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#128 - 📑Journal Club

Hello Friends 👋

We have a fresh episode of journal club today! This week, we reviewed a number of papers ranging from neonatal opioid withdrawal syndrome, deregionalization of neonatal care, vasopressors, and much more. If you missed out on swag giveaway during PAS and would like to grab some incubator gear check out our brand new online store at

Have a good sunday!


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

Zaveri PG, Walker AM, Upadhyay K, Talati AJ.Am J Perinatol. 2023 Apr;40(5):513-518. doi: 10.1055/s-0041-1729558. Epub 2021 May 14.PMID: 33990125

Christie FG, Kelly R, Boardman JP, Stenson BJ.Arch Dis Child Fetal Neonatal Ed. 2023 May 4:fetalneonatal-2022-324833. doi: 10.1136/archdischild-2022-324833. Online ahead of print.PMID: 37142388

Young LW, Ounpraseuth ST, Merhar SL, Hu Z, Simon AE, Bremer AA, Lee JY, Das A, Crawford MM, Greenberg RG, Smith PB, Poindexter BB, Higgins RD, Walsh MC, Rice W, Paul DA, Maxwell JR, Telang S, Fung CM, Wright T, Reynolds AM, Hahn DW, Ross J, McAllister JM, Crowley M, Shaikh SK, Puopolo KM, Christ L, Brown J, Riccio J, Wong Ramsey K, Akshatha, Braswell EF, Tucker L, McAlmon KR, Dummula K, Weiner J, White JR, Howell MP, Newman S, Snowden JN, Devlin LA; ACT NOW Collaborative.N Engl J Med. 2023 Jun 22;388(25):2326-2337. doi: 10.1056/NEJMoa2214470. Epub 2023 Apr 30.PMID: 37125831 Clinical Trial.

Boghossian NS, Geraci M, Phibbs CS, Lorch SA, Edwards EM, Horbar JD.JAMA Netw Open. 2023 May 1;6(5):e2312107. doi: 10.1001/jamanetworkopen.2023.12107.PMID: 37145593 Free PMC article.

Garvey AA, El-Shibiny H, Yang E, Inder TE, El-Dib M.Pediatr Res. 2023 Sep;94(3):1011-1017. doi: 10.1038/s41390-023-02580-8. Epub 2023 Apr 6.PMID: 37024670

Donà D, Gastaldi A, Barbieri E, Bonadies L, Aluvaala J, English M.Am J Perinatol. 2023 Apr;40(6):646-656. doi: 10.1055/s-0041-1730364. Epub 2021 Jun 14.PMID: 34126646 Free PMC article.

Yozawitz E.N Engl J Med. 2023 May 4;388(18):1692-1700. doi: 10.1056/NEJMra2300188.PMID: 37133587 Review. No abstract available.

Berlin KEK, Gray MM, Myers PJ, Scheurer JM, Robin B, McLean C, O'Reilly D, French H, Vasquez MM, Castera M, Redford KM, Edgar L, Johnston LC.J Perinatol. 2023 Apr 24. doi: 10.1038/s41372-023-01683-8. Online ahead of print.PMID: 37095228 Review.

Kole-White MB, Saha S, Werner EF, Chawla S, Keszler M, McGowan EC, Wyckoff MH, Laptook AR; Generic Database Subcommittee of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.J Perinatol. 2023 Apr;43(4):430-436. doi: 10.1038/s41372-023-01631-6. Epub 2023 Feb 22.PMID: 36813902 Clinical Trial.

Lode-Kolz K, Hermansson C, Linnér A, Klemming S, Hetland HB, Bergman N, Lilliesköld S, Pike HM, Westrup B, Jonas W, Rettedal S.Acta Paediatr. 2023 May;112(5):934-941. doi: 10.1111/apa.16590. Epub 2022 Nov 18.PMID: 36333892 Clinical Trial. ----

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

Ben 0:54

Welcome Hello, buddy. Welcome back to the incubator podcast. It is Sunday. How are you guys?

Daphna 1:05

I'm doing good. Set. My fire alarm is

Speaker 3 1:08

how are you? Hey, Ben, and Daphna? How are you guys? Yeah, it's good to have you want to say I had some FOMO you guys were at PHS tweeting, talking to everybody in here. I was I was not there for the first time in a long time. But really glad to be here today.

Ben 1:25

Toronto 2024.

Daphna 1:27

We did have fun though, didn't we?

Ben 1:28

We did have

Daphna 1:29

fun and the swag. So next year you'll come with

Speaker 3 1:33

I would love it. And the swag. I love the swag. I'm sure you got a lot of questions about it. Ben is wearing his today. I see. He's obsessed with it.

Ben 1:44

By the way, yeah. By the way, Priya, your your jacket is at my house. So I have to find a way if we're not going to find a way to get one to see one. And to see each other in person. I'll have to match it. But it was funny because we made for the people who don't know, we made these North Face jackets with the incubator logo on it because we wanted we told people that we were going to be at PBS and we thought if you stop us in the halls, and you say, hey, and you said hi to us, we're gonna give you swag, right? And we said maybe we should have like something that we were that people recognize us because they know our voices. Nobody knows what we look like they may know not know what we look like. So we made those jackets, right? And those jackets turned out to be more expensive than I anticipated. But, and so we handed out swag, which was like stickers and T shirts and stuff. And some people were like, Oh, the jackets are really nice. And I'm like, Yeah, I mean, I don't have we're not making that much money that I can actually hand these out. But it was funny that the jackets were very popular. I must say the store on the incubator podcast is up. So if you want to buy some incubator swag, or some funny NICU shirts and mugs and stuff, it's there. And yeah. And well, we'll have new stuff. So yeah, we're gonna try to take down some of the, we'll leave some incubator swag permanently on the store. But we'll try to refresh the little collections here and there. So definitely is our creative content director for that. I don't know about that. But the big news of today is that Daphna is having some fire alarm issues. If during Journal Club today, we will be to disrupt if you hear a little beep, it's deafness. It's not the

Daphna 3:18

beep. It's the lady that's like, battery is low. It's

Ben 3:23

don't really hear that. We can't hear that. We could hear a very loud and screeching beep, but suddenly upset

Daphna 3:29

with the smoke alarm lady. As much as I record for the record. I have tried to fix it.

Speaker 3 3:34

There's a good meme about that. I bet you've pulled the batteries out. It still beeps

Daphna 3:38

Yeah, I'll have it. I'll have it changed him. Yeah.

Ben 3:43

All right. We are here with the journal club. This is fun. I mean, there was so many cool articles this month and and lots of different things. I don't know who someone wants to get started.

Daphna 3:58

Well, Priya, you're you're a guest of honor when he

Speaker 3 4:00

i Yes, more. She's just a regular. I love this article, because I think vasopressors are very interesting topics, especially for pharmacists. So I'm going to present to you today the use of vasopressors in extremely preterm infants in the first week of life. And this, it is, it is and the first author here is poor rolls of Zaveri. And she's from the University of Tennessee, and this was published in the American Journal and Perinatology. So as you all know, systemic hypertension is really common in the NICU and about 50% of extremely preterm infants will receive treatment for hypertension. And this can be fluid boluses, vasopressors, I know trips alone or a combination of any of these. And much like everything else, there's a lot of variability in the NICU, when we are diagnosing and treating hypotension. So many places use the map or the mean arterial pressure, and when it's less than two weeks of gestational age at birth, that's considered, you know, hypotension or they're in newer studies that sort of say that this superior vena caver or SVC, blood FFO might be a better indicator for end organ perfusion. So the question these authors wanted to answer is can we identify characteristics of extremely preterm infants, and they define that as less than or equal to 20 weeks of gestational age, who received vasopressors in the first week of life, as well as the association between the clinical outcomes, and the use of vasopressors. So the study design was a single center retrospective study that reviewed medical records for a three year period, and that was 2012 to 2015. And I think one thing that's really important here to note is that they didn't do delayed cord clamping, no cord milking, that was not standard practice. Therefore, none of the study, infants receive this placental transfusion at birth. Patients that were excluded, were infants who died in the delivery room and those diagnosed prenatally or soon after, with congenital anomalies, chromosome or chromosomal abnormalities. They collected a lot of endpoints, so a lot of maternal data and neonatal data was collected, but I won't go through all of that. And when they analyze the stats, they looked at infants divided into two cohorts. So did you get pressors? Or did you not during the first week of life, so the results, I think they're what we would have expected. So there were 224 infants born 11 were excluded because of the exclusion criteria. So 213 Study infants, 90, or 42%, receive vasopressors for hyper hypotension, as determined by the treating physician in the first week of life. When we look at the demographics, they were pretty similar between the use and non use. And when we look at the univariate analysis in table one, it shows that lower gestational age, lower birth weight, small for gestational age, multiple births, C section delivery, hypothermia, at the time of NICU administers admission, were all associated with a higher incidence of having vasopressors. And that correlates with the lower systolic blood pressure on the map at the time of admission. So those are things I think we would have expected, right. But one thing that they did bring up is that there have been studies that have shown that antenatal steroids might have a protective benefit, and they didn't see that. So they showed no difference in vasopressor use with antenatal steroids, but they did have a really high use at baseline. And so let's talk now about timing. So in infants with vasopressor, use 83% of those patients got that within 12 hours, 91% within 24 hours, and all but one within 72 hours. So that's again, something that I think we would have expected. The mean map was 22. And systolic blood pressure was 31 millimeters mercury at the time of starting vasopressors. And this is where I think this is where you guys can all weigh in. So the initial drug here in all of the patients was dopamine at five mics per kilo per minute, it was titrated, up to 20 50% had dope beauty mean as a second agent, and 17% had all three drugs. So a third of these patients also received hydrocortisone one milligram per kilo Q six, which is pretty standard. And almost all of this hydrocortisone use was once there was two pressors on board. So I have a question for you. You all. First line agent always the same, sometimes different. Is there a protocol?

Ben 8:54

I think there's no protocol. I think for sure you. You want to set Twitter on fire. You want to be trending on fire. If you want to be trending on Twitter just start talking about pressors and Yannick.

Daphna 9:04

Yeah, I think I think this is such a critical topic right now. I mean, I said it's a hot topic. But I think because and this is true across the country, that dopamine is frequently the the first line agent, and we're finding that that's probably not the best choice for all the babies. So you know, I think there's so much work going on right now to decide to decide what is the right agent slash How can we get better at deciding what is the physiology behind the hypertension, and then we can pick the right agent? Yeah, I

Ben 9:39

think you're right. I think there's this. There's a lot of work. We reviewed some of the work especially from the team coming out of Iowa with hemodynamic screening, where maybe volume is what you need and not really pressors. I also think now we have so much more data when it comes to adrenal insufficiency in micro preemies. Then you may want to say maybe steroids hydrocortisone should be your first line agent But also I think what matters most is why is the baby presenting to you with hypertension? Is this a case of infection? Is this a case of hypovolemia? Because the mother, unfortunately had an abruption or something of the sort. I think all these factors matter as to what you start and the decision to make one agent, the standard first line is probably a mistake.

Daphna 10:20

Yeah, I think the protocols that will follow in the next five years will say that, like, why is your baby hypotensive. And if it's this, do this, do that do that.

Speaker 3 10:33

And I think that that, that maybe this is reflective of the time period, right? 2012 to 2015. It's like, you know, these things are coming out now. So when we look at the outcomes, the univariate analysis showed significant increase in early mortality, death before discharge, ivh and BPD in infancy received vasopressors, there was also a significantly higher incidence of ivh, even after controlling for confounding factors. Again, we know that these patients are these babies are smaller, they're sometimes sicker. So not something that is surprising. The limitations of doing a retrospective chart review may make it really difficult to assess whether the treatment for hypotension was just based on the blood pressure readings, or if there was clinical evidence to indicate poor perfusion or if there was both. Unfortunately, this article, this study did not assess the data on the volume of fluid boluses, they did say that their first line is the 10 CC's per kilo of normal saline prior to starting vasopressors. But we don't know how many boluses each patient got. And in the discussion, they talked about the need for hypothermia. So this population, there was a high percentage of hypothermic babies. And they did say that, you know, this is a big intervention for the golden hour that they're tracking this. Another thing that I thought was interesting, interesting it and it's also Hot Topic is targeted echocardiogram to evaluate the SPC blood flow as it could improve the ability to determine when therapy is needed. They mentioned other other medications that are being studied steroids. Mo mil renowned vasopressin. And then, you know, I think there's a lot of mixed data out there on dopamine. So dopamine has been shown to be a superior blood pressure agent, versus dobutamine. But that doesn't always result in better and organ perfusion, there's actually data that shows dobutamine might be more so superior and increasing SVC blood flow, and then also the starting dose of dopamine. And this is where I think my passion comes in, is that some places start dope dopamine as low as two mics per kilo per minute. But there are so many variables on that. So standardized concentration, the baby's weight, the type of pump, you're using, the size of syringe, can all play out, you know, a factor in deciding that. So oftentimes, when you have a tiny baby, even the lowest standard concentration is not going to give you the lowest flow rate. And then some of the infusion devices can't really guarantee that that's the flow rate that you're getting that you might be getting these micro boluses of drug which could be causing that flow in, you know, that change in cerebral circulation, which possibly could result in the ivh. And so, you know, in conclusion, like you both said, it's important to treat the underlying cause of hypotension. And that we know that this hypotension is associated with increased mortality and morbidities. But there's really a lack of evidence that treating hypotension procures any benefit. So the author's pose, you know, the most important question here to address is whether, you know, it's the low blood pressure value in the absence of other evidence of compromised and organ perfusion, whether that has any adverse effects on the neonate is less more in this population. And they concluded that more studies are needed.

Ben 14:16

Yeah, I mean, the study is, is interesting, because the title will really grab you right use of vasopressors. In extremely preterm infants in the first week of life, you're like, Oh, my God, what is this study about? I read it? Yeah. And I think it's important for us to just try to get some of the work out of the way for our listening listeners. It's it's a study of 200 patients, but it is retrospective, it is. There's no systematic use of pressors or address or treatment of blood pressure, or hypotension in this in this study. So that's a difference. I

Daphna 14:44

think that's one of the major limitations is that how do they define hypotension? So they talked about it in vague generalities, but it was really up to the attending, so yeah, you know, so that's the biggest I think that's the biggest

Ben 14:58

concern and And it's not like they were randomized. So basically the ones who got depressors were saying were could be essentially sicker babies and then that would explain why they are ivh. rates are higher, why they're BPD. rates are higher.

Daphna 15:12

Yeah, I guess so. I mean, the study would be that the babies are at this blood pressure threshold so that they get vasopressors. Some of them don't. But I don't have equipoise. for

Ben 15:21

that. So it makes it makes it difficult to to, I think it makes it difficult for us to steer away from. I think it makes it so the reason I'm interested in this study is because I think it shows I think the Hot Topic obviously is is hemodynamic screening, and it's ultrasound. But I think for many of us who don't have hemodynamic screening, yet, in our units, we're still reliant on pressors. And I think this is a study that you could you could say, oh, well, maybe pressors are bad, and I shouldn't use them. But I think the study is now really making this case, I think this study is just showing that vasopressors probably are not as benign, as we make them out to be I don't believe anybody thinks they're benign, but maybe to be used with caution. Yeah.

Daphna 16:02

But to your point, Ben, I think there's still some clinical physical markers that we can use on our exams. We can make sure our mean airway pressures aren't too high. You know, there are other things we can do to assess human dynamics.

Ben 16:18

Absolutely. All right, who's next? That's definitely I mean,

Daphna 16:23

I let you go because I, you have a list I have to get through here.

Ben 16:28

Sure. I can start I have an interesting paper from the archives of disease in childhood, called measuring oxygenation in newborn infants with targeted oxygen range. It's the acronym is monitor, a randomized crossover pilot study, Fraser Christi is the first author, they actually listed all the Twitter accounts of all the people in the in the study, that's kinda nice. So then now we're going to be able to tag them.

Daphna 16:55

So that's our request for the community. That's been

Ben 16:58

a request and it's true. So there's considerable uncertainty that paper says about the optimal approach right to providing oxygen therapy and preterm infants, and the new prime collaboration which is published. Cochrane Reviews and meta analyses show that really a higher target saturation 91 to 95%, rather than lower one like 8985 to 89%, reduced mortality, and necrotizing enterocolitis, but has been associated with an increased rate of retinopathy of prematurity requiring treatment. And at 18 to 24 months of age meta analysis have shown that there's no difference in the primary composite outcome of death or major disability between the two targets. Now, while there's good evidence that targeting targeting extreme premature infants to saturations of 91 to 95%, is associated with improved outcomes relative to lower sets SPO, two targets higher than any one to 95% have not really been studied. And so the question really becomes like, what about if I want to target like 97% 98%, and they say there needs to be a greater understanding of the likely achieved SPO two and Transcutaneous po two patterns that might be observed if clinical care is targeted at higher SPO two range. So it's almost like a physiologic study that they're going to conduct. And I think that's interesting because I think the target saturation range is something that is still remaining a mystery to us as to what's the proper range to aim for. The aim of the study is to explore the achieved oxygenation pattern observed when targeting SPO, two ranges 92 to 97%. In preterm infants. So this was a prospective single center randomized crossover study of two target saturations, either the standard care which was 90 to 95%, or a higher, higher range 92% to 97%. Infants who were born at less than 29 weeks of gestation, who were greater than 48 hours of age and who were receiving oxygen were considered to be eligible for the study. And they excluded infants who had congenital anomalies that would impair oxygenation, like cardiac defect, congenital diaphragmatic, hernia and so on. The intervention was basically rather straightforward. Each infant underwent two sequential six hour periods where the target sets were changed from 90 to 95. And then from 92 to 97%. And all FY two adjustments were made by hand by the clinical team meaning there was no such thing as like, auto. What is it called the Auto Fit adjustment, I'm losing my words, but you know what I mean. Another important point is that there was no washout periods between the two. So like, they didn't really wait any certain time periods. And then what they did was that both in both study groups, whether it was the high or the low saturation, they followed the saturation and the trends cute taneous o to monitor so we're all familiar, I think with the Transcutaneous co2 monitor. And so yeah, so same same concept just measuring specifically, oxygen. The primary outcome of the study was the percent of time spent above the SPO, two of 97%. And the percentage of time spent below a saturation of 90%. And secondary outcomes included percentage of time where the SATs was less than 85%, the percentage of time where they said was less than 80%, the percentage of time where the Transcutaneous auto detection was within above or below 50 to 80 milli millimeters of mercury, and the oxygen variability as measured by standard deviation in the Transcutaneous, OTU and the South. Okay, so the results. The it was a small study 20 patients that were studied over a period of two years, the median gestational age was 26 weeks and six days and the birth weight was 878 grams, the median study age was about 22 days, with a median fit of about 29% at randomization. At the time of the study, to infants were on SIV, eight warranties or CPAP 10, were on high flow nasal cannula. So with the set range of 92 to 97%, versus the lower set range 9095, the mean percentage time spent above 97% was 11.3%. In the higher range, versus 7.8%. In the lower range, which is not really surprising. If you're targeting 90 to 95, you're expected to be less often above 95%. Now, the percentage time of sets spent below 90% was 13%. In the higher set targets, versus 17.9% in the lower set targets, and that was statistically significant. Now the percentage of time with sites below 80% was 1% versus 1.6%. In both the higher SAT and lower sat, respectively, that was not statistically significant. When the targeted when targeted to this set of 92 to 97%. Compared to the lower range, there was not a significant difference in time spent within above or below the recommended Transcutaneous OTU level of 5080 millimeters of mercury. And I think that's very important, right? Because we're this is what the whole point of this paper is, is that you target the set range, but the gold standard for measuring oxygen is basically your your PA or two, right? Obviously, they're not doing art sticks, and they're not measuring this arterial Lee. But this measure of the Transcutaneous, or two level is interesting to see that it's not really changing very much whether you're on 92 and 97 versus 9095. There was no significant differences in variability of auto set when targeting the different targets. So the different auto sets targets, the variability of Transcutaneous are two was the same between the different periods. And the mean set was 93.4% in the higher range, and 92.5% in the lower range. Finally, they showed that on the plots of cumulative distribution of all pooled SATs and otusa and po two values, that targeting a set range that was higher produced, they control the right shift in the SPO to end in the Transcutaneous OTU distribution across the whole observed range without an excess of trans continuous or two values above 80 millimeters of mercury. Now, you may say why do we care then? And I think what's very interesting is that we are always wondering what is the proper set range. And what these authors have been able to show is that moving the targets at higher produce this right shift in the SPO t distribution with reduced time at sets less than 90 increase time with SPO to above 97%. But really without increasing the high Transcutaneous OTU levels, meaning the distal effect of these changes are not readily appear appearing appear apparent at the distal level. And the findings of this study, the authors suggest will be useful in the design of future clinical trials looking at targets of otusa because they show that SPO two range of 90 to 97% can be targeted without really resulting in too much exposure to severe hyperoxia. And I think it's this kind of study while relatively small and maybe a little bit nerdy on the side, but it's just like it's going to help us redesign these next trials looking at target sets that has become now a bit taboo after the support trial where everybody's really afraid of studying it because you're afraid of it's always a trade off. I'm going to cause more ROP and I'm going to do this and that but knowing what is the distal effect is actually weights relevant and interesting.

Daphna 25:03

I liked it. Okay, I have a paper on eat sleep console. Oh, I know you're excited about that. But before I get started, I wanted to share it a thing that I learned this week, because, you know, we try very hard to say people's names correctly. I'm incubated something we're really working on. And I just saw this in somebody's email signature. It's called a name coach. And you can get a what is it called a name badge. And from your email tells people how to pronounce your name. So I'm doing one for my name. So anyways, we're we're, we want to we want to hold on

Ben 25:48

hold on so that means that I did you just explain to the entire audience that we have no excuse for mispronouncing names now.

Daphna 25:54

Yeah, now we have no excuse. Now.

Ben 25:57

What is that thing called? Name? Coach.

Speaker 3 25:59

I thought that was your disclaimer for what you're about to say like, Hey, guys, working. God,

Daphna 26:06

I feel like we're always working on you to name it is so important. So important. So anyways, I just want to I just thought that was such a neat

Ben 26:16

thing that name coaches a paid service, by the way, I'm just telling you right now,

Daphna 26:20

I tried to find it, how much does it cost?

Ben 26:23

I'm gonna find out, you can start you start the review. I'll know.

Daphna 26:29

I'm sure there are other things were to find a way right Ben to make it free for everybody. Not named Coach. We're not coach named Coach, I'm just saying you'll find you'll meet you reinvent. He's gonna

Speaker 3 26:42

make everybody put the phonetic spelling on the article. So that when you so when you pull the article, it tells you the phonetic spelling.

Ben 26:52

All right. So if we keep getting it wrong, is because we don't have the kind of money to purchase this licensing thing. I'm looking at seven. All right, we're getting the fact that the price is not apparent is not good news, but that's okay.

Daphna 27:03

That's fair. Okay. Anyways, this article is entitled eat sleep console approach or usual care for neonatal opioid withdrawal. The lead author is LW young, from the act now collaborative. And this was in the New England Journal of Medicine. So this was a multicenter stepped wedge cluster randomized controlled trial conducted at 26 sites in the United States, again, part of the act now collaborative. So what did they do? They took these Infants who are born greater than 36 weeks gestation, or more, who had been born at or transferred to a trial site within 60 hours after birth, anyway, to evidence of anti natal opioid exposure and who are being treated for opioid withdrawal. So what did the intervention look like they each study site all the study sites had three intervention periods. The first was usual care for that site, whatever their practice was for opiate withdrawal, while the team was kind of learning about eat sleep console, and they were training just Team Champions. So not the whole team, but just people who would then rollout the next epoch. So in the second intervention period, and they had this three month training period where there was implementation of the deep sleep console practices. And then the third epoch was really what they considered the ESC or the eat sleep console intervention period. And if you're not familiar with the approach, I'm just gonna read this to you. So it's a function based assessment of opioid withdrawal severity focused on an infant's ability to eat, sleep, and be consoled, kind of like the ADLs the activities of daily life for for an infant. Infants are assessed by means of the eat sleep console care tool to determine if they have difficulties with any of these activities. For example, does an infant take greater than 10 minutes to coordinate feeding, breastfeed for less than 10 minutes or take less than 10 ml or whatever their age appropriate duration and volume is, does infant sleep less than one hour? Does infant take greater than 10 minutes to be consoled or cannot stay consoled for at least 10 minutes. And it's really a technique to optimize non pharmacologic intervention. So keeping the environment low stimulus, optimizing skin to skin contact, clustering, hands on care, promoting breastfeeding as first line treatments, and it's really about engaging and empowering families or caregivers in the care of this infant. So what were they looking at the primary outcome was a time from birth until the infant was quote unquote, medically ready for discharge. You all know that sometimes babies who are being treated for nows maybe medically cleared but not cleared for some other reasons. So I thought it was really interesting that they picked this as their defined outcome and the criteria for medical Ready to Go ahead?

Ben 30:01

That seems like the right thing to do. No,

Daphna 30:05

I absolutely. But it would be easy to say let's pick the length of stay. But the length of stay could be misleading. Yeah, you're right. Yeah. So the criteria for medical readiness was prospectively defined as an age of at least 96 hours, a period of at least 48 hours without receipt of an opioid, at least 24 hours with no respiratory support. And with 100% oral feeding, and at least 24 hours from initiation of maximum caloric density. Totally reasonable, I think, measures the secondary outcomes. So key secondary outcomes included the receipt of a pharmacologic treatment. So did you get any medication for opiate withdrawal, and they did measure the overall length of stay safety outcomes, I thought this was cool too. And in hospital composite safety measure, so seizures, or some sort of accidental trauma, like a fall, or apnea, and a composite safety measure through three months of age, so any acute or urgent care visit emergency department visit or hospital readmission, and a composite critical safety outcome at discharge, and through three months of age, so looking for things like non accidental trauma, or death. So they had 13 105 enrolled infants 702, during the usual care periods, and 603, during the eat sleep console period, the characteristics of the groups were balanced at baseline except for there was a proportion except for the proportion of Hispanic mothers and the proportion residing in metropolitan areas. And these differences in factors kind of reflected the timing of say transitions. For example, it just so happened that the sites with the larger Hispanic populations transitioned later, so more Hispanic moms enrolled in the usual care epoch. And then the more metropolitan sites had more data in the eat sleep console epoch, but they did account for these in the adjusted models. So the primary outcome, the trial definition, medical readiness for discharge was not actually met by bps, it was met by 837 of 1305 infants 64%. And the most common reason infants did not meet the trial definition were discharge before the age of 96 hours to that was interesting 211 infants and discharge less than 48 hours after the receipt of an opioid 231 infants also very interesting. But among the 837 infants who met criteria for the primary outcome, the mean length of time from birth until medical readiness for discharge was shorter in the EC console group than in the usual care group. So I'm going to babies did you say 837?

Ben 32:44

Okay, sorry. So, I heard 8000. And I was like, eight.

Daphna 32:50

How did that happen? The numbers increased. And so in the eat sleep console group, and those babies were, quote, unquote, medically ready after 8.2 days, compared to 14.9 days. And in the infants who did receive pharmacologic therapy. And this has a rate ratio of point five, five, and it's statistically significant. And in a post hoc analysis, and by involving 89% of the infants in which the modified definition of medical readiness was used, the adjusted mean between group difference was, so they had a mean between group difference was 6.4 days. And I told you about the secondary outcome. The mean overall length of hospital stay was 7.8 days in the eat sleep console group compared to 14 days in the usual peer group. The proportion of infants who received opioid treatment was 52% in the usual care group and 19.5% in the eat sleep control group, that composite measure of infant safety through three months of age so that infants in the eat sleep console group had a risk of adverse outcomes that was similar to the usual here group and the composite critical safety outcome at discharge, and through three months of age was also similar in the two groups. And of course, not surprisingly, there, there was still significant heterogeneity of treatment effect observed across sites. So what are the takeaways easily consoled care approach decreased the time until infants with opioid withdrawal were medically ready for hospital discharge by mean of 6.7 days, as compared with usual care, the use of the approach also decreases the proportion of infants who receive pharmacologic treatment without increasing any of the pre specified safety outcomes. So

Speaker 3 34:33

I've, I've a question for you, Daphna. And you may have already said this, but do they look at the maternal exposure if mom was on like mixed medications versus just one like methadone versus other things, because sometimes you feel that if mom's on many meds, it's harder for those babies to be, you know what I mean? That's the theoretically But was there any demographic data on that?

Daphna 35:00

So I was I'm trying to answer your question you're asking for as it did they just have opiates or benzos or something else. So they did measure poly substance abuse, and so that it can include exposure to opioids and any additional psychotropic agents, excluding nicotine. So they included amphetamines barbiturates, benzos, kratom, which we are seeing here in South Florida, cocaine, gabapentin, marijuana, methamphetamines, phencyclidine, and SSRIs. So it was seen in, in similar amounts in both groups 60 in the usual care 57 in the eat sleep console care group. But it's a great question. Because it's certainly a different clinical scenario with the polysubstance. Ease.

Ben 35:52

Yeah, I thought this was a very interesting paper, obviously, I think, to me, it's interesting how the primary outcome really was the time to, to medical clearance at discharge, which I think is very impressive, because at the end of the day, it's almost like I mean, close to a week, right at the end of the day of difference in how long these babies stay in the hospital, which is huge. But to me, the the reduction in exposure to opioids is is fascinating, right? So I think 20% from from 50% to 20%. That's phenomenal.

Daphna 36:22

Yeah, I was actually surprised, I thought good. I felt given the reduction in an opiate exposure, the neonates that the length of stay would be much longer because I feel like babies either stay have a handful of days or you know, their observation period, or, you know, stay for a very long time on medication. But I think this is the point some of these babies would have gotten medication if they weren't getting, it flipped unsold,

Ben 36:50

I guess. Now, how likely is it for? Let's say, you're an institution, right? And you read, you read this? And you're like, Okay, this sounds really great. How, like, how easy is this to implement? You think?

Daphna 37:04

So I mean, this is not the first paper that's done the data on a sleeve console, most of the other papers show similar efficacy. And I haven't seen a paper about this specifically. But I mean, hospitals are rolling it out. I mean, they really are. I think for some of them, they're showing less resource utilization, because they're really engaging families and doing the care.

Ben 37:33

I think also the always, as I always advocate for go check their supplemental material. And we have, they have a lot of the stuff that they're using the the sleep console care tool that they have is available on the on the supplemental material. As usual, they don't do such a good job of making sure that the resolution of these things are high. So it's very pixelated, but you can gather what they're doing. And they list all the different things, their care plans to consoling. And I think they do things. I think one of the things that I appreciated from their from their tool was that they're really accepting nice expectations. So for example, they'll say, takes more than 10 minutes to coordinate feeding or breastfeed less than 10 minutes, right do and then you sort of have an idea of what what's reasonable to expect for these babies to do. I think this is this is helpful, but this is obviously a very interesting study. And again, being able to reduce both length of stay, or I guess, clearance to discharge. And the exposure to a period is quite important.

Daphna 38:33

I think it also represents sorry, and I'm moving from how we assess these infants, because some non exposed infants, right, have, you know, reasonably moderate Finnegan scores, right. So I mean, I think that's part of it as well.

Ben 38:51

This episode is proudly sponsored by Wreckit. To me 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 All right. Priya, you you want to you want to go and

Speaker 3 39:13

then you have more than me, you go next, and then I'll go after I go. Next. I'll

Ben 39:16

talk about this paper very quickly. Then there was this paper in JAMA Network open by I mean, it's a maybe pronouncing it wrong, but I know this friend is the French name. So Nancy Burgos. Young, right, but Gaussian, I don't know how you pronounce it in English, but in French, it would be Bucha

Daphna 39:31

I think you should feel free to email us.

Ben 39:35

There's a very famous French French soccer player who won the World Cup was in 1998, who was named Bucha. And I'm pretty sure about that one. So I'm gonna I'm gonna stick to my guns. But anyway, we'll see. It's called trends and resources for neonatal intensive care delivery hospitals for infant born younger than 30 weeks gestation 2009 to 2020. It's a very interesting paper. It mentions how in 1976, the March of Dimes committee On perinatal Health published recommendations on perinatal care regionalization. In the US, they included the referral of mothers and infants with high risk of adverse perinatal outcomes to a hospital with a regional neonatal intensive care unit, right. And so this is really the beginning, historically, of us trying to provide regionalization of care where we're going to have centers that are going to be our parasitology, regional whatever. I forget what they're called here in the US repik. I think they retake anyway, I forget, it doesn't matter. I'm I'm tired is service week, I'm just not doing this, however. And there's a significant body of evidence demonstrating the importance of perineal care regionalization, given the substantial reduction in both mortality, and morbidities for newborns at high risk of adverse outcome, particularly very low birth weight infants. And so there has been this incentive to deliver these infants and these mothers at higher level NICUs. So what the study did is that it looked at data from the Vermont Oxford Network, which is probably one of the largest collaborative, it's a voluntary collaborative, where units can can voluntarily share their data from 2009 to 2020. Looking at data from the US, among the newborns born between 22 and 29 weeks gestation, and they looked at the regionalization trends in the birthplace, Nicu level, and the NICU volume. So what they did was looking, we said 22 to 28 weeks, and then they classify the NICUs into three sort of three categories, right, so you have Level A, which is your lowest level NICU, and there's restrictions on assisted ventilation, nose and nose surgeries. Then you have your level B, which is your intermediate level, where really the only thing that they will not really take care of is major surgery. But level B centers were further divided into either low volume, which is less than 50, inborn micro preemies a year or high volume, which is 50 or more infants born between 22 and 20 weeks gestation. And then finally you have C with which are your highest level acuity. Now, high volume B and Level C centers were combined. And so they resulted in three distinct NICU categories. So you had Level A, low volume B, and then high B and C NICUs. Okay, so that's because if you go through the paper that can get quite confusing. So I thought this is important to just go over this right now. The main outcome they were looking at was the change in the percentage of births at hospital with Level A, low volume B and high volume B, or NICU see overall by US census and region. I'm not going to go into great detail about the results because they go into very granular pieces of data. And, but I want to give you the overall theme. So there was a total of 357,000 infants that were included in the analysis. And across region, the Pacific had the lowest while the South Atlantic had the highest percentage of births at a hospital with a high level high volume B or C NICU. Births at hospital with a level NICU, meaning the lowest level increased by 5.6%. And births at low volume B level NICU increased by 3.6%, while births at hospitals with high volume B or C level decreased by 9.2%. And what this data is actually going to show you is that this trend that we had seen up until now of regionalization of care is being reversed and we're seeing a higher number of babies being delivered in we're basically seeing a D regionalization of care. And I think this is a big shift for our profession. I'm going to go through a few more results by 2020. Less than half of the births for infants 20 to 20 weeks gestation occurred in high volume B or Level C NICUs. Most US Census region follow the nationwide trends are basically when they looked at, for example, birth at hospital with high volume BOC level NICU decreased by 10.9% in the East North Central region, and by 21.1% in the West South Central region. And the graphs are pretty impressive. Now, concluding this paper the retrospective cohort study does identify this de regionalization trend in birthplace hospital level of care for infants born at 22 to 29 weeks. That's also an important point when we're not talking about 30 weekers 32, because we're talking about micro preemies and this finding should serve to encourage policymaker to identify and enforce strategies, I think. I mean, I'm not sure what you guys think about this. Actually. I'm curious. I'm curious to hear your thoughts because I think this is such a big deal. And yeah,

Daphna 44:49

I've mixed thoughts. I hope that's right. I think we know that the more you do something in a unit, the better you are at it and Even with the way we were regionalizing care, there was still so much like inequities in in access to care. I mean, I think it as we do this, it will have to be. Also, there will also have to be this increased education and resources to these to these hospitals.

Ben 45:23

That's sort of what they're saying. Right? They're saying that they want to enforce strategy to ensure that the infants with the highest risk of adverse outcomes are born in hospitals where they have the best chance or optimal outcomes. And I think, I think we've we've agreed that the higher level centers are going to be the places, but it does create these sort of deserts where babies are born, and they're born in places where the time to get them to the regional center could be very detrimental. And so

Daphna 45:48

and I think, as we regionalised care, those outlying hospitals did less than I was gonna

Speaker 3 45:55

say, right? Yes. Like I can see they lost their I can't do event, I've got to send this kid out. Like I'm not, you know, an hour, I don't have the resources, the equipment, I think the equipment is a huge thing to consider in terms of budget of the hospital in terms of training. The personnel, I think, is sometimes there's no neonatologist night. So yeah, I think that this is I think it's really interesting, though, I did not know this that. And I think it'd be interesting to follow the trend.

Ben 46:27

Yeah, I mean, I think what's interesting is the fact that like, we've seen this with HIV, right, where we're now you have these regional, these outlines hospitals that really have to resort to passive cooling, because they no longer cool these infants. And then how long does it take to get the transport team? And I mean, let's be honest, it's, it's kind of the literature is good in terms of doing studies, but like, How many times have we seen some transports just getting delayed, and there's like, oh, and the ambulance went to the wrong, like, these things happen everyday. This doesn't always surface in the literature. But then what does that mean for an infant that ends up arriving at a cooling center at seven, eight hours, 12 hours, because the Transfer Center just so was an issue, right, these things do happen. And so you wonder whether that's either good or bad. I think again, like I'm probably sound like a broken record, but I think at the end of the day will be a proper middle ground where where outlying hospitals can do more things. And especially as technologies become like, I mean, as we see, with the use of AI and so many things, hopefully, smaller hospitals can do much more, and make sure that we can get the better outcomes for infants. But I think I think this is a no, I was gonna say, this is an interesting paper that

Daphna 47:46

I also think with our technology and the way we can communicate virtually those bigger referral centers can, can do different modes of communication, instead of just send me the baby like, maybe we can still be a part of this baby's case.

Speaker 3 48:02

And there's a lot of that telehealth people are working on it will be really, it's so fascinating to see how this works. Like, you know, there's script wars, Daphna could be in a rural NICU, coaching somebody through something without being there. It's it's it's mind blowing how this is working now. So I think that as that spreads, it still requires a lot of resources. You can't have the technology go down. Yeah, yeah.

Daphna 48:29

I also think we have done so many papers about the differences in, say, resuscitation thresholds across the country, right. So there are some babies who never got the opportunity or won't get the opportunity to depending on where they live. And so I think this, this may increase that equity. We'll see. We'll see. Okay, I have one. Go ahead. Is it my turn? I'm going to do this one that's called differences between early and late MRI and infants with neonatal encephalopathy following therapeutic hypothermia. The lead author is Aisling Garvey. But of note, there are some big hitters on on this paper. So definitely want to take a look at it's from the Society of pediatric research. So the study aimed to compare a day for MRI, so right after rewarming versus the second week MRI in infants with neonatal encephalopathy. Obviously, there's still there's still debate in the community about the right, what is the optimal timing for MRIs. So I thought this was a really cool study. It's a retrospective cohort study, including infants who received therapeutic hypothermia for neonatal encephalopathy between 2016 and 2020 and had two MRIs, so they only included babies who had two MRIs one in the quote unquote early time period less than or equal to seven days and one in the late time period greater than seven days. Inclusion care criteria. It was basically infants that were cooled and had to memorize but we'll review the cooling criteria they were actually including babies greater than or equal to 34 weeks gestation. With with one of the following a pH of less than 7.1, or base deficit of greater than or equal to 10 on a cord blood or postnatal gas within 60 minutes of birth, a sentinel event prior to delivery an Apgar score less than or equal to five at 10 minutes or the requirement for prolonged resuscitation. And in clinic plus clinical evidence of neonatal encephalopathy. Of note, they were they're using the neonatal encephalopathy scale, the N E S, which is is different than the Sarnat exam. So they that's easy to search for if you just search for an E s, I think it gives a lot more detail to the examiner about which category to choose. So definitely something to take a look at. Infants are classified as mild if they have abnormal neurologic findings on clinical exam but do not meet the criteria for moderate to severe neonatal and soft encephalopathy. Moderate is defined as having three or more clinical findings consistent with moderate or severe neonatal and stuff encephalopathy. But more domains are moderate and severe, and an infant score to severe if they have three or more clinical findings consistent with moderate to severe neonatal encephalopathy, but more domains are severe than moderate. And infants with mild, moderate and severe grades of neonatal encephalopathy receive therapeutic hypothermia with an NPS score of greater than equal to four. So that is their eligibility criteria for therapeutic hypothermia. So they had 94 infants included in this study with a median gestational age of 39.3 weeks and median birth weight of 3180 grams 40 infants 43% had mild neonatal encephalopathy. 49 or 52% were moderate and five, or 5% had severe. So let's get to the primary outcome. When comparing early scans to later scans. No changes were noted between the scans in 76 infants or 81% of infants. So that doesn't mean they were all normal, but it just meant that they didn't find a difference between the first and the second MRIs and 81% of infants. Wild changes were noted in 18 infants or 19%. So let's break that down. The first MRI scan was performed at a median age of four days. 70 infants 74% had abnormalities noted on this early MRI 39 infants 41% had Frankel signal abnormality with diffusion restriction 10% had parenchymal signal abnormality without diffusion restriction 10% had printable or intraventricular hemorrhage 12% had extra axial hemorrhage and two infants had incidental findings that were probably my group diarrhea or an immature gyro pattern. What else did I want to tell you?

I have thought I wanted to tell you a lot of things. Okay. Hold on. Why did I Why did they want to tell me about these three buttons? Let me tell you exactly why.

Ben 53:29

I don't know if you need to go into into specifically those three. Those three babies. But I think

Daphna 53:37

I think what's interesting about these babies, for example that they picked, were that the babies had pretty normal MRIs, but had very abnormal clinical pictures. And so when they had a change on the second MRI, I think that's a valuable piece of information that like I mean, they felt like what they saw on MRI was unexpected given the baby's clinical pictures.

Ben 54:07

It's more than then significant. I think it's it's it's it's insane, right? I mean, look at these numbers. 7676 infants had no change between early and late MRI 18 had a change between an early and late MRI. I don't really care which direction the change goes. Regardless, this is it. So it's over 20% And I think think about think about it from both the clinician, I mean, every kid where you see the MRI and the MRI is abnormal to me as a clinician, that's like a dagger. It's like, oh, man, what is in store for this kid? And it's so stressful. And then think about it from the perspective of the parents. What if you get an initial MRI that says it's abnormal, and then those changes sort of get better within the late MRI? This is a dramatic difference when you go home. I mean, microphone was fell off. The question then becomes, is this Do you Do you think that this is going to really force us to do both now late and late and early and late before? Maybe more

Daphna 55:07

about the second MRI? You didn't let me tell you Okay, fine. The second MRIs were performed at a median age of 16 days, which is also interesting of the 24. Infants with a normal early scan had negative MRIs. 13% had abnormal findings noted on their late MRI scan, including abnormal T one and two signal deep nuclear gray matter, restricted diffusion punctate white matter lesions and punctate paraventricular hemorrhages. Of the 70 infants with abnormal findings noted on the early MRI 16% had complete resolution of the findings of the 70 infants with abnormal exam on the early scan 79% had stable findings or expected evolution of the original injury for infants or 6% had worsening or new findings on the late MRI. And injury in this group included a variety of injuries, extension of injury to the cortex or to involve more areas of the white matter and new injury noted in the cot aid and the globus pallidus. The other thing people might have questions about is was the MRI where the change is more common in some degree of neonatal encephalopathy. So there was no difference in the incidence of change in MRI between the grades of neonatal and SEPA encephalopathy. The 40 infants with mild 13% had an abnormal early MRI and a normal late MRI. And four or 10% had worsening or new injury noted on their lead MRI of the 49 infants with moderate 12% had an abnormal early MRI and a normal late MRI and 4% had worsening a new injury noted on their late MRI. And then the infant's was severe one infant 20% had worsening or new injury noted on their late MRI. So I think I think you have to take into account your clinical picture and the MRI. And that's still not perfect, because we know that our clinical picture doesn't always predict which babies will have normal MRIs.

Ben 57:11

Yeah. I mean, I mean, now my question, then I have to ask you a question. Does it mean that we should get to MRIs before discharge?

Daphna 57:22

I think if we want to give parents the most comprehensive information, then the answer is yes. Is that the right answer given a resource utilization? For example? Will it change how you ask the parents to follow up with the therapies and things like that? No, it might right, because I don't think it should change our counseling. I think any baby who got

Ben 57:51

with normal MRI, your counseling is the same as what you're saying. As importantly. Yeah.

Daphna 57:56

And I think for example, hope the team had hoped for HIV. And the work that Betsy is doing is saying that a lot of these kids went home. They are they said mild, you don't need to be cooled or they got cooled and MRIs were normal. And the kids are still having new complications come up that are felt to be related to this perinatal situation. So yeah, no, I my counseling is always the same that that therapy is highly, highly valuable for all of these babies. I don't know. What do you think?

Ben 58:34

No, I think I think I agree with you. I think and I think this is going to change. I think to me, it looks like this is going to be leading to a change in practice. I think could be wrong, though. All right, Priya. We've been bit neglect to talk

Speaker 3 58:52

about your antibiotics empirical coverage for neck. So this this article is empirical animal microbial therapy of neonates with neck. It's a systematic review by Daniela Donna, out of Italy. And I think I you know, I think this is an interesting article, because it's it's looking for an answer to a question that unfortunately, is still I believe, unresolved. So we know that there's this lack of clear evidence based consensus on empirical and abiotic strategies or surgical timing for NEC. And the article tells you in the background, so in 2010, the surgical infection society and IDSA recommended amp gent and metronidazole or amp, Sefo, Taksim, and metronidazole or meropenem with the avoidance of clynder myosin due to the increasing resistance of bacteria bacteroides fragilis for neck and 2012. So two years later, the WHO recommends IV or I am amp or pant penicillin and just gent as first line antibiotic treatment for 10 days, then giving Vanko plus Sefo Taksim as a as a suitable alternative. And they said that although this regimen is more expensive and not applicable to low and middle income countries, that's the way they felt about it, they felt that there was no need for anaerobic coverage. But this was all based on evidence of three studies that you know, where the evidence was very low, too low. And again, in 2012, there was a Cochrane Review comparing antibiotic regimens in preventing mortality and the need for surgery and neonates with neck, but insufficient evidence to recommend a specific antibiotic regimen. So thinking about like all of this, how many randomized control trials do you think have been done for neck? Hundreds, two, they could find two. And this is they they their end date was 2020. So the question they asked was, can we assess the

Daphna 1:01:00

level of day that studies about antibiotics in that yeah,

Unknown Speaker 1:01:05

antimicrobial prophylaxis?

Unknown Speaker 1:01:08

There are still plenty, yes, yes,

Speaker 3 1:01:10

yes. But this specific question like antimicrobial, you know, therapy empiric. So their question was, can we assess the level of certainty for the effects of different antibiotic regimens with the available evidence that we have, and this is a systematic review, and it went up to 2020. They looked at randomized controlled trials, non randomized studies, anything that had reported on a predefined outcome, so mortality, the need for surgery, bowel perforation, and stricture form formation related to antibiotic treatment in neck for neonates and infants were included. And there were two reviewers who independently assess the risk certainty in evidence using the grade approach. So out of 2000 records, there were only 27 full text articles that they could find that met eligibility. And five studies included were included in the meta analysis, three from the US, one from Canada and one from South Korea. And I think one thing is, it's important to note here is that these are all considered high income countries. So to two of these were randomized control trials, and there were three observational studies with a total of 3161 patients. And they stated that there were no new randomized control trials in eight years since that 2020 2012 Cochrane analysis, but they said that this was a different analysis, because they were including the grade level for certainty and using the grading strengths. So this is this is the way they phrase the study, four of the five studies had a standardized definition for neck using the bells criteria for patient inclusion and the other use to clinician diagnosis for neck. So one of the things I thought was interesting is that both of these randomized control trials from the were from the 80s. So there from 1980, and 1988, was when they republished. And then three of the observational studies, two were published in 2015. And they looked at the addition of anaerobic coverage to different IV regiments, and then one was published in 1987. So the data here is really old. I will add that in 2021, at the Duke group did look at five different regimens for they, they were looking at safety for five different regimens for infants with complicated intra abdominal infections. But every single one of those five regimens had anaerobic coverage, so anti anaerobic agent there. And so the results really were that the mortality rate was variable. And that could have been due to infants age, the next staging, the all of the studies had a moderate to critical risk of bias and the certainty of evidence was low. And so really, the conclusions here were, you know, we don't have any, we don't have any recommendations for antimicrobial regimens. And that amp in general, is superior in decreasing mortality and preventing clinical deterioration, and that there's really weak evidence for adding metronidazole. But that could be added for complicated neck that is going to require surgical treatment. And there really is no evidence to support other broad spectrum regimens as first line, and that we should be reserving those, especially in our V LBW patients, due to considerations of cost than multi drug resistant bacteria. And that, you know, there's lots of things that have been stuck

Ben 1:04:40

until the first author is you can tell the first author is an ID physician, right there with us.

Speaker 3 1:04:46

Well, and there's lots of them that have been studied for preventative factors. So they did give, you know, a nod to probiotics, prenatal steroids, breast milk, standardizing feeding protocols, but they're they've The you know, the conclusion here was that there really needs, there's a need for a well defined antimicrobial strategy. Using comparative trials. I think for me, I would have expected, like, I know that there's data, like you just don't expect at least five trials, right or, and it fell off, like in the 80s. It fell off. And so we have one trial from Duke from 2021. That includes, you know, big, big drugs. And they showed no difference. And so yeah, I just thought it was it was interesting, something that we do every,

Ben 1:05:32

it's probably Yeah, it highlights the fact that it's so hard to to randomize these babies to randomize them at a time that is so sensitive, and it goes back to what we were talking about with Gen. canvasser last week, where it's like we, we really don't have a good grasp on how to handle neck even like we used to, before even talking about prevention, we don't know really how to manage it. And, and, I mean, I've worked in multiple institutions that I don't think we did the same antibiotic regimen. In every place, we had a different one, so and your rights when we want to do these meta analyses, there's not that many RCTs there's a lot of observational data. That's true, but not a lot of trials in favor.

Speaker 3 1:06:11

And then three, it was what two RCTs and three observational that met the criteria. So five trials out of yeah, a lot. So that looked

Ben 1:06:19

at that specifically.

Daphna 1:06:21

Yeah. Well, I'm sure Friends of the next society have are working on the next iteration. Yes. See, we'll have to ask them. And then I had two papers that I just wanted to mention, but I have another one you wanted to review.

Ben 1:06:35

I'm gonna do a little rapid fire because I think I have three or four more. Oh, what? Okay, but I do I do want to just mention them like you. So I just think we can do a we can do. Yeah,

Daphna 1:06:47

I wanted to draw people's attention, especially our trainees to the journal apparently otology article, a new era of assessment for neonatal perinatal medicine trainees, milestones, 2.0. So I just think that people should know what it is that they are being evaluated on. And so it does show kind of a shift in the competency assessment. And so I just thought that was a interesting article. It's, I mean, specific to neonatal perinatal medicine fellows, so definitely something for people to take a look at. And there was this review article in the New England Journal of Medicine about neonatal seizures. Dr. Years outwits from the Montefiore Medical Center in the Bronx, New York. And so I just thought it was a really good review. I'm trying to better classify seizures. And and what is the treatment look like? And you know, we've had a lot of discussion about that. But also, what is the workup look like for acute neonatal seizures? So I thought it was a really good comprehensive review for anybody who needs who needs it.

Ben 1:08:06

Yeah, I think they have figure one in that paper that goes over like the different causes of acute reactive seizure in term neonates. And it's a good review. That is amazing. And it's and it's very evenly split. I mean, I know that it can be the causes can be varied and so on. But it was very nice. And then the workup is broken down whether it's suspected HIV suspected infection, it's very well done. Very nice paper. So I wanted to bring I have a few papers that I wanted to review because they were interesting. There's a paper in the Journal of parasitology public published by the neonatal research network called maternal hypertensive disorder and survival without major morbidities among extremely low gestation newborns. I think this is a very interesting paper that aims to investigate. Preterm newborns born to mothers with hypertensive disorders have increased odds of survival to hospital discharge without major morbidity compared to newborns who are born preterm to mothers without a hypertensive disorder. And there's been a lot of data that's been published on this topic, obviously, and it and the general sense if you if you want a quick brief review, is that there's this idea that babies were born to mother with hypertensive disorder tend to have better survival, they also have higher incidence of BPD. But what the neonatal Research Network results show is that there's not that much difference. So survival without severe morbidity did not really differ. It was obviously retrospective review of prospectively collected data, but the survival without severe morbidity, including BPD was not different. And obviously you do have to review this data. It's very important. If you look at the adjusted versus the unadjusted analysis, I'm only talking about the adjusted analysis and then even looking at I'm even looking at some of the specific complications. They haven't seen much of a difference. And I think this really begs the question of how do we look at these infants and how do we address them? I think this is interesting. And it's an interesting paper that that sort of asks a question when it comes to revisiting this type of data. So something to look at. Another paper that I saw that was very interesting was published in ACTA paediatrica. It's called cortical activation and oxygenation perfusion in preterm newborns during kangaroo mother care, a pilot study. It's a very small study of 15 preterm infants. And basically, they looked at multichannel near infrared spectroscopy after 15 and 30 minutes of kangaroo mother care, right. And what they found was that after 15 minutes of kangaroo mother care, there was bilateral activation that was observed observed in frontal somatosensory and motor cortices. After 30 minutes, the right motor and primary somatosensory cortices were found activated. And this this among there's other results, obviously, but this idea that the significant activation is seen during kangaroo mother care is also another great illustration of the beneficial effects that this intervention can have, beyond just the obvious bonding between parent and child. But this this, this, this brain, these figures on this paper are quite impressive. And so that was in the journal in ACTA paediatrica. Finally, the last paper that I wanted to review I am going to, I just lost it but I'm going to, I'm going to have to pull it up there. This is a paper published in JAMA peds called preterm birth, small for gestational age and large for gestational age, and the risk of atrial fibrillation up to middle age first author is Fen Yang. The group is out of Europe, mostly Scandinavia. And this is a study that looked to investigate whether preterm births small for gestational age or large for gestational age are associated with increased risk of AFib later in life. This was a multinational cohort study that included Danish, Swedish and Finnish national health registries. It looked at health registries when it came to the birth records. It looked at health registries when it came to AFib data. And they looked at data from like way back when like in Denmark, they started the data review from 1978, Sweden from 1973, in Finland from 1987. And they went all the way to the to the mid 2010. So like 2016 to the end 2014. The exposure was obviously preterm birth, small for gestational age and large for gestational age, the main outcome and measures was a diagnosis of afib. And the cohort included about 8 million study participants. So hugely large population. And what they found was that preterm birth and large for gestational age were associated with the increased risk of developing atrial fibrillation in both the full population cohort and in the sibling analysis that they did. The multivariate hazard ratio for from the cohort analysis were 1.3 and 1.55, respectively. preterm birth was more strongly associated with afib in childhood than in adulthood, and the children born SGA had an increased risk of AFib in the first 18 years of life, but not really afterwards. The conclusions of the paper were that preterm births and LGA births were associated with an increased risk of afib, up to middle age independently of familial confounding factors, and that individuals born SGA had an increased risk of afib. Only during childhood. I think it's another insight into the future of the babies that we care for in the NICU. And, and I think we're seeing these, like these papers that are quite specific that are not just looking at cardiovascular disease in general, but like, yeah, you can now this is very good. 8 million patients spending four years so interesting. Theory. Yeah. Well, that's it. These are the papers that I reviewed this this week. Alright, we didn't have to add. We didn't. I thought we're gonna go for an hour and a half or something, but all right. We will be back tomorrow with board review. And we have we have a very interesting interview coming up next week with Dr. Katie Fritz, who we're going to talk about finding jobs as prospective neonatology fellows. So that's going to be exciting. Priya Daphna, thank you so much. Thank you.

Daphna 1:14:53

Thanks. You guys. Have a good one.

Ben 1:14:55

See you next time. Yes. Thank you for listening to the incubator podcast. If you'd like to 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 podcast, 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 that 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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