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#045 - Journal Club 22

NICU journal club the incubator podcast

Hello Friends 👋

This week we have a jam-packed journal club. We reviewed a few papers looking at phyisiologic changes in neonates. How does pCO2 and pO2 affect cerebral blood perfusion? How does PRBC transfusion impact PVR, cardiac function and splanchnic saturation? Daphna reviews a bunch of interesting papers looking at salivary cortisol levels in neonates as measure of nicu induced stress, what are the long term outcomes of babies born during the pandemic. She also reviews a paper from Brown University senior authored by Dr. Betty Vohr on how "high risk" neighborhood can affect long term outcomes of neonates. We also review a paper by our friend Dr. Camilia Martin on breast milk xenobiotics and their effects on the devlopment of BPD and ROP in a cohort of preterm neonates. And we review the newest AAP policy statement on Vitamin K and a clinical report on alternative birth practices that is quite informative.



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

Impact of Carbon Dioxide on Cerebral Oxygenation and Vital Parameters in Stable Preterm and Term Infants Immediately after Birth.Wolfsberger CH, Bruckner M, Schwaberger B, Mileder LP, Urlesberger B, Pichler G.Neonatology. 2022;119(1):10-17. doi: 10.1159/000519636. Epub 2021 Oct 28.

NICU-based stress response and preterm infant neurobehavior: exploring the critical windows for exposure. Zhang X, Spear E, Hsu HL, Gennings C, Stroustrup A. Pediatr Res. 2022 Nov;92(5):1470-1478. doi: 10.1038/s41390-022-01983-3. Epub 2022 Feb 16.

The impact of a PDA on tissue oxygenation and haemodynamics following a blood transfusion in preterm infants. Smith A, Armstrong S, Dempsey E, El-Khuffash A.Pediatr Res. 2023 Apr;93(5):1314-1320. doi: 10.1038/s41390-022-01967-3. Epub 2022 Feb 12.

Association of Birth During the COVID-19 Pandemic With Neurodevelopmental Status at 6 Months in Infants With and Without In Utero Exposure to Maternal SARS-CoV-2 Infection. Shuffrey LC, Firestein MR, Kyle MH, Fields A, Alcántara C, Amso D, Austin J, Bain JM, Barbosa J, Bence M, Bianco C, Fernández CR, Goldman S, Gyamfi-Bannerman C, Hott V, Hu Y, Hussain M, Factor-Litvak P, Lucchini M, Mandel A, Marsh R, McBrian D, Mourad M, Muhle R, Noble KG, Penn AA, Rodriguez C, Sania A, Silver WG, O'Reilly KC, Stockwell M, Tottenham N, Welch MG, Zork N, Fifer WP, Monk C, Dumitriu D.JAMA Pediatr. 2022 Jun 1;176(6):e215563. doi: 10.1001/jamapediatrics.2021.5563. Epub 2022 Jun 6.

Acetaminophen and Xenobiotic Metabolites in Human Milk and the Development of Bronchopulmonary Dysplasia and Retinopathy of Prematurity in a Cohort of Extremely Preterm Infants. Santoro KL, Yakah W, Singh P, Ramiro-Cortijo D, Medina-Morales E, Freedman SD, Martin CR.J Pediatr. 2022 May;244:224-229.e3. doi: 10.1016/j.jpeds.2022.01.030. Epub 2022 Jan 31.

Nwanne OY, Rogers ML, McGowan EC, Tucker R, Smego R, Vivier PM, Vohr BR.J Pediatr. 2022 Jun;245:65-71. doi: 10.1016/j.jpeds.2022.01.042. Epub 2022 Feb 2.

Vitamin K and the Newborn Infant. Hand I, Noble L, Abrams SA.Pediatrics. 2022 Mar 1;149(3):e2021056036. doi: 10.1542/peds.2021-056036.PMID: 35190810

Risks of Infectious Diseases in Newborns Exposed to Alternative Perinatal Practices. Nolt D, O'Leary ST, Aucott SW.Pediatrics. 2022 Feb 1;149(2):e2021055554. doi: 10.1542/peds.2021-055554.

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

Daphna 0:00

Hello, everybody. Welcome back to the podcast stuff now. How's it going?

I'm good. It's been a it's been not not a long service week, but it's been in service. We've been recording when we can. So

Ben 0:59

yeah, it's every time we either you or me are on service, it becomes a scheduling nightmare to try to find the time to. Because it's not just I mean, you say the time to record but it's the time to record the time to read the articles. app. So

Daphna 1:15

we've been we've been piecing it together. Oh, yeah.

Ben 1:19

Oh, yeah. But it's what? It's one of I guess it's it's usually we record like a few days before, but it's what it's Saturday night. And yeah. Okay, so there's a bunch of very cool articles we're reviewing today. I don't think we have any specific announcements before that. So we should just get right into it. Okay, sure. Do you want me to go ahead or yeah,

Daphna 1:42

you start?

Ben 1:43

I start. Okay. So the first, the first paper I'm going to review is called the impact of carbon dioxide on cerebral oxygenation, and vital parameters in stable preterm and term infants immediately after birth. first author is Christina Helling. Wolf's burger. And this is from a hospital Medical University of Graz in Austria. So, yeah, so the reason I really liked this paper is because it's one of these like, super physiologic papers, like it's just like, bread and butter physiology. And I just love that. So what's so this is, what's the premise of this study? So the premise is p co2, right? So we know the effects of P co2 on cerebral blood flow. And we know that the higher P co2 leads to vasodilation and increases your cerebral blood flow, and a decrease in P co2 leads to vasoconstriction. And in turn, a decrease in cerebral blood flow. And this is I'm saying all these things for all our friends out there who are studying for the boards, this is a good, good review. Then they were thinking, What about there, so then, using nears to look at cerebral tissue oxygenation, maybe we could measure these things. And so the gap in the in the literature that they've identified is that the parameters that are influencing cerebral oxygenation during the immediate uncomplicated transition after delivery, they are not completely well understood. And so what their aim was, was to evaluate the potential correlation between co2 and cerebral regional saturation, tissue, oxygen extraction, all that stuff measuring nears, and routine, like monitoring parameters like heart rate, SATs, blood pressure, etc. And in addition to that, partial pressure of OH two obviously. They did this in preterm Antrim, infants without any medical support 15 minutes after birth. And so this was really like, that's what I was saying earlier. It's really a study about medical physiology, where they wanting to understand how does this work in babies that don't need any support? What I liked about this study is that they formulated the hypothesis, which was based on the on the known physiologic facts, that higher P co2 Then should be associated with a higher Cerebro Cerebro regional saturation and lower tissue extraction of oxygen after 15 minutes after birth, an intern that should increase also cerebral blood flow as a result of this vasodilation. And they were expecting a slight difference in that between terms and preterm, considering that preterm infants have more immature autoregulation. What are we going to call this mature autoregulation system? So this is a study that they conducted between 2009 and 2018. It's a post hoc analysis. I don't know what came. I don't know what happened. I wanted to find out what post hoc meant and actually it's means after this, so it's just like, I know it's after a study was already done, but I was like what it's hoc Anyway, so that was cool. Anyway, inclusion criteria were babies that received nears monitoring for 15 minutes after birth, that had capillary blood gas within 14 to 18 minutes after birth. And the excluded obviously any babies with major congenital anomalies and any need for oxygen or any form of non invasive?

Daphna 5:20

Gets it quick time to blood gas?

Ben 5:23

Yeah, yeah. And I guess this is why it's important for these studies to say those things, because in this case, if you, if you had a baby that needed some type of support, you could make a case and yeah, need a gas within 15 minutes fine. But in a baby that doesn't need any monitoring. That's where consenting families is very important because you are getting a gas and, and and that may not be always clinically indicated. And so that's why these study protocols need to be drafted carefully and explained to the family as well. They placed the near infrared spectroscopy on the frontal parietal region, they perform full set of vitals, we said the blood gas, and that included hemoglobin F, which made me wonder definitely, if our institution we get hemoglobin F, from our blood, gas or anywhere. Okay, so let's go into some of the results. So they had 659 infants that were eligible, but that narrowed down to 95. That could be included in the study based on various issues, obviously, mostly related to the need for a support after birth, or the lack of blood gas. It was 95 infants were divided into 11, preterm and 84 full term infants. So, the first the first finding that was very interesting and unexpected is that in preterm infants, P co2 correlated negatively with cerebral regional saturation, and positively with C, F to E and C to E, which are the cerebral fraction of tissue oxygenation extraction. And so that's how much the tissues are pulling for oxygen from the blood vessels. And that was statistically significant. In preterm infants, they also showed a lower OTU set and P O two with increasing P co2. In term infants, they found that P co2 did not correlate with cerebral regional sat tissue oxygen extraction SPO to heart rate, blood pressure, rectal temperature, or blood glucose. But they did see also like in preterm infants, that P co2 correlated negatively with co2 in term infants as well, even if, in term infants that correlation was was slightly weak. And that's pretty much it for this paper, right? And so you're like, alright, so I was I was. So the results are feel almost a bit underwhelming, but you should really take a moment, the discussion is very, very interesting. So what is so what does this tell us? So number one, it tells us that there's a very interesting interplay between p co2 and co2, and the effects of each one on cerebral blood flow, and that they may both be very significant. So the oxygen is a potent mediator inducing changes in the tone of the cerebral vessels, and influences the cerebral autoregulation and cerebral blood flow. And what they found was that below a certain threshold of Kyoto, so like, if you're below 50 millimeters of mercury, any increase in co2 has a very, very strong vasoconstrictive effect on cerebral vessels. And the pure two levels usually increased from 15 to 20 millimeters of mercury to like 46 to 57. And the big question is, does this potentially outweigh some of the effects of any variation in the co2 that is also seen at that time. What they found also is that preterm babies obviously had a higher degree. And I think I forgot to mention that in the results, but they had a higher degree of hemoglobin F, which obviously leads to a left shift in the oxygen dissociation curve, which means that they're less basically less likely to release oxygen to the tissue. And hemoglobin F is more is cheaper when it comes to releasing oxygen to the tissue.

Daphna 9:16

I think the term has higher affinity.

Ben 9:18

Listen, what we're doing for boards, I'm thinking of hemoglobin F, like you want to know, the isn't the way I remember hemoglobin F. And the oxygen dissociation curve is like I'm thinking this is a fetal hemoglobin. It's like a baby. And have you ever tried to take a toy away from a baby? Getting it? Exactly. So this is hemoglobin F. And and then if you can remember that, then you know that yeah, that's a left shift in the oxygen dissociation curve. The last thing I wanted to mention was the PCO two as well as ink was associated with an increase in pure co2 was correlated with an increase in heart rate. And they asked a lot of interesting question as to well if the heart rate what does that mean? Because if a PCO to has a positive effect potentially on cardiac output, shouldn't that increase cerebral blood flow, but they really acknowledged the fact that with heart rate alone, they can't have any idea as to truly what the Cardiac output is without either more more information. And so the conclusion of the paper is that higher P co2 is associated with lower cerebral regional sets and higher CFTR. Ease and CTO is the tissue oxygen extraction. And that in term infants, there was no associations that were observed. The presence findings suggest that the vasodilation of daily TATIVE effects of PCO two are less pronounced in preterm infants during the immediate postnatal transition. And they also are suggesting that in preterm infants, the visual dilated effect due to HyperCard via may not outweigh the vasoconstrictive effects of the increasing Putu values after birth. And I thought that this is fascinating. Obviously, it's a small study, they were very clear about their limitation. But these are the type of paper that started challenged a little bit, the way we think about neonatal transition and neonatal physiology. And that to me is super cool.

Daphna 11:11

Yeah, I think you're right, it says, you know, we know that they haven't this immature autoregulation, right, it's the it's one of the major board tip, it's one of the major reasons that they have they have this high risk for intraventricular hemorrhage, is they have this poor, cerebral artery regulation. So I think confirms all of that. I think what's really interesting is when you think about what happens in the delivery room, you know, NRP gives us a really good starting oxygen, you know, we should where we should start, but then lots of things happen in the room, right? Doesn't tell you how high to jack up the oxygen and how quickly to bring it back down. And so, you know, there's some probably major fluctuations of FY oh two, and then you know, the, the co2 as a yo twos during during resuscitation. So it's, it's interesting. It shows, though, that they're probably developmentally, there's, there's trying to be some attunement of those fluctuations, as as the baby is transitioning, but but then we that, but then we show up. So you know, it's interesting, it makes you really think about being more maybe judicious with the oxygen, which is what studies are showing, but then we still don't know what to do with it when your baby needs more than, you know, the starting oxygen.

Ben 12:42

Right, right. I mean, I think to me, what that means specifically is, are we being very archaic in how we assess these babies by just looking at like do to something right, maybe now we should look at our nears. And maybe we should titrate things based on a New Year's monitor that you would have in the delivery room? Because why do we care about the SATs to be honest with you? We don't the stats hats doesn't make any difference. It's really the the nears goes so much more distally. To what matters more, which is how much oxygen are you giving this baby's brain working? Right, exactly. So I think this is, to me, this paper shows a shift number one and how we think about things and also what tools were using at the bedside to assess the well being of these infants. So very cool paper.

Daphna 13:25

Yeah, and I mean, that's true, right? Even if you are doing frequent blood gases, there's still time in between the blood gases where you have no idea what's happening, right. So we're just making assumptions between time points. Very interesting.

Ben 13:41

Where are you taking us next?

Daphna 13:44

Let's see. I'm going to go to the totally different realm from the basic science. So there is this an interesting article in pediatric research and NICU based stress response and preterm infant neuro behavior, exploring the critical winters windows for exposure. Lead author, Xu, Ying Zheng, and this is coming from the Cohen's Children's Medical Center in New York. In the Mount Sinai,

Ben 14:15

the last author is none other than Dr. Anne Marie Sue stroke, strep, who I had the pleasure of working with who was basically my my front page recommendation letter for fellowship. She is She is an amazing educator, and I wanted to give her a little shout out on the podcast because she really is amazing. Like she's the type of educator that gives you the passion to pursue neonatology. So if she's listening, thank you.

Daphna 14:43

I hope I hope she's listening. And I knew you were gonna say something because this is you're here, not just to strep is a medical home.

Ben 14:53

It's New York, but she was working with her at Mount Sinai Medical Center, which I Think she's now moved to Cohen's children. But anyway, I wanted to give her a shout out because she's really an amazing physician and amazing educator. So Dr. Seuss strep. Thank you. And if she's not listening, somebody will tell her Hey.

Daphna 15:14

It's funny how that works. Well, this was an interesting study. So it was part of this kind of overarching study called NICU health. And NICU, it was the NICU hospitals, exposures and long term health, which is really focused on defining the impact of like hospital based environmental exposures between birth and NICU discharge, which is really cool. And, you know, a personal passion of mine. And so they included preterm infants born between 28 and zero and 32, and six, seven weeks. And infants born less than 1500 grams between September 2011 and march 2020, who required hospitalization in the NICU fallen birth. But they indicate who have low rates of physiologic derangement, such as hypoxia, or hypotension, or other medical predictors of poor outcomes. So it sounds like it's a relatively healthy cohort. So they're, they're the primary measure was looking at salivary cortisol, which is actually a really interesting area of study, it's gaining a lot more popularity, and that is a good thing, because there's still lots of things that we are learning about cortisol measurements, especially in the preterm infant. And so as more and more studies are, are doing it, we're getting much better, like baseline information about parties,

Ben 16:49

and and it's giving, in my opinion, a lot of substance and objectivity to a lot of the things that have been posited when it comes to trauma informed care. And, and, and this approach of the stress of the NICU. If you could, I mean, it makes sense. And the theory is sound. But if you could measure like, certain blood levels,

Daphna 17:10

I think it's, it's helping people buy in to the, to the stress theory, which, which is good. And so they were doing salivary cortisol, and the way they were measuring that is they were getting an am and a pm measurement on one day, for every week during the neonatal admission. And as someone who has collected a lot of salivary cortisol samples, it's not an easy task, especially in the youngest babies. So

Ben 17:43

did you have you done salivary? Yeah, you've done

Daphna 17:46

my very my primary fellowship project.

Ben 17:52

And why is it hard? Is it like you have to get a certain volume? What's the

Daphna 17:57

Yeah, so you don't want it to be too close to feeding, which is all the time you and it's some some of the babies just don't make saliva, especially if they're not orally feeding. So a lot of our babies who are getting like, ng OG feeds make a lot less saliva,

Ben 18:14

and the and even if you humidify some of the oxygen they can it can dry them up. Some

Daphna 18:19

Oh, yeah, yeah. So. So I'm, I'm happy to see more people. It's a lot of work. And then what they looked at was, they were using the NN s to look at the neuro behavioral performance, just prior to NIC you discharge. And so for people who aren't familiar with ns, it's basically a structured physical exam that looks at kind of behavioral and motor reactivity. There are 13 subscales, to score an infant. And it looks at motor function, reflex attention, social reactivity, and like response to stimuli. And then they used a reverse distributed lag model, which I had to do some reading on this. But what they then do is kind of like peel it back to try to find critical windows for repeatedly measured exposures and outcomes. So they wanted to see they wanted to track the exposures and track the outcomes and see if there's a period of time in which they have some association. And the point is, for this specifically was to look at is there a time in this postnatal period where there's a specific sensitive time for development, where certain exposures may impact health outcome? And then the other outcomes they looked at are, were really interesting. They had, you know a lot of other associated projects, they had the dyne project, which is called developmental impact of NICU exposures cohort, and the echo cohort, environmental influences on child health outcomes. So they're doing a lot of follow up work, which is really cool. So in this cohort, they had 139 infants, the mean gestational age was 30 weeks, plus or minus 1.4 weeks, a total of 840, cortisol measurements. And then one thing they did show, which comes up a lot and criticisms of cortisol work is, well, it depends what time of day you get it. But that's really not true in our population, because they really don't have the diurnal variation yet. So but they did prove that they took the am and the PM, and they really didn't have a big difference. So they actually use the two measurements and create a kind of an average daily cortisol measurement for each baby. The other thing they looked at was the cortisol is over time. And so again, when you have babies that start at multiple gestational ages, you have to decide are you going to use the postnatal day or you're going to use the gestational age. And so they used, what they looked at was kind of timecourse over admission. And so they showed that higher cortisol were earlier in admission. And the study team felt that the this made sense, because of, you know, higher number of interventions, higher acuity of care earlier in admissions. And then they wanted to look at the cortisol as it related to all the NS subscales. So they identified statistically significant associations between cortisol and the NS subscales, which we'll talk about infant sex, and developmental age. And so sex is another thing that we really have to look at when we're looking at cortisol. So for basically all of the parameters and they separated by female and male sex. So they found significance for the lethargy and habituation subscale for both males and females, when compared associated with the cortisol is less than 30 weeks. So basically, they found that increases in cortisol, less than 30 weeks, demonstrated higher scores on the lethargy and habituation scores. And so for people who aren't familiar with that, the higher the habituation scores are indicative of really kind of better habituation. So it takes less exposure, less number of exposures to a stimuli for BB to habituate. Interestingly, they showed, like I said, higher scores on the lethargy sub score with increases in cortisol less than 30 weeks. So here, higher lethargy scores actually indicate more effort of the examiner to bring an infant to kind of a steady alert state. So this was interesting, because so higher scored, assaults fell to reflect higher stress early in admission, actually showed better habituation at term, you know, near discharge. And it showed higher lethargy scores, which is interesting. So one was like kind of a positive effect and one was not so positive effect. They also saw association for both sexes between cortisol measurements in the first week of life, and in week six to seven associated with decreases in the intention score and regulation score. So in these subscales, a higher score for the attention score, is kind of better attunement to and following have the items presented to the infant. And likewise, higher regulation scores indicate that the baby has kind of an easier ability to maintain a quiet alert state. So here they found, like I said, higher cortisol measurements in the first week of life and higher cortisol measurements between weeks six and seven, showed decreases in the attention score and decreases in the regulation score. So there's some thought that early stress can lead to worse neurodevelopmental outcomes, and so they kind of have like, a mix of outcomes here. But again, they postulate that stress early in admission, may modulate the NS scores. I think it's a really interesting study, I think it's something we really have to look at. Not everything was in the same direction. So that's that's of interest. And and there are a few theories probably that come into play here that over activation of the HPA axis can lead to poor stress response later in life. Or, really, over activation of the access may totally dysregulated the axis and so, you know, how do we monitor? How do we use cortisol as a marker in babies who may be like, totally dysregulated? This was a small study, but I think it shows that there's definitely something there something, you know, signals for us to, to follow. And I'm interested to see what other work they they come out with super cool.

Ben 26:05

Yeah, yeah, I think from the standpoint of methodology, that was really interesting. I mean, again, to me, I was not so familiar with salivary cortisol measurements. So I think it's opening to me, it's opening the door to a lot of other potential for studying this, this this level. And, and I also think that, again, it's a methodological study where so many things are giving you ideas, it seems like something that has the potential to give tremendous volume of information. The crafts are super welcoming. Yeah. Yeah. And,

Daphna 26:40

you know, it's interesting, because, I mean, we're still I mean, the, these studies are even helping us to delineate really the normative values for these. That's

Ben 26:51

exactly right. I was looking at some of these. So you have these graphs with with basically, it's a scatter plots of the different causal level based on sex. But then you look at the numbers, and you know, wow, the variation like some kids have low, some kids have really, really high levels. I think this is all these things are just very much interesting to me. Yeah.

Daphna 27:11

If you didn't have us recording around the clock, maybe I'd get out my cortisol

Ben 27:17

or it's my it's my fault.

Daphna 27:21

Okay, your turn.

Ben 27:25

Maybe you can maybe you know, what, you can have your study shared on the podcast as a proof of unbiased look completely peer reviewed by your co host. Okay, so the next paper I would like to go to is another physiologic paper because that's just the theme of the month for me. This is published in pediatric research. It's called the impact of a PDA on tissue oxygenation and hemodynamics, following a blood transfusion in preterm infants. first author is Aisling Smith. And last author is our Twitter friend, Doug, Professor FFL, Kuvasz, from Dublin, in Ireland. So I'm going to be perfectly honest with you, this is a very interesting paper, but the As expected from from our friend, if the level of of sophistication in the methodology and the echo measurements was very high level. And so it required a lot of a lot of googling on the side, to really grab, grasp the full spectrum of the of the information being presented. So I'm going to do my best to represent the information as as as accurately as possible. So what where is this? So this study was done at the rotunda Hospital in Dublin, as we've said, and it took place between 2019 and 2021. The premise that the study starts off with is that there's there's a there are saying that there's a need to better characterize the effects of a blood transfusion on neonatal hemodynamics and myocardial performance, both in the presence and in the absence of a PDA. And the the authors are saying that this is important because there's conflicting evidence regarding the impact of blood transfusions, on blood transfusion. I mean, PRBC is, by the way, and I'm going to use this term interchangeably just for the sake of convenience, on peripheral vascular resistance, vascular resistance myocardial function in the neonatal population. And I think they're right about that. There's a lot of debate about should we really, is there such a thing as transfusion related birth injury, all this data that is now starting to come out about babies who get transfusion actually do better when it comes to neck and stuff? So anyway, there's a lot of controversy. And so I think this paper is great because it's going to add more information to the edifice. So the the objective of the paper is to to examine the hemodynamic impact of PRBC transfusion on to pulmonary vascular resistance systemic vascular resistance myocardial function using echocardiography and nears both cerebral and spank neck, in pain in babies with and without a PDA. The stated the hypothesis, which was that a PRBC transfusion should impose divergent hemodynamic effects in the presence and in the absence of a PDA. So they were really looking for a difference. The way they conducted their study was using a prospective observational design. They included all infants with a birth weight below 1500 grams who received a blood transfusion at day of life 10 Or after? They were very worried about any physiologic transitional issues before that. So they wanted to start a date 10 exclusion criteria? I thought it was interesting, the dimension lack of consent. And I was like, doesn't that go without saying but I think it's it's good to mention that as well. Any congenital anomaly or a high likelihood of death within the first 10 to 15 days of life? So what did they measure? So the measure the bunch of clinical variables ivh, sepsis, or a P BPD. Whether they were given steroids for BPD, NEC and death prior to discharge? Interestingly enough, they it's important to mention their transfusion policy. So their transfusion policy was that a baby will receive PRBC if the hemoglobin was below 10, and the babies were on mechanical ventilation, or if the hemoglobin was under eight. In any other scenario, how did they approach the treatment of their PDA? It was at the discretion of the physician and they do however, disclose that their approach, medically speaking is to start with ibuprofen firstline and potentially repeat the course of ibuprofen if the PDA still open. When did they echo these babies, they could the babies before, before the transfusion, 18 hours post and 24 hours post. They did a bunch of measurements when it came to echocardiography, pulmonary artery acceleration, the pa t, ventricular eccentricity index, left ventricular and systolic wall stress myocardial strain velocity time index for the brachiocephalic artery and celiac artery. So we have in there the pulmonary artery acceleration, which basically is a measure of pulmonary hypertension. We have myocardial strain, which looks at how much work the myocardium is doing. And then these velocity time index really are looking at the flow through these arteries, and specifically the brachiocephalic, which is predictable and celiac, which is was Dr. He did Cerebro and Spike next nears, and the nears was applied during the transfusion. And for 24 hours after the transfusion was done. They had a hypoxic threshold for cerebral saturation of 63%. And they calculated the tissue oxygen extraction from that. So how many babies Oh, mostly. All right, going off again. So 30 infants were included in the studies 10 had an open PDA 20 had a closed PDA. Looking at the gestational age, they were pretty small. So the mean gestational age was 25 weeks in the open PDA group 27 in the closed PDA group, birth weight was 770 grams in the PDPA group, and 130 in the nuclear group 5050 age, the sex distribution, and the age at the transfusion was on average day 14 For the PDA group and 22 for the closeby group. So I'm going to try to summarize the results in a way that should make sense without going too much into the different measurements. But obviously, you can refer to the paper we'll have the paper on our website and and read it in full. So when it comes to coronary vascular resistance, so following a blood transfusion, they saw a significant change in the pa t in the left ventricular eccentricity index, and all these measurements indicating a fall in the pulmonary vascular resistance. And that happened independently of the PDA status. So very interesting that deployment, the PVR went down after a transfusion. When it came to myocardial function, they saw no changes, especially when they were measuring the global longitudinal strain or the strain measurements over the study period. Now, what they are, and again, I'm going straight into conclusion as I'm talking about the results to help us understand a little bit of what what's going on. So they saw no change in the strain. And they're very honest about the fact that they're realizing they're doing these measurements up to 24 hours post transfusion. And they're saying it's very likely that we're not giving enough time also. And maybe if we had echoed further down the road, maybe we would have seen something so that's also something to take into consideration. A observed a significant increase in the right ventricular free wall strain following a PRBC trend. diffusion in the no PDA group, and this improvement in the right ventricular function is likely related to the drop in the pulmonary vascular resistance and disease and reduced right ventricular afterload. There was no change in right ventricular function in the PDA group throughout the study period. It was no demonstrate demonstratable change in the PDA caliber following the transfusion. However, they did see a small fall in the PDA systolic velocity by 24 hours following a transfusion. So let's talk a little bit about the near infrared spectroscopy. Their their results shows an increase in cerebral oxygen saturation and a corresponding decrease in the tissue oxygen extraction, which makes sense over the study period, or both open and closed PDA groups. The data reveal the differential effect of the PRBC transfusion on the splink Nick nears right and and that's obviously something that's interesting, between the premature infants with and without a PDA. So babies in the PDA open group had significantly lowers plecnik, oxygen saturation, and higher tissue extraction values, compared to the PDA close group at baseline, which persisted over the study period and were unaltered by the PRBC transfusion. Which means basically, that there's a still phenomenon, as we probably know, and so they were seeing a difference between the babies who had a PDA versus the people who didn't have a PDA. And the transfusion never really completely bridged the gap. In contrast, yeah, in contrast, the PDA close group experienced a significant increase in the splinting oxygen saturation, and a decrease in their tissue oxygen extraction, following a PRBC transfusion. And when they looked at the celiac artery, velocity, time index, is that what it's called velocity? Velocity time index, yes, got it. Correct. The celiac artery VTi was lower in the PDA group throughout the study period with significant differences occurring in the first and third scan which were statistically significant from the babies that had no PDA. And over time, looking at the celiac or the VVTi, in each group independently, it was no statistic like they were different between the groups of PDA versus no PDA, but they're within their group that was. So

what their conclusion was, is that there's this this work they're saying is providing you insight into the impact of PRBC transfusion on pulmonary vascular resistance, right ventricular function, cerebral and Spike Nick oxygenation. And in the presence and absence of a PDA, they're showing that the ongoing impact of Dr. patency on gut oxygenation, and that further studies will be required to fully elucidated potential clinical impact of these observation on some of these important and neonatal outcomes. So yeah, there's definitely a bit more to this paper. And like I said, it's it's very technical, but the graphs tell a very important story. And yeah, I thought that was that was interesting.

Daphna 38:06

Yeah, what's so cool about this paper is, is, you know, we're all still debating on, you know, what defines the hemodynamically significant PDA. So same thing, they're giving us a lot of measurements, a lot of data, because it's, it's helping lay the the framework for, you know, just evaluating the PDA, you know, so like, in real time, we're collecting the, you know, normative values, which I think is really cool. And I didn't, I didn't know that I that, you know, that change that a blood transfusion or changing that blood flow may decrease the pulmonary vascular resistance. So yeah, that was cool.

Ben 38:51

That's, that's yeah, that was very interesting. And like to go back to the point you were made just previously as the fact that it's, it's striking to tie in all the all the tools that we have, where it's like, oh, it's not just going to be nears or it's not just going to be point of care ultrasound with hemodynamics. It's going to be a combination of all these things, that's going to tell us a very accurate picture. And it seems like I mean, again, I'm only on the on the lip here. It seems like we might be able to understand a little bit better what's happening during a blood transfusion. As we're utilizing these tools more readily. And following these babies more closely. In this case, I'm not saying they didn't do it correctly, but obviously it's a small study, but as the data starts piling on, then probably have a better understanding as to as to what truly is happening and not just so theoretical.

Daphna 39:37

Yeah, and like you said, it was important to know what their transfusion criteria was, obviously. So I think that's the only other information I would have wanted to see is you know, what were what were the absolute hemoglobin numbers, you know, for the for babies, how low did they get? What was the change in concentration, you know for, for transfusions, right?

Ben 40:04

And so, so the pre transfusion hemoglobins were around like 10 and nine, like around 10, basically. And their post transfusion was around 12 for the hemoglobin. So they do mention that and there was no. So that's interesting. I'm curious, as you're mentioning, I'm curious to see when people do the same type of study with a different transfusion protocol and it's much lower, are the effects going to be more pronounced? And then when they looked at some of the outcomes that we mentioned, BPD, all these things. There was no statistical difference. I forgot to mention that as well. All right, we need to move.

Daphna 40:33

Okay, so I'm sticking with my neurodevelopmental theme. I wanted to do this JAMA Pediatrics paper and association of birth during the COVID 19 pandemic with neurodevelopmental status at six months in infants with and without in utero exposure to maternal SARS cov, two infection lead off into Lauren chiffre. This is coming from a Columbia University Irving Medical Center. And I think this is data that people have been waiting for. So this is part of the combo initiative, the COVID-19 mother baby outcomes, a prospective cohort study, again established at Columbia, and spring of 2020. To look at associations between in utero exposure to maternal COVID infection and the health and well being of moms and babies living in New York City, that's obviously their population. So they looked at dyads who were exposed to SARS, cov, two during pregnancy between March and December of 2020. And then they invited 123 unexposed matched dyads for each of those groups. And in addition, they included a historical cohort, especially when we were talking about development. So they kind of re recruited from this other separate protocol. They were doing a study in the well baby nursery at Morgan Stanley children's, to look at the association between gestational diabetes and six month neurodevelopment. So they were using as cues in that study the Ages and Stages Questionnaire. And so those infants were born between November 2017 and January 2020. The one thing I'll note is they did have 15 babies who were born were part of the historical cohort, but were tested during the COVID time because they were delivered they could have been delivered in January 2020. So they were they still lived part of their pre testing during during the COVID time. Their final sample included data from 317 infancy 255 in the pandemic cohort, 114, exposed 141 unexposed and 62 in the historical cohort. The other thing we wanted to look at was exposure timing. So they were to able to determine the timing of COVID infection for 85 out of the 114 mothers 75%. And in the analysis. If they couldn't determine the exact date of symptom onset, then they used the date of peak numbers of Kobe to SARS cov two infections during the first wave of the pandemic, and that was the date April 6 2020. To identify the trimester of exposure. And like I said, they tested all the babies using almost the same protocol from the historical cohort. So between five months, zero days and six months, 30 days, they did neurodevelopmental screening with the ASQ three. So moms with COVID infection significantly differed from non infected mothers on a number of factors in self reported race, ethnicity and educational level. Which, given what we know about disparities during COVID, a higher proportion of mothers with infection identified as other or mixed race, Hispanic or Latin x, and the lower proportion reporting a graduate degree compared with the healthy full term pandemic cohort, the historical cohort, significantly different in race, ethnicity, educational level and mode of delivery. So in the historical cohort, there were more black or African American self reported more Hispanic or Latinx, and lower levels of education. But they accounted for all of the group differences and they're fully adjusted. models. And then regarding the neonatal characteristics, it was actually kind of interesting. There were slightly more preterm births in the unexposed. And compared to the historical cohort, there was actually a higher proportion of vaginal deliveries in the pandemic cohort, which I thought was unexpected. There were no significant differences between exposed and unexposed infants on any of the five ASQ. Three subdomain scores in either the initial models or the fully adjusted models. So I mean, that's the main takeaway point. They, I they I think everybody anticipated that we may see some differences in those scores in and babies who were exposed in utero. Interestingly, though, most mothers experience asymptomatic infection. So that was 34% of mothers or mild infection 62% of mothers, and only 4% had severe disease. The majority were infected in the second trimester 47%, or in the third trimester, 31% 22% were affected in the first trimester. And neither symptom severity nor timing of infection showed in association with any of the ASQ, three subdomain scores, either in initial modeling or the adjusted models. So I thought that was kind of reassuring data. We can talk about that a little bit at the end, compared with those in the historical cohort, infants in the pandemic cohort had significantly lower mean scores on gross motor, fine motor and personal and social domains in both the adjusted models, and these differences persisted in the fully adjusted models. So lower gross motor, fine motor, and personal social. So I think that's kind of the second takeaway point is that it didn't matter if you were exposed or unexposed, but babies who were born during the pandemic compared to historical cohorts had lower ASQ scores. Let's see, oh, they wanted to talk about these 15 infants in the historical cohort who were still assessed during the pandemic. This didn't alter the findings on fine and gross motor scores. But interestingly, the personal social scores no longer differed significantly, between cohorts. So there does seem to definitely be something about being being having your first few months in in the, the time of pandemics, they also wanted to look at another post hoc analysis, to look at whether the timing of pregnancy relative to the peak of the pandemic was associated with scores. And they did see a significant association between trimester of pregnancy on infant gross motor phone, more fine motor and personal social scores. So compared with the historical control cohort, infants born to mothers who are in their first trimester of pregnancy, during the peak of the pandemic, had the most significant reduction in gross motor, fine motor and personal social scores. And these results were consistent across peak pandemic dates. So I think this is a really interesting study. I think, obviously, we're just looking at babies up to six months, I think there's still so much we have to learn about this cohort of babies who are were born during the pandemic, and you know, all of our children in the pandemic, and they that's going to come out over time, obviously, but this was, I think, I think the first study to look at the developmental outcomes, so I can't wait to see their follow up. Very cool.

Ben 49:00

Yeah, I think this is something that reminds me of a lot of the studies that I came across when I was doing some of my studying in Israel, where there's a big focus in that area, on the effect on children of our time, right? Where effect and, and I think there's in the case of COVID, there's maybe we'll find, hopefully, we don't find anything but if we do find anything, in terms of a of a farmer of a physiologic effect of being infected with this virus, and does that cause anything in in the children but also like the mentality switches and I'm very curious about these rescues and the Bailey's of the infant as we raise them and now we're like, oh, just don't social distancing. And all the effects of of that can have on a baby in their in their social socially, most socio socio emotional, state and, and, and back to interactions with others. So I'm very curious and this is very interesting, and it's only six months you want to read the paper like man, I just want wish. I wish it was more Yeah, I guess it's coming.

Daphna 50:03

Yeah. And I guess, you know, I wasn't, I wasn't surprised by this social emotional subscore. Unfortunately, I think that's potentially to be expected, but starting to see some of those fine motor and gross motor. subscale differences. Yeah, scary.

Ben 50:20

Maybe Maybe they can make it up. Hopefully they're six months old. Hopefully they make it up.

Daphna 50:26

Well, we'll keep watching.

Ben 50:27

That's right. Okay, your turn? Yes, I have a paper that I wanted to go over that's published in the Journal of Pediatrics. It's called, listen, people. The fact that I'm presenting this paper is a testament to how much I care. It's called acetaminophen and xenobiotic metabolites and human milk and the development of bronchopulmonary dysplasia and retinopathy of prematurity in a cohort of extremely preterm infants. first author is Kristin Centauro. The reason I'm presenting this paper, it came across my Twitter feed, because it's published the last author is our friend, Dr. Camilla Martin. And this is from the Division of newborn medicine at Boston Children's Hospital. The reason I saying I care is because those xenobiotic metabolites there, I was like, I was reading the paper, I'm like, I'm really going to have to pronounce these things on the podcast. But I think,

Daphna 51:14

I think you think it's so important, you're willing to put yourself out? I don't know

Ben 51:18

if that's not what I'm saying. But I'm saying I think the study is very interesting. And it's another one of these I think, proof of concept studies. I don't think it's it's such a large study that it it makes a huge, huge change tomorrow in the way you care for babies, but it's really opening. It's an eye opener, in my opinion. So this study is a retrospective cohort study that was looking at the association between certain xenobiotic metabolites and maternal breast milk and the diagnosis of BPD and ROP and extremely preterm infants. What are Zeno? biotics? xenobiotics comes from the Greek Zeno means foreign biotic means life, so anything that's not supposed to be within your system, right. And so they looked at, they looked at several things. So the aim of this study was to analyze, analyze maternal breast milk samples of preterm infants, for the presence of xenobiotics, or chemical substances that are foreign to the intrinsic metabolism of the mother. The second aim of the study, the second aim was to determine sorry, if the changes in levels of these metabolites in breast milk were associated with the odds of adverse neonatal outcome. So this was a study that was done between 2009 and 2011. And the inclusion criteria were babies less one less than 28 weeks of gestation, they had to have maternal breast milk available at two times, two time points on day 14, and day 28. And the babies had to be obviously feeding predominantly mother's own milk, which they defined as greater than 75% of their total enteral volume. They had a total of 75 infants, representing 91% of the infants who were otherwise eligible. Yes, to include in the study, so they did a bunch of variable measurements. So they looked at some maternal data, looking at age, BMI, race, mode of delivery parody, gravedad rupture, the duration for the rupture of membrane, pregnancy related maternal complication, and others. There's also a bunch of neonatal outcome that include the snap score that includes a PDA BPD ROP, overall mortality late onset sepsis. BPD was defined as requiring supplemental oxygen at 36 weeks of gestation, and ROP was defined based on the presence of ROP by an ophthalmologist examination. The Zeno biotic analysis was performed and they give you all the different technical details about the machine they were using. So they had 75 infants in this study, and 4949 of them 65% had BPD 61% of them had ROP. The obviously mentioned some things about the baseline characteristics of these babies, the babies with BPD were usually lower gestational age or birth weight, they had a higher snap score, same thing for our p lower birth weight or birth and etc. So they there was a total of 140 xenobiotic metabolites in the maternal breast milk at postnatal days 14 and 28 that were identified. And these xenobiotics these metabolites range from benzoate to exempt teens, metabolite, chemicals and drugs such as analgesic analgesics and antibiotics. But I'm, I guess we don't have to, I'm gonna go straight into the multivariate logistic regression model because I don't want to I don't want to take too much time because we have more papers to go. But the multivariable logistic regression models for the odds of BP De adjusting for confounders that include the gestational age, birth weight, five minutes, Apgar score and snap score. So after that multivariable logistic regression was done. What they found was that on day 14, a one unit increase in the mean rank of the maternal breast milk caffeine metabolite, three, seven dimethyl urate was significantly associated with a self centeredness with a 70% decrease in the odds of BPD and three dash acetaminophen was significantly associated with a greater than three fold increase in the odds of BPD. So, coffee good, Tylenol, not so good. On day 28 For additional downstream acetaminophen metabolites and maternal breast milk were significantly associated with increased odds of BPD and infant including for a seat Amido, phenol, or acetaminophen sulfate and for a serum acidum middle funnel like Corona aid. So interesting, I mean, right? Okay, I'll tell you my thoughts in a second. Increased values of maternal breast milk xenobiotic metabolites on day 14 and 28. Were also significantly associated with the odds of ROP in the multivariate regression model. On day 14, a one unit increase in the mean rank of the benzoate metabolite hyper rate, and foodplant component Cinemag glycine, and Piper reading are associated with a decreased odds of ROP and infancy, which is kind of odd, right? Because it bends away usually it's like an preservatives in cosmetic products in baby wipes. So I was happy to see that can keep probably using our baby wipes. In contrast, the increase in three methyl methyl Z catcall sulfate, a foodplant component was associated with an increased odds of ROP on day 28 increased levels of for acid or acid Amido. phenol, the primary acetaminophen metabolite was significantly associated with an almost three fold increase in the odds of ROP and the foodplant component N two floral glycine and two three dihydroxy. So valerate was associated with a decreased odds of ROP. So fascinating, fascinating things. Asking a lot of questions about so I think why did why was I so fascinated by this paper number one because it brings back this idea of I love the idea of mother baby connectedness, pre delivery, post delivery. And I think this is one of these things where it's like, well, now the baby is born, I can have a talent, I can take those medications. But if a baby is feeding breast milk, that connection with the mother is very, very strong. And does this paper we ask the question whether mothers should not take acetaminophen after delivery because of the risks of of BPD and so on? That's a great question. Now, there you mentioned in the discussion that we know mothers who need an analgesic cannot take ibuprofen. And so what is left? Yeah, I

Daphna 58:03

mean, it's, it's, it's a tough concept, because, you know, mommy's new mommy sacrifice a lot. You know, and we're gonna take everything away from the coffee. Coffee. That's good. That's good. That's nice to know. No, but I think it's, it's it. It's just more information about, you know, what are the safest things to do, right?

Ben 58:29

Yes, I think it's I think the reason this paper is so is so great is because it starts bringing shedding light on looking at the breast milk in a new way. I think Dr. Martin is so innovative when she comes when it comes to these these approaches. And I mean, I want to I'm sorry, I mean, I also want to include other Dr. Centauro, as well, who's the first author, but it's just so interesting to start looking at this and start tracking some of what the mother's current practices are, and how does that affect the outcomes of the baby? Epigenetics is something we're all familiar with, we know that the lifestyle that we lead affects a lot of things in our lives, including the DNA of our kids. So I think this is, this is a great scientific way of showing this. We like that paper. It's a pre proof. So hopefully, the PDF formatted version comes out soon. But yeah, very, very cool.

Daphna 59:21

Yeah. And it's exciting that, hopefully, they'll be looking at a lot of other things, right. So you know, looking at how can we lacto engineer milk and can we give mom's things that have protective effects right through the breast milk, so that's really exciting. Okay, moving on, I'm sticking with the neurodevelopmental theme. This is another pre proof in the Journal of Pediatrics, high risk neighborhoods and neurodevelopmental outcomes in infants born preterm.

Ben 59:49

I was gonna say, you know, people are asking, I was like, how do you guys manage to read all these papers? And that's the key. I mean, you're saying like you're sticking to the neurodevelopmental theme, but it's like, we enjoy right right. Yeah. Pick the papers you're gonna enjoy reading, right? I mean, if it's if it's if it's not enjoyable to read then don't don't don't kill yourself. I mean, we do this for the podcast or sometimes we do have to kill ourselves. But yeah, this week we,

Daphna 1:00:11

I mean, we try to be not so biased and in what we pick but

Ben 1:00:16

we try to try to try to always pick a different mix of neurodevelopment and nutrition co so we try to mix it up. So you guys noticed that but anyway, go ahead. Let's well feel bad about about neurodevelopment

Daphna 1:00:27

Yeah, no, I'm happy. I'm happy. I was very happy to be okay. The lead author Ogu, OBO Chukwu wanting, and I want to do I want to do it better next time. So I hope ogutu Gu will correct me and so I can do better next time. Be the anchoring author is Dr. Betty vor. Who I'm just going to put it out there, you know, we're trying to invite Dr. Vor on to the podcast. If

Ben 1:00:59

you guys know Dr. Vor or a way to reach her, then we are interested because what we realized was that our, our series giants of neonatology was, unfortunately, by default, going to be male dominated. We're very interested in bringing in a female perspective.

Daphna 1:01:15

Well, anyways, Dr. Laura, we've got an email out to you. We did find her.

Ben 1:01:20

I know, but we haven't heard back. So if you know of another way, if you get her cell, send her and her cell and we'll get a hold of her.

Daphna 1:01:28

Okay, well, so this is coming to us from Brown University. Another really important study. So this was a retrospective study of a convenient sample of infants born less than 34 weeks between 2005 and 2016. And follow up data at 22 to 26 months of corrected age. exclusion criteria included infants with severe congenital and major chromosomal anomalies and events who didn't have the Bailey three follow up data and any family whose address could not be geocoded because what they did is they geocoded all of the addresses and they used to blocked groups of communities, which were then assigned a risk index based on eight measures a paint obtained from the 2012 2016 American Community Survey. And so these these measures were percentages of adults without high school education, single parent households household crowding, which is defined as greater than one person per room. renter occupied housing units, vacant homes, families below 100% of the federal poverty level, non white residents housing units built before 1950. And then they stratified the neighborhoods by risk index, and they categorize them to either high risk so greater than 75th percentile, or low risk less than 75th percentile. They compared baseline maternal and infant characteristics. And then they looked at the 22 to 26 month child neurodevelopmental outcomes by neighborhood risk level, and can have a variety of unadjusted and adjusted analyses. So the independent variable was neighborhood risk, and the dependent variables were moderate to severe neurodevelopmental impairment and moderate to severe cognitive language and motor delay. Other covariates included maternal education non English speaking gestational age, grade three four IBH hemorrhagic or cystic PVL periventricular leukomalacia bronchopulmonary dysplasia, defined as oxygen at 36 weeks, neck defined as Bell stage two or greater sepsis and breast milk at discharge. So they had 1337 infants, and the selected follow up sample with developmental outcomes included 874 of the 1300 81 survivors less than 12 150 grams, so 63% and 463 of the 1200 35 survivors greater than 1200 50 grams 37%. So overall, the eligible infants were 51% of the 200 602,616 survivors. Overall, mothers living in high risk neighborhoods were significantly more likely to be adolescents, unmarried, racial or ethnic minorities, non English speaking have public insurance, and less than a high school education. Maternal medical factors including prenatal care, gestational diabetes, hypertension and anti natal steroids were similar in both groups, which I thought was interesting and and I was pleased to see that however, there were lower rates of cesarean delivery and multiple births in high risk neighborhoods, which I also thought was Interesting given previous data that we've looked at the percent of infants with birth weight small for gestational age, and bronchopulmonary dysplasia was similar between the two groups also interesting. And infants living in high risk neighborhoods had lower birth weights, lower gestational ages, higher rates of neck and were less likely to be receiving breast milk at discharge, which, which is similar in previous studies. Children living in high risk neighborhoods had greater risk of moderate to severe neurodevelopmental impairment. They had lower mean cognitive composite scores, and greater risks of moderate and severe cognitive delays and children living in low risk neighborhoods. Children in high risk neighborhoods had lower mean motor scores and greater risk of moderate and severe motor delay. The other components that they looked at of neurodevelopmental impairment, cerebral palsy, permanent hearing loss and bilateral blindness were similar in both groups. Their main language composite scores were lower in children and high risk neighborhoods. And they had, they also were found to have greater risk of moderate and severe language delay. And when they looked at the multivariate analysis, children living in high risk neighborhoods had greater odds of moderate to severe neurodevelopmental, neurodevelopmental impairment, with odds ratio 1.4 maternal education less than high school ivh grade three, four and PVL and bronchopulmonary dysplasia contributed to a greater risk of neurodevelopmental impairment, whereas breast milk at discharge was protective. The odds of moderate to severe motor delay was similar in both groups, and children and children living in high risk neighborhoods had greater odds of moderate to severe cognitive impairment and language delay with an odds ratio of 1.6 and 1.58, respectively. sepsis and non English language also were significant predictors that contributed to greater odds of language delay, breast milk discharge was protective in all four models. So I thought this was interesting, some of the kind of baseline characteristics that I thought might be different, were not. And still, they had this real disparity in in neurodevelopmental outcomes. So I think it's just a reminder that what we do in the unit is only part of the ongoing care for these babies, which, which is what we talked about, I guess, on our last Journal Club, with Dr. Montoya Williams,

Ben 1:07:41

that's exactly what I was going to say I thought it was dovetailing very nicely with a discussion we had last week, not last week, two weeks ago about social determinants of health, and how that matters tremendously. That's something that we're working on with a few partners about looking at sort of the environment, environmental health, and not just environmental health in the in the common sense of the word, but like how environment really impacts health directly in spaces, things like that. So fascinating paper. Alright, I have to mention two more papers quickly, very better hustle, I'm hustling, it's not going to be it's not going to be long. But there are two ways. So the first one we have to mention, obviously, is the policy statement by the American Academy of Pediatrics called vitamin K and the newborn infant. first author is Dr. Ivan hand. And second author is my former residency mentor, Dr. Lawrence noble. Berry if you're listening, good job.

Daphna 1:08:36

We had lots of shadows today.

Ben 1:08:38

And it was it was not done on purpose. I was actually surprised that he wrote this this policy statement because his field of expertise is really lactation and breast milk. So I did not expect him to see his name there. But I was very happy surprised. So this is a very important policy statement. It goes over everything related to vitamin K. And briefly the few things I highlighted with a dimension. There's a few questions, I guess, that have been coming up. Many parents are now choosing vitamin K. And so how do we approach that? So number one, prenatal vitamin K supplementation, they're mentioning that it's interesting because it does raise the levels of vitamin K in the court, but it's not sufficient to prevent vitamin K leading deficient vitamin K deficiency bleeding. Right after birth. Then they talked about the vitamin K prophylaxis given to newborn infants, right. And obviously, they're recommending a single item dose in order to prevent both classic and late onset vitamin K deficient bleeding. Now, what's interesting is that there's been I mean, I've seen this as well. There's a lot of parents that are asking about oral vitamin K saying, well don't give my baby a child giving them oral vitamin K. And and that I knew that like if you substitute the im for oral, it doesn't work. But this policy statement is really good because then it goes into very granular details about well, maybe one dose doesn't work, but what if the baby does get altered? or doses oral Can you just maintain their vitamin K level until they were out of the woods. And one of the things that they mentioned was this, this, this Dutch sort of protocol where they give 150 micrograms daily for three months. And they showed that it reduced the late onset vitamin K related bleeding from 3.2, per 100,000 to 1.8, per 100,000. And so, so I guess, here's why the two papers I'm going to mention are very important, because I think parents are asking very good questions. And it's irresponsible for us to just say, Oh, no, no, that's no good, right? I mean, we have to know the evidence. And I think this is very helpful. Because and,

Daphna 1:10:40

you know, I mean, parents have led the charge on a lot of changes in medicine. So

Ben 1:10:45

and I feel like sometimes you're, you're tempted to say to parents, no, that's not good. without you knowing both sides of the of the of the argument, and to me, I am very I'm a libertarian type of person, you, you're free to do whatever you want. And I think if people are asking a question, then before you you're deemed fit to give an answer, you should know your stuff. And so I think in this case, it's very interesting oral vitamin K, even if you give it daily, it shows that it does reduce late onset vitamin K bleeding, but it's not as good as intramuscular. And I think that's something that you could definitely take the debate side and and explain to parents, obviously, there's this big

Daphna 1:11:24

and this is a much prolonged course,

Ben 1:11:27

well, yeah, oh, yeah. And it's good to know that say, Hey, you know, Vitamin K, oral is not as good and we know about it. And now you can even quote this Dutch Dutch protocol. Obviously, there's a whole discussion about dosing for preterm infants. And that the dose that they require is not as it's not the same, it's not point five to one, but more like point three 2.5. And there's a big discussion about IV versus I am, and I think this is going to lead to a lot of discussions in a lot of units, because what they're saying is that giving vitamin K a v, leads to a huge spike in the early levels of vitamin K, and doesn't provide this prolonged coverage of vitamin K. And so whether we should give it i m, is very much being suggested here. And in babies that are less than 1000 grams, risk benefits, that's really something that's going to be a thorny subject to discuss. I know we have our quality meeting soon. And that's on the top on the on the list of things to discuss. So that like, they do talk about breastfeeding, saying that breastfed infants are usually the ones most at risk of vitamin K related bleeding. And so that's something that the parents need to be counseled on. And then they have this whole section on parent refusal, saying, Here are usually the reasons why parents refused. And here's what information to provide to them in order to help them make a decision. And I thought that was that was very helpful. So that's this paper. And again, we'll have it on our website, if you want to take a look at it. Fine.

Daphna 1:12:58

And you know, not all, not all parents who are refusing are, are totally opposed to hearing what you have to say. So, you know, and having this concise resource, I think is potentially helpful.

Ben 1:13:14

They're also citing the two CDC PDFs that are available for it. And I check them out again, they're really, really good. Another thing to bring it to the bedside and also think like, like, you're saying, I think parents are much more likely to listen to you. If you have a true argument saying, Well, I think this is a valid idea. But here's the data, and then you let them make their choice rather than saying, Oh, no, no, no, no, no, it's not. Right.

Daphna 1:13:37

Yeah, my favorite initial question is will tell me about your concerns. And in some, some parents have very real concerns that we can address. Some parents don't have any concerns, because it just somebody told them not to get it, and then we can address it. And anyways, why have a 5050 50% conversion rates?

Ben 1:14:00

And also, as they mentioned, in the paper, it's important to make sure parents understand why we're getting a vitamin K. Many times people think it's just a vitamin deficiency, but they don't really realize that we're talking about

Daphna 1:14:13

it. Yeah. Especially given the current climate. A lot of parents think it's a vaccine, which it's not asking them in their own words, what they're concerned about, which which this paper addresses.

Ben 1:14:26

Yep. The last paper I wanted to mention is also a clinical report from the American Academy of Pediatrics. It's called the risks of infectious diseases in newborn exposed to alternative perinatal practices. first author's Dawn not. And this is exactly along these lines. It's basically a paper reviewing all different types of practices being done at the time of delivery, and some of the evidence for or against, and they go over a lot of things. So the first one that they talk about is water immersion. And again, one of these things where the AP is doing a very good job were saying, well for the first two stages of life labor, it probably is okay if the tub is clean and so on and so forth, but they don't recommend it pass that. They talk about vaginal seating, which obviously can and they are talking about it in a very practical manner saying, well, there is some benefits when it comes to the breakroom microbiome. But what about if the mother has some infection that could potentially be transmitted? And what to look for in terms of prenatal labs and so on and so forth? What else are they talking about? They're talking about not cutting the umbilical cord, also known as the Lotus birth, talking about what are the potential risk for the baby when this necrotic tissue really becomes a strong source of nutrients for colonizing bacteria? And how do we counsel parents about that? You're talking about percent of Fiji, which parents wanting to eat the placenta? And what are some of the risks associated with that? They're talking about deferring hepatitis B vaccine, I thought that was that was the best part of this paper, because it really goes over again, an argument that parents can send saying, Well, I've been tested for hepatitis B, and I'm negative, so doesn't my baby really need it. And then when they're talking about the fact that when you're talking about some of the numbers, when you're looking at some of the numbers, that they're that they're quoting, like 850,000 to 2.2 million people living in the United States with chronic hepatitis B vaccine, with Hepatitis B virus, and that risk factors for Hepatitis B infection cannot be identified in more than 30% of infected people. Now, you start understanding a little bit more as to why they're recommending it so early. And saying even deferring it to the first pediatrician visit may not be the right thing to do. They're also talking about erythromycin prophylaxis. And that's another really eye opening discussion. Because basically, they're, I mean, I'm going to be paraphrasing here, but they're making the case that if you can convincingly know that a mother who delivered is negative, or gonorrhea and chlamydia, you may not you may forego the prophylaxis. And that may be

Daphna 1:17:00

and there is some irritation associated with improved flexes. Yeah. And

Ben 1:17:04

they were talking about the fact that maybe it almost seems like they are about to change recommendations when it comes to saying, Well, if the mother's prenatal labs are unknown, then maybe you do want to give erythromycin a bit like you're doing with him. No immunoglobulin for hepatitis B, I thought that was very interesting. They're also talking about delayed bathing, and how that can actually improve breastfeeding rates early on. So it was a very interesting paper, because I think, having been trained in a hospital, I'm not familiar with all these different practices. And sometimes, like, in my case, my only experience with a water immersion for labor and delivery was when I was a fellow and got called for a case of drowning. Right. So I could be Yeah, but I'm saying

Daphna 1:17:51

it really, we trained in very different places. Why? There's a lot of water birthing, we're a trained,

Ben 1:17:59

but my perception from this one experience may be very biased. And and this is where these papers are very helpful. Because it's very pragmatic and very, so

Daphna 1:18:10

yeah, and I think it comes down to, you know, shared decision making with families. And it's tough, right. And as we have less and less time to spend with families, and we spend more and more time at the EMR. And, you know, it's it's it's tough because these conversations take time. But I think parents are grateful when you are willing to have you know, a discussion about things that they think that are important to them, so I couldn't be more glad that he presented them today. Alrighty, well, we overtime. But that's.

Ben 1:18:46

That was fun. And we will see you Monday for board review. We're doing genetics and dermatology.

Daphna 1:18:53

Mm hmm.

Ben 1:18:54

Yeah. It's a fun week. You said it's a fun week. I don't know what it is. That's right. All right. Definitely. Your Monday. Have a good one.


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