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#063 - Journal Club 30

Hello Friends 👋

A few announcements, this week we released the first episode of Journal Club in spanish. We have a dedicated post on our website but you can subscribe to that show here:ñol/id1629042188

Also this week, we are happy to finally announce that CME credits for Journal Club episodes are now available. Claiming CME credits is easy, go to the form below answer two content questions (we have to make sure people actually listened to the episode ;) and a few survey questions and you will be emailed a CME certificate automatically. Each Journal Club episode will provide you with 1 CME credit.

There are many interesting articles this week. We review the potential effects of antibiotics in preterm infants at low risk of EOS, the organizational factors that can influence the rates of unplanned extubations in a NICU, methadone vs morphine for neonatal opioid withdrawal syndrome, the effects of transport on mechanical ventilation, and many more articles.


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

Early Antibiotic Exposure and Adverse Outcomes in Very Preterm Infants at Low Risk of Early-Onset Sepsis: The EPIPAGE-2 Cohort Study.Letouzey M, Lorthe E, Marchand-Martin L, Kayem G, Charlier C, Butin M, Mitha A, Kaminski M, Benhammou V, Ancel PY, Boileau P, Foix-L'Hélias L; EPIPAGE-2 Infectious Diseases Working Group.J Pediatr. 2022 Apr;243:91-98.e4. doi: 10.1016/j.jpeds.2021.11.075. Epub 2021 Dec 21.

Acceleration during neonatal transport and its impact on mechanical ventilation. Lantos L, Széll A, Chong D, Somogyvári Z, Belteki G.Arch Dis Child Fetal Neonatal Ed. 2023 Jan;108(1):38-44. doi: 10.1136/archdischild-2021-323498. Epub 2022 Jun 15.

Active Treatment of Infants Born at 22-25 Weeks of Gestation in California, 2011-2018. Chen X, Lu T, Gould J, Hintz SR, Lyell DJ, Xu X, Sie L, Rysavy M, Davis AS, Lee HC.J Pediatr. 2022 Oct;249:67-74. doi: 10.1016/j.jpeds.2022.06.013. Epub 2022 Jun 15.

Clinical outcomes of preterm infants while using automated controllers during standard care: comparison of cohorts with different automated titration strategies. Salverda HH, Beelen DML, Cramer SJE, Pauws SC, Schalij-Delfos N, Te Pas AB.Arch Dis Child Fetal Neonatal Ed. 2023 Jan;108(1):26-30. doi: 10.1136/archdischild-2021-323690. Epub 2022 May 16.

Morphine versus methadone for neonatal opioid withdrawal syndrome: a randomized controlled pilot study. Sutter MB, Watson H, Yonke N, Weitzen S, Leeman L.BMC Pediatr. 2022 Jun 15;22(1):345. doi: 10.1186/s12887-022-03401-3.

Multisystemic Inflammatory Syndrome in Neonates: A Systematic Review. Shaiba LA, More K, Hadid A, Almaghrabi R, Al Marri M, Alnamnakani M, Shah P.Neonatology. 2022;119(4):405-417. doi: 10.1159/000524202. Epub 2022 May 5.

Organizational Risk Factors and Clinical Impacts of Unplanned Extubation in the Neonatal Intensive Care Unit. Le Blanc G, Jabbour E, Patel S, Kazantseva O, Zeid M, Olivier F, Shalish W, Beltempo M.J Pediatr. 2022 Oct;249:14-21.e5. doi: 10.1016/j.jpeds.2022.06.012. Epub 2022 Jun 15.

Breastfeeding and overweight/obesity among children and adolescents: a cross-sectional study. Liu F, Lv D, Wang L, Feng X, Zhang R, Liu W, Han W.BMC Pediatr. 2022 Jun 16;22(1):347. doi: 10.1186/s12887-022-03394-z.

Decreasing delivery room CPAP-associated pneumothorax at ≥35-week gestational age. Stocks EF, Jaleel M, Smithhart W, Burchfield PJ, Thomas A, Mangona KLM, Kapadia V, Wyckoff M, Kakkilaya V, Brenan S, Brown LS, Clark C, Nelson DB, Brion LP.J Perinatol. 2022 Jun;42(6):761-768. doi: 10.1038/s41372-022-01334-4. Epub 2022 Feb 16.

Extremely premature infants born at 23-25 weeks gestation are at substantial risk for pulmonary hypertension. Sallmon H, Koestenberger M, Avian A, Reiterer F, Schwaberger B, Meinel K, Cvirn G, Kurath-Koller S, Gamillscheg A, Hansmann G.J Perinatol. 2022 Jun;42(6):781-787. doi: 10.1038/s41372-022-01374-w. Epub 2022 Apr 1.


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

Ben 0:48

Hello, everybody, welcome back to the podcast. It's Sunday Journal Club. Lots of announcements today.

Daphna 0:54

That's right.

Ben 0:56

So what did we start with?

Daphna 1:01

The incubator in Espanol, I think.

Ben 1:05

Yes. So this week, if you haven't noticed, we released a, our first episode of the incubator in Spanish. This was a long time coming. Daphna has been planting the seed for this to happen for what months now. And so yeah, thank you for your persistence. And we are going to release basically translations of the journal club episodes in Spanish, this is going to be our first order of business, we're going to try to keep up with the journal club episodes in English as much as possible. We want to give a special shout out to Valentina to Marla to Laura, who are the people hosting this version of the podcasts. They've been great in, in doing this professionally. So yeah. Yeah. Thank you. Thank you guys. I guess the biggest delay and the biggest bottleneck on this on this journey is the problem of making sure translation and everything is is there's a high degree of fidelity that there's a lot of redundancy so that we make sure that whatever content we provide in Spanish is, is of good quality. We have a lot of Spanish speaking, proof, whatever we call it is a proofreader proof listeners. Yeah, that's a good, that's a good way to put it. So. So we, we are very conscious of that aspect of it. So yeah. Now how do you access the episodes? They're basically a separate podcast on on on Apple, podcast, Spotify, whatever, whatever platform you use to get this particular podcast, you should be able to type in the incubator, and then we actually do it as we speak. So that I think it's the incubator parentheses a spaniel?

Daphna 2:58

Yes, it does, I checked it.

Ben 3:02

And then we've created on Apple podcasts, which channel with all the as the as the number of episodes are, are increasing, the number of podcasts are increasing, there's a little channel and you can see all three shows on there, the new review the incubator in English and the incubator now in Spanish, it's called the incubator parenthesis Espanol. And this is the first fully of a new array of podcasts where maybe next we can devote a podcast in French. So yeah, this is very, very exciting. Alright, so that's announcement number one. announcement number two is finally finally, I mean, you guys probably don't feel as drained as I am from this process. But we finally have CME credits available for the incubator podcasts.

Daphna 3:54

We probably should have been announcement number one is very exciting.

Ben 3:58

This is well deserved that thing for all the work that we've done to get this done and for the podcast. But first of all, we want to think I wanted to give a special thank you to Jane Duncan, who's basically the person responsible at Nova Southeastern University for all CME activities. She's been very nice and making helping us making this happen. So every, the interviews will not get CME credits. They're they're kind of entertaining more than educational, obviously. But the journal club episodes will each offer you one CME credit, and then the neonatology review episodes. Some of not all of them, because obviously the educational content is different depending on what exactly happens. But each episode that will be given CME credits will be given a half a credit. So the big question is, how do I get credits? And the answer to that is you go on our webpage and on the episode page, there will be a button that you can click to access a form that you have to fill out just like any conference or anything where you have to show that Have you pretended and that you can give some feedback? These are standard CME credit questions. We also have questions regarding the content of the episode. So we are that was a big issue with giving credit for podcasts is how do you make sure that people are writing in, in conferences you can get people to sign in, sign out, whatever. But in the podcast, how do you know that people have listened to the episode? So we have like one or two questions to make sure that you did listen to the episode. And they're not hard questions. They are not hard questions, but

Daphna 5:35

and So to clarify, you're saying that after, after someone listens to this episode, they can find it on the website and in start rolling?

Ben 5:45

Yep. So you get to that you get to the website, you access the form, you fill it out, you're gonna get two emails, technically one of them that confirms you fill out the form, and another one will have like a little CME certificate with your CME credit. So this is neat. And that's it for our show today. Thank you for joining. See you next week.

Yeah, today for the people who don't know, we're recording this podcast. It's interesting. Yeah, it's interesting. Some people have asked me how do we manage to record these episodes so early on Sunday mornings. But we are not recording at 5am. On Sunday. We are recording this ahead of

Daphna 6:26

times we are but not.

Ben 6:29

But we have a long recording ahead of us. So yeah, we are tired before we even begin. So let's let's go. So we have Journal Club. And we have a bunch of very interesting articles, as usual. Definitely. You want to get started today.

Daphna 6:43

Sure, yes, let's do it. So I guess I'll start with this paper, which is another iteration of the EPA page to study. Do I say that right? I've actually never epi publish, of course, the French study, epi Paje. Okay. So it's entitled early antibiotic exposure and adverse outcomes in very preterm infants at low risk for early onset sepsis. The epi PIs There you go, then it should be it should be epi posh cohort study Lita up in Mathilde Lattanzi of the epi pas infectious diseases working group, there you go. I got it. I nailed it.

Ben 7:36

Okay. You did? You did?

Daphna 7:40

Okay. And

Ben 7:41

there are times when one of us can actually

Daphna 7:43

correct. And this is in the Journal of Pediatrics. So the question was really to evaluate early antibiotic exposures. And looking at later neonatal outcomes in a specially selected group of very preterm infants who are at low risk for early onset sepsis, and I will talk about exactly what that means in just a minute. So is it a valid question? So really, they're asking is kind of our knee jerk reaction to put the very preterm and been on antibiotics harming babies. So that's what they wanted to look at. So this, like I told you is a secondary analysis of the French cohort of babies born between 22 and 31 weeks gestation. And numerous analysis have been performed on this cohort. We most recently reviewed the five year developmental outcomes. And the EPA patch team plans to study the group until 12 years of age, I think, as it stands. So for this particular analysis, what they did is they excluded these babies that were at high risk for early onset sepsis. So they excluded all babies who were delivered after preterm labor or after a premature prolonged rupture of membranes, where there was clinical chorioamnionitis or the mother had received antibiotics in the 72 hours prior to birth. They also excluded babies who died in the delivery room on the first day of life, severe congenital malformations and multiples, who had a comorbidity of 20, a twin transfusion syndrome. So really, this cohort of babies was really infants who were delivered for maternal indications like hypertensive disorder or preeclampsia, or for some infant factor like intrauterine growth restriction. And when we talk about some of the definitions, the early antibiotic exposure really meant that they were started either on day zero birthday or day one of life, regardless of the type of antibiotic or length of exposure. And they wanted to look at the primary outcome was a composite outcome accounting for Are these competing risks, death and adverse outcomes, including at least one of the following. So late onset sepsis, which was a positive blood culture, after 72 hours of life and neck, they also wanted to look at secondary outcomes and death, or severe neonatal complications, death or severe cerebral lesions, and then also looking at death or moderate severe BPD. So, well, there's a lot of data in here, but we'll work through it as usual. So the baseline characteristics, so they had a total of 648 infants. There were no antibiotics in started in 74% of these infants. And then these early antibiotics in 26% of the infants, which I thought was actually quite good maternal maternal characteristics of the whole cohort were a median age of 30. Other kind of demographic factors. 20% of these moms were smokers. 58% were prime, MIPS and 45% were overweight. Most babies received antenatal corticosteroids, which was also incredible, and almost all delivered via C section, which I thought was interesting, especially where we practice now a lot of even the moms with preeclampsia are being induced vaginally. And then infants exposed to early antibiotics were more frequently mum multiples, they were less likely to be born at a level three maternity unit, I don't actually know much about the levels, I tried to look them up to you now in France.

Ben 11:41

It's very different from the US. But yeah, so they they do have different levels based on weather. So it's an interesting concept, right, because most of the larger academic institutions are public. So it's a bit it's a, it's a complete different system. And then the private hospitals in France are usually smaller, because they try to just do whatever makes money. So it's completely backwards when it comes to how it looks, what it looks like in the US. But they do have, I guess, maybe three levels of care where you do have a level one where they may have an isolette, just to wait for transport. You do have level twos where they can do maybe a little bit of CPAP or something like that. And then you do have level threes, I don't know, which is the highest I don't know if they, to be honest with you, where my knowledge of the healthcare system may be failing is whether or not they have several distinction within the level three, whether they do cardiac ECMO, I don't know if that level of distinction is present there. But

Daphna 12:46

other maternal and obstetric characteristics were similar between groups. The group as a you know, as a cohort had a median gestational age of 30 weeks, a median birth weight of 1040 grams. Interestingly, and I think this is important infants exposed to early antibiotics had slightly lower gestational age 29.6 weeks compared to 30.3 weeks and lower birth weights 1010 versus 1060 grams, they were more likely to be intubated in the delivery room and need surfactin administration. And they did note that despite these differences, when they looked at initial crib scores, which is an illness severity score, that they were not different between the two groups of babies who received antibiotics, early antibiotics and those who didn't, but they did have this these these not insignificant differences, I think in in clinical picture regarding antibiotic exposure, so those babies who got antibiotics 88%, who got any antibiotics received it on day of life zero, so birthdate for babies who had all the information about the antibiotics. All of them receive two types of medication. amoxicillin was among the most common 112 out of 165 Babies cephalosporins even more so in 129, over out of 165 VANK was given an 11 and Metro night is all in five. The good news was the median duration of antibiotics was three days. The less good news is that four infants were diagnosed with early onset sepsis on day two or three of life in this group of babies who got antibiotics. None of them, though, had received treatment on the first day of life. Those babies were found to have either group B strep in one and Staph aureus in this three, and unfortunately, one of the babies with staph aureus died on day of life three. So, for the outcomes, so, while mortality was higher, In the early antibiotic group 12% Compared to 6.3%. The odds ratio of early antibiotic exposure in the association with death was 1.78. So they actually listed that as no association, but I'm giving you the odds ratio that you can do with that information, what you like. They said there was no difference in NEC an odds ratio of 1.47. No difference in late onset sepsis. So an odds ratio of point nine, three, the overall incidence of late onset sepsis was 25%. And the total cohort, they were immediate diagnosis of 12 days, the most common bacteria were cons 75%, Staph aureus, 15%, and Enterococcus 3%. And then they did find an association between severe cerebral lesions, and early antibiotics exposure and odds ratio of 2.71. They also found an association between moderate to severe BPD, and early antibiotic exposure and odds ratio of 2.3. And then when they looked at these composite outcomes, so composite outcomes of death or late onset sepsis or neck, there were no difference in odds ratio 1.04. And there was no association between early exposure and compositive. of severe neonatal complication, which was any of these late onset sepsis, neck cerebral lesions and moderate to severe BPD when they did the composite outcome. So I think they were trying to show that we should feel good about not starting antibiotics on these extremely low birth weight babies who are not at risk, given, you know, pre existing factors for for sepsis.

Ben 17:01

Right. So that's, yeah, I mean, yeah, that's, that's, that's obviously Yeah. You mentioned death and saying that they didn't find a physician, I guess that was probably driven because the for the people who are wondering the the confidence interval crossed one right in that specific one. So that's why but I mean, you look at the numbers, and I mean, it's double. Yeah, it's just like this. This is what it's what Daniel Kahneman always talks about, like this loss aversion where you look at the numbers you like 12% versus 6%, I don't really care what the conference interval says, I'm still a little bit in shock. And it's completely not scientific. And I know it's not scientific and yet.

Daphna 17:39

And that was, you know, higher in the early antibiotic groups. So even more reason. Yeah.

Ben 17:47

Yeah. And I think I think this is, at the end of the day, a very important paper, just because it's we have we're so fearful. I mean, I say we and I generalize, because I'm include myself in this group, but like, we're so fearful of the vulnerability of the extremely low birth weight infants that were like, you know, what, like, Oh, I'll deal with whatever I have to deal with. But I just don't want to adjust don't want to be the one who loses any LBW to an infection, because I didn't start antibiotics, right. But if you can have a little bit of, it's a bit like the marshmallow experiment, right? Where it's like, if you can have a bit of delayed gratification, and you can think about this from the standpoint of cerebral injury, when you're thinking about even I mean, I guess even death in this case, but BPD, then maybe, maybe we can be a bit more cautious in giving antibiotics to these extremely low birth weights. And

Daphna 18:43

so well, and what they did I mean, they were very selective, right? So I mean, these were babies that one might say, they potentially have no, there's no such thing is no risk, right. But they didn't have any risk factors. obvious risk factors for for infection. I would have liked to have seen a little more detail about the babies who did have late onset sepsis and what that looked like,

Ben 19:13

I guess, I guess, or risk stratification calculators probably on the way, probably on the way so maybe not by them, but by other groups. But anyway, yeah. Fascinating. I was really not expecting these outcomes. I have to say that this paper eventually just concluded that moderate to severe BPD insert severe cerebral lesions were the ones it's like, I was not I was surprised. In any case, okay. Your turn. It's my turn. Yeah, it is my turn. I have to locate. Okay. So what should I start with? I'm going to start with this one. It's a paper that comes out of the Netherlands it's in the archives of disease in childhood fetal, neonatal condition. First Arthur is hulky cell Verda title is clinical outcomes of preterm infants while using automated controllers during standard care, comparison of cohort with different automated titration strategies.

Daphna 20:15

We've been waiting for this paper.

Ben 20:17

Well, that's the sad, the sad thing, Daphna is that I have like sort of picked this paper to highlight how the rest of the world is moving along, and especially the US in the US are just lagging behind. So. So the background information is interesting, especially like I said, if you're in the US, and you're not using automated fit to control, but yeah, so to make us feel even worse, that's not the intention of the authors, obviously. But they mentioned how there are many options out there for automated fit to control. You're saying there's no excuse, like, there's so many options out there, it's time that we look into and say, Oh, my God, we don't even have one. And so they're talking about the fact that these different fit to control tools use different algorithms. And the difference between these algorithms could be important. And I'm going to quote the paper just that, because they said it very well. They said, the one algorithm x if we call that may, on average, keep oxygen saturation higher and have fewer saturations at the cost of more hypoxemia. Whereas the other algorithm may adhere better to a defined oxygen saturation limits at the cost of more short but frequently saturation, right? So I mean, the how frequently is the oxygen saturation going to be adjusted is really at the core and at the root of these algorithms, right? Do you average the auto set over one second over two seconds? And then and then are you going to allow a few drops in the in the saturation? So it's interesting to compare the different the different tools that are available. And I thought this was an interesting paper too, because again, our audience is is global. So yeah, maybe we don't get to use these tools, but maybe a lot of our audience members actually might benefit to to make a practical decision. So they looked at two different algorithm, they looked at the creo. Two, which usually comes in via ventilator, and then they have the oxygen D algorithm, which is in the SAE 6000 ventilators, I'm familiar with the via the SLE 6000 Looks like something that I've not had the pleasure of working with. So they, they have a very nice review of how this algorithm functions. We'll post the link to that separate paper on our website, if you're interested. Briefly, when they when they had compared these, these two before, they had seen that the oxygen algorithm was more effective in keeping the saturations within the range to prevent hypoxemia. And just as effective as preventing hypoxemia. The clearer to was showed that it spent less time in the actual target range. So the big question was, they seem to say that from an algorithm standpoint, the oxygen UI is a little bit better at making sure that your goals are achieved from keeping the oxygen in the right range preventing hyper hypoxemia. So the question was, does that even matter? Like is this a big difference? Are these difference clinically relevant, so they wanted to look at the effect these differences could have on short term clinical outcomes. So they conduct the they conducted a propensity score matched observational study with electronic patient record data from the NICU, which is a tertiary hospital with 25, neonatal intensive care unit beds, and around 100 admissions per year of infants at less than three weeks of gestation. What was what lends itself what lends itself to this study was the fact that the they actually used the Clio to algorithm from 2015 to 2018, and switched to the oxygen from 2018 on and so they were able to actually compare these two algorithms as two cohorts, one of them historical, and one of them a bit more current. They looked at infants that were born between 24 and 29, and six weeks at birth, and they excluded any infants with major congenital malformation. So in total, they were able to get 121 infants between 2018 and 2020, which was the time where they were using the oxygen any algorithm, and they basically matched all these infants to infants born in the historical cohort where they were using the Clear to algorithm. The median gestational age was 28 and 320 weeks and three days, median birth weight was 1000 grams, 1034 grams. So let's look at some of their actual outcomes. The respiratory outcome, the oxygen the cohort had significantly more time during which they received supplemental oxygen Um, so 17 versus seven days, the p value was point 04 Or five. Now, the big caveat to that is high flow nasal cannula was not available in the historical cohort when they were using the via, or the with the clear to. So when excluding periods where infants were supported using high flow from the analysis, there was a non statistically statistically significant difference, which, to me is awesome that this is actually reported, because it goes to show that sometimes we leave kids on high for way too long. And we just don't have the guts to just try to win that race. And you see this that when the high flow was not available, the kids got got wind a bit faster, and on high flow, they just linger. And like I've said this on the podcast before, Dr. Ben Clary used to say, Never tell me that a baby requires a certifier to because they require whatever you give them just to for them for you to know that they actually require something you need to actually test that they can try them off. Yeah, exactly. So the mean inspired oxygen in the first week of life was similar in both groups, as was the main inspired oxygen during the entire stay. The infants in the oxygen II cohort had fewer days of continuous positive airway pressure, 8.4 days versus 16.7 days. They I'm not going to talk about invasive mechanical ventilation, just because, for for, for the for one of the cohorts, there was no days on mechanical ventilation. So these kids were pretty healthy. And there was no difference in the need for nitric oxide, dexamethasone or surfactant. So in terms of the clinical outcomes, they saw that fewer infants received laser coagulation for ROP in the oxygen, the cohort, one versus 10 infants. There were no statistically significant difference in mortality, culture proven sepsis, BPD, NEC ivh and PVL. Infants had a significantly shorter duration of stay in the NICU in the oxygen II cohort, 28 days versus 40 days, with a mean difference of 13.5 days. And so they conclude that the oxygen epoch was associated with less morbidity when compared to the clear to epoch. So my thoughts on this paper are that number one, there's a lot of issues, obviously, with this study. It's small, the cohorts are historical. So obviously, the practice you want to believe improves over time. So the all the all the biases that can be introduced with with a historical cohort, are there. It's a small study, it's a small unit. I mean, the fact that they didn't have I forgot the I'm going to tell you actually, there was one cohort where the more recent cohort had the median number of days on invasive mechanical ventilation was zero. So clearly, you see that they're improving. And they were not very, very sick children. So. So there's there's everything to take with a grain of salt. But it's a very interesting study. Number one, it highlights for us in the US that we're we're falling behind. Obviously,

Unknown Speaker 28:15

they're not crashing on, obviously.

Ben 28:17

I mean, I was actually able to work with the Clio to at the University of Miami, because we were part of the trial that is trying to approve the algorithm for by the FDA. But I mean, they made it just a few machines, obviously. And, and so yeah, I mean, this is something that that I mean, we were we're falling behind and yeah, applying pressure to the US and giving people outside the US a little bit of a of a an inside look as to which algorithm works best. I also think there's going to be an arms race when it comes to these ventilators to be able to provide these algorithms in an exclusive manner, I think, right? I think some ventilation and say, Oh, we're going to give you this algorithm and they're going to try to push to compare algorithms. There's going to be a lot of competition there as the clinical outcomes are going to be demonstrated to be improved. So interesting, interesting study.

Daphna 29:12

All right. Thank you, buddy. My next study is entitled morphine versus methadone for neonatal withdrawal syndrome, a randomized controlled pilot study lead author Mary Beth Sutter. This is in BMC pediatrics open access from the University of New Mexico. So the question is really would treatment for now's neonatal opioid withdrawal syndrome have shorter length of stay, and length of treatment using morphine or methadone? And obviously this is an important question. And as we're learning more about now's, as we're seeing more babies with now it's about how can we really reduce length of stay for these babies who require treatment So this the study design, it was a single site randomized control study between October 2016 to September 2018, infants were enrolled within 24 hours of birth to either the methadone or the morphine arm. The babies needed to be greater than 34 weeks gestation with an in utero exposure of either methadone, oral opioids or heroin by history, or maternal or infant urine drug screen. exclusion criteria were serious medical conditions, which they don't delineate. They excluded babies who had in utero exposure to buprenorphine, because their standard there was already morphine therapy. And they initially excluded all NICU admissions like even if you met the criteria, but you came in for transitional respiratory distress or something. But in 2017, they allowed enrollment of infants who were admitted to the NICU for less than 24 hours. So all infants within utero opioid exposure underwent 96 hours of Finnegan scoring. In infants with two scores greater than or equal to 12, or three sequential combined scores of more than 24. were initiated on treatment, based on again the randomization at the time of enrollment. clonidine could be used as deemed necessary as a second line therapy, as deemed by the physician caring for the baby. The primary outcome was a hospital length of stay, the secondary outcomes were length of treatment, the need for second treatment agent total morphine equivalents. So this was an interesting and they use to a ratio of four to one for methadone to morphine, need for assisted feeding, breastfeeding and other adverse events. So the baseline characteristics, they had 126 exposed infants admitted 39 infants were excluded given that exclusion criteria. And another 26 infants who were who were eligible were not enrolled because either the parents declined or they weren't available for consent. And they do discuss the you know how to reasonable component of things like DCF holds or babies who, whose parents weren't going to be taking them home. Differences in the groups included. The fact that mothers in the methadone mothers of babies in the methadone treatment group were more likely had to have received prenatal care in the first trimester, which was interesting 69 versus 33%. But both overall the two groups had a similar total number of prenatal visits. Other substance abuse other substance use was present and in both groups, but the morphine treated group had higher rates of tobacco use methamphetamine use benzodiazepines and SS Attari, SSRI use again this is no small confounding factor. And then when they looked at the primary outcome, the length of stay was not statistically different between the two groups methadone, 16 days versus morphine, morphine 17.9 days P value 0.5. The treatment length was also not significant significantly different, though there was a trend towards shorter length of treatment and shorter length of stay in the methadone treated group. The methadone group received significantly more morphine equivalents 33 versus 9.68 P value less than point oh five. And in terms of adverse events, one baby in the morphine group required. clonidine, so as the secondary agent, three infants treated with methadone required transferred in the NICU for over sedation, or decreased respiratory effort and or oxygen D saturation. More infants in the morphine group required additional caloric support. But this was not statistically significant. And infants in the methadone group spent more time rooming in, but was also not statistically significant. So those are the those are the details. I think the things to point out were that this feature that the baby's in the methadone group, again, it wasn't statistically significant, but more of those families were able to room in and that was also the group that had lower length of stay and length of treatment. And we know that parent involvement in these babies reduces medication need. The other thing I wanted to mention, which is becoming an increasing area of interest is that their hospital you're a drug screenings did not include marijuana. So we don't we don't have details about that. But that's obviously becoming a hot topic.

Ben 35:07

You open the can of worms right there. I

Daphna 35:09

know. Well, just putting it out there.

Ben 35:14

Yeah, no, that was that was an interesting paper. I mean, this is the these are the types of I mean, I think I had that question this week on service. And I was wondering to myself, like, what are the practical implications of ordering morphine versus methadone? Granted, it was not a full term baby like that was otherwise deemed worthy of just going to the nursery? No, it was it was a sacred child. But this is an interesting discussion. And to me, what one of the pieces in the results that is, to me very important to is the fact that like you said that infants treated with methadone ended up receiving up to three times the opioid based on morphine equivalents, as infants treated with morphine alone. So that's interesting. And that's interesting. And we know, we know the difference between methadone and morphine, but that's always nice to see in parenthesis, good reminder. Okay, we have a lot of papers to cover, so I'm not gonna waste any time. So the next one I have is a paper that maybe I don't know, it's an it's a, it's a technical paper, but I just loved it so much. For many reasons. Its first author is Lajos lentos, from Hungary, in publishing the archives of disease in childhood, the title is acceleration during neonatal transport, and its impact on mechanical ventilation. So that title grabbed me, the background information is very interesting, obviously, as as they correctly point out, we're regionalizing our care, which means we're relying more and more on transport, and even with dedicated neonatal ambulances and specialist, neonatal transport team. postnatal transport can and certainly does present significant trauma and risk for vulnerable infants, that you mentioned, what we're all familiar with that severe ivh is also more frequent after X utero transport. And it's unclear, obviously, whether this what what drives this association, we know it's there. But why is it just because the baby is born at a center that cannot handle this baby that has to transfer to begin with? Maybe he's not really stabilized as well as it should? All these things are questions we're not even gonna get into. But they do mention that nearly all ground transport is associated with significant vibration, significant acceleration during road and traffic conditions. And that critically, critically ill infants requiring transport are often needing also mechanical ventilation. And so vibrations, and sustained acceleration during transfer can potentially influence how mechanical ventilation is delivered through a multitude of mechanisms. So they aim to look at two things. Number one, they wanted to determine the acceleration levels occurring during neonatal transfers, and whether they are predominantly due to change in speed or direction of the ambulance or due to vibrations. And the second question they had was, does sustained acceleration of vibration impact the maintenance and variability of the ventilator parameters? Meaning like, is your tip changing a lot is your tidal volume changing a lot because of these changes? And so the reason I, I'll tell you at the end, but anyway, so it's the study design is that it's a clinic clinical. So the ventilator and ambulance acceleration data were collected from 153 infants transferred from the neonatal emergency and transport service of the Peter Cerny foundation in Hungary between 2018 and 2020. Their transport team involved a neonatologist with experience in transport and a neonatal transport nurse practitioner. All transfers were completed using blue light sirens and ambulance priority, which is interesting, right? I mean, if you've ever gone on transfers many times and blue lights and sirens makes you feel like you're going to get there faster, but it's actually quite dangerous because the ambulance has to just go as fast as possible and it does increase the risk of accidents and issues on the road. So if your baby is stable My advice to you for somebody who's been in a few transfers is go slow. It's fine. Just no need to get into an accident with a critically ill baby in the back. The transports had they were included if they lasted more than 10 minutes, which is good because it means that the transports were significant babies received sedated medications for the transfer but we're not fully sedated or paralyzed. Obviously they have to mention that our vehicles were Mercedes Benz Sprinter vans with air suspension now it's such a cool paper just because of all the things they report so there are Mercedes Benz Sprinter vans with air suspension and that are used as dedicated neonatal ambulance and The transport ventilator, or the transport incubator was the trigger ti 5400.

Daphna 40:08

Yeah, and I'm just thinking it's an interesting point, right? Because transportation vehicles are not all the same, right? And they're, they're a little, little, I don't know anything about vehicles. Right. They're like shock absorbers and things that like would probably make a big difference for transport.

Ben 40:28

The so when I was a fellow and we did transport, sometimes the ambulance that would come pick you up would be an oldie. Yeah. And the shock absorbers were not like, it's a bit like a school bus. You know, like, yeah, when you get on the school bus and you're like, oh, this this, oh, this should be rattled around a little bit. It's exactly right. It's exactly right. The, the ventilator that they were using is the Fabian plus and CPAP evolution neonatal ventilator, which actually made in the US, apparently, I think, in any case, I wasn't unfamiliar with that ventilator. Okay, so the infants were on a vacuum pillow and vacuum mattress, they collected data from a variety of standpoints. And you can look at that it's in the it's well described in the methods. Interestingly enough, their data analysis was done using Python, which is, which is something that is used by a lot of people for coding, and the steps describing the data analysis and processing is available on GitHub. So it's what coders used to create software's create stuff. So it's very bizarre to see these things show up on a on a scientific paper in neonatology. So for the people out there who are into coding or into a bit of computer science, just for the fact that this paper was analyzed using Python, and that all the OB code, or the code sheets are on GitHub. It's kind of neat. Yes, super neat.

Daphna 41:51

So you know, you know, I don't care about those things. But it's, it's just nice to be sharing how we're doing things, right.

Ben 41:58

Yeah, I mean, GitHub is exactly that. So it's cool. So the analyzed accelerometer, and ventilated ventilator data from 109 infants receiving mechanical ventilation during inter hospital emergency transfers for a total duration of 82.4 hours of recording. Overall, the acceleration component in the direction of the ambulance movement was the largest ranging between point one six and 1.37 meters per second squared. And that was significantly larger than the side to side or up or down acceleration. So obviously, the forces felt moving in the direction in which the ambulances is driving are significantly superior to anything related to side to side or up and down. There was no alignment period, there was no alignment I'm sorry, between periods of high or variable accelerations and variability of title or minute volume, respiratory rate, peak inspiratory pressure and fraction of inspired oxygen, as they represent different physical forces and potentially impact differently on the ventilator and the baby. They studied the impact of vibrations and sustained accelerations separately, there was no difference in the average expired tidal volume, the average peak inspiratory pressure, the average minute ventilation, and fraction of inspired oxygen between these periods, no differences were seen even in extremely preterm infants. Interestingly enough, during volume guaranteed ventilation, the tidal volume was maintained equally well during periods of high vibration compared with periods of low vibrations. During pressure limited ventilation, the PAP was delivered as set by the users, and in SI MV, without pressure support, infants did not trigger more inflation. I mean, in not in synchronism, mechanical ventilation in assist control ventilation, I apologize, this is important. The infants did not trigger more inflation during the vibration period, which is something that I actually have wondered in the past, which is as the ambulance is moving, we know that the trigger to the ventilator to detect a baby's breath is quite sensitive, does that movement will lead to more breaths. So it was interesting to see that data. Another interesting result of vibration frequently made the PV loops more irregular, and they actually have that displayed on the paper. And overall, the complexity, expressed as the number of PV data pairs during a period of the PV loops was higher during the one minute period with the highest vibration than during the minute with the lowest vibration. So to be honest with you, I think this is interesting, but I mean, I've seen my pupils do sometimes funny things even in the ICU. So I'm gonna try all the time. I also I'm not sure if that's such a So in conclusion, the infants that are exposed to significant acceleration and vibration during emergency transports, and while these forces do not interfere with the overall maintenance of ventilator parameters, they make the pressure volume loops more irregular. I don't know what you guys are going to make with this data. But if you've ever wondered like, what are some of the forces these babies are exposed to in in an ambulance? I think this is kind of nice to see this data out there close to the people from Hungary. Very cool people.

Daphna 45:13

Yeah, I would have liked to see just even more of the like vital sign data, right? Because it in my observations. Yeah, it seems like respiratory rate goes up, heart rate goes up, blood pressure goes up. We know all of those things, which may in and of itself, explain some of the findings. I'm

Ben 45:31

gonna look maybe that data is out there. I'm going to do a little digging.

Daphna 45:36

Okay. My turn then. Yeah. So this next paper, multi systemic inflammatory syndrome in neonates a systematic review. Lead author, Lena, a Shaybah. Journal, neonatology, it's a collaboration. There are authors from Saudi Arabia, Qatar and Mount Sinai in Toronto. And basically, what they were trying to do was compile some of these smaller case reports and case series of babies who have the Mi s n, which we think is related to the MIS C, multi systemic inflammatory syndrome in children and seen after COVID infection. So, mis en in neonates just like in children is sought to be related to immune mediated multi system injury due to transplacental transfer of maternal SARS cov, two antibodies or late response to neonatal mounted antibodies. They included any article, like I said, that was a case report or case series cohort study, or retrospective observational study or even a correspondence without major patient data so that they could get as much information as possible. And so basically they categorize neonates as having Mi s n as babies who either met the who or the CDC criteria for mis see, since we haven't totally all agreed on a definition for it in neonates, the only difference for those who don't know about the who and the CDC criteria was duration of fever. The babies also had a had to either have confirmed infection or exposure to SARS cov, two infection before 28 days of age, and who presented before 28 days of age, with exclusion of other causes for their symptoms. They also wanted to look at which babies had early mis en within 72 hours after birth, or late beyond 72 hours of age. So they found a total of 16 studies reporting on 47 neonates, there were 14 case reports two case series. And one thing that again, I think is interesting is they had 15, quote, unquote, confirmed cases. So the babies met all the criteria and 32 suspected cases. So I'm not sure all the TVs met all the criteria. And I'll talk about one component in particular, since fever is a definitive component of the who and the CDC criteria through only fever in 17 of the babies 36%. So I don't know what to make of that. But I'll tell you what else was in the paper. They had 34 neonates in the early group, so within 72 hours and 13 in the late group, which I was also surprised by. And then they talked about basically what were the common I mean, what were the presentations like? So, the most common presentations were actually cardiovascular and I think this is useful because there really aren't so many things that cause cardiovascular compromise in neonates early on. So 77% of the babies in this group had some cardiovascular finding. And the findings were cardiac dysfunction and 14, arrhythmia and 11 dilated coronaries and arteries and five pericardial effusion, and four PPHN in three and an intracardiac, thrombus, and two of the babies regarding lab testing, again, so not all of the studies reported on all of the lab tests, so eight babies who had proponents tested, all of them had high proponents eight out of 880 4% of those tested, which was not everybody had elevated D dimer. 67% of those tested had elevated ESR hours 65% of those tested had elevated CRPS 63% had anemia 60% had elevated BMPs 48% High ferritin 48%. High lactate 30% lymphopenia 29% with high prolactin it's sorry, I'm sorry, that proactive at all. That doesn't make any sense. 29% had high procalcitonin INS 28% had thrombocytopenia. 21 21% had a nutro Philea. They were printed on chest X rays. Actually only 18 infants of these babies got chest X rays 11 had opacities forehead cardiomegaly cardiomegaly. Three had pulmonary edema and three were quote unquote normal. And then they talk about how did they identify the SARS cov two exposure, which is complicated. So they had a maternal card SARS cov, two swabs positive for 13 out of these 23 moms who had them so 37% of mothers, but serology was positive in 87% of mothers, among neonates 27% had a positive RT PCR test for SARS, cov, two, but 19 out of 26, almost two thirds had a negative PCR test. 21 had no PCR test done. 85% of the neonate had positive Serologies 32 neonates had positive IgG and a two headed quote unquote nonspecific positive serology, seven babies had no Serologies reported. So, again, you know, when we talk about exposure, I mean babies had some evidence of exposure. Most neonates actually received immunoglobulins as part of their treatment, almost 77%. The dose of immunoglobulin ranged between one gram per kilo for one or two doses, or a one to two gram per kilo dose once and then most neonates also receive steroids as part of the management 83%. They gave some other immune modulators. In very few patients. 60% of babies needed respiratory support. 45% of babies need an iron a tropic support. 40% of neonates received heparin 89% of these babies survived till discharge, five neonates died, two neonates died due to multi organ dysfunction today, and AIDS died due to shock with left ventricular dysfunction. One neonate died due to necrotizing enterocolitis. length of hospital stay range between 60s to 11 weeks, but some of those babies were preterm. And so that impacted obviously, their length of stay. The only other interesting, I mean, there's lots of potentially interesting things we could talk about here. But they wanted to provide kind of more clinical features. So if you are having suspicion of a post COVID, exposure, multi inflammatory syndrome of things to look for. And the only thing I think that that I'll note is that when they talk about when is the most likely time of presentation, that it really depends on what time when is the exposure and and that antibody production may take two to four weeks? So this may complicate presentation, findings. Thoughts? You

Ben 53:47

might know Yeah, I don't have you have a lot of thoughts? No, I actually have no thoughts. My question to you is, Daphna, would you if you had to use now the data presented in this paper? What would you say? What would you say if a kid shows up in the NICU and has COVID? Right, had this mis n? What do you think is the is the is the group of symptoms you should be seeing them?

Daphna 54:18

Yeah, I mean, it's, it's interesting, because it's not even so much these clinical symptoms, it's really evidence of inflammation. And so the baby's present really in a sepsis like picture. And that can be as we know, and babies and hold the constellation of symptoms varies significantly. But, and I think if we have more

Ben 54:44

of these, I guess, I guess, I don't mean to put you on the spot either. No, but I'm saying when I say this, I mean, I don't mean to ask you like alright, like what is the definition and but I'm saying what would what would make you suspicious like, right, I'm thinking that's from a listener, and I'm saying alright, like I listen to this pit to this report now, I have a baby showing up in the NICU, some respiratory distress, like how do I know like, should I? When do I know when to be suspicious? of MIS?

Daphna 55:09

Exactly. So I think it's like when we were in pediatric residency and you're like, is this Kawasaki? I don't know. And, you know, did it matter what the preceding viral infection was? So I mean, I think this would be a sick baby with no, you know, bacterial or viral, right, you sent the viral panel, there's nothing else is positive, I think you should suspect it if there was a recent COVID exposure, and why does it matter? Because potentially you would treat it with steroids or immunoglobulin if you had a high suspicion? Right. So that's, I don't know, what do you think?

Ben 55:50

Well, I'm thinking, a baby that shows up with respiratory distress and cardiovascular compromised. And obviously, these will really make me think of sepsis to begin with. Yeah, I mean, it's, it's like you said, it's inflammation. So it's not. But it's interesting, what you mentioned also about the fever, that it's not like it is it is there quite often, but it's not like a go to thing, right. It's not a good thing. So. So it's, I mean, I feel like

Daphna 56:26

unless we make it a criteria, and then it is.

Ben 56:29

Yeah, but when you see that it's only present in like 36%. Right? So 36%, you said, or something like that 36 by 36%. Then, then it's not something that like if you're saying alright, like 64% of the kids. Yeah. So what I'm saying is, it's very interesting for me to see this paper, which is a systematic review of people who have done the work to look for these cases. And I don't think this paper gives us a nice little vignette that you can say, Oh, I'm gonna write it right. It's so be

Daphna 57:02

No, I think it's it's babies who are looking like sepsis and you don't have another explanation, or these strange cardiovascular findings with no other explanation would be another reason. All right, we gotta hustle, like a lot.

Ben 57:22

But real quick, my next paper is a paper in the Journal of Pediatrics. It's from Montreal. Its first authors, Gabriella LeBlanc, and Gabriella LeBlanc, if we're pronouncing it the French Way, organizational risk factors and clinical impacts of unplanned extubation in the NICU. God knows we're all working constantly on reducing the number of unplanned extubation. So this paper looked at organizational variables, such as the nurse provision rates, the nursing overtime ratio, the unit occupancy, and trying to see how all these system based stuff impact the number of unplanned excavations. So the question, there's two questions that they're officially stating, number one, they're trying to assess the association between organizational variables and unplanned excavation in the NICU among infants on mechanical ventilation, and to evaluate the association between these unplanned extubation and BPD in a subgroup of babies that are less than 30 minutes. So this is a retrospective cohort study that included all infants admitted to the Morwell Children's Hospital McGill University Hospital Center NICU, between 2016 and 2019. They have administrative database that links basically all the things they need to look at the nurse to patient ratio, the overtime the occupancy, obviously, so that's that doesn't not really difficult. The number of recommended nurses based on the number of patients physically present in the NICU along with their corresponding dependency category using provincial guidelines. And those words that if a baby is deemed quote unquote, unstable, that's a one to one assignment. A baby that's an intensive care requires. It's just as awkward to say like this, but intensive care requires point seven nurse, Intermediate Care point the readers and continuing care point to five nurse. So obviously, the continuing care patient means that you can have a one nurse to four patients ratio, right. But it's a bit I don't mean to be demeaning or disrespectful to our nursing colleagues. So but that's how they presented it and I don't want to do the math as to what point seven really. So yeah. Okay, so the data on the unplanned events were retrieved from a specific database that they have, documenting and tracking that and the inclusion criteria they looked at any babies on mechanical ventilation and the clinical data was taken from the data that they're collecting for the Canadian neonatal network database. They did some propensity score matching. So to assess the association between unplanned extubation and outcomes for babies that are less than 29 weeks, they created a propensity score matched cohort using the following criteria. The gestational age, mechanical ventilation, admitted before three days of before three days after birth, having no major congenital anomalies, and bunch of other stuff, and the rent and the and the match them one to one based on this propensity score matching. And they looked at obviously, BP was defined as oxygen requirement at 36 weeks. And that's it. Let's get into the results. We're short on time. So in terms of organizational factors associated with the risk of unplanned activation among intubated infants, they had 2775 infants admitted to the NICU during the study period 25%, of which of which received mechanical ventilation, the median length of mechanical ventilation was three days. So some really, really impressive stuff. But total of 113 unplanned extubation events were recorded among 87 patients. In this study. 66 of infants had one event 17 had two three had three and one baby had four unplanned this division, we've all taken care of that one kid who just manages to get that. And that corresponded to 2.1, unplanned extubation per 100 days of mechanical ventilations. Most unplanned extubation, 62% of them were, quote, unquote, related to care. And what that means is a loose state or they were doing something with the baby and the tube came loose. So that's what they mean by related to care, quote, unquote. Overall, there were about 1200 1200 days with no unplanned exhibition, and 108 days with more than one unplanned exhibition per day, in the unmerge, just in the unadjusted comparison days with unplanned extubation, compared with days without higher over time, like the nurses were using over time, more and more numbers of infants have mechanical ventilation. So the number of days, the number of babies on mechanical ventilation makes sense, right? I mean, the more you're going to have, the more likely you are to get an anti switch. But the nursing overtime ratio was actually interesting, right, that they noticed that when they had a higher overtime ratio, the number of panics division increase, the Association of overtime ratio with higher odds of unplanned extubation remained significant in the adjusted analysis. So this is very, very cool. In terms of the nursing provision ratio, we're going to give a big kudos to our nurses because that was not a factor. So that was not significantly statistically significant. Also, the unit occupancy rate was not a factor.

Daphna 1:02:58

I was hoping it would show that they need the lower nursing ratios.

Ben 1:03:03

I know, I know. But But I mean, again, we're going to talk to you about a project that we're doing. Another project we're doing that's super inspirational, in my opinion. And it goes to show that I think you tell the nurse, you're going to have four babies, and they will multiply them signed away. Yeah, they do it. Yeah. Yeah. So I don't think that it means I think it's not, it's not showing, I'm taking so much time, I'm sorry. But it is not showing that the nurse ratio is okay. It's showing that our nurses will go above and beyond no matter how many beats. And we see this in our unit, because obviously everybody's struggling with finding nurses these days, because everybody went on travel assignments and stuff. But you tell a nurse, you have three sick babies, and they run the whole shift and they take care of these babies. So yeah, that was my shout out to our nursing friends. Outcomes of intubated babies less than 29 weeks there, there were 190 intubated infants, less than 29 weeks that met the inclusion criteria, and their median length of mechanical ventilation was about 13 days out of these infants 29% had at least one unplanned extubation. And the median age at which the first unclean exhibition happened was 15 days. I thought that was interesting, because sometimes, you know, in the beginning, you're careful and anyway, compared with infants without unplanned extubation, the babies who had unplanned extubation had a longer and that's only in the less than 29 weeks, as I mentioned, just a second ago, these infants had a longer total length of mechanical ventilation, and no significant difference in the odds of BPD. Let's watch a few more things. among infants with unplanned extubation 59% were re intubated and 49% had two or more unplanned extubation events. Among the 49 re intubations. The four numbers are intubation 71% of them occurred within one hour of the unplanned extubation and 13 happened between one to 24 hours and 2% in one and seven days. So it was interesting to see that most of them usually desaturations is the is the 63% of the time the reason for an immediate need to reinstate in terms of the sensitivity analysis. That's what I wanted to get to sensitivity analysis using non conditional logistic regression models, Hmong, the complete cohort of infants born at less than 29 weeks, which was about 200 Babies showed similar results. So when they looked at the sensitivity analysis, this found that there were higher odds of BPD among infants with unplanned extubation, who were re intubated when compared with infants without unplanned extubation. But they found no association between BPD rates and unplanned extubation in the non re intubated infants with unplanned extubation compared to the babies that have that didn't have an unplanned extubation. You'll have to play that over to too much. You could just go to the paper. But no, but I think I think that was that was very interesting. That really reached that level of significance. Where, like, yeah, so it was it was interesting that you needed to have an unplanned, extubation re intubated, and that was actually more predictive of a risk of BPD down the road than if you never had an unplanned extubation. So okay, so the conclusion was that the nursing overtime ratio is associated with increased unplanned exhibitions in the NICU. And among babies that are less than 29 weeks reintegration after an unplanned extubation is associated with increased length of mechanical ventilation, and odds of BPD compared to infants without unfixable. Alright, that's it. Definitely done with my paper. Okay. That was good. That was

Daphna 1:06:50

good. That was good. And, you know, we were recently having a discussion about I know panics. So it's nice. It's not nice to see, but that, that everybody's still trying to solve the problem. Yep. Yep. I will be quick. And then I know you have some, as we call it, rapid fibers to go through. So yeah, so this one, and it's actually I mean, right now, as it stands a pre approved for active treatment of infants born at 22 to 25 weeks gestation in California, it was a 2011 to 2018. This is coming out of the California Perinatal Quality Care Collaborative in the Journal of Pediatrics. So they're really looking at trends of active treatment, and factors associated with active treatment, in these view, very premature babies 22 to 25 weeks. So I'll just, I guess, get into the meat of the paper. They had 9000 infants born in 132 of the hospitals, between 22 and 25 weeks, and, and I'll just get to the primary outcomes, I guess, they lifted again, active treatment, and they defined the active treatment as either intubation mechanical ventilation, CPR, and or CPAP, or nippv, where the infant survived greater than 12 hours of life in I'm just going to highlight this because they said this was to avoid including infants where they were using palliative respiratory support, but not aimed at prolonging life, which is not something that is done in the majority of institutions. And so it is an opportunity maybe for parents to spend more time with their babies when they're anticipating

Ben 1:08:36

correct me if I'm wrong, what they mean by that is that you're delivering some form of oxygen support that is clearly not appropriate for the degree of the patient is experiencing. So for example, you would give him give him being very difficult. So yeah, yeah, simple description, but it's like you're giving like blow by to a baby. That's that's passing away. Right? You just just right. Okay, fine. That's what

Daphna 1:08:55

I mean by that. I mean, they were using I mean, see, see PAPR and I envy in a family who did not want intensive care. Does that make sense?

Ben 1:09:03


Daphna 1:09:04

Okay. Okay. So what they really wanted to look at so the overall active treatment was 19%, and 22 week infants. And what was interesting is that this has not changed significantly between 2011 and 2018, and 23 weekers. This has changed significantly over time ranges from 64% in 2011, to 83% in 2018. And we're at a point where we're greater than 94% of active treatment for 24 to 25. leakers. This didn't increase significantly over time in the 24 week group, but it did increase significantly for 25 weekers. Interestingly, the rates of active treatment were increased significantly if say you were de force to six of the week, versus zero to three days. So if you were 22 in five days, you were much more likely to get active treatment then, if you were 22, and zero days, which makes sense, but this was found across all weeks of gestation.

Ben 1:10:08

And now people are gonna say, well, 23 and 22 and three versus 22 and four, maybe we're gonna move the needle further.

Daphna 1:10:18

factors associated with increased odds of active treatment included, maternal reported Hispanic ethnicity, maternal reported black race P prom bleeding antenatal steroids, and cesarean section, factors associated with decreased odds of active treatment included lower gestational age and being small for gestational age. Interestingly, centers with lower levels of care had increased odds of active treatment when compared to level four units. And I mean, there's a lot to digest there, actually. But we

Ben 1:10:51

have to move on. So that's the data. That's interesting. What do you think that is?

Daphna 1:10:57

So they talked about see you, you're holding us up, but they talked about a lot of possibilities that maybe if it was an unexpected delivery, where you couldn't have the prenatal consultation, you know, they were just coming in and delivering at a low level, like lower level NICU availability, that they would resuscitate or maybe they weren't as comfortable having those prenatal conversations about not resuscitating

Ben 1:11:29

interests. Interesting. Okay, rapid fire. Rapid Fire articles. Let's go where's my page? Okay. So the articles that I wanted to mention, there's an article in neonatology called left ventricular dysfunction persists in the first week after rewarming following therapeutic hyperthermia for hypoxic ischemic encephalopathy. first author, panic Iran, Yasmin young, this is data out of the UK. And really their the the idea of the paper was they did serial. Might they assessed serial myocardial function in newborn infants receiving therapeutic hypothermia in moderate to severe HIV? They did. They did these echocardiography in 20 term infants between day on days 123. And again, after rewarming. What was very interesting is that all myocardial velocities were significantly lower. In the cases, on day one, they increased during therapeutic hypothermia, but the left ventricular indices remained consistently lower compared to controls even after rewarming. Left Ventricular myocardial performance index was higher in cases compared to controls on day one improved during therapeutic hypothermia, but remained again abnormal after rewarming. And so this paper is interesting because I think it goes to give us information really, when we think our therapeutic hypothermia is completed were right, I mean, and it's good to know that that the we can anticipate some left ventricular dysfunction potentially after we warming So an interesting paper. A very cool article, I'm not going to talk too much about it. intrapulmonary in neonatology intrapulmonary volume changes during hiccups versus spontaneous breaths in preterm infants, first author events and gurtner Gertner. Basically, they had they had this baby it's report of a single case, but they had this baby enrolled in a trial for like nebulizer fact. And so they had all this other stuff hooked up to the baby, and the baby had hiccups. And so they're reporting a little bit as to what exactly happens. So about what a what exactly happens when a baby has a spell of hiccups and compared lung volume changes during hiccups with spontaneous breathing using electrical impedance tomography. What they report briefly is that hiccups mostly occurred during the expiratory phase of breathing, and are associated with a shorter eye time and a shorter inspiratory time and the larger tidal volume compared with spontaneous breath mix. Yeah, volume changes were mainly restricted to the larger airways but some gas flow also reached the lung parenchyma. It's just it's a cool paper. Kudos to them. There was a very interesting article in pediatric pulmonology called prediction of weaning readiness off nasal CPAP and preterm infants using point of care lung ultrasound. We have some episodes coming your way about point of care ultrasound. First off, there is Mohammed Abdullah Mala. This is from Saudi Arabia. And so basically they're going through the system that you could use where you can use the lung ultrasound severity score, the x plus and also the, the LTR, the long title recruitment, and they're basically showing you images of lung ultrasound and actually doing creating an algorithm where using these these these two numbers, you can actually predict babies that will be successful weaned off nasal CPAP. So I'm not going to get into too much of the details, the outcomes are pretty interesting. And they're significant. So take a look at that. I wanted to give a shout out to our friend, Twitter friend, Lindsey nakki. Lindsey, I hope I'm pronouncing your last name correctly, who published in? I think it's the Journal of Pediatrics, a paper called factors associated with initial tidal volume selection during neonatal volume targeted ventilation. And to Nick use a retrospective cohort studies cohort study, they wanted to see if people were using what kind of tidal volume were people using. And so they did this multicenter retrospective observational study into NICUs of including 300, something infants on volume targeted ventilation. And what they found was that, depending on the birth weight, the tidal volumes were a bit different. So for babies that were less than one kilo, people tended to use five, sometimes a bit more six mL per kilo tidal volume. But for babies that were bigger, the tidal volumes, mostly were around five. And they compare that there's a very nice graph that will post on Twitter, where they're looking at the literature informed tidal volume range. And they were showing that people actually are being consistent with the evidence, which is not always that we're consistent with the evidence. So yeah, so the conclusion is that most infants usually receive an initial tidal volume of five. But But for most infants, that was consistent, and I think the scattering of the dots on that graph is very interesting. Last paper, see quality associate associated with systemic hypertension in infants with severe bronchopulmonary dysplasia. first author Arvind Seagal from Australia, the goal of the paper was to ascertain the correlation between systemic hypertension, right, so we're not talking about pulmonary hypertension, we're talking about systemic hypertension, and respiratory squarely among infants with BPD. And so what they found was that for babies with BPD, they were more likely to have hypertension. And then they looked at their their their mean blood pressure, their systolic blood pressure, it was pretty compelling stuff. And the only reason I wanted to mention that paper is because the authors are gutsy enough to actually talk about why do we think this they were noticing this and so they're going to just read you this little paragraph it says that the mechanisms underlying the higher blood pressure in infants with BPD could have multiple underlying explanations. And they're saying hypoxia and hypercar via increased systemic vascular resistance through stimulation of peripheral arterial chemo receptors. The latter could cause catecholamine release an increased vasomotor tone, decreased pulmonary vascular resistance, sorry, decreased pulmonary vascular clearance, or even net production of circulatory catecholamines has previously been noted in infants with BPD. inflammation causes abnormal collagen deposition and endothelial dysfunction via multiple pro inflammatory cytokines complementing the role of angiotensin two. So it's an interesting, it's an interesting paper, because even if you're not going to leave the paper with a good understanding as to why exactly this happened, because that's not really well known yet. It's it wasn't we've, we see this all the time that these babies very often have have elevated blood pressure. So it was kind of nice. There's a nice graph as well, that will post on Twitter. That's it.

Daphna 1:18:17

You have even more papers in the in the folder. I know. Are you gonna post them all? The links? The links?

Ben 1:18:25

I could post all the links? Yeah, yes, sure.

Daphna 1:18:28

Okay, sure. All right. That's definitely all we have time for.

Ben 1:18:32

All right, that sounds good. Don't forget to grab your CME credits, and on the website on the app is on the episodes page. Thank you to everybody. Thank you, Daphna, for your patience.

Daphna 1:18:42

For sure. For sure if people are having trouble, just let us know.

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