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#109 - 📑 Journal Club 43



Good morning friends 👋

We have an exciting episode of journal club for your today. We discussed a variety of topic ranging from the effect of maternal voice on infant feeding, whether second twins have worse outcomes compared to their twin, the benefits of transpyloric feeds in BPD patients, the long term effects on therapeutic hypothermia into adolescence, and more.


We are so thankful for everyone who registered for the Delphi Conference. If you are planning to join us in March, take advantage of our early bird rates before February 1st. Check out the conference agenda right here: https://web.cvent.com/event/77b278fb-b74d-4c1d-a4e5-1ca15783a878/summary?RefId=1%2F&ref=the-incubator.org



 

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

Robertsson Grossmann K, Eriksson Westblad M, Blennow M, Lindström K.Arch Dis Child Fetal Neonatal Ed. 2023 May;108(3):295-301. doi: 10.1136/archdischild-2022-324418. Epub 2022 Dec 9.PMID: 36600485 Free PMC article.


Jensen EA, Zhang H, Feng R, Dysart K, Nilan K, Munson DA, Kirpalani H.Arch Dis Child Fetal Neonatal Ed. 2020 Jul;105(4):399-404. doi: 10.1136/archdischild-2019-317148. Epub 2019 Nov 4.PMID: 31685527 Free PMC article. Clinical Trial.


Chant K, Bitner-Glindzicz M, Marlow N.Arch Dis Child Fetal Neonatal Ed. 2023 Sep;108(5):464-470. doi: 10.1136/archdischild-2022-324331. Epub 2022 Dec 23.PMID: 36564163


Del Pino Hernández IL, García Domínguez MJ, Urquía Martí L, Reyes Suárez D, Avila-Alvarez A, García-Muñoz Rodrigo F.Arch Dis Child Fetal Neonatal Ed. 2023 Jul;108(4):354-359. doi: 10.1136/archdischild-2022-324724. Epub 2022 Dec 30.PMID: 36585246


Nakanishi H, Isayama T, Kokubo M, Hirano S, Kusuda S; Neonatal Research Network, Japan.J Pediatr. 2023 Jan;252:61-67.e5. doi: 10.1016/j.jpeds.2022.07.057. Epub 2022 Sep 16.PMID: 36116533


Batra D, Jaysainghe D, Batra N.Arch Dis Child Fetal Neonatal Ed. 2023 Jul;108(4):408-415. doi: 10.1136/archdischild-2022-324464. Epub 2023 Jan 11.PMID: 36631252


Chhikara A, Hagadorn JI, Lainwala S.J Perinatol. 2023 Jan;43(1):68-73. doi: 10.1038/s41372-022-01493-4. Epub 2022 Aug 18.


 

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

Ben 0:54

Welcome Hello, everybody. Welcome back to the incubator podcast. It's Sunday we are back with another episode of journal club Daphna. You You've been under the weather.


Speaker 3 1:10

Yeah. My hope is recovering. But we're getting there. Better. Yeah.


Ben 1:15

Better. Not not COVID But somehow, somehow this like really knocked you out?


Speaker 3 1:20

Yes. Gross viral illness. You know, the the winters are so tough in Florida.


Ben 1:25

Yeah. I mean, when the air conditioning goes too cold, it's really freezing. And it has been cold though. It has been Yeah.


Unknown Speaker 1:36

My second Cold Snap, you know, my letters on


Ben 1:39

my family's visiting from New York. And they came down the weekend and you're like, Man, this is cold. They was like, they were it was like 10 degrees centigrade. And, and the like, man, it's called and I'm like, still better than where you're coming from? Like, True. True. But


Unknown Speaker 1:55

we were hoping to go to the beach.


Ben 1:57

They went to the beach. It's like, all right, people. What kind of announcements do we have? Please, if you haven't noticed the neonatology review podcast is back, we are looking at MFM the episodes are out. Please follow along, we're learning a tremendous amount of things. It actually ends up for the people who are wondering about the board review format, it ends up allowing us to cover much more material. So So I hope I hope this is helpful. If you are training in training, then definitely check this out. We have our foreign languages podcast are continuing to churn out episodes. So if you're new, kind of


Speaker 3 2:41

amazing actually. Like that, like yesterday when I looked at all the episodes, yeah, languages.


Ben 2:49

Mariana and Merola in Brazil are doing a phenomenal job. They've already done two interviews and, and and they're very interesting topics that they're covering. The French podcast is releasing an episode today of journal club, and the Spanish podcast has released an episode last week and should have one either today or tomorrow at the latest. We're waiting for the editors to finish the post production of the episode. We are looking forward to meeting all the people who have registered for the Delphi conference. It's very exciting. We are trying to we're trying to finalize the agenda. We have 32 speakers or so and so getting sometimes the title from the last few rogue speakers can be difficult. Definitely I wondering if we should just publish the agenda with TBD on some of your speakers. Because we have their names. We know they're coming, but we just don't have their titles. And we're just like, come on. So if you are a Delphi speaker, and you're listening to this episode, please, and you haven't sent your title for the presentation, please indulge us. And,


Speaker 3 3:50

you know, I think I think it means that they're being very thoughtful about what we have tasked them with. Because we add we were specific, right that they could some of these big names. Don't just come and give us a lecture you've always given right? Like we want you to do something out of the box. We want you to give us a spin on your area of expertise. And so honestly, the lectures, the lectures that we do have titles for our are quite graded. You know,


Ben 4:20

they're they're awesome. They're awesome. I mean, what do we have Fumihiko from from Japan is going to present the management and outcomes of paravertebral infants born at 22 to 23 weeks of gestation and experience based medicine in Japan. If you've always wondered, how did they get these amazing outcomes in Japan? Fumiko will be here and present to us on that. We're going to have what other I love this, this top this this title from Elizabeth Symington, the power of empowering parents to be active participants in their babies NICU care. I think this is a great, great one. We have Gabriel who's going to present on the new cardio lab. If you don't know what new cardio lab is, then he's he's calling it bringing him today. namics to the web 2.0. Look,


Speaker 3 5:02

I think if you've never been to that website, it's gonna blow your mind. Yeah, it's an amazing site. And he'll


Ben 5:07

be there. And again, she'll be there. Which means if you are a fellow and you want to work with Gabriel on his stuff, like you'll meet him, he'll be there. Doug Campbell is presenting on noninvasive negative pressure ventilation and neonates times to rethink how we help babies breathe. He has some cool stuff he's presenting, Doug, thank you for agreeing to come on site, Mokhtar param is going to be there. He's presenting on advances in chest imaging and infants with BPD. There's tons of topics the we're trying to make this like so fun, almost like, we're trying to be your substance dealers, you know, because it's like 20 minutes, quick hits, you know, and they're gonna be so good. Yeah. So yeah, and there's there's many more, there's many more topics. We're going to release the agenda very soon, we'll get CME CME credits will be available for people attending. And then we have the TEDx event on Wednesday, which is kind of cool. We'll tell you more about that in the weeks to come. But that's it. We have exhausted the first five minutes of the show, and we are ready to do some journal club. Since you're sick. I'm not even going to ask. I was gonna go first. You were gonna go first. Well, no, I wasn't. Alright, you know what, I'm going to start with a I'm going to start with a light paper. Okay. And because it's not meaning, like, I have a paper on nitric oxide have a paper on like vents. But this paper, I saw the title, I was like, Man, I want to read this. It's called effect of maternal voice on proportion of oral feeding in preterm infants. first author is Aditya Shikara. And it's in the Journal of parasitology. It's from a group out of the US. And there's the background basically says that the following there's a delay in achievement of successful oral feeding that is common in preterm infants and may prolong your hospital stay. We all know that. One such potential intervention is exposing preterm infants in the neonatal intensive care unit to their mother's voice. And previously reported benefits of exposure to maternal voice in preterm infants include increased cardio respiratory stability, improved feeding tolerance, development of a larger auditory cortex and improve neurodevelopmental outcomes. I actually spoke to somebody at TED last year, where you could use a software that changes your voice. And so technically, you could record the mother's voice. And then, by speaking into this microphone, everything that comes out could be said in the mother's voice. It's very, very cool. It's actually not hard to do. I never really, I mean, as people know, we're busy. I never really thought about like implementing this. But I saw this paper I was like, this is very interesting. Now preterm infants hearing, pacifier activated maternal singing, once daily have better non nutritive sucking, increased oral feeding rate, increased oral volume, and a really cool device, the more oral feeding per day faster achievement for feeding compared with control. It's basically like a pacifier. And I think as soon as it could bite into it, like it activates, like like like your thank you cards, your birthday cards, and then it just like gets the mother to sing. Now, this paper had an intended purpose to determine the feasibility of exposing preterm infants to maternal voice before feeding and whether exposure to maternal voice immediately prior to attempting feeding will improve the proportion of feed taken orally, during that feed. It was a prospective interventional cohort study. It looked at two study sites that were opened by Nick us where parents could basically had very liberal visitation, visitation policies, 24 hours per day, and they could stay at the bedside as long as they wished. They included babies who were between 28 and 34 and six weeks of gestation, they had to have English speaking mothers that were above the age of 18 that were treated at one of the two participating NICU is between June 2020 And September 2020. And that we're taking less obviously than 50% of enteral feeds orally in the two days prior to starting the exposure to the mother's voice. The excluded babies with neurological issues, obviously, like PVL, severe ivh and also History of neck and congenital CMV. The intervention itself was basically exposure to maternal voice in the form of a live or recorded reading from a selection of children's books, or any other book of the mother's choice. The voice exposure occurred for more than 20 minutes beginning 20 to 30 minutes prior to the oral feeding twice daily, once during the day shift once during the night shift approximately 12 hours apart each time. And the intervention was stopped after the baby's achieved for oral feeds, which sort of feels like well, you don't need to stop but I mean, I understand that for for study purposes, it concluded and and it was I read those papers. You see how like today what is considered we have such high tech in our pockets. You could do stuff that would be low friction, maternal voice was recorded using an iPhone On or an iPad with a voice memo software, basically, they just use the voice memo and they just basically stored it on a on an iPad and played it. Very straightforward. I mean, when you think about the 80s, like, if you wanted to record and play, you had to get all sorts of equipments, you have everything you need in your pocket, the recording device. Alright, so let's go over some of the results of the 37. Mothers approached 78 consented, no infant met exclusion criteria of the 29 consented preterm infants 25 completed the study, and 4% It took more than 50% already within the first two days overall fees initiation. It's funny attrition rate was 12%. One mother was uncomfortable with recording her voice. And I felt like as we've done the podcast, it's like, I totally get that you get it. Yeah. See that 8% of infants, recording had some technical issues. So the assuming the recording didn't record Well, or something like that. The mean gestational age at birth was 31 weeks, and the birth weight was 1.6 kilos respectively. That's not super small babies. But it's it's almost a proof of concept. So compared to preceding baseline intervention feeds were associated with an adjusted 7.1 percentage point increase in oral intake that was statistically significant. And in the post hoc analysis, a 71% increase likelihood of having the highest feeding readiness score, that was statistically significant for people who are not familiar feeding readiness score, basically as assessing a baby's work readiness to take in an oral feed. And there's been multiple cues that therapists providers can look at to determine whether a baby is ready to take a feed. And so in conclusion, there's two centers. Two centers are a prospective interventional cohort study showed that exposure to maternal voice immediately prior to feeds was associated with improved proportions, proportion of fields taken orally. Obviously, they're mentioning that it's a small study that we need probably to test this on the larger. But I mean, right. I mean, in the paper, you talk about the decibels, do we exactly right? It's like it's exactly right. That's exactly my points, like so I think


Speaker 3 12:07

I know, we all feel like we have to say that at the end of our studies, but like, we don't like this is a slam dunk.


Ben 12:13

Like, exactly what I thought I was like, you don't need to say that. Like,


Speaker 1 12:16

it's a slam dunk. And and it doesn't cost anything, potentially, depending on what you have in your unit. Right? Like,


Ben 12:24

even beyond the cost. It's like what's the harm?


Unknown Speaker 12:28

Right, right.


Ben 12:31

Right, what's the harm mean?


Speaker 3 12:32

Exposing babies to stimuli that is like soothing, calming, and helps them regulate. I mean, it's a slip that


Ben 12:39

they didn't mention to their, to their credit, I want to mention something, obviously, which is that they didn't mention that they were controlling for the levels of decibel, and stuff like that. So obviously, it was not like they made sure that it was not blasting and stuff and stuff. So anyway, but of course study, so great way I thought


Speaker 3 12:56

there's no good reason not to take that one to the,


Ben 13:00

it's so easy to do. Like, literally we could all do this tomorrow. How many how many of your babies in your NICU? I mean, I'm asking I'm not asking you that obviously, because I work in the same place. But like how many times you walk by and there's like, like some iPad turned on to something either like some some soothing music from YouTube, or like some some cartoon that somebody somebody is playing. So


Speaker 1 13:20

let's get out to all that I will say I will say you have to cuz that, you know, I, you know, I've tried to all it given our resources, you have to have a system in your unit for a parent to just be able to record there and leave it with you. Because I tried all sorts of things, especially during the pandemic, to get parents to record at home and send it to their babies I've had, they just they don't, they don't have the bandwidth. They are not comfortable with it. And so you have to just normalize like, this is what we do in our unit, we record your voice and we leave it here at bedside and when you're not here, your baby can still feel like you're here. So


Ben 13:58

all right. So this was my first paper. You're up next. Okay, I have another paper sorry.


Speaker 3 14:09

I really liked this paper. It's the Jensen paper. I'm surprised you didn't pick this paper.


Ben 14:14

You know, I have to I have to hold myself back sometimes.


Unknown Speaker 14:19

I like this paper mostly because of


Speaker 1 14:23

just a unique way to do the study. Right. And I it's on my soapbox you know Heidi, but I think that especially for trainees like you feel like I got to do this major randomized control trial like Like, no like walk it back do something that can be hypothesis generating. You know this, I thought this was a really cool small study. That should be a model for just thinking outside of the box


Ben 14:54

and you presented on transpiler work feeds and and an oxygen and VPD not too long ago. I started paper and I'm like, if I pick this people are gonna say, oh, again, this guy with the BPD stuff. So I read it. And I was like, I can't, I'm gonna pick some things that are a bit more varied. Yeah, it's the it's the plague of the editorial role, which is I don't I force myself not to read and present all the things that I just enjoy, because otherwise it would be very, very one sided. So anyway, but it's a cool paper. I'm very excited you.


Speaker 3 15:25

Okay, well, I wanted to read it. So I read. Okay, so um, it's called individualizing care and severe bronchopulmonary dysplasia, a series of n of one trials comparing trans Pyloric and gastric meeting.


Speaker 1 15:38

Lead author, Eric Jensen, senior author, her rush, Kurt Kripalani, and the skimming test from chop. And the question, what they were really looking at was to compare rates of hypoxemia during trans Pyloric gastric feedings in very preterm infants with severe bronchopulmonary dysplasia, they use this n of one trial designed to basically every infant served as his own control. So the trial lasted 16 days and consisted of two blocks. And each block consisted of a four day gastric and for the trans Pyloric, feeding period. So there were overall four feeding periods to gastric to trans Pyloric. And babies were randomized using a computer generated sequence to one of these block sequences.


Ben 16:31

So it ended up being basically 4444 phases separated by two blocks block one, for example, let's take one of these kids, you could be trans Pyloric for four days, then you went gastric that was block one, and then you would go into block two, where you would then go to trans Pyloric. And then another four days of gastric wishes 4444. That's 16 days in total.


Speaker 1 16:51

Right? Okay. So that's that. And so there were different obviously, combinations of of how the sequence went, and babies were randomized to different sequences. And the other things of note, so obviously, the transplant word feeds were continuous. The gastric feedings were run continuously for the first 24 hours of each assigned period. And then thereafter, clinicians were allowed to condense feeding. So that's just something to note. inclusion criteria. So they used infants born less than 32 weeks gestation, with severe BPD, receiving positive airway pressure and full enteral nutrition at 36 07 to 55, and six, seven weeks postmenstrual age, so they are born early. Now they're corrected to at least 36 and 07. Squeaks and they have severe BPD and they're in full NRL fields. In addition, infants who are already like by the clinical team have clinical signs attributed to reflux by their medical team. So frequent regurgitation history of suspected aspiration. Those were the babies that were targeted for enrollment, so they were trying to get as much information as they could, and loot do they exclude the excluded babies with recent significant changes to their medical care like changes in the ventilation mode or a new medication if they had a gastric window placation or severe congenital malformation. And then the outcomes they looked for were the daily number of intermittent hypoxemic events. And they define those as oxygen saturations less than 80%, lasting between 10 seconds and three minutes. So they really wanted to get through kind of hypoxemic swings. The secondary outcomes were the proportion of time per day with an SPO to less than 80% daily number of prolonged hypoxemic events. So OSAT less than 80% lasting greater than one minute, and the daily time averaged fraction of inspired oxygen. We looked at a number of other secondary outcomes. So they had these pre specified adverse events and absolute increase in fit greater than 20% above baseline for greater than or equal to eight hours. The second was a need for non elective endotracheal intubation. A third aspiration pneumonia divided is an observed regurgitation event with a new infiltrate on chest X ray increased respiratory needs and antibiotic therapy for that bag valve ventilation for an acute hypoxemic event by water loss, stools and electrolyte abnormalities. So like evidence of dumping, six necrotizing enterocolitis or intestinal perforation and seven deaths. So the baseline characteristics they had they ended up enrolling 15 infants between 2014 and December 2014 in July 2016. The majority were male, the majority were receiving non invasive positive airway pressure. And they were already the majority of them clinically on the trans Pyloric feeding At the time of enrollment, five of the infant's 27% Were already receiving proton pump inhibitor or histamine to antagonists during their end of one trial. Okay, so the primary outcome, five events, or 20%, experienced a significantly higher frequency of intermittent hypoxemic events per day while receiving the transpiler and feeds compared with a gastric feeding. And I think that I mean, this is another thing where a picture's worth 1000 words. So you can you can see every single infant, you can see what their block assignment was, and when they were in gastric and transpiler feeding, and you can see their bar graphs of the hypoxemic events for the day. So I think it's really easy to see the data so I props to the team for for presenting it in that manner. Um, rates of intimate hypoxemia were similar between the two feeding routes in the remaining 10 infants, so kind of equivocal. There was evidence of infant level heterogeneity of treatment effects for this outcome, obviously, and then the transplant work feedings were also associated with a higher frequency of prolonged hypoxemic events in to infants, and a greater proportion of time per day with an oxygen saturation later, less than, less than or equal to 80%. In three minutes. Three infants received more supplemental oxygen during trans Pyloric feeding, and only one receives more during gastric feedings. Of note the trial intervention was stopped early in two infants for clinical worsening during gastric feedings. The first had been receiving trans Pyloric feeds and his oxygen requirement acutely worsened after 48 hours of the initial gastric feeding. But he they did suspect that he had a post emesis aspiration event, though it didn't meet the predefined stopping rule for this aspiration pneumonia, which I read you earlier and gastric feedings were discontinued. And then infant, the second infant was removed from the trial during the second gastric feeding period, following an acute rise in FY oh two. But after review, they thought this was due to a concomitant decrease in the ventilator mean airway pressure. So eventually, the team decided to restart transpiler feeds on on this, four or five infants whose intention to treat analysis showed greater intermittent hypoxemic events during transpiler feedings or prescribed gastric feeding by their medical team following the trial. And this was a change from their pre trial transpiler. Sorry, this was a change in the trick the pre trial transpiler feedings and two of the four infants. So now they wanted to look at like what happened after the trial, depending on what the medical team chose to do. And of the infants with equivocal trial results for the primary outcome. Six are prescribed post trial gastric feedings, and five of whom were previously receiving transpiler feedings and four were prescribed trans Pyloric feedings, two of which were receiving pre trial transpiler feedings so not all the babies went back to their pre feeding pre trial regimen in either direction, interesting. Rates of gastric final vacation or fundable vacation or J gentle tube feedings a discharge were similar among the infants whose n of one trials favored gastric feedings, and those with equivocal results, the same 60% versus 50% A P value of one. So that's what they did looked at for all the individual babies one, one kind of one to one. And then the pool data analysis and transpiler compared with gastric feedings significantly increase the frequency of intermittent hypoxemia events, and the proportion of time per day with an SPO to less than 80%. Stated just in time, the differences in SPO two levels equated to an average of three additional minutes of hypoxemia per day during transpiler feedings. And that range anywhere from point three to eight minutes. The feeding rate was not associated with differences in FY oh two, which was interesting, I think that speaks to what's going on at the bedside and how much we're chasing babies, you know, oxygen requirements. So I thought it was a really unique way to do the study. I'm feeling disappointed about the outcomes.


Ben 24:43

Yeah, I'm gonna be honest with you. I don't know what to make of this study. Because on the one hand, it's meant to be describing n of one trials where we do this individually. And I have a feeling that every baby is different and I think we never I don't I would not have liked the approach of saying, Well, if you are a baby with severe BPD, then you must be on transpiler recognition, we do know that transpiler refeeds are not physiologic at all. Optimally, you would want a baby with severe BPD. To be on bolus gastric feeds, that's the that's the ultimate goal, because that's probably the closest to physiologic nutrition. Now, sometimes you're forced into doing transpiler work because they have severe reflux because they're still on a significant amount of non invasive support. And, and what you do is you always do a trial. And that's why initially I thought was going to be interesting was that when they said the N of one trials, I thought they were going to try it and see if it worked for each baby, but doing these back and forth. And if a baby is doing better on on transpilers, than then leave them on transpiler, I can tell the the better.


Speaker 1 25:49

So I think it was they really wanted to take away the influence of like time, right? So I think that's why they went back and forth back and forth to see, you know, is it the feeding? Or is it something else that we're doing?


Ben 26:03

And then you can argue whether the N of one trials of a four day four day intervention, is that sufficient? Obviously, they do mention, it's a funny line in the paper where they said that they couldn't do a washout period between the interventions, because they're like, babies do need to


Unknown Speaker 26:16

eat something.


Ben 26:18

So I mean, that too, could have contributed. But anyway, it was an interesting paper than that it is and I think many people will have probably, we're all very busy these days, you probably see this article, and maybe you don't get around to reading it. So this way, we're happy to present the information.


Speaker 1 26:31

I also think, listen, the papers that Eric Johnson writes, they're easy to read, they're easy to digest, you totally understand what they were doing. The data is easy to see. So I just think it's a model.


Ben 26:46

If you are interested in the in the model in which to publish papers like Gary Johnson, he was on the podcast quite early on, I forget which episode it was, I'm sure you go on Apple podcast, and you Google his name in our in our channel, and you will get the paper and he will talk about like how he thinks you can hook somebody with with your paper in terms of figures. He also talks about how do you pick an interesting question. So no, it was it was very insightful, very, super insightful episode. Yeah. Okay, so I'm taking you to Japan for our next paper. And this is a paper that was published in the Journal of Pediatrics. It's called inhaled nitric oxide therapy in the post acute phase in extremely preterm infants of Japanese cohorts that definitely are going to love this paper, because it was not easy to read, mostly because because you have to sort of wrap your head around all the intricacies of what they do in Japan in terms of regulation and stuff like that. So once you understand what they're doing, it's super interesting, but it took me some time to look at, look up some stuff, but let me give you the background first. So nitric oxide therapy is not recommended as an off label medication for infants born at less than 34 weeks gestation in the US because of lack of clear evidence. Now, this thing, in contrast, under insurance coverage applied in Japan since 2009, I know is widely used as not only the first line treatment for PPHN, even in extremely preterm infants, but also for rescue therapy in BPD related hypoxic respiratory failure and pulmonary hypertension in the late phase, and right there, you start seeing that you start seeing that


Unknown Speaker 28:24

their insurance companies start sweating.


Ben 28:26

Yeah. But you see already that there's a difference number one, they're separating the early use of nitric oxide for PPHN. And then the late the late things for for the late use of nitric oxide now in Japan, so what is what is the deal, right with their, with their insurance coverage. So what happens was that there was in 2009, the use of nitric oxide was significantly regulated by insurance companies in Japan. And we'll see how that plays a role now. What they're saying is that the insurance legislation in Japan really started regulating the use of nitric oxide for PPHN early on, but they're saying that I know use in the late phase which is called post acute I know which is the name in the in the title of the of the paper is not, is currently off label in Japan. So there's a lot of regulations for a yawn, but still off label for for late postacute item. So this was a retrospective analysis of data from the neonatal Research Network in Japan, the NRN J, to characterize the recent trends in post acute I know therapy and extremely preterm infants in Japan between 2003 and 2016, so 13 years worth of experience. Furthermore, the study sought to determine the perinatal and neonatal factor related to post acute I know use and further explore the impact of post acute Dinah on long term northern mental outcome of extremely preterm infants in Japan. So, super interesting study, it's a retrospective cohort study, they included infants who were born less than 32 weeks, or had a birth weight of 1500 grams or less that were registered in the neonatal Research Network of Japan from 217 tertiary perinatal center. They included all extremely preterm infants who were born at less than 28 weeks. What I just gave you, by the way, were the criteria to be registered in the network, right? The inclusion for this study were less than 28 weeks and and then you were enrolled in one of these centers, the excluded infants with congenital anomalies birth outside the hospital, perinatal death, incomplete medical records and from hospitals with no nitric oxide experience. Again, how did the study define post acute I know it's I know administration in the late phase of hospitalization and extremely preterm infants without PPHN without a history of pulmonary hypertension early on. Post Acute use is distinct from the use for acute PPHN and includes use for evolving BPD with suspected or documented pulmonary hypertension, accompanied by hypoxic respiratory failure. Sometimes, I guess we refer to this as BPD induced pulmonary hypertension, right, so they defined up with the 2001 definition. They collected a ton of clinical variables, and they tried to follow these babies up until three years of age. So let's get into some of the results. Between 22,003 and 2016. They enrolled about 16,000 Extremely preterm infants of these 71.2% With PPHN. Received I know in the acute phase, while post acute I know was administered to 462 of 14,000 infants without PPHN. After excluding 130 some deaths within the first 20 days of age 14,000 preterm infants without PPHN were included in the evaluation of demographic characteristics and short term prognosis between infants with and without post acute no treatment of the 14,000 Surviving non PPHN infants seven that 8000 were excluded from the follow up study at three years of age for either deaths or loss to follow up. Okay, so now that we've laid this out, let's look at some of the results. So prenatal and Perinatal characteristics of extremely preterm infants receiving postacute, I know which was these 14,000 infants are reported in Table two, the birth weight and gestational age were significantly lower. And the prevalence of clinical and histological chorioamnionitis was higher in the post acute iron ore group than in the non iron ore group. So I guess the gestational age, being in the birth weight being smaller is not really surprising. I think the prevalence of histologic and clinical chorioamnionitis is very interesting. Another interesting result was that the prevalence of all INR use among the 16,000, extremely preterm infants increased from 3.3% in 2003, to 13.4%, in 2016. So a very dramatic increase over these 13 years. And then they say something that could be, I guess, both well interpreted and misinterpreted. Also, they said over the same time period, the survival rate of extremely preterm infants registered in the network improved from about 80% to 91.7%, in all extremely preterm infants, and from 58% to 78.8%, in 22, to 23 weeks of gestational age. So let's unpack this for a second. So they're saying you could interpret this by saying, well, their numbers got better because they were using the freaking nitric oxide. But you could also I think, what the intention in the statement was, and they talk about in discussion is more and more very small babies are surviving, which if you just read the previous result, which is that the babies were smaller and more immature, do require more nitric oxide. Maybe that's the reason why it went up. I just want to mention how casually this has mentioned also, these numbers, that extremely preterm infant survival went to 91.7%. And that their 22 to 23. Week, survival went from 58 to 78.8%. I mean, this is this is the reason why I wanted from eco number to come to the conference, because we need me to learn how they get these amazing numbers. And so they're very meticulous groups in Japan. So there's definitely stuff to learn. Alright, moving on to some of the other results. The weather, I don't know the law, right. Okay. The use of I know for PPHN increased significantly during the study period in all extremely preterm infants and for infants at 22 to 2324 25 and 26 to 27 weeks of distinction. Now, when they're looking at the use of post acute Ayano, it showed the biphasic pattern different from that of PPHN, which I just mentioned. The number of extremely preterm infants with post acute I know initially increased but sharply decreased in 2009, consistent with the timing of vinyl insurance coverage approval in Japan. However, surprisingly, the number of post acute no cases has increased again, despite strict insurance coverage rules starting in 2009. After 2009, the number increased again in all gestational age groups, from nine in 2009 to 52. In 2016, and particularly the proportion of 22 to 2323 weeks of gestational age infant receiving postacute, I know increased approximately six fold from in 2000, from point 3% in 2009, to about 2% in 2016. The number of implementing facilities with similar fluctuation and increased from eight in 2009 to more than 20 in 2012. A few more results, and then we can conclude the median duration of no treatment was longer in the post acute I know group than in the PPHN group. That's not really surprising considering the pathophysiology of why you're using it. And then table four in the paper was interesting because it showed the factors that were associated with the use of post acute iunknown. And this was gestational age, small for gestational age status histologic chorioamnionitis, the five minute Apgar score of four or less the presence of pneumothoraces, and this bubbly slash cystic appearance on chest X ray. This was obviously the multiple logistic analysis results. And finally, Table five shows the long term Norther mental outcome at three years of age and multiple regression analysis demonstrated no correlation between postacute I know and northern mental outcome, even between 22 to 2324 25 and 26 to 27 weeks of gestational age. And so the conclusion is that the number of post acute Ayano cases among extremely preterm infant has significantly increased over time, especially for 20 to 23 week infant born at that gestational age, despite nuclear evidence, and the financial costs of I know, extremely premature, extreme prematurity, prenatal infection and severe BPD were significantly associated with post acute I know, and considering that there is no correlation between the posts, the use of post acute I know and the other mental outcome, further investigation is warranted to confirm the benefits of post acute I know, for extremely preterm infants over medical cost with optimal targets. This fascinating, fascinating pattern of use, and it's always the same with I know, we like our AI. No. And we like to try it. And I think we use it more and more. And I think we don't really care that it does. We just want to keep using


Speaker 1 37:56

we well, yeah. I mean, it depends on what outcome you're looking at. I mean, I'm glad that we're looking at neurodevelopmental outcomes. That's that's just not the immediate outcome that I


Ben 38:08

I have a feeling that people are going to are going to read this and they're going to say, Great, neuro D'Amato outcomes are not worse. They're not worse. I can keep using my No,


Speaker 3 38:18

I guess that I mean, it's good to know then to pick a tool, study it and then find out in a decade that, you know, mixtures of the top comes bad. Right. So I think that hopefully,


Unknown Speaker 38:32

they'll share a lot of this a lot more data.


Ben 38:34

Yeah, I don't know. I don't know about that. I was thinking about that. I was thinking do we do what if we were to do this in a prospective fashion? Like, can you imagine being being asking someone to say no, your baby's randomized to know, I know, and like you're in a pinch and you need to use I know.


Speaker 3 38:48

Well, I mean, that's true of lots of things, right? Yeah. I mean, not that's why so many studies have a bailout, you know, for


Ben 38:56

you, but I think we would use that bailout everybody over at some point. This episode is proudly sponsored by rocket meat Johnson. Recognized Johnson is dedicated to the research and development of nutrition products that help support baby development at every stage, including an extensive and female portfolio for premature and low birth weight infants. Learn more at HCP dot meet johnson.com. Yeah, anyway, we're digressing here. We normally do another one to give you a bit of a break and then No, I'll


Unknown Speaker 39:25

go I'll go. Okay.


Speaker 1 39:28

I have this article outcome of early school age and adolescence after hyperthermia treated hypoxic ischemic encephalopathy and observational population based study. Lead author Katerina Grossman, trailing author Katerina Lindstrom, this is in the archives of disease is coming to us from Sweden. And so they wanted to look at the long term outcomes following HIV treated with therapeutic hypothermia. All in all, they it's 66 infants treated with therapeutic hypothermia due to HIV between 2007 and 2009. And then their long term follow up consisted of at six to eight years. And then again, for the majority of infants at 10 to 12 years of age children were assessed using this a standardized neurologic exam. They were assessed using the movement assessment battery for children. The second edition, oh of the of the MA BC, the movement assessment assessment battery, they use the Wechsler Intelligence scales, and then parents use this five to 15 questionnaire which is a screening for developmental and behavioral disorders. This study included all events with gestational age greater than or equal to 34 and Oh weeks treated with therapeutic hyperthermia due to HIV in the greater Stockholm catchment area from January 2007 to December 2009. And the way their system works, and there are two tertiary level neonatal intensive care units, there's one at Carolyn in Karolinska that serve as Sorry, there are two tertiary level Neonatal Intensive Care MC use at Karolinska University Hospital which serve as the regional therapeutic hypothermia center. So all infants that meet the treatment criteria for therapeutic hypothermia are funneled to those centers.


Unknown Speaker 41:29

And then the primary outcome


Speaker 1 41:32

among survivors was defined as Cerebral Palsy epilepsy hearing or visual impairment full scale IQ below 85 Attention Deficit Disorder with or without hyperactivity, Autism Spectrum Disorder or a Developmental Coordination Disorder. So basically, what they did is they wanted to see what was the kind of frequency of having any of those disorders at the eight to eight to 10. There's the six to eight checkup, and then at the 10 to 12 year check. So a little bit of baseline criteria, I told you they had 66 infants and under a period of hypothermia during the time period available follow up, or infants were born late preterm at 34, and oh, 35 135 and 335 and six weeks for infants were cooled with mild HIV is Sarnoff grade one. There were three infants in whom active therapeutic hypothermia was initiated late after six hours due to the onset of seizures. Seven infants died after discontinuation of intensive care given poor prognosis. The neonatal mortality was 10%. And so the total they had of these infants to discharge was 59. One infant was found to have genetic syndrome, so it was then later excluded from further analysis. So at this group of babies that they had, and the mean age at the first assessment was 7.4 years and the mean age of the second assessment was less than two years. So first, they looked at the group among survivors without cerebral palsy. So three children or 6%, had a diagnosis of a Developmental Coordination Disorder at the early school age. And then by the second observation by early adolescent, two more additional children were diagnosed with DCD Developmental Coordination Disorder, bringing the incidents to 10%. The proportion of children scoring less than or equal to the fifth percentile in the movement assessment battery for children with significantly increased compared with arms at both assessments, specifically at the early school age 11. Children are 25% had an M ABC less than 50, less than or equal to 15 percentile, and then in early adolescence is increased to 13. Children are 30% significantly higher compared to norms. Yeah. And they looked at, again, children without cerebral palsy, what were some of the other kind of daily problems so at early school age, three children had a diagnosis, a diagnosis of ADHD, one of them had dyslexia, and one also had, in addition, Developmental Coordination Disorder. One child had autism spectrum disorder, one child had profound bilateral hearing loss of one child had unilateral blindness. On the repeat assessment in early adolescence, executive difficulties were evident in seven more children. In an early school age, the results of the five to 15 questionnaire were unremarkable compared with norms. However, in early adolescence, the proportion of children with a score greater than 95th percentile so kind of flagging on the on the assessment was significantly increased compared with norms within the motor skills, executive functions. perception memory and language domains. So again, a much higher proportion of children kind of meeting that criteria. At early school age, when they looked at IQ 46 children compared to completed the whisk, the mean, full scale IQ was 104. The mean index scores were all within the normal range. This included the child with ADHD and dyslexia. Who though had this? Let me tell you what this is deaf borderline and textual function. Sorry, let me say that again. So the one child with ADHD and dyslexia had this kind of borderline into intellectual functioning. In early early adolescence 45 Children completed the whisk. And the mean full scale IQ was 100.9. The mean index scores were all within normal range. And in early adolescence, the two children two children with previous diagnoses, one ADHD and a Developmental Coordination Disorder in one child, and this CP, cortical visual impairment and epilepsy in the second child, were then later found to have borderline intellectual functioning. Furthermore, for children with favorable outcomes, that early school age now also had diagnosis of borderline intellectual functioning, the number of children borderline intellectual functioning, that's increased from one 2% to seven 12%. By early adolescence. They had some other data on the children with CP one child was CPE, and cortical visual impairment took the test with the aid, revealing a cognitive ability equivalent to two to three years, another child with cerebral palsy was not able to complete all included tests. But those that did indicated normal, intelligent three children with CP had results within normal range on both occasions. So I mean, the overall, the overall gist of the study is we see so just the gist, the gist is that, and in children, the history of hypothermia treated Ha, even those who have kind of a seemingly favorable outcome at this early school age evaluations exhibit emerging deficits by early adolescence. So this is kind of consistent with what when we spoke to Betsy peon from hope hope for Hae is that, you know, it's just not it's not just a diagnosis that you get. And then Nick, you, you know, it needs ongoing reevaluation and assessment and families have changing needs as as children age through the specially the educational system.


Ben 47:50

Yeah, I mean, this just, this is one of these papers that just makes me feel a bit powerless, you know, because it's, we work so hard and you feel proud, I'm going to say something that's completely wrong, but like, you feel so good when you when you capture the baby and you and you start decoding you're like, Ah, I was able to intervene. Right? Right. And if you're so comfortable,


Speaker 3 48:10

this treatment, and it helps babies. Yes, it's


Ben 48:13

right. It's like, ah, the baby is born in our center, we get to be able to do this. And then you see these papers. And it's like, it's not. I mean, because granted, right? This paper does not compare. It's only about babies who underwent therapeutic hypothermia. So and


Speaker 1 48:29

we don't know much about we don't know much about the clinical picture. We don't know much about the MRI findings. We don't know those things. Yeah,


Ben 48:36

it's tough. All the babies,


Speaker 3 48:38

all the babies that they call during that time, it's even


Ben 48:42

tougher to hear that this is like all the way like to see these results all the way up to adolescence. And you're like, Oh, this is gonna follow them that late. God dammit anyway. So it's kind of


Speaker 3 48:51

I think the message is, when parents ask for our opinion on long term prognosis and, you know, those of us involved in kind of follow up is that


Speaker 1 49:02

we have to just continue to provide the resources and continue to do the screenings, so that kids have all the access, they need to get opportunities.


Ben 49:11

I have two more papers. One of them is kind of cool. One of them is is a real paper. I'm kidding. They're both real papers. But the first one is called. It's a very serious paper. It's called supporting all breaths versus supporting some breaths during synchronized mechanical ventilation and neonatal systematic review and meta analysis. First author is do Shante Batra and it's in the archives of disease in childhood, and it's coming to us from the UK. It's a very interesting paper because it's I've been giving my my vent talks to a few of our onboarding physician assistants that are rotating through a unit this these days and we talked about this. So in the UK, the National Institute for Health and Clinical Excellence the nice is published guidelines for specialist respiratory Care in preterm infants in 2019, recommending the use of volume targeted ventilation for preterm infants. This guideline supports the use of SMD but recommends against the use of ventilation modes that support all breaths, including assist control ventilation, and pressure support ventilation. The authors from this paper claim that the network meta analysis that was used to make this recommendation did not review head to head comparisons of studies comparing si MD with modes of with mode supporting or breaths. So to summarize, if you need a bit of a refresher in your ventilation, make settings right you have a says control ventilation where every breath that the baby triggers on the vent is supported to the same extent, right. So you set the you set the target volume, or if you're performing pressure, you set a target pressure, and every time the baby triggers the vent, the pressure that pressure is being delivered. When you compare that to si MV or pressure support, si MV with no pressure support, basically, the baby can trigger the vent. Sure, but the supportive breaths are happening at a certain frequency which are corresponding to the respiratory rate that you set on the vent. And in between those breaths the baby can breathe, but won't receive any support. You can introduce pressure support in those modes, where in between those mandatory breaths the baby can trigger the vent and will be supported to an extent that you determine with your pressure support setting I hope this is clear, but this is going to help us continue talk about this paper. The question is basically the they wanted to conduct a systematic review and meta analysis of studies comparing modes of synchronized ventilation supporting some breaths and I guess IMV versus mode supporting all breaths like assist control, pressure support ventilation, or Nava. So they looked at patients the meta analysis the query was done the following way they were looking at neonatal received mechanical ventilation, and the intervention was si m v meant ventilation. The comparison was mode that supported all breaths, which as we just mentioned, the outcomes of interest were death before discharge and bronchopulmonary dysplasia at 36 weeks of gestation, weaning duration incidence of Ehrlich's extubation failure postnatal steroid use piton ductus arteriosus, requiring treatment severe AVH PVL and northern mental health coma two years, the looked at randomized or quasi randomized clinical trials, comparing a time these SIV with triggered ventilation modes supporting all breaths and neonate reporting on at least one outcome of interest to be eligible for inclusion in the review. Sadly enough, only seven publications describing eight studies fulfilled the eligibility criteria, they found no significant difference in mortality, or BPD, at 36 weeks, but the winning duration was significantly shorter in support all breaths or breaths group with a mean difference of 22.7 hours. There were no difference in any of these other outcomes. extubation failure, which is one that I was sort of interested in, because we'll talk about that in a second, was reported by five studies and included the 188 neonates extubation failure had a trend favoring supporting all breaths. But this difference was not statistically significant. The conclusion of the article are that compared with its IMV, synchronize modes, supporting all breaths are associated with a shorter weaning duration with no significantly, no significant differences in mortality BPD or other outcomes, larger studies to compare these modes are needed basically. I think what's very interesting about this paper is that it goes back to intent, in my opinion, why are we doing what we're doing? I think, as I was trained by Dr. banglori, these these, you want to support all breath because the the resistance of the tube is is quite significant. Now the extent to which you support all these breaths can be varied, you can set a lower pressure support, or not. But you really have to understand whether you're in a winning phase of a patient's ventilation stage or not. I think if the baby that's not doing well, you don't want to make them work too much. You may want to support old breaths, equally, letting the nurses control fashion. And as you're getting on your path on your way to getting excavated and maybe you can start introducing pressure support weaning that pressure support, and so on. So I thought this was very interesting. It was kind of let me say it was kind of ballsy for them to just go like, hey, the guideline says this, and we think they're missing. They're missing some things and we're going to show you so kudos to the author's very, very cool paper.


Speaker 1 54:44

I think your point is well taken, though, you know, we can't use the same mental literary mode for most babies across an admission right like unless you pick event dilatory mode that is more self weaning. Right that's a difference. Oh,


Ben 55:00

absolutely. Should I do my last one? Sure. Okay, the last one that actually is another one that just the title grabbed me and I had to read this. So it was published in the Archives of disease in childhood, and it's called birth order and morbidity and mortality to hospital discharge among inborn. Very low birth weight, very preterm twin infants admitted to the neonatal intensive care unit a retrospective cohort study first author is Irisa del Pino Hernandez del Pino Hernandez I didn't mean to put an NDA on the piano. Sorry. The background of the paper is that the incidence of prematurity is three to five times higher in twins than Singleton's now compared with Singleton's infant mortality and twins has been estimated to be more than six times higher. And then they say historically, the second twin has experienced a higher risk of perinatal morbidity and mortality. And it's funny because I was like, Sure, but like really like, and they talk about it as if like, it's very well known. Right. Right. And so I went back,


Speaker 3 56:05

I mean, it feels that sometimes it feels that way. Right, exactly right.


Ben 56:09

I was like, it feels like that. I'm like, I totally agree. But I'm like, it's like well known as if it's like it's been extensively published and then the put references and especially in the OB literature, there is a ton of data to show that like the second twin does worse. This disadvantage is hard,


Speaker 3 56:25

right? Like what why were you the second the BB assigned the you know, why are you the second twin? Where is it by C section or vaginal delivery.


Ben 56:36

We will address some of these concerns that you have. So this disadvantage has been attributed to differences in sex birth weight mode of delivery, Apgar score or time interval between births. The aim of the current study we're talking about was to determine the association of birth order with risk of morbidity and mortality in V. LBW, very low birth weight preterm in twins, less than 32 weeks of gestation in the context of modern perinatal care, what they're basically saying is say, you know, Perinatology and neonatology has evolved. We're really good at what we do these days. Is that still true like because these papers talking about the second twin are a bit older, so they're like maybe, maybe it's no longer true. So this is a retrospective analysis of prospectively collected data from cohort of VW twins delivered in the Collaborating Center of the Spanish neonatal network, the Sen. 1500. Over a 10 year period, they included babies who were born alive in born with 23 within 23 to 31, plus six weeks of gestation. Pairs of patients in which both twins were admitted to the neonatal intensive care unit. They excluded out born patients patients who died in the delivery room those with severe congenital anomalies and triplets or higher order multiples also excluded the defined major morbidity as the presence of severe ivh or PVL, moderate to severe BPD. Next stage two or more ROP, stage three or stage three are requiring treatment and late onset sepsis. So let's get to some of the results they included 4222 infants among the 166 patients who died in the delivery room 45 were twins 55.6% were first twins and 44% second twins. Second twins had a lower birth weight, and were more frequently small for gestational age. No significant differences were found for other entro and anthropometric data. By the way, let's talk about this for a second. We're talking about the second twin as the second child being delivered. There's like we've talked about this with I forget which guest maybe Nick Campbellton Nick Campbellton is the one we spoke about twins a lot with and there's a lot of cultural differences as to what do we consider the first born the first twin, whatever. And it's kind of cool, but in this case, it's the second child that is born. First twins exhibited more frequently a premature rupture of membrane and the longer time since rupture of membranes to birth. Second twins showed lower Apgar scores and need for more oxygen in the delivery room. Second, twins develop more frequently respiratory distress syndrome and required more frequently surfactant administration after adjusting for birth weight. Some other findings, these ones we're not seeing that statistically significant. Second, twins also needed more oxygen and invasive mechanical ventilation after admission to the NICU and pharmacological closure of the PDA, exhibited more frequently late onset sepsis, but all these differences disappeared after you adjusted for birth weight. And the majority of morbidities after admission to the NICU were similar between twins. The length of stay was similar between first and second twin and second twin. So that's the other thing that I wanted to mention the last finding I want to make because I knew you were going to ask about This so I wrote it down. Second twin born by C section after a vaginal delivery of the first twin tended to have worse results, although they were only statistically significant for major brain damage, survival and survival without major brain damage, which means I almost want to take that category separately. Because if you like you're dealing with kind of a mess when the first one goes, right, especially the C section you have to convert. It's not it's not it's I mean, from my experience, at the very least, it's not common. And


Speaker 1 1:00:31

send it's a little bit. It's chaos. Yeah, exactly. And the reasons why that happens are right are part of the problem,


Ben 1:00:39

right. But definitely, if that that scenario enters the equation, you could see very significant differences between the two twins. Now, the conclusion of the article is that in modern paleontology advances is apparent, okay have reduced the differences in morbidity and mortality related to twin orders. And the second twin are at an increased risk of maladaptation. Immediately after birth, as we as we spoke, the need for oxygen and stuff like really immediately after birth, and the need for sort of respiratory support in the delivery room and such. But after recovery of these acute events, no differences in chronic lung disease or in the risk of mortality are observed. Survival, and survival without major morbidity are currently similar between twins, regardless of birth order, with the exception of second twins delivered by C section after vaginal delivery, as we just spoke, who are at an increased risk of major brain damage and less likely to survive without major brain damage. So the second twins have a lot to look forward to this


Speaker 3 1:01:38

makes you really happy, you know, because, gosh, when you think about perinatal risks, it's just seems like, well, some kids have a really stacked deck and to say like, just because you were the second twin, because of the way you guys were lined up in there, you know, like,


Ben 1:01:53

so I was very happy to see that, and very happy to see that. They have equal chances. And, and I think that's it for me today. I mean,


Unknown Speaker 1:02:03

yeah, I have one more,


Speaker 3 1:02:04

let's do it. Okay. This is a it's, it will be quick, but I thought this was


Ben 1:02:09

just rushed.


Speaker 1 1:02:12

It's called cumulative risk factors contributing to hearing loss and preterm infants. And lead author Cathy chant. Senior author, Neil Marlowe, this is also in the archives of disease of childhood. So this is coming to us from the UK. But I think this is a question that parents ask us a lot. And in general, I don't feel like I give great anticipatory guidance about this. So I was happy to see it. But I thought their background section was very useful. So I'm just gonna give this little blurb neonatal hearing impairment has a prevalence between one in 701 in 1000, in the general population, and this second is the second most common developmental disability worldwide, hearing loss and infants born between 28 and 31 weeks of gestation is six times more frequent than in bursts that term, then that's not in the that's not in the extremely low birth weight, populate, you know, that's in 20 to 31, weaker, right? And this rises to 1.1 to 2% of survivors for bursts before 28 weeks, and has not decreased Despite improvements in neonatal care. So I think that's a serious, you know, complication of prematurity that we don't talk enough about, they wanted to look at the individual and the concomitant risk factors associated with hearing loss and prematurity including I thought this was really cool. You know, we know that gentamicin is a risk factor for ototoxicity. But there's a specific mutation that predicts ototoxicity Follen, gentamicin exposure, it's the M dot 1555. A to G mutation. So, they also wanted to evaluate this in this group of preterm infants. So they had this study of infants less than 31.6 weeks gestational age between 2009 and 2013, who were found to have hearing loss and for each child with hearing loss, they had matched controls and they controlled for sex, gestational age calendar year of birth and neonatal unit. exclusion criteria were known genetic condition other than this mutation that they were looking for. The intervention they really were just comparing the clinical data between the two groups. I thought it was neat. They use salivary swabs for genetic testing and the mutation just to reminder that more and more things can be tested via salivary swabs. It's not an easy process, but just something to to consider as people are designing their research protocols. So the definition Okay, they wanted to look at a variety of risk factors. So they looked at this quote unquote, physiologic risk factors. So poor renal function, a creating greater than 90 millimoles per liter acidosis of have a pH less than 7.2 or lactate greater than two and high bilirubin levels. They also looked at medications that are known to be owed to toxic including, I'm sorry, they the medications were ama case in Gent, VANK, Li six and indomethacin or ibuprofen. They also looked at other medications to forget that lasix is out of town. Yeah, they talked


Speaker 3 1:05:37

about that specific, right. Did you really need that dose of lasix? Yeah, that's right.


Speaker 1 1:05:44

And then they looked at other medications that would indicate, you know, severity of clinical picture. So I know tropic support and steroid medications. And they looked at morbidities of PVL, oxygen at 36 weeks sepsis and a PDA. So the results, they had 180 Children normal hearing, they had 57 children with hearing loss that included 86% of the babies with hearing loss had bilateral impairment, and 3% was mild. So this 21 to 40 decibel range. And if you remember the decibel range, we're supposed to keep the NICU is less than about 45. So kind of a like,


Unknown Speaker 1:06:28

just above a whisper just kind of a normal talking voice.


Ben 1:06:31

Keep it less than 40. No,


Speaker 3 1:06:33

no 45. Okay, it's tough to keep the


Speaker 1 1:06:38

less important. 51% is moderate 41 to 70 decibels 21%, severe 71 to 95 decibels at 25% profound hearing loss. Children did have an increased frequency of auditory neuropathy spectrum disorder. And that's versus like having kind of cochlear hearing loss. And the babies with this auditory neuropathy spectrum disorder had higher birth weights were more likely for multiple pregnancies and were more likely that PVL the children with hearing loss had lower birth weight and lower Apgar scores, Apgar scores. Interestingly, only one child was found to have that mutation and they were in the control group of notice infant did receive gentamicin but had normal hearing in two years, and then was later found to have a high tone hearing loss after three years. So for the primary outcome, more children with hearing loss had one or more episodes of acidosis are more likely to have either trophic support or elevated creatine, they were more likely to receive djent VANK, steroids Lasix, but not in my case in the medicine or ibuprofen, and in our cumulative days of gentamicin bank, or lasix administered as well as more total days of any antibiotic. Over the first two weeks of admission, the total number of risks each day were significantly higher in those with hearing loss. And then the subsequent clinical period from week three to 12. children with hearing loss additionally, had a had an higher number of weeks, in which they receive gentamicin, vancomycin, or lasix than normal hearing children. And overall, the number of days exposed to risk factors is much higher for children with impaired hearing in comparison with children with normal hearing. So none of that is surprising.


Speaker 3 1:08:31

I think the sicker the baby is, the more likely they are to have hearing loss.


Ben 1:08:36

Let me interrupt you then the way you should conclude this paper is by telling us how are you going to now reframe your counseling since that's how you opened because


Speaker 1 1:08:44

because I think we think okay, oh, this baby, oh, this baby was on gent and vain, right? This is a baby that we really got to look out for that, that hearing tests, we got to make sure they get the hearing test before they you know, go home when we get you know, get them the follow up. But it's not just the baby that had a normal hearing screening like these babies who had a lot of a tenuous course need need real hearing follow up, I think is what this paper tells me. And even if we avoid Jain gent, which we do a pretty good job per unit.


Speaker 3 1:09:23

Even if we avoid Vang, which is potentially harder.


Speaker 1 1:09:30

It's this combination of the clinical status that if you had a really rough clinical time that that hearing loss is is you're really at risk. Right? I think Anyways,


Ben 1:09:46

that's all already.


Speaker 1 1:09:49

Wait. I wanted to tell you one more thing, please. They did do a logistic regression. They looked at obviously multiple regressions and in the final model, brain injury The presence of a PDA were independently associated with hearing loss, in addition to the use of inotropic medications, and there was an unexplained protective effect of ibuprofen administration to treat the PDA. So, just another, just another egg in our basket for the VA discussion.


Ben 1:10:22

All right, Daphna. Any parting thoughts before we close our journal club? No, thanks for bearing with please take care of yourself. Drink some. What is it drink some hot tea?


Unknown Speaker 1:10:31

Yeah, I got it.


Ben 1:10:35

And we'll see you guys were I think we may be releasing more in your reviews neonatology review podcast this week, so we'll see each other this week. Thank you have a good rest of your day. No, no, goodbye. All right. I had a cough. Hi, everybody. 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 podcast@gmail.com. You can also message the show on Instagram or Twitter, at NICU podcast or through our website at WWW dot the dash incubator.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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