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#011 - 📑 Journal Club 6


Journal Club on The Incubator Podcast



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


Pan, J., Zhan, C., Yuan, T. et al. Intravenous immunoglobulin G in the treatment of ABO hemolytic disease of the newborn during the early neonatal period at a tertiary academic hospital: a retrospective study. J Perinatol 41, 1397–1402 (2021). https://doi.org/10.1038/s41372-021-00963-5


Bhandary, S., Lambeth, T., Holmes, A. et al. Using buprenorphine to treat neonatal abstinence syndrome: a quality improvement study. J Perinatol 41, 1480–1486 (2021). https://doi.org/10.1038/s41372-021-01035-4


DuPont, T.L., Baserga, M., Lowe, J. et al. Darbepoetin as a neuroprotective agent in mild neonatal encephalopathy: a randomized, placebo-controlled, feasibility trial. J Perinatol 41, 1339–1346 (2021). https://doi.org/10.1038/s41372-021-01081-y


Broni, E.K., Eke, A.C., Vaidya, D. et al. Blood biomarkers for neonatal hypoxic–ischemic encephalopathy in the presence and absence of sentinel events. J Perinatol 41, 1322–1330 (2021). https://doi.org/10.1038/s41372-020-00850-5


Twitty, G., Weiss, M., Bazacliu, C. et al. Hypertension in neonates treated with intravitreal bevacizumab for retinopathy of prematurity. J Perinatol 41, 1426–1431 (2021). https://doi.org/10.1038/s41372-021-01021-w


Gerday, E., Brereton, J.B., Bahr, T.M. et al. Urinary ferritin; a potential noninvasive way to screen NICU patients for iron deficiency. J Perinatol 41, 1419–1425 (2021). https://doi.org/10.1038/s41372-020-0746-6


Pollack, R., Rana, D., Purvis, J. et al. Effect of prenatal marijuana exposure on sleep wake cycles and amplitude-integrated electroencephalogram (aEEG). J Perinatol 41, 1355–1363 (2021). https://doi.org/10.1038/s41372-020-00911-9


Ottolini, K.M., Basu, S.K., Herrera, N. et al. Positive fluid balance is associated with death and severity of brain injury in neonates with hypoxic–ischemic encephalopathy. J Perinatol 41, 1331–1338 (2021). https://doi.org/10.1038/s41372-021-00988-w


Fleig, L., Hagan, J., Lee, M.L. et al. Growth outcomes of small for gestational age preterm infants before and after implementation of an exclusive human milk-based diet. J Perinatol 41, 1859–1864 (2021). https://doi.org/10.1038/s41372-021-01082-x


Van Mechelen, K., Meeus, M., Matheeussen, V. et al. Association between maternal cervicovaginal swab positivity for Ureaplasma spp. or other microorganisms and neonatal respiratory outcome and mortality. J Perinatol 41, 1–11 (2021).


Pulju, M., Pruitt, C., Reid-Adam, J. et al. Renal insufficiency in children born preterm: examining the role of neonatal acute kidney injury. J Perinatol 41, 1432–1440 (2021). https://doi.org/10.1038/s41372-021-01097-4


Vermeiren RRJM, Peeters-Scholte CMPCD, Steggerda SJ.J Pediatr. 2021 Jul;234:46-53.e2. doi: 10.1016/j.jpeds.2021.02.005. Epub 2021 Feb 10.


Effect of a Novel Oxygen Saturation Targeting Strategy on Mortality, Retinopathy of Prematurity, and Bronchopulmonary Dysplasia in Neonates Born Extremely Preterm. Srivatsa B, Malcolm K, Clark RH, Kupke KG.J Pediatr. 2021 Jul;234:33-37.e3. doi: 10.1016/j.jpeds.2021.03.007. Epub 2021 Mar 16.PMID: 33737029


Actual and Potential Impact of a Home Nasogastric Tube Feeding Program for Infants Whose Neonatal Intensive Care Unit Discharge Is Affected by Delayed Oral Feedings. Lagatta JM, Uhing M, Acharya K, Lavoie J, Rholl E, Malin K, Malnory M, Leuthner J, Brousseau DC.J Pediatr. 2021 Jul;234:38-45.e2. doi: 10.1016/j.jpeds.2021.03.046. Epub 2021 Mar 28.PMID: 33789159


Maternal Self-Report of Tetanus Diphtheria Pertussis Vaccination during Pregnancy Correlates with Patient-Specific Electronic Medical Records. Song A, Sherin M, Cleary S, Spino C, Bernstein HH.J Pediatr. 2021 Jul;234:220-226. doi: 10.1016/j.jpeds.2021.03.015. Epub 2021 Mar 18.PMID: 33745997


Association between Baseline Cortisol Serum Concentrations and the Effect of Prophylactic Hydrocortisone in Extremely Preterm Infants. Renolleau C, Toumazi A, Bourmaud A, Benoist JF, Chevenne D, Mohamed D, Alberti C, Biran V, Baud O; PREMILOC Trial Study Group.J Pediatr. 2021 Jul;234:65-70.e3. doi: 10.1016/j.jpeds.2020.12.057. Epub 2020 Dec 24.PMID: 33359303


Rates of Bronchopulmonary Dysplasia Following Implementation of a Novel Prevention Bundle. Villosis MFB, Barseghyan K, Ambat MT, Rezaie KK, Braun D.JAMA Netw Open. 2021 Jun 1;4(6):e2114140. doi: 10.1001/jamanetworkopen.2021.14140.PMID: 34181013


 

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



SUMMARY KEYWORDS

babies, bpd, group, study, intervention, interesting, author, infants, g tube, looked, paper, weeks, hydrocortisone, data, day, care, nicu, outcomes, patients, bundle

SPEAKERS

Daphna, Ben


Ben 00:05

Hello, everyone, welcome to the podcast. Welcome to another episode of journal club Daphna. How's it going today?


Daphna 00:52

I'm doing great, but I'm not the one on vacation. So how have you been?


Ben 00:57

reading papers on vacation?


Daphna 01:01

That's such dedication to the cause? For sure.


Ben 01:05

Oh, yeah. Oh, yeah. I almost want to go around the audience with the tip jar. For the effort that it took me to read all these papers this this past two weeks. There was so many of them. I was secretly hoping for a light two weeks of benign articles, but they were all bangers literally. Yeah. Anyway. But thank you, we are still in the worst prospect of getting our journal. Our book club, sorry, aired on August 1, with author Don raffel. On her book, The Strange Case of Dr. Cooney, where we talk about the origins of the neonatal ICU. If you have read the book or about to read the book and want to send us questions you can do so until July 23, you can send them to our email address NICU podcast@gmail.com, or to our Twitter at Nikki podcast send us a written questions, audio messages. We'll play them on the air. Again, this is a chance for all of the community to interact with an author and an in the story that is fascinating. Anyway, yeah.


Daphna 02:15

It goes by it goes by fast. It's a really easy, interesting read. So if you haven't picked it up yet, it's not too late.


Ben 02:25

Yeah. And that's, that's really good. Have you been on service definitely these days?


Daphna 02:32

while you're away? So that means Yeah, we're I know,


Ben 02:35

I know.


Daphna 02:39

I come back. That's right. Well, trade.


Ben 02:44

All right. So this week, we're reviewing articles from from Jama from Journal of Pediatrics from Journal of parasitology. We also have some articles from pediatrics from children. But I mean, are we going to be able to get around to all of them? I don't know. But we


Daphna 02:59

know we won't be able. But I always finish. And we never get around to all the papers we intend to talk about. And we were trying to limit ourselves to an hour an hour, 15 minutes an hour, 20 minutes. And every time we hang up, I say, oh, gosh, I really wanted to talk about that.


Ben 03:21

I know, we have to sometimes, at some point, we should pull the audience and see if we should extend it to another half an hour or two hours. I don't know. Can we even do that ourselves? I don't know. Anyway, the first paper is in JAMA. And it's an it's a paper that has a title that will grab your attention rates of bronchopulmonary dysplasia following implementation of the novel prevention bundle by first author Maria Valle osis. And this is a study from the California perinatal collaborative. It's a very interesting article, where the objective was to develop a consistent sort of BPD prevention bundle in order to approach BPD as a preventable disease. It's funny because this is something we've talked about before. And it's interesting to see other centers approaching BPD in that sense, what the what the group there did, I want to clarify that it is the California perinatal collaborative, but it is a it is a single center from that collaborative that is that is publishing this data. And they pretty much created a bundle that they followed. And then they compared in a plan, do study act cycle, sort of the outcomes and they looked at whether or not they were able to reduce their rates of BPD. So this study included 484 infants from birth weight 500 to 1500 grams. The this was obviously a level three units from the Kaiser Permanente Southern California system, and they looked at data from 2009 to 2019. They divided this timeframe into three periods. They had their baseline in 2009. And then they had an initial set of changes, followed by a plan, study act cycle. So that was 2010 2014. And then a full implementation of their bundle followed from 2015 to 2019. And the primary outcome was to look at BPD in infants with less than 33 weeks gestational age, and they use the von definition, looking at the degree of oxygen requirements at 36 weeks of gestation post conceptual age. What the The actually also I was, I'm going to stop the discussion right there for a second because they didn't just use the Vaughn definition. They also looked at another gradation in terms of not just following into the VPD, SBPD. Know, they had, they looked at the different interfaces as well, and they call the grade one, using nasal cannula airflow, two liters per minute or lower grade two was nasal cannula higher than two liters, and the grade three with invasive mechanical ventilation. Following a little bit of the Jensen criteria, what they were able to find is that they're just the usual age was was was small, but the, the, during the mystery period VPD, decreased from 31% to 1.6%, after the implementation of this bundle, and that's obviously a huge, a huge reduction in BPD. That was worth noting. And when they looked at the different rates of these grades, the rates of combined grade one, two and three BPD, decreased from 24% to 9.3%, with a P value of less than 0.08. And so the list of mortality was unchanged, if that matters to anyone listening, but obviously, these reductions in BPD. Were, were striking. And, and so I think that was that was very interesting. I'm curious to see, to hear what your thoughts were?


Daphna 06:58

Well, I think yes, absolutely. Just listening to the data, you think, Well, what yeah, what did they do, and I think that's probably the coolest thing about this study is, obviously it's a bundle. So they had a bunch of key drivers, which we can, we'll mention. But I think some of it is something we can all do in every single unit. So basically, the biggest I think driver for their unit was that this they put here a shared mental model, that BPD is avoidable, but requires aggressive preventative care. And so, you know, big initial changes, were just discussion on daily rounds of compliance to the bundle, which we know is so important in quality improvement work, discussion at weekly neonatal meetings of challenges and opportunities regarding care agreements, and changes, major changes in management made only after consensus of neonatologist. And I think that's so important. And you and I have seen how effective that can be when you really have a team of people who know the babies who reevaluate the case frequently. And you can remind each other of the components of the care that individually we may miss. And I think that's, I think that's a huge thing that we should underscore. Obviously, there are other key drivers are components that we know are important to BPD management, but again, are not are not earth shattering. So basically using the minimum necessary ventilation or intervention, low thresholds for surfactant use babies getting surfactant dosage on a ventilator, using volume ventilation. Good criteria for extubation.


Ben 09:00

They have they actually, and I think we should post this on our Twitter account after the show, especially on the sub in the supplemental material, they had the bundle. And they had two bundles, basically one for babies less than a kilo and babies above a kilo. And I think we will share it just so that people can take a look at at what they did, because it's obviously very extensive. And and it includes a lot of the stuff that we all know.


Daphna 09:25

Absolutely. Yeah. And in the individually none of those are, you know, groundbreaking. But that's the group right? It's about getting them together. Being consistent, having the good consistency and being really in, you know, really feeling about what you're doing with each each individual baby.


Ben 09:51

So it's it's actually what you said plus more, I believe, number one, it's nothing in you, but even the intervention that they used on an honor singular basis, you could contest that they're beneficial. I think, for example, and I'm not going to dissect their roadmap, but NICU management, they have lived one, they wrote high frequency ventilation as the primary mode of ventilation. Well, I think there's some evidence that's quite old to support that. Does that mean that we should all start putting babies on forever? No, absolutely not. And that intervention, for example, is just one of the many things that they've done. And yet we know that this is not the standard everywhere, but and they and they acknowledge that in their discussion, they're saying we know that at face value, each intervention, the benefits have not been proven. But we looked at what our groups could do, what were the consensus lies, and they they built that they built that that bundle this way.


Daphna 10:49

And we now see, so much of our care, you know, it's not about necessarily the technology, right, or the ventilator, but it's how you use it, how comfortable is the team using it, and sometimes doing what your team is comfortable with? If if we don't have concrete data, may may be the safest thing. But I think it's just like the consistency that they had. And it sounds like they had some really good buy in from the rest of the team, the nurses and the respiratory therapists. And that's, that's, I think, a big update.


Ben 11:22

Yeah, and they did some things that were a bit they were they were definitely controversial, some of the things that were a bit novel in terms of their use of azithromycin, to try to really tried to screen for ureaplasma that I think should be done more. And, and there were some questions, I think, at the end of the day, their data can be torn apart. And you can make a case for either way, that the end of the day, the baseline characteristics were taken out of 45 patients, which is a low number, the following changes were measured on 200 Plus patients, which is much larger. Their mean gestational age was about 28 weeks. The one thing that was interesting that they didn't mention that to me, caused a significant problem was that they had a change in the functioning of their unit throughout the study period, where they used to send babies to lower acuity centers for after 32 weeks, which went down significantly by like 30% during the implementation, so then you wonder if those babies now are staying in your unit does that, I guess in code, dilute your numbers, I'm sure they they thought about this, but I didn't see anything in the paper that was mentioning how they accounted for that. But the bottom line is, the point is, what if we're not going to come up with a mat with a silver bullet to fix BPD, we need to come up with these bundles where we can be sort of homogeneous in our care. And there's no doubt that BPD rates can come down if you put in bundles of evidence that have been sort of tested before and you bring this multidisciplinary model that the BPD collaborative sort of is advocating for, there's no doubt that the outcomes are going to be better.


Daphna 13:01

Yeah, I agree. And then having had being able to have the components of that care and, you know, regionalizing care, and maybe if you aren't able to have the components for that care, you know, it's to do our due diligence to get babies to places where they can get all of Absolutely.


Ben 13:21

Yeah. And then in the end, it doesn't matter whether the baby's got transferred, didn't get transferred. What I wanted to know is did they still account for the babies that they had transferred to these level two centers in their data? And it's just, it's just some tedious points. But anyway, that was a very interesting paper. That was a very interesting paper and novel approach to BPD, for sure. And just this mindset of saying, Well, this is potentially preventable if we do the right things, is really the novel aspect of BPD care that we need to push forward.


Daphna 13:50

And a reminder that like you said, there's no there's no silver bullet, we just have to do consistent, weekly revaluations for each baby about how we can optimize the care and that starts on day one. And it doesn't end until until really they go home. Right until really they're off of oxygen or they're on their, you know, home readiness support. So that's a good reminder.


Ben 14:14

Yeah. All right. We're going then it was nothing else really significant in JAMA Jama piece this this time around. Let's move on to Journal of Pediatrics. Is there an article that you want to start us off with dogma?


Daphna 14:33

Well, I think there are a few we definitely have to talk about. I guess maybe we can start since it does sometimes pertain to BPD babies is this big secondary analysis of the criminal act trial. So Oh, boy. It's just it's a sticky paper, but we might as well do it early right. association between baseline cortisol All serum concentrations and the effect of prophylactic hydrocortisone in extremely preterm infants. So again, this is a secondary analysis from the premiere lock trial, which as a reminder is early low dose hydrocortisone. And so the objective for this secondary analysis was to better define kind of some serum cortisol normative values before in the first day of life, and then to evaluate whether those cortisol values had any effect on the benefit risk ratio of receiving this prophylactic hydrocortisone course. So we enrolled in the criminal acts study babies before 28 weeks of gestation. They included 325 babies in this kind of secondary analysis. And they have some neat scatter plots of the hydrocodone of the cortisol levels, which we'll talk about which are very interesting. And we can again, post to the Twitter account if you're following along. And what that shows is there's really a wide wide range of cortisol levels for babies in the first day of life. And we know that that's probably true for neonates across an admission. But the results that they found were that again, they looked at, one of the things they did look at was BPD, free free survival. And so increased cortisol levels. So they used a cut off Z score for cortisol, were associated with a significantly higher chance of BPD free survival, but only in the babies who did not receive hydrocortisone. And so that difference was lost in the babies who were in the intervention group of the hydrocortisone. And the other things they looked at were, they were looking at some of their adverse events, in particular, ivh, highgrade, ivh, and spontaneous intestinal perforation. And so I thought this was very interesting. So what they found was that the cortisol Z scores for infants treated with the intervention group that prophylactic hydrocortisone predicted a risk of high grade ivh, and sip, so basically, the babies with higher cortisol levels, and who received the prophylactic intervention, were at higher risk for those adverse events, but not show the babies who had lower cortisol levels at baseline. So I thought this is very interesting. And you and I are always talking about on the podcast, and article after article just reminds us how important that individualizing care is. And I think that this really underscores that that we need more data for for some of these sweeping interventions that we're we're trying to use in the in the unit, I see you you have something to say.


Ben 18:26

No, I mean, the one the one thing this article highlights to me, is the fact I may have gotten this wrong clinically so many times, because you're like, you have a baby that could benefit from hydrocortisone. And you say should I get a level and you say after all, they're very small, they're probably a little bit adrenal insufficient. And, and that is, again, wrong, you should potentially get hydrochloric cortisol level before you make a decision. And then the other things we've just never really taken into account. Not that it was intuitive, but all these pre natal factors that affect the that affected the outcome in terms of the cortisol level after birth. I thought that was I thought that was very interesting. So they said, multiple, multiple gestation. Let me see No, that's not really. That's not really what I wanted to look at. But they looked at basically, major perinatal events were correlated with cortisol Z scores, which lasted for sex to better determine covariates. Anyway, antenatal steroids, Periodontal analgesia was significantly associated with lower cortisol levels, whereas multiple gestation, clinical choreo and early onset sepsis were significantly associated with higher cortisol serum concentrations, which I just didn't know what to make of this on the one hand, right, they say hydrocortisone levels in the beginning are good, but on the other hand, these are sort of clinical pairing Nero factors that cause pneumonitis is known to cause more BPD down the road. So which one is it? So?


Daphna 20:08

Is it the stressor that cause the cortisol elevation? That is the risk factor? Or is it the combination of getting a medication you don't need because you already have the support? It's it's tough to say one thing I do think this underlies is a lot of people will say, well, we don't we don't know what to do with the cortisol level. And and I think this just shows that we don't know what to do with the cortisol level yet. But but probably with enough work, which has kind of been kind of poo pooed. In the last decade, I think about even evaluating cortisol and when you know, because it because when you look at the scatter plots, you say, how can we make sense of any of this data? But


Ben 20:53

that's the thing they did, they didn't acknowledge it. They said the cortisol serum concentrations were not normally distributed, right? So you would expect a nice little bell shaped curve or the hyperbole curve in terms of having rising, right, that's the thing that we always thought it's like, oh, the lower you are in gestation, the lower your cortisol and the more material and it's not true, it just doesn't hold the graphs, the plot is all over the place. So I don't know if, again, it's hard to say they have like 500 Something babies, I think, no, they have 300 samples that they were using 25 which is which is which is big. I mean, it's kind of difficult to say, hey, maybe they need more, but maybe we do need more.


Daphna 21:35

Learning about those phenotypes, right? We've we've talked about this on almost every episode that are your prenatal risk factors, your your body risk factors, you know, are you infected? Are you not infected, your your weight? All of those things? I think we will help us individualize care. Eventually, once we once we can really delineate you know, which phenotypes mean what?


Ben 22:05

Yeah, I think that to me, at the end of the day, what do you what do you take to the bedside? I'm just curious to hear what like, how would you approach supplementing hydrocortisone? Yeah,


Daphna 22:14

well, you know, in our you are in our unit right now, we're not we're not doing prophylactic hydrocortisone. I think there's definitely a role for it. And something that, you know, we have been talking about, but just like I feel about almost every of these early interventions is that it probably is the right answer for some babies. And we just have to decide which babies are most at risk for an intervention and which babies will get the most benefit for it. But I potentially, if I had a baby who had a very high cortisol already, it may make me say, Well, maybe they don't need more steroid. Maybe that's not the right thing to take away from it. Because like we said, maybe it's the stressor that's causing the the long term outcome. But it's hard not to pay attention to


Ben 23:06

this. No, I agree with you. I think that's the same takeaway that I had as well. More work needs to be done for sure. And it's definitely not yet the time to put every small baby on hydrocodone some sort of low dose. And I think if you're considering it, then definitely get a cortisol level and make a decision because those those adverse events are not benign. When you're talking about grade three for ideation sip, these are major. So yeah, we'll see. Let's take a little bit of a break, and go over quickly another article that I thought was just it's it initially was funny to me, but it is not funny also. It is also introduced general pediatrics and it says maternal self report of tetanus diphtheria pertussis vaccination during pregnancy correlates with patient specific electronic medical records. And it's by first author, Eileen song. And I think this group is out of New York and North Carolina. And what was funny is that this was a survey completed by a convenience sample of postpartum patients in the New York metropolitan area that you're Rich Barton hospital, and what they did is ask them about their vaccination status. And then they compared based on the EMR and whether or not they had received vaccination. And what they found, which was the funny part is that most of them others if they tell you that they did get it or not, that usually correlates oh my god, what a what an earth shattering sort of novelty, which reminded me of this famous joke about the ER where you call the orthopedic surgeon saying, Hey, I have a kid with a with an amputated arm and they're like, did you get an x ray? Right? I mean, it's like unless it's in the EMR. It doesn't exist. And but that's, anyway.


Daphna 24:52

Now that we know that patients lie to us, right, we know that they lie because because everybody wants to look at that. It's exactly why patients lie. But there is something about moms and this responsibility of housing a fetus that I think that pregnant women lie less than the general population.


Ben 25:16

Probably. And the one thing that then I was I was amused by the paper, because obviously they have like this little two by two table of this is per the mother. This is per the EMR. They had yes, no. And basically, at the end of the day, it's like almost 90 something percent that are concordance. And they said, No, then there was no and if they said, Yes, that was etc. And then I looked a bit deeper at the paper just again, why I don't know why did that but they looked at so for the person that we did not match, why did it not. And then this is when exploring factors associated with discordance between maternal self report and the EMR. univariate logistic regression showed significantly increased or for an I'm quoting, non white, non Hispanic backgrounds, and public insurance, household income below 75,000 with a P value of less than 0.5. And that made me think, because then, that made me think of people who are obviously, either more strapped financially in have poor background. And to me, it made them look not really as malignant, but more as not almost aware of what's being done to them in the process of the medical system. And it made me think that, for patients that where there is limitations, whether they're financial, whether they're based on on, on education, we have to be doing more to make them take ownership of their care, so that these types of things that made me really sad about our health care system, in the sense that, well, then we should be explaining to these parents better what's happening to them, because then they shouldn't be any discords. And so, it, it took a serious turn for me, they're


Daphna 27:02

sure Well, I'm yeah, that's, that's, I'm glad you found that that pearl of wisdom in this paper, but certainly, you know, concern about the medical system, mistrust of the medical system is still alive and well, and rightfully so aspersion, especially for for major groups, you know, in our country. And so, you know, I'm not surprised that patients lie to us, I guess, is the point. And for some of these families, especially when it comes to children, they wonder, you know, what happens if I am truthful about some of these things? You know, and so,


Ben 27:49

and that's the thing, I'm not sure if that was an issue of being of lying or being truthful, I was wondering if it was like, I don't remember, they gave me a bunch of shots. And I don't remember what they were, I don't remember, I don't even know what is teed up. And if that's the case, because again, just based on income, which often correlates with education, if you cannot recall where these things were, then maybe we should dispense. Again, like for kids get vaccination cards, like, Hey, this is what we've done to you so that if you're being asked and you don't remember, then you can pull this out and refer to this. Again, we need to do a better job. And so I thought that was interesting. Because initially, I thought, what if it was almost like a funny paper, but it highlighted something pretty serious and pretty systemic, which


Daphna 28:28

was interesting. Yeah, absolutely.


Ben 28:32

All right, breaks over. Next paper,


Daphna 28:35

got some other big papers.


Ben 28:38

So the one the one I really liked. The one I really liked was actual and potential impact of home NG tube feeding program for infants whose neonatal intensive care unit discharge is affected by delayed oral feedings by Joan de Gata. And this is a group out of Wisconsin. Do I'm gonna go over the article quickly, and then you'll tell me what you think the the objective was to compare healthcare use and parent health related quality of life in three groups of infants discharged from the NICU. And basically what they did is that at three months of age after discharge from the NICU, they compared healthcare use quality of life. And the three groups were kids discharged on oral feeds, kids discharge on energy feeds, and kids discharged on G Tube feeds. And they had 180 infants. And I'm just going to give you the conclusion, and we can talk more about the data compared with infants who had NG tube feeding. Infants with G tubes had more GI or gastrointestinal or tube related readmissions, and emergency encounters. And orally fed infants should know difference in use, meaning Ng and orally fed showed no difference. Ng and G Tube showed a significant difference. multivariable adjustment did not change these outcomes to the quality of life assessment at three months did not differ between groups. Infants discharged home with ng two Oops, save 15 174 NICU days. The conclusion is NICU discharge with ng feeds is associated with reduced with reduced NICU stay without increased post discharge healthcare used or decreased parents health related quality of life, whereas D tube feedings were associated with increased post discharge healthcare use. All right, I'm going to hold off on my overall impression of this paper. What do you think?


Daphna 30:26

Yeah, well, I think there are a few points to make. And they had, I think, really good criteria for who would be eligible for an NG tube. And I think that's important when we're making, you know, decisions. Just for the, for our listeners, their babies had to be greater than 36 weeks, they had to be greater than two kilos, five days without events, post the discontinuation of caffeine 48 hours in an open crib and less than point five liters of oxygen, and already consuming about 25% of their feeds Po. And I think all of that is reasonable criteria. And I think all of us have been in that position where you say, gosh, the only thing really left for this baby is to learn to eat. And then the baby's going home with G Tube obviously had higher respiratory support. Most of them were consuming less than 25% po after two weeks of meeting their discharge criteria, which I also thought was was reasonable, you know, the babies were term corrected age and still having significant difficulty with feeding. This unit did use bridle placement to secure the NG tubes, which is also I think, an important factor because it may have limited how many times that ng fell out and parents had to return for care. But if we just look at the feeding related re you know, connections with the health care system, the oral group actually had four feeding related events, the N G group had four also feeding related events, and the G Tube group had 19 G Tube related concerns dislodgement bleeding, irritation, so they actually had more kind of interaction with the health care system. Given the the G tube which we we hope when we send parents home will have is a is a, you know, safer, more, we say much more secure alternative. And so I definitely wanted to mention that the other thing, by the three month study period 77% of the babies on ng feeds, were on all all PTO feeding. So when we talk to families about you know, how long will I need a G to? Or how long will I need the NG tube, I think that gives us some good data there. But what I was really impressed by is that there was really no change in the health related quality of life of that was parent reported. And and I guess it wasn't so surprised. I was pleased that there wasn't a difference between the NG group and the G Tube group. But I, I was surprised by a few things. The G two babies who did go home in this group with G's tubes were sicker right higher acuity had multiple medical comorbidities. And I it's just so refreshing that that actually, that their quality of life, parent reported scores weren't hired to be perfectly honest. And it's just a reminder how parents rise to the challenge and that what we as providers think impacts their quality of life is different than than what parents think about quality of life. But those parents did, document feeling less prepared, needing much more equipment, much more training to do the care for their baby, which is which is true. With the G two care versus the the NG care.


Ben 34:14

I almost dismissed the G Tube group outright in that study, and the reason being that, honestly, I think we think very much about putting a baby through a G Tube. I mean, this is a very multi I mean, in our case, it's a multidisciplinary decision where we talk among multiple neonatologist, we talked to the surgeon we talked to the gastroenterologist. And when you look at their babies in that group, it's 65 babies but but they clearly were obviously sicker and 46% of them with congenital anomalies. There was there was the number that went home on room air just to give you an idea as well was 34% in the Gt group, compared to like 80 plus percent in the other two groups. So I was like I find so these babies are very sick, and they you think through do I put I think If anybody puts a baby through a G tube on a very nonchalant way, you're doing it wrong. So it doesn't look like this was the case here. And we know, it's usually an unavoidable situation. But the question was, so many times you have parents with you like they could potentially do well at home that's within GE, do I wait, like you said, or do I keep them in the NICU for just send them home? Now? I think the study was great, because it shows you if you think the parents can do okay with it again, that's a big, that's a big thing, then send them. And like you said, I was very happy to see that there was no significant difference in the number of readmissions, and the quality of life stuff, like you said, is key. Some questions I had that were not addressed is that the numbers of babies who went home on energy fields 34 Plus week was 51%. And I didn't see them address that. I'm like, that sounds like a large number. I am not sure if this was again, is this in order to minimize length of stay? In which case fine, or was this? It just I would have liked to know more about that. And, and that's really it. But I think that the dilemma that we often have as to do I send these home? Or do I watch them here till they learn to eat and potentially catch another infection? I think that paper shows you you should really consider ng fees, again, small numbers, ng group to feed was like 35 patients. But I mean, again, this is data that's published in a major journal that that's been reviewed, peer reviewed, and I think it helps us with making decision.


Daphna 36:27

Well, I think one of the things we frequently say is do I think this is safe, do I think this is a safe thing for families. And I mean, the readmission, the you know, re presentations for care to babies with reflux. One for replacing the NG, which I thought was incredible. And really, I think supports the, the bridle use of the bridle, and then one baby who came with significant it sounds like abdominal compromised, requiring an x slot. But this is a baby who previously it was a known gastroschisis. So I don't even know what to say about that. But, you know, do I think this is safe, I think, you know, a key component is is, is maybe the bridle, you know, can can we can a parent keep the NG tube in the right position. You know, we know that they're frequently in the wrong position, even in the hospital. And so I think if they can keep it in the right position, they don't have to come back because it keeps falling out. And, you know, we think this is a parent who can adhere to the instructions, that that this is something we have to consider. Because, you know, this also wasn't a, you know, two epochs or two randomized arms where we were keeping kids in the hospital versus sending babies home. But potentially, we may even see a greater change, right, because maybe the babies do eat better at home. So that's, that's something else that we haven't even considered. But I think the data is striking that this is potentially a safe thing. The other thing they had, which is very unique is that they had a specific clinic to manage to help these families navigate that, and I think it just underscores the importance of good follow up care post discharge also. But I don't know. Sorry, the you know, it wasn't really about do we give them a G Tube? Or do we give them an NG tube? It was really, can they go home with an NG tube? Or do they stay here for potentially weeks to two months, three months, right to to learn how to eat? So


Ben 38:43

when you want to talk about the bridle, the bridle system for people who may not be familiar with it?


Daphna 38:48

Well, yes. And I'm no I'm no expert. But it's it's basically it's basically like almost like a ring and that goes in the the Nair that attaches to the to the enteric tube so that it's it's adherent at that correct position within the Nair and some hospitals are even using bridles inpatient, not just for discharge. Yeah. I don't have a lot of experience with them. I haven't used them very frequently.


Ben 39:21

I have I have never, I have never used it either. But my understanding is that it it looks basically right, everything goes in one there. And then you sort of catch the other side of the tape in the oropharynx. And you bring it out in the other air, and then you just tie it the annual this, this podcast is not sponsored by bridle. But


Daphna 39:44

no, but the biggest argument, I think is Is this safe. Is the baby gonna get a lung full of feed, and I think they've at least shown potentially the safety of the intervention.


Ben 40:00

So, what else


Daphna 40:01

I think we have to talk about. I know you're excited about this one with our oxygen saturation targeting. Yes. Also, from the Journal of Pediatrics effective a novel oxygen saturation targeting strategy on mortality, retinopathy of prematurity and bronchopulmonary dysplasia in neonates born extremely preterm lead author, Dr. Srivastava, and this is coming from the neonatology associates of Atlanta. So basically, what they did is what many hospitals have been doing as new literature's being presented is they evaluated three different epochs during their kind of history. So the first epoch between 2007 and 2010 second epoch between 2012 and 2014, and 30 Park between 2016 and 2019, which as as we all know, the data was very much changing on oxygen saturation targets. So they again, we're looking at what most of the oxygen saturation target groups we're looking at incidence of any ROP, especially severe ROP, and that requiring treatment BPD and mortality. So their first epoch was basically kind of standard of care, before using any any technical technological intervention, and the second epoch with targeted oxygen saturations. They used a monitoring tool, in addition to their patient monitors that help them formulate histograms, that look at what percentage of time babies are spending in each saturation percentage. And then in the third epoch, they had an additional In addition, the technology enhancement was incorporating simultaneous oxygen saturation and fraction of inspired oxygen measurements. And so what they found I'll tell you kind of what the data looked like. And then we'll get into the nitty gritty but they had 600 babies in the first epoch 380 babies in the second and 550 in the third. So total of 1500 babies and mortality any ROP severe or Opie ROP, needing treatment and BPD all showed significant downward trends across the three epochs. And so I thought that was interesting. I think our discussion will mirror that discussion about the BPD bundle in that, you know, it's it's very much about kind of the culture in the unit and attention to the intervention. So what I really liked about the study, is that histograms, something for us individually to talk about, because not all units are looking at histograms. And I think that's an important feature. Not all monitors do histograms, you and I have worked in facilities that have histograms and facilities that don't have histograms. And at some point in time, you feel like you're walking blind if you don't have the histograms, because you don't know how much time the baby has been D saturating except for nursing report. And nurses can't be at the bedside around the clock. I think some of their other interventions, which, you know, were not stated as concrete interventions, but they had 12 hour printouts of the histogram, which they reviewed with the nursing staff. And so go ahead. No, no. Yeah. And so they in 12 hour, it has printouts that both listed time spent in hypoxemia, time spent in hypoxemia. And using this lability index, so how, how labile were the oxygen saturations? So again, they probably spent a lot of time focused on a few babies who were the most extreme. The other thing they used as this oxygen contract with the staff annually, so they were having staff it was voluntary, but read, you know, a small document about the education about the intervention, giving, empowering the team that they were also going to be invested in this intervention. And so I had that was remarkable. It just shows I think, how important some of those things are when we're trying to roll out a new intervention, I'll let you say your piece.


Ben 45:04

Well, not my pieces not far from what you're saying, I think this paper is, is showing the stat, the sad state of affairs with the desperate need that we have for an approval of automatic FiOS titration. That's right. So we know that this technology is out there where the event will basically adjust your fire to based, right. And this is still not available in the United States, it's available in Canada, to their will in other countries. And if you have this, it really negates all this new interventions that the paper has suggested. But I was very happy to see this paper, because it provides you with an alternative until you can have the technology outside. And, and the the technology that they're using here is very basic. At the end of the day, I mean that you just need to have these monitors, I think these are the Philips monitors that can provide you with histograms. And then they have like you said, that little attachment, that the it's basically a fire to the sensor at the level of the tubing. And they basically monitor the fire to and give you an basically in real time. And they were able to get these printouts with the SATs with the fire to requirements. And, and again, if you it's by having this continuous type of data that you can impact outcome and it's not surprising that they were able to see improvements in both mortality and your OPR be recording treatment, treatment and BPD. So we need to monitor FIU and SATs very closely. And I think again, this is a type of MacGyver situation will be useful. And whenever the Clio the Clio is the is the continuous adjusted, if I have to wonder event, once that comes out, this will become the standard. I have no doubt about


Daphna 46:41

it. Yeah, I mean, I study after study has shown that, you know, tight to take control, the saturations is effective. I'm always weary about, you know, studies where the data collection is really the epochs are linear, right? Because our overall care is getting better. It wasn't the oxygen saturation, or was it all of the other things that we're learning and doing differently, but, but I think this was well written, they gave us all of the information about how they got their staff invested. And so I think they probably didn't get a lot of somebody saying, Well, I'm not going to chase that baby, you know, but you have to, we know that you have to chase the baby, if they need a little bit more oxygen, they need a little bit more oxygen, and if they need less, they need less. And that may change multiple times throughout the day. Very interesting fever.


Ben 47:35

We done with general pediatrics, or you want to go to general parasitology. Do you have anything else you want to talk about?


Daphna 47:40

Gosh, let me see my my list here. I did. I did want to highlight this article associations between neonatal MRI and short and long term neurodevelopmental outcomes in a longitudinal cohort of very preterm infants or preterm children. That's the one you want us


Ben 48:00

to want to Well, so that's the one that's the one I was gonna mention. Yeah,


Daphna 48:03

and lead author list, set Janssen. This is a paper out of the Netherlands. This is more data from their proud study, preterm brain injury, long term outcome and brain development study. So they wanted to look at neonatal or MRI markers of brain injury, and then reassessing babies that behave by behavioral outcomes using the Bailey at two and 10 years of age. And in a longitudinal cohort. And I mean, it's just amazing. Anytime we can get a longitudinal cohort, obviously, we can learn so much from them. It's very difficult to do in especially in in our country here in the United States. But they were able to get 112 Children born less than 32 weeks of gestation. It and they had very, very good follow up actually even at the 10 year mark. So we looked at cognitive motor and behavioral outcomes during follow up. And this short is after adjusting for some perinatal factors and level of maternal education. The global brain abnormality score was associated with differences in cognition, and motor skills and behavior at two years of age. But this is very interesting was not associated with cognition at 10 years of age. And the biggest predictor of cognition at 10 years of age, almost despite their brain injury score was level of maternal education. And so this didn't hold true for things like motor skills, which we know that changes on MRI, very much predict long, even long term motor outcomes. But I thought this was important Um, I think some people can read this article and say, well, there's nothing we can do about it. And and I thought differently, I think even more so it matters, right what their post discharge environment is like. Some of it may be genetic, obviously, and we don't have any influence on that. But even as neonatologist, we have to be advocates for early, you know, early intervention, good strong childhood education. Because not every baby has a mom with very high education. And so if we're really going to change outcomes for preterm babies, and we have to give parents more resources and focus on on some of the environmental factors, what it was,


Ben 50:52

like, like we spoke with Betsy Pilon. On a podcast, it should be that once parents do go home, we have to surround them with an environment that would allow mothers to continue on their journey to becoming a professional becoming, getting getting educated, because you see that it matters so much. It shouldn't be that Oh, my God, I had my preterm baby when I was 21. So I left college and then just working. It shouldn't be like that. Because if you can help this mother get to the highest level of education possible, it will indirectly or directly, I guess, benefit the baby. I thought that was cool.


Daphna 51:24

Super cool. Yeah. I'm glad we could talk about it. Yeah, yes. I think now we've got to move on.


Ben 51:32

Now we've got to move on. I don't have I don't have many more. I think I have four or five articles. And we can go quickly through them. The first one while you move on to the Journal of PDF parasitology is in the Journal of parasitology. There was this paper by the group that I used to work with at Mount Sinai in New York, during my residency that looked at something that was quite interesting. I don't know if you picked up on it. We know insufficient renal insufficiency. I'm sorry in children born preterm, examining the role of neonatal kidney injury. first author is Margaret Poole. True and all the authors I know personally, and Marie's to strip wrote my letter of recommendation for fellowship. And Robert Greene is an amazing guy. Andrea Weintraub is amazing. Dr. Reed, Adam is a good nephrologist as well that I've got briefly to work with and their study.


Daphna 52:23

So you'll be you'll be unbiased and your review completely,


Ben 52:26

completely unbiased. But it was an amazing study, I think, no, I'm gonna be very honest. The reason I'm very impressed by this study is not because of the strength of the data, or the strength of the analysis. It was the story that it said that it shows it was aimed to identify the prevalence of renal insufficiency, insufficiency and children with a history of prematurity and acute kidney injury. So then they prospectively collected their cohort, and they follow them at five to nine years of age. And obviously, they had categorize them using the I think it was the K the K D IG or the kid No, they use the 8k and I'm sorry, the Aiken staging criteria and they categorize them as having either no Aki, stage one stage two stage students, okay. And then the follow them and I'm going to read you the results because it's just very interesting. 15 of 43 participants had previously undiagnosed Renal Insufficiency only children with no Aki history, or stage one Aki presented for follow up. So when I read that, I was like, Oh, my God, this is terrible. Like they're only getting only that segment of the population that had either very mild Aki or no Aki at all. And then the results came out children born preterm with a history of stage one had higher serum creatinine that followed, but were not more likely to have renal insufficiency compared to children without stage one. And that was what's shocking is that all these kids, the 15 kids that they did follow, that came back had some renal insufficiency, even though they did not meet criteria for kidney injury in the neonatal period. And all these infants obviously were born extremely preterm. The gestational age on average was 27.6 weeks in the no Aki group and 25.8. In the stage one Aki group. The what was striking to me is that I was expecting them to have relatively good renal function. And it shows that even if their kidney function in the preterm in the very immediate neonatal period was not great, they still have a high risk of renal insufficiency at five to nine years. And they even had to refer one of the kids in and then they looked at, they looked at the mother history, which obviously played a role there were five children born to mother with hypertensive disease during pregnancy, who presented at follow up. While none of these children had Aki during the NICU stay three of them. So three out of five had signs of current renal insufficiency. Only one child had elevated BPH follow up in addition to low GFR. Which, I mean, this is this is a big deal. You And, and some of them had to be referred immediately for for renal follow up. And I think these patients probably present much later in life with severe kidney disease. And this is another sign that I think this should be part of the discharge bundle. If you're born below some gestational age, follow up with a nephrologist, I think, to everybody listening, do not skimp on the nephrology follow up after discharge. I think these are very, very important. And I was I was baffled by the fact that these babies had this degree of kidney injury so late in life, considering their immediate neonatal history.


Daphna 55:37

Yeah, I think it comes back to we like things we talked about with Juliet, who you, our listeners will meet on our episode that airs on the 18th. That that being preterm affects your long term health. And so you know, we have to consider that as part of, you have to continue to include that as part of the history when when these patients present for care, the only thing that was almost a little scary is that they weren't having high blood pressure, right. So they're gonna go no diagnosed. Unfortunately, we feel like, well, if your blood pressure is good, and everything's probably fine, but no, you know, that's, that's our biggest screening tool. And in fact, I think a lot of pediatricians are moving away from things like routine urinalysis, and so maybe this is a cohort, you know, a subgroup of the population that that still needs them. I'm not making that recommendation. I'm just saying, we don't have any other way. You know, we don't have any other way to follow them unless they're following up.


Ben 56:40

I think it's good that this data is is out there, because I think at some point, the the societies of pediatric nephrologist are going to come out and saying, if you're less than 30 weeks, you should follow up with us, regardless, and the data is going to substantiate that it's not going to it's going to be because if you don't have the data that gives like, oh, we just want to stack up our clinics, right? It's not true. This is really, really needed. All right. Yeah.


Daphna 57:07

I think we have to talk about we've already we've already broached the topic, but this article association between maternal maternal cervical vaginal swab positivity for ureaplasma, or other micro organisms, and neonatal respiratory outcome and mortality. Because your ureaplasma is becoming a much, much more common topic of discussion and lead author Karen van Micheline, I may have butchered that name. And so this group out of Belgium in the Netherlands, we're looking to investigate the association between the cervical vaginal cultures, treatment and then neonatal outcomes. So they enrolled 480 neonates born prior to 32 weeks gestation. And then they were divided into groups according to culture results. So they looked at babies who were they looked at babies born to moms whose cultures were either ureaplasma, negative, other bacteria, negative ureaplasma, positive, other bacteria positive ureaplasma, negative other bacteria positive for babies, mommies who just had ureaplasma. So I thought that was really important for them to distinguish. Was there something else going on? Or can we really say that it's urea?


Ben 58:38

Can you blame it on the ureaplasma? So that's really,


Daphna 58:41

I think they did a great job of setting that up. So and the swabs were done in about? Let's see. Let me tell you here. So what they found were that maternal swabs showed that ureaplasma colonization was independently associated with BPD at 36 weeks with an odds ratio of 8.3. In neonates with and without maternal ureaplasma colonization BPD occurred at 12.3% with colonisation and 3.8%. Without,


Ben 59:20

that was huge. That was, that was a very impressive 13% Compared to 4%, just based on on colonization of the moment is It's nuts.


Daphna 59:30

Yeah. And they did find, which is also not surprising, but maternal colonization with other microorganisms, in addition, separate from your in plasma was associated with higher neonatal mortality, lower gestational age at birth, and lower birth weight, and I believe also an independent predictor for BPD. So I thought this was a really interesting study, I think, you know, makes us a think that eventually you reapply asthma screening will be part of routine OB care. I also think that HSV screening will become more of a routine part of OB care. But I think if we can pick up, potentially some of these moms earlier, could we could we even prevent some preterm birth by treating ureaplasma? I don't know. And then certainly in our group of babies who, you know, should we be screening our babies? Should we be treating our babies for ureaplasma? I think that's really the question.


Ben 1:00:36

That's the key. Somehow, I'm not exactly sure why testing for ureaplasma in cervical vaginal swabs is very easy and cheap. Yep. Somehow, I don't know why. And then


Daphna 1:00:47

it's easy and cheap to treat also.


Ben 1:00:51

But that's the thing. And then to test it on the baby to take an airway aspirin, read it from from the sputum, or from any air from this anyway, it takes such a long time. And I've seen many neonatologist, myself included, who wonder saying, Well, do I treat the baby right away? Or do I wait for the real plasma culture to come back? Well, this paper seems to lead us in the direction saying, Well, if the mother is positive, and the baby is small, and you have a concern, might as well just treat with azithromycin. I mean, it clearly shows that you almost don't need that link of the baby being positive for it, to try to reduce that risk. I think that's very interesting. Because it feels very silly sometimes where you have done this as well, where you send it on the baby and you treat anyway, and then it comes back negative and you're like, but, but at it's it's nice to see again, this we have to quantify this, the numbers are small, they're not that small, but they're small. But yeah, the data is there. And so I would say this is this is great in terms of making clinical decision at the bedside of the baby that is born small that the mother's ureaplasma positive. Are you going to give a course of a zero? Again, I don't think it should be part of the engine sort of bundles you've not given to every baby. But if the mother is positive and the baby smile, and you're intubated after birth, well, I would consider it.


Daphna 1:02:10

Yeah. And then the question becomes, right, when do we?


Ben 1:02:16

What? Oh,


Daphna 1:02:17

there I said, the question becomes when do we treat, right? Do we treat right away? For a baby who's sick? We know that mycoplasma pneumonia and neonates typically presented about the third week, do we wait until the third week? Or can we prevent some of those respiratory D compensations by by by treating earlier? I think this is also a reason why, you know, we it's important that we don't work in our silos, and it's nice that we've we've got, I think, a little bit of a pick you audience to that, you know, pick us are using azithromycin in addition to other antibiotic courses, because of its anti inflammatory properties. And so, you know, does that play a role for us? Also, I don't know, but I think we're gonna see more and more literature. I'm hopeful we're gonna see more and more literature that we can have some something else in our in our armament.


Ben 1:03:13

Yeah, absolutely. Um, another article I wanted to mention, since we're obviously running out of time, but we're going to go through them is also an additional paleontology called growth outcomes of small for gestational age preterm infants before and after implementation of an exclusive human milk based diet. first author is Lindsey flag, and they are from Texas. What was interesting is that they basically looked at it's a multicenter retrospective cohort study, and they looked at babies who were born small for gestational age preterm. And they looked at the difference between putting babies on an exclusive human milk diet and babies on a cow's milk diet. And they looked mostly as their primary outcome as the growth, I don't want to I don't want to the primary outcome from growth measurements between between the two, showed basically no difference and even show that maybe the length at discharge was greater on average in the human milk group. So I thought that was very interesting, because sometimes when we have babies who are SGA, we tend to think that we need to give them more. And this paper shows that you can actually them on human milk, and they will do better. They also showed significantly, and that's a big deal. Obviously, the reduction in necrotizing enterocolitis. With which is obviously a huge concern, when you have SGA. So the rates of neck went down from 17% in the cow's milk diet, to 8% in the human milk group, and surgical neck went down from 9% to 4%. So these were, these were pretty big. I don't know I don't know what you felt about that because I feel that it's always so hard to it's not the decision to put a baby on human milk which is difficult. It's the right thing to do, but it's to watch them not gain weight for a while, and you're like, do I supplement? Or do I just sit? I like this data, it's sort of conference, you and just this sort of watchful waiting on human milk. And the one thing that this study is missing, which the authors should consider is, it's very population based, I don't know, what is the chromatic rate on these mother's milk. Maybe mothers in Texas have higher calories in their breast milk, I have no idea. Maybe people in Miami have less, I don't know. But what I'm saying is that if, if human milk in in this area of the US or the globe is higher, in fact content or higher in calories in whichever way, then you may get a benefit that somebody else in another place of the world may not get. And so I think this study needs to be followed by the same data with saying, well, we also did the chromatic weight on our mothers. And on average, we have 20 calories, which would make me feel good about leaving my babies just on on your window. But anyway, that that was an interesting study. Well, that's


Daphna 1:05:57

that's a separate issue, right? Should we be doing chromatic crits? What can we do to lacto engineer milk and optimize mom's own milk? Instead of instead of more additives, we should mention, obviously, that the study does did does appear to have some proactive support. So that's just something of note. But I think I think the data is very good. And especially that the growth didn't suffer, like you said, I do think the fortification protocols were somewhat different. So sometimes they fortified for the, in the human milk fortifier group, they were fortifying early 60 mL per kilo per day. And then the other groups, the cow's milk groups, cow's milk fortification groups, they were fortifying much later. For some babies, that's only a few days for some babies. That's a lot of days. So just just something of note, but I think a lot of hospitals are looking at this and saying, Can we afford the cost? And I, you know, at some point in time, we also have to weigh the cost of, you know, an admission that neck or SIP or death or a prolonged length of stay because of feeding and tolerance, and what does that do to growth? And so, you know, this can't be a cost only decision. And in fact, I sometimes wonder if the cost might be less than and I think we have some studies that that show that also from the proactive trials.


Ben 1:07:41

And so that was key, that's where not only did you do you match in terms of growth, but you also can reduce potential length of stay and cost by reducing NBC seven that was Yeah.


Daphna 1:07:52

Yeah. I thought this was interesting to to know, we will get into I think we were like you said running out of time, we can't get into the nitty gritty but this positive fluid balance associated with death and severity of brain injury and neonates with HIV. first author, Catherine M. Otellini. This is coming from Children's National and George Washington University. They looked at the association between fluid balance during therapeutic hypothermia and severity of brain injury on MRI and babies with HIV. So it's a secondary analysis of data that had previously been collected on this group. And they looked at the Daily net positive fluid balance, and they used a cut off of about 25 mils per kilo per day as their net positive fluid balance. And they included 150 Babies 50, they say suffered adverse outcomes based on their MRIs which were scored using the bark which criteria and had significantly higher net positive fluid balance. So that was statistically significant. So basically, the what they found is that babies who had a net higher positive fluid balance more frequently were found to have worse injury on MRI. And so I think this is interesting. I think that it it definitely may lead to practice change. Most people are obviously using restricted fluid volumes in babies with HIV. One thing I couldn't quite tease out, though, is is they said adjusted for covariates. But I couldn't quite tell if they adjusted actually for creating or kidney injury, which which means that you know, that's the


Ben 1:09:49

that was that's the key. And that's the problem with this retrospective data that I think I think it's a valid I think it's valid. I mean, it was not retrospective, but it was prospective. Land was prospectively prospective observe prospective observational data. And that was the problem is that if the fluid balance is high, because the kidneys kidneys are completely damaged, then could that just be that is not the fluid balance that is a marker of higher mortality is divided into organ, multi organ damage, I know. But that's why I think it's a good step in the right direction to be followed by a more prospective sort of trial for sure.


Daphna 1:10:25

And they may have the data. So that will be interesting. Interesting to see for sure. Let's see, oh, I wanted to just touch on this one. Effective prenatal marijuana exposure on sleep wake cycles, and amplitude, EEG.


Ben 1:10:43

I knew you were gonna bring that one up. First author,


Daphna 1:10:47

Rebecca, pull lock the I'm sorry, I don't have the this is


Ben 1:10:54

from Memphis, Tennessee. That's


Daphna 1:10:55

right from Tennessee. And so well, you know, I like amplitude, EEG, I'm a I like, I like studying sleep. I also am someone who doesn't to totally rule out breast milk from mommies who test positive with marijuana. So this was a, I was excited to see this. I'm a little conflicted about it. But I'll tell you about it anyway. So they looked at THC expose newborn. So mommy's screened positive for having used marijuana. And then they basically followed these 30 Mother infant dyads, and followed the babies with amplitude EEG and monitoring for sleep wake cycle, which we know is very important for long term brain development. And so unfortunately, they did find that and there was an absence of sleep wake cycles on amplitude EEG, in many of the babies who were prenatally exposed, not all of them, but many of them, and it was statistically significant as compared to the cohort of unexposed babies. So this puts me in quite a predicament because I think both breast milk and sleep are important. So I think, obviously, we should try to find a way to give babies milk that is not containing any other substance. And so in counseling is counseling is key. That's exactly and I think if we really talk to parents, and we say we want you to provide milk, we're going to help support you provide milk, but we we need you to stop if you can, we can help you stop. I think that that maybe we can do both. I'm not sure we always have to pick.


Ben 1:13:01

I think it's the same thing. Because Because pot American marijuana is becoming more and more legal around the country. There's this there's this jump that people create in their mind, were saying, well, because it's becoming legal. It's okay for me to take. And, and we haven't really recategorized marijuana in the alcohol, cigarettes sort of category, which is, yes, it's legal. Yes, you can purchase it, but it's not good for you. And if you had asked a prospective mother, hey, do you think it's good to drink alcohol all the way through during your pregnancy? Everybody agrees? No, it's not good. So it's the same we have to keep counseling the mothers because again, we're still in that phase where it's becoming legal and people are saying well, since it's becoming legal it's okay to take rights like No, still not okay. But yeah, to be considerate and moderated in how you use it.


Daphna 1:13:47

Well, especially because you know, in THC levels I don't know I am not sure how how how useful they are but in this study, the THC levels did not correlate with the EEG abnormalities and so I you know, I we don't know what is what is in acceptable dose response, and we certainly don't know B because because of the way marijuana is manufactured and sold in this country, we don't know what everybody's getting. Anyways, that's a whole nother discussion. So I'll leave the listeners to I'm not going to tell them what it changed my practice about it a little longer. What else did you want us to cover?


Ben 1:14:34

Let me run through a few articles. I liked that one called urinary ferritin a potential non invasive way to screen NICU patients for iron deficiency. It's from first author Eric good day and it has a bunch of star neonatologist in their last author is Robert Christensen. Second to last author is Robin, Robin OLS. And yeah, so what was interesting is obviously as we're using more and more eco Darboe we're trying to make Under ferritin levels and hemoglobin levels, and it's always blood draws, and if you're using equal, you're trying to be mindful of how much blood you're using. And so this study was looking at whether we could use urine ferritin as a sort of correlate for serum ferritin. And this prospective analysis basically was very well designed they they collected pairs of sample paired serum and urine, and they find Irin limited erythropoiesis by a ra T, H, E, which is the which is the Farrington the ridiculous site hemoglobin content of less than fifth percentile, and they got 4549 pairs. And you're in Farren correlated with serum ferritin. And corrected urine ferritin of less than 12 had a sensitivity of 82%. And a specificity of 100% for detecting iron limited erythropoiesis with a positive predictive value of 100%. I thought this is this is cool. I've worked on a protocol for our institution on eco and monitoring of ferritin levels. I think urinary fairing is potentially a game changer. We should use it, it's less blood from the baby urine is readily available. We should start using it. So that's that's one article


Daphna 1:16:22

is easy to collect. But neither is blood. Really, when you think about how many times you have to stick a baby


Ben 1:16:27

does doesn't have to be on steroids. It's great. That's right, and you can just put a bag and if it falls and you get it again, it's so much better than having to pack the baby


Daphna 1:16:35

well I'm sure some of the some of our listeners are nurses and I'm sure they'll say yeah, but curse me out took me 48 hours to collect that bag. Because sometimes it does but um, but but so what if it takes that long right in this particular instance? And the iron certainties are a lot of blood. So I think anytime we can use urine, it's a it's a slam dunk. There's a lot of correction that has to happen with that data, but I think that could be easily done.


Ben 1:17:08

So yeah. Another one that was interesting from again, the University of Florida, called hypertension in neonates treated with intro vitriol. Beavis Beavis Siza Mab, for retinopathy of prematurity. I'm making fun of us because you come from us. I don't want listeners to believe if they haven't listened to the prior episode, they're gonna think I'm like dissing the University of I'm just saying, this is where you train. Second author is Michael Weiss. That's right. And they looked at twice, right? So babies who received IV, IV, monoclonal antibodies, Bevacizumab, developed new onset systemic hypertension after treatment, I thought this was a very interesting study for friends in ophthalmology. And again, one more problem with with this new I know, it's just it was so for such a promising intervention, and more and more stuff is coming out. So now, on top of the long term outcomes that are now a bit less stellar, we have this issue of systemic hypertension. So anyway, I thought this is an interesting paper for people to look at.


Daphna 1:18:16

Yeah, I don't think it takes away from the intervention. And obviously, we're using more and more of it. But it's something definitely to be monitoring for.


Ben 1:18:25

Yeah. But another one that I thought was interesting was called blood biomarkers with neonatal HIV, and the presence and absence of sentinel events. This was by first author Eric Bruni, and they wanted to determine if there was some serum biomarkers that could represent different pathways of injury. I thought that was interesting, because you know, there's sometimes babies that have had an insult in utero. And when they come out their base success is corrected, but they look really sick. And I've seen that before, where they come out their limp, you have to intubate them, and you do the initial gas and the P successes like plus one. And it makes no sense. And you wonder, did they auto correct, because it happens a long time ago. And so you don't really have a perinatal event, because at the time of the delivery, there's nothing really acute going on. But the perinatal event happened maybe at home, the mother wasn't sure doesn't matter. But so what was interesting is that they looked at some of these, they looked at some of these assays, and they were able to identify 277 babies that were 190 that were treated with with cooling. And the markers that they looked at, were il 10 and VEGF and they found that babies so I'm just going to quote the the article, or the the order the degree of metabolic acidosis was similar repeated measure analysis showed that during the initial three days of life, so in the first 72 hours, babies with HIV in the absence of sentinel event, had a 41% decreased VEGF P value point 02 And 62% increase in aisle 10 P value 0.005. And so I thought that was interesting. Because sometimes you can get taken off track if you don't have a sentinel event. And so I thought these are interesting markers. Now, I think we should be very careful in not using these markers too lenient, clear and saying, Oh, I'm going to just check it. And then you're going to start calling everybody because you see a little rise in in the il 10, or decrease individual. But anyway, I thought this was interesting. I think people should check out this paper as well.


Daphna 1:20:29

Well, and we're learning more and more about those biomarkers. And there are lots of groups in this across the world that are studying biomarkers, particularly for their predictive, you know, use in determining outcomes, but certainly just in diagnosing HIV. So I do think in the future, they will be part of our diagnosis can the diagnostic consideration for getting


Ben 1:20:58

the last paper that's my last paper of the of the week, the journal parasitology effect of blood transfusions on cognitive development and very low birth weight infants. This is another paper from Robin OLS. And again, making a comeback for the for people and our people as a sort of protective entity against cognitive impairment at 18 to 22 months. And they basically looked at cognitive scores 18 to 22 months, and they found them to be inversely correlated with transfusion volumes. And among those who receive more than one transfusion, cognitive scores were significantly higher. In the ESA treated group, ESA includes EPO and rdquo. At three to five to four years transfusions were not correlated with cognitive scores. Again, I think there was this big trial that looked at people as a potential neuro protector, and it was not really conclusive. Does that mean that eco is not beneficial? I'm sure it is somehow beneficial. I think this is what this paper is showing. But again, eco was a neuroprotective agent making a comeback on this one.


Daphna 1:22:00

Yeah, yeah. And we know that anemia in Childhood Studies is is related to you know, cognitive outcomes. So it would stand to reason that you know, your, your exposure to anemia in the perinatal period has some has some effect on that. And then obviously, what happens with your nutrition your genetic your biology, and that that changes into childhood, so very interesting. Yeah, I had a few to I'd like to highlight I thought this also the Journal of Perinatology using buprenorphine to treat NAS a quality improvement study. first author Sagar Bhandari so this came out of Wake Forest University. And so, in brief, basically, this this was a facility that sees, you know, with not insignificant amount of any assets, but they were trying to see what what can we do better. So this was a quality improvement study using a number of PDSA cycles, but this cycle, they highlighted babies who received buprenorphine, and I think, importantly, they didn't see any adverse reactions reported. They did still need some adjunct therapy. But they showed a reduction in both days of treatment from 14 and a half to eight and a half days, and a reduction in length of stay from 18 and a half to 13 days, which I think is no small, no small amount of days. So no, I thought that was interesting. That's right. That's right. The other thing I thought that we should highlight and you know, I'm a stickler for Billy Rubin's was this article. intravenous immunoglobulin G in the treatment of abo hemolytic disease in the newborn during the early neonatal period. A retrospective study lead author, J. Ron pan, and so this was a study out of the Children's Hospital Yep, in the People's Republic of China. So they were looking at Babies who got IVIG and babies who didn't get IVIG for moderate to severe abo incompatibility at less than seven days of of life. And so they enrolled 46 patients into the IVIG group, and 28 patients into the phototherapy only group. And there was no significant difference in duration of phototherapy, hospitalization, period, need for exchange transfusion, other transfusions, or other bilirubin induced neurologic sequela between the two groups. And so, you know, IVIG has been in discussion and more recently about its potential adverse effects. And so, you know, we were always saying, Well, if it prevents, you know, exchange transfusion, then you know, potentially the risk is worth it. But if it doesn't prevent exchange transfusion, then it's it's definitely something for us to really think about before we administer.


Ben 1:25:27

I mean, is this I was I was purposefully staying away, because I think it's a little bit. I mean, I mean, right? Are you going to change your practice and hold off on IVIG? I mean, you're giving phototherapy the levels?


Daphna 1:25:42

Something you feel like you have to do something. But I just, I just think and that may not be the right answer. Sometimes doing nothing is the right or keep keep doing what you're doing the things that we know have proven benefit. I think we need more data, but I think the data is coming. For sure.


Ben 1:26:02

Right. And that's the thing, I think they they're briefly mentioning in the background, this this famous Cochrane review, that was published on IVIG for hemolytic disease of neonates, and I think it was published in 2018, or something like that. And it's true that it could not make a definitive statement in terms of IVIG being definitely beneficial in preventing exchange transfusions. But there was a lot of issues with the data, obviously, in the Cochrane acknowledge that, and I remember the Cochrane I mean, I have the Cochrane review now in front of me, and it says overall results show a significant reduction in the need for extension infusion in infants with treated with IVIG. And the applicability of the result is limited because of low to very low quality of evidence. And the two studies that had the least risk of bias showed no benefit in reducing the need for exchange transfusion. So at the end, when you combine all these things together, they couldn't really make a definitive recommendation. So I think that's where we are. Yeah. And I think I would be so be careful with that article, especially also considering that their number of patients again, is very small. Yeah, I'm not going to stop using IV age.


Daphna 1:27:13

Yeah, I don't I don't. I think we have to keep talking. There are still more articles, but we are really pushing the limits on time here.


Ben 1:27:23

Nobody's listening at this point. Exhausted. It was like it, we're done.


Daphna 1:27:29

Okay.


Ben 1:27:32

Should we call it a day?


Daphna 1:27:33

I think we have to.


Ben 1:27:35

We have to. You want to read us a review before we head off into the sunset?


Daphna 1:27:41

Sure. I will. That we have. I'm going to read you two reviews from our from the same reviewer. But we really touched us we really appreciate We love getting reviews and feedback from you guys. This one comes from Dr. Mona she has I'm not a 13 year old teenager, I'm greater than 16 years old. And if you saw her, you wouldn't believe it. Very uncomfortable with social media who became mesmerized with these discussions on Twitter. Let's grow the neonatology family on social media and learn from each other. Thank you, Ben and dolphin. Thank you, Dr. narvi. An additional tweet that I couldn't help but it just made me chuckle I loved it's my favorite favorite response to peanut butter and jelly that is Daphna. And then the chemistry and energy in your podcast is so spot on. I look forward every week to be educated that go the next day and impress my colleagues with the knowledge I got from the incubator. So I don't know for really peanut butter and jelly. But I'm pleased that people are finding the stuff they learned here useful. We know Mona and Flynn, full disclosure, we really appreciate her support. So and


Ben 1:28:57

she has very, yeah, the reason I was very happy about these tweets is because Mona has a very high standard. So I was very afraid when she started listening. She's a tough we made, we made the cut.


Daphna 1:29:10

So please keep sending in your reviews. You know, we read every single one, we really appreciate it.


Ben 1:29:16

And continue. Continue engaging with us on Twitter. And please send us questions for the book club. And if you feel like you want to share something on the show and want to be on the show, let us know we were more than happy to have anybody on the show. We're not We're not very strict. You can come and talk to us about your experience. And we will make it easy for you so so please engage with us. And let us know.


Daphna 1:29:36

We do love to chat. We do love to chat. That's all right, then the rest of your trip. Be safe. And


Ben 1:29:47

well. Thank you. I'll see you next week, I guess. Okay, all right. Definitely. It was fun. Thank you for listening to this week's episode of the incubator. If you liked this episode, please leave us a review on Apple podcast or the Apple podcast website. You can find other episodes of the show on Apple podcasts, Spotify, Google podcasts, or the podcast app of your choice. We would love to hear from you. So feel free to send us questions, comments or suggestions to our email address, the queue podcast@gmail.com. You can also message the show on Instagram or Twitter at NICU podcast. Personally, I am on Twitter at Dr. Nikhil spelled Dr. NICU. And Daphna is at Dr. Dafna MD. Thanks again for listening and see you next time. This podcast is intended to be purely for entertainment and informational purposes and should not be construed as medical advice. If you have any medical concerns, please see your primary care practitioner. Thank you

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