, they said, we thought that this change would result in less infants receiving platelet transfusion. But more importantly, they said, we would not see a change also in death or major morbidities. Now, they have a nice table. I love these senators who are just giving us a glimpse into their practices, where they have the old protocol where basically, they will transfuse platelets. If the baby was considered stable, if the platelet count reached less than 25,000, they would transfuse platelets, if the platelet count was below 50,000, if it was, quote, unquote, unstable, and they would keep platelets above 100,000, if you either were on ECMO getting surgery or were actively bleeding. So when the new protocol was designed, the keeping platelets above 100,000 was the same ECMO surgery or bleeding. Now, please, less than 50,000 became a trigger for babies were at risk of ivh in the first five days of life, which I think is very interesting. And then everybody else now fell into that other category of platelets less than 25,000. Now, the question they're asking are what are the transfusion rates and patient outcomes during the three year period before versus after the change in their multi NICU practice? This is a retrospective analysis of their data. The data is retrieved for from every patient who receive the platelet transfusion in any of the level two or level three NICU is in the Intermountain Healthcare System during the two consecutive three year periods, so 2016 to 2019. That's the pre change 2019 to 2022. That's the post change. The practice change was officially implemented in April 2019. After publication of the planet to study. The specific aims of the analysis were to compare two three year periods before and after regarding the platelet transfusion rates. The features of the NICU patients who received one or more platelet transfusion, the percent of platelet transfusion given when the pre transfusion platelet count was either above 100, between 50 and 100, and less than 25. The pre transfusion platelet count that triggered the order of platelet transfusion. And number five, a composite of adverse outcomes of neonates receiving platelet transfusion including death, major new bleeding, following platelet transfusion, moderate to severe VPD, severe ROP moderate to severe and other mental impairment at 24 to 30 months of age, what are some of the results, the platelet transfusion rates did not really change. It was 15.9. Before and 12.9. After the guideline, the p value is like point one. The number of transfusions given per 1000 NICU admissions increased from 33 to 37.8. After the guideline change, and the mean number of players transfusion given to each transferred, transfused neonate did not significantly decrease decrease after the guideline change. What's very interesting is that after the guideline change, fewer transfusions occurred for a platelet count of 50 to 100,000 range, it went from 27.8% to 20.2%. But there were no significant changes in the proportion of platelet transfusion given for the other pre transfusion platelet count trigger categories. After the guideline implementation. The mean platelet count that immediately preceded the transfusion decreased from 43,000 to 38,000. The proportion of platelet transfusion recipients with the composite adverse outcome of death major new bleeding following the first platelet transfusion, moderate to severe BPD. Severe ROP moderate to severe no other mental impairment was similar before and after the guideline implementation. So the conclusions are that changing the platelet transfusion guideline in their network did not was not associated with a significant reduction in the number of neonates receiving platelet transfusion. The guideline implementation was associated with a reduction in the mean platelet count triggering the transfusion. And they said that if they increase education and accountability tracking, they can reduce the number of clicks transfusion further. And I kind of disagree with their conclusion, because they had a pretty modern transfusion threshold before. So I think the kids who aren't the kids who are getting transfusions for platelet counts below 100, who are on ECMO surgery and building those stay the same, so you don't expect to see any changes there. They were already transfusing, quote unquote, stable babies for less than 25. And so the big change really happened in that middle section for the babies who had a platelet count of less than 50,000. And they saw a change in that specific group. So I think I think it's encouraging for people who are considering a change of practice, especially if you're, I mean, if you're platelet transfusion, if you don't have protocol, and you play transfusions, or all over the place, you will see, you will see change it in a pretty dramatic fashion early on. So I think I'm not as I wanted to bring up this paper because it's puzzling. You read this, you read the abstract you like, wait, what, like they implemented a new guidelines and nothing happened. But when you go back, and you're already following part of the game, almost exactly right. Almost. So that's why that's how I was like, Okay, maybe we should so good

Speaker 1 1:11:20

for them for being ahead of the curve. That's right. That's right. But yeah, okay, definitely. Okay, buddy.

Ben 1:11:30

Do you want to do one more?

Unknown Speaker 1:11:31

I have one more. But I but wait, we're already. We're way over time.

Ben 1:11:35

I'll save you trouble for next week. That's right. That's true. Like, give me all right. All right. Definitely. That was fun. I will see you on Monday tomorrow for board review. We have a bunch of Tech Tuesday episodes coming up. We have a special series on advocacy. We are back after Delphi with more content than you can take. So be ready. That's right.

Unknown Speaker 1:11:58

Hit the ground running.

Ben 1:11:59

That's right. All right. I'll see you tomorrow. Thank you for listening to the incubator podcast. If you liked this episode, please leave us a review on Apple podcast or the Apple podcast website. You can find other episodes of the show on Apple podcasts, Spotify, Google podcasts, or the podcast app of your choice. We would love to hear from you. So feel free to send us questions, comments or suggestions to our email address NICU You can also message the show on Instagram or Twitter, at NICU podcast or through our website at WWW dot d dash incubator. Dat org This podcast is intended to be purely for entertainment and informational purposes and should not be construed as medical advice. If you have any medical concerns. Please see your primary care professional. Thank you

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