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#084 - Journal Club 34

Hello Friends 👋

On this week's episode of Journal Club, we review a couple of articles dealing with hyperbilirubinemia to top off the discussion we had two weeks ago after the updated AAP guidance was published. We also look at numerous interesting topics. Should BPD patients attend daycare, at the risk of catching more pulmonary infections? Are semi upright swings in the NICU safe? We also have an interesting conversation about the use of supraglottic airway instead of facemask for neonatal resuscitation. And much more. Thank you once again for supporting our work and for being a loyal member of our community.

Best, Ben.


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

Predicting the Need for Phototherapy After Discharge: Update for 2022 Phototherapy Guidelines. Kuzniewicz MW, Li SX, McCulloch CE, Newman TB.Pediatrics. 2022 Sep 1;150(3):e2022058020. doi: 10.1542/peds.2022-058020.

Automated prediction of extubation success in extremely preterm infants: the APEX multicenter study. Kanbar LJ, Shalish W, Onu CC, Latremouille S, Kovacs L, Keszler M, Chawla S, Brown KA, Precup D, Kearney RE, Sant'Anna GM.Pediatr Res. 2023 Mar;93(4):1041-1049. doi: 10.1038/s41390-022-02210-9. Epub 2022 Jul 29.

Maternal acetaminophen use and cognitive development at 4 years: the Ontario Birth Study. Lye JM, Knight JA, Arneja J, Seeto RA, Wong J, Adel Khani N, Brooks JD, Levitan RD, Matthews SG, Lye SJ, Hung RJ.Pediatr Res. 2023 Mar;93(4):959-963. doi: 10.1038/s41390-022-02182-w. Epub 2022 Jul 7.

Transcutaneous bilirubin levels in extremely preterm infants less than 30 weeks gestation. Sankar MN, Ramanathan R, Joe P, Katheria AC, Villosis MFB, Cortes M, Bhatt DR, Truong H, Paje V, Tan RC, Arora V, Nguyen M, Biniwale M.J Perinatol. 2023 Feb;43(2):220-225. doi: 10.1038/s41372-022-01477-4. Epub 2022 Aug 5.

Daycare Attendance is Linked to Increased Risk of Respiratory Morbidities in Children Born Preterm with Bronchopulmonary Dysplasia. McGrath-Morrow SA, Agarwal A, Alexiou S, Austin ED, Fierro JL, Hayden LP, Lai K, Levin JC, Manimtim WM, Moore PE, Rhein LM, Rice JL, Sheils CA, Tracy MC, Bansal M, Baker CD, Cristea AI, Popova AP, Siddaiah R, Villafranco N, Nelin LD, Collaco JM.J Pediatr. 2022 Oct;249:22-28.e1. doi: 10.1016/j.jpeds.2022.06.037. Epub 2022 Jul 5.

Supraglottic Airways Compared With Face Masks for Neonatal Resuscitation: A Systematic Review. Yamada NK, McKinlay CJ, Quek BH, Schmölzer GM, Wyckoff MH, Liley HG, Rabi Y, Weiner GM.Pediatrics. 2022 Sep 1;150(3):e2022056568. doi: 10.1542/peds.2022-056568.

Effects of semi-upright swings on vital signs in NICU infants. Kadakia S, Isaiah A, El-Metwally D.Pediatr Res. 2023 Mar;93(4):953-958. doi: 10.1038/s41390-022-02161-1. Epub 2022 Jun 25.

Influence of maternal and perinatal factors on macronutrient content of very preterm human milk during the first weeks after birth. Borràs-Novell C, Herranz Barbero A, Balcells Esponera C, López-Abad M, Aldecoa Bilbao V, Izquierdo Renau M, Iglesias Platas I.J Perinatol. 2023 Jan;43(1):52-59. doi: 10.1038/s41372-022-01475-6. Epub 2022 Aug 5.


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

Ben 0:54

Welcome Hello, everybody. Welcome back to the incubator Journal Club. How are you Daphna? I'm sorry. I'm stumbling out of the gate. I'm sorry.

Daphna 1:07

No, I you know, it's funny. I feel that way a little bit, too. We did so many interviews in the last few weeks. journal clubs seems like a faint memory. But here.

Ben 1:19

Here we are.

Daphna 1:20

We had a lot. There's some there's, it is neonatology research heavy these days.

Ben 1:26

Yeah, duh. So what's interesting is that there's very few journals that are specifically dedicated to neonatology. So if you go in the Journal of Pediatrics, for example, you may get a few articles to knit related to neonatology a lot more related to general pediatrics or other sub specialties. And so sometimes, sometimes it's even difficult to find, to find neonatology focused papers, if you've been checking every two weeks like we are doing. But this this time around, holy moly, folder filled up. So we're not going to go over all of them today, obviously. And we have saved some of the best for today and some more for next time. And we'll keep keep up to date as to what's happening. So yeah. Thank you, everybody, for listening to the episode last week with Sarah De Gregorio. Always phenomenal to have the parents insights, and how they're like, you know, my daughter is reading these days To Kill a Mockingbird. And so this, I think, yeah, so but like this idea of like, understanding people's perspective, walking a mile in their shoes. That's very important for us as neonatologist to understand what the perception of families are, so that was cool. And next week, we have the, I mean, he's kind of kind of kind of a big deal. Yeah, Dr. Ravi Patel is going to join us on the podcast so we're super excited to finally released his interview. Yeah, he's, he's, he's a he's a superstar, like, the likes of Eric Jensen. You know, this new generation is interesting that we interview the giants of neonatology and, and we also get to interview the people who eventually will be known as the giants of the totality. That's kind of cool.

Daphna 3:17

That's exactly right. It's almost like feeling like history is being written for our eyes. Yeah.

Ben 3:25

Okay, so, we are doing journal club, you have some papers, I have some papers. I'm going to let you begin then.

Daphna 3:34

Oh, you are okay.

Ben 3:36

You want me to begin? I don't mind beginning it's fine. I can start with a very,

Daphna 3:42

I never begin

Ben 3:45

out of preference. By the way. Let me just make that clear. Because I have I have I have the clips of all of you saying no, you start. Okay, so I'm going to follow up on the discussion we had last time on Journal Club about phototherapy. There's lots of articles since the release of this of these guidelines by the AP that have come out that are looking at all the different things you're going to talk to us about Transcutaneous. But the group out of California led by Michel Cousteau weeks as he I'm pretty sure I'm pronouncing this incorrectly published in pediatrics, a paper called predicting the need for phototherapy after discharge update for 2022 phototherapy guidelines. So what they're saying is that in in 2021, the same group reported that the difference between the last serum bilirubin level before discharge and 2004 American Academy of Pediatrics phototherapy threshold was an excellent predictor of post discharge barely, according to these 2004 guidelines. But now they've changed. And in the end, the phototherapy thresholds are now about one to three milligram per deciliter higher than they were in 2004. And so if you have listened to last week's episode, you kind of, you're gonna know what the answer to this question that they're asking is because the data that they're using is integrated into the new guidelines. But they wanted to know if the pre discharge serum bilirubin level predicts post discharge serum Billy exceeding the phototherapy thresholds. And and that's something that obviously is it's something that was a very, very big deal in the guidelines and is a very big deal for us, especially when we have to deal with discharges from the nursery. Because it's always like, oh, is the belly rising is the ability to close to the threshold? I

Daphna 5:41

think I said, I think that's the hardest thing. We have to do discharges from the nursery.

Ben 5:49

And that's why I have a lot of respect for pediatricians for outpatient pediatricians. And I have respect for all pediatricians. But the outpatient community is in the nursery. It's like you have so little information. And you have to make such important decisions in the NICU. I mean, we are kind of kind of spoiled. We everything is monitored, and all I don't have to worry about, like our vital signs are continuous. How luxurious is that? Amazing? Yeah, so this was. So this this study included 163,930 infants that were born before, after 35 weeks of gestation between 2012 and 2017 in California, and of these infants, they were able to identify a cohort of 146,679 infants, so a huge number of babies, all the babies, obviously, in the Kaiser, it's the Kaiser Permanente group collaborative metric, which what term to use there, but the babies get universal serum belly screening. And with at least one pre discharge belly level. And so what they were looking at was the primary predictor, which was the Delta TSB the difference between the total serum bilirubin level at the time of discharge and the 2022, AP phototherapy thresholds. And so they created this five category, Delta TSB variable to match the new guidelines, and also an eight category Delta TSB. So basically, how far off are you from the from the phototherapy thresholds, and they measure these outcomes to where a TSB reached the phototherapy threshold, either within 2448, or within 30 days from discharge. So the paper is really, really short and table one is so good, you can just look at that we'll post that on our Twitter account, you can take a look at it. But the results were that results showed that by either one milligram per deciliter categories of Delta tsp or in the five categories used in the 2022 guidelines. They were consistent with those previously reported showing excellent prediction and discrimination in terms of infants who will need phototherapy in the future. And interesting statistics is that 84% of the infants had Delta tsp so a difference between the serum bilirubin level at discharge and the threshold for phototherapy. That was superior to 5.5 milligrams per deciliter. So like, for example, the threshold is 15.5. And the dischargeability is 10. With a risk of and when that difference is 5.5 or greater, the risk of crossing phototherapy threshold is less than 0.3%. And so I want to walk you through table one, because you have two big categories, you have the eight category difference. So basically, they've looked at or how far off are you from the phototherapy threshold, and it could be either zero to one, one to two to three, and so on. And then they give you what is the percentage predicted probability of the baby crossing the phototherapy threshold within 24 hours within 48 hours or within 30 days. So as you would expect, if the if the difference is zero to one, the risk of crossing phototherapy threshold is 43% Within the first 24 hours, 57% within 48 and 56% within 30 days, if you're between zero and two, so let's say you're using a wider range, then the risk within 24 hours is 29% 46% under 48 hours and 49% under 30. And those numbers obviously go down as the threshold as the difference between these these. This number is pre dischargeability. And the threshold for therapy gets wider and wider and wider. And, and that's due at the root of this very nice algorithm that was published relative to pediatrics in pediatrics in pediatrics in the Journal of Pediatrics with the new guidelines and To give you a little bit of guidance as to how to manage these babies around the time of discharge, if I remember correctly, in the, in the in the guidelines, they were using five, five to six, I think they will had five, five to six, it was either zero to two to the 3.5, and so on, all the way up to greater than seven. So here they give you two different categorization, but they're both they're both, they're both very useful. The conclusion was that a single number, that single number that's available at the time of discharge, the Delta TSP is a strong predictor for the probability of exceeding the phototherapy threshold. And they're saying, interestingly enough, that the excellent discrimination that they're seeing could be largely the result of the fact that 84% of the infant's in their, in their cohort were identified as being low risk if their population had been skewed one way or another. Could that probability be different? They're not sure. But they're there at least being honest and acknowledging that so very interesting paper.

Daphna 11:11

Yeah. Yeah. Well, I think we're gonna get more papers on the new guy, right, with their new thresholds. And hopefully, it will show no, you know, no increase in Billy ribbon, severe events, right. So we'll see. Let's stay on the Billy Rubin theme here. So I have this paper Transcutaneous bilirubin levels in extremely preterm infants less than 30 weeks gestation. And this is from the journal appearing a tautology. And the lead author is Mira sand car, with, uh, with senior author Minaj, Ben and Wally. And this is coming to us from California, as well, some of the Kaiser Permanente hospitals, but it looks like not all and some of this has been presented at PHS. And in the hot topics conference, so their question was do Transcutaneous bilirubin measurements compared to total serum and Billy levels drawn at similar time points? And can these Transcutaneous measurements be followed and in extremely preterm infants less than 30 weeks? And can we follow them under phototherapy? Which we're not really doing even for most of us for term infants, older infants. So I'll tell you how they did that. This was a prospective multicenter observational study at at level three and level four NIC use across California. inclusion criteria all infants less than 30 weeks with serum Billy Rubin's were eligible for the study. And infants were stratified by gestational age and they were stratified by birth weight subgroups, to study the correlation between Transcutaneous Billy and total serum Billy levels. So basically, the intervention was any baby who required a serum bilirubin level had a transcutaneous measurement obtained within 30 minutes to 60 minutes of the serum Billy measurement and the babies could be enrolled in the trial. The only exclusion criteria as they had were congenital malformations, chromosomal abnormalities, or any infant with direct hyperbilirubinemia was excluded. A little bit more about the Transcutaneous bilirubin measurements he took three independent measurements, and the highest of the three values was the recorded Transcutaneous Billy measurement if the baby qualified for phototherapy, again, based on the old guidelines and babies got phototherapy and this is how they monitored sear the Transcutaneous levels on phototherapy. They use this thing called the Billy Eclipse which I had to look up but it's a commercially available photo pig patch which shielded the area of the skin on the sternum or the forehead where they were going to get the Billy Rubin measurements. So it was it's hiding under the phototherapy so keeps a little patch of skin available without exposure to so

Ben 14:32

like like the like the lead. The thing that we use for radiology is like Yeah, exactly interesting,

Daphna 14:39

are very good sensory. So the primary outcome was looking at the correlation between serum and Transcutaneous. Billy measurements, they also again wanted to look at the age stratification and the weight stratification. And then they wanted to follow they wanted to look at this for babies who got phototherapy as a separate group. So, one center they had 24 infants 174 measurements use the Billy check Billy meter. The other seven centers 117 infants 581 measurements use the Drager Billy meter to measure Transcutaneous levels. So they did look at this first by Billy meter. So the Billy check Billy meter did not perform as well as the Drager Billy meter. So the Billy check Billy meter read 2.85 milligrams per deciliter higher than trance than the serum bilirubin with a coefficient call correlation coefficient of point five. So not not not well correlated at all. But for the Drager there was a strong direct linear correlation and the correlation coefficient was point 786 between the total serum and the Transcutaneous Billy Rubin's, so they were able to make a little predictive formula, which is still off by a bit, but a total serum belly equals 2.37 plus, plus point five times the Transcutaneous. Billy levels, so plus, like half of a transcutaneous Billy levels. So that's an interesting formula you can do with that what you'd like, but they wanted to look at the correlation across all three gestational age subgroups. So for the youngest group, which I'll tell you sorry, lesson 225 weeks the correlation was point 757. For the group that was 25 to 27.6 weeks, a correlation was point 795. And for the oldest group 28 to 30 weeks, the correlation was point 773. So all pretty similar. All four birthweight subgroups also showed good correlation between serum Billy and Transcutaneous. Billy levels. So for the smallest wheat group, that's the less than 750 grams, the correlation coefficient was point 726. For the next group, 751 to 1000 grams, it's point 740 for the 1000 to 1250 grams, point 894. And actually, I thought this was surprising, but the biggest baby is greater than 12 150 grams. The correlation coefficient was actually the weakest point six one. They did have a variety of racial and ethnic groups listed. And they in particularly highlighted infants of Asian descent, because of the risk for hyperbilirubinemia. And there was continued strong correlation. Correlation was stronger in infants more than one week of age compared to infants were less than one week of age, which notably is where we get most of our Billy Rubin measurements. So for some of those secondary outcomes, they had a total of 274 Transcutaneous measurements taken while the infants were receiving phototherapy, and the correlation was similar to the groups receiving phototherapy and the babies who had measurements but never received phototherapy. They found disparities and only 2.5% paired measurements, in which the total serum Billy read higher than two milligrams per deciliter from the Transcutaneous ability levels and infants needed physiotherapy based on that level. So like 2.5% of measurements that the baby would have qualified for phototherapy based on the serum, but not the Transcutaneous. What else did I want to tell you? I think I think those were the the biggies.

Ben 18:55

Far we we have looked at these Transcutaneous belly meters right before and full term infants and they correlate pretty well. But the interesting question now is, if we crossed a certain gestational age and age threshold, is one more reliable than another? And should we be careful about which one we use? I think that's that's an interesting one. And that's something that even the manufacturers can can use this data to improve the sensitivity of their of their devices. So I think that's interesting. And yeah, yeah.

Daphna 19:28

Yeah, we'll see. I think something I learned about was this Billy patch. I thought that was a cool way to think about how can we continue to use Transcutaneous measurements in with phototherapy? So, that was

Ben 19:46

okay. I guess I'm next. Which 1am I going to do next? I want to get this out. We're

Daphna 19:53

only two of us. So yeah.

Ben 19:58

It's been a long week. Dufner. Alright, so the next paper I want to talk about is related to extubation. It's published in pediatric research, and it's called Automated prediction of extubation. Success and extremely preterm infant. It's the apex, multicenter study. first author is Laura Kanbar. And its data out of Canada. There's the premise of the paper starts from the fact that we all know that ideally, excavating small infants who are on mechanical ventilation improves outcomes. Now, predicting which baby is going to do well after extubation has always been a source of great frustration, because there's so many variables to take into account. There's hasn't been a great tool to help us make clinical decision. And so the objective of this multi centered study was to basically develop and evaluate a prediction model. I'm going to read you the actual objective, because it's quite tedious, but it's evaluate, develop and evaluate a prediction model with balanced accuracy for extubation success and extremely preterm infant using machine learning algorithms that combined clinical and automated analyses of cardio respiratory signals. And so it's interesting right, we're we've we've talked on the show with with Andrew beam and and Kristen beam on on artificial intelligence. And when is that going to come to the NICU? Well, this is the type of paper that addresses that right? Where can we bring in machine learning algorithm to look at extubation successes and failures? And can it help us pick up on trends that are important in defining what will be a success and what will be a failure. So this was a prospective multicenter study that was done between 2013 and 2018. It was including babies were 12 150 grams or less, who were receiving mechanical ventilation, and undergoing their first extubation, obviously, right, so these are not babies who failed exhibitions multiple times, they excluded babies who had undergone unplanned extubation, before who had congenital anomalies, cardiac defects, cardiac arrhythmia, who were on pressors at the time of extubation, and patients who were excavated directly from high frequency ventilation or directly to Oxy food or low flow nasal cannula. And this had to do with their ability to collect the measurements that they needed. So that was a technical exclusion criteria, I guess. The outcomes were interesting, right? So they were per protocol outcomes. And extubation success was the outcome that they were looking at. And it's interesting, because the way they define extubation success varied during the study. So initially, it was defined by the absence of specific criteria, including oxygen needs, blood gases, and apnea within the first 72 hours post extubation. And then what they realize was that the data was not recorded consistently within and across in centers, and I'm quoting directly, I'm not making this up. Obviously, they're the ones disclosing that information, I wouldn't, I wouldn't have the potential to say they didn't do it correctly. But they said that because they saw this variability, they had to go and redefine it. And they changed it to basically the absence of reintegration within 72 hours. So they removed all these oxygen, but gases and apnea stuff. And then they looked at predictors, right, they looked at, right, so the machine learning algorithm needs all these predictors and all these variables to be entered. And they said that candidate predictors for the development of the classifier included 109 clinical parameters pertaining to patient demographics and pre extubation characteristics. They have cardio respiratory signals, they have all sorts of stuff, EKG, abdominal movements, etc, etc, you can read it, it's a very technical paper, obviously, I'm going to try to make it less technical to give you the gist of it. But they're, they know what they're doing. You know, they're not like a bunch of amateurs dealing with machine learning algorithm. They're doing this very thoroughly. But obviously, there's a lot of technical aspects of the paper. So if you're interested in that, please, you should go and read the paper. So they defined some. So they defined all these parameters, and they and they use that in their, in their algorithm, the machine learning algorithm. They also identified risk groups, because they were saying that considering that this is a pragmatic study, it really is plausible that predictors of extubation success can vary dramatically, depending on the age of the baby. And so they said, let's look at Babies afterwards in terms of their age, because if a baby is less than seven days old, or seven days or more, maybe the predictors should be different. So they actually looked at their population separating them by whether they were in the first week of life or not. So in total, they were able to get a total of 266 infants that were enrolled and 241 that were actually included in the development of this classifier, their estimation success rate was 82%, which is really good. I'm going to keep saying this every time we talk about exhibition success, if you have 100% success rate, you're doing something wrong, because you're not trying enough. 44 infants failed extubation. And so they have two different they have, in the they have two different decision algorithm, we'll post those on the on the on the Twitter page, but in the clinical decision stage, the threshold of gestational age of 28.6 weeks or more, and awaited extubation of 11 160 grams, automatically classified 22% as successful extubation no failure, and the remaining 78% passed through this balanced random force stage. 23% of those failed extubation and I'm one going to what is a bounce Random Forests digits about like how do you handle data that is unbalanced. But that's that's a different story. The model the model performance so how did their their machine learning algorithm do from the diagnostic standpoint 137 out of 197 infants with successful activation and 33 over 44 out of 44 infants with fell extubation were correctly identified by the classifier, which gives it a sensitivity of 70% specificity of 75% with a balanced accuracy of 73%. Clinically, when used as an adjunct tool, the classifier agreed with the decision to extubate in 61% of infants, and of those 137 were classified as extubation success 93% however, the classifier predicted that 39% would fail. And that's about 93 kids, and of those 60 were successfully estimated. Exactly the performance. I know the performance of the apex classifier was computed for the subgroup depending on seven days less more than seven days. As I've mentioned in the group of babies who were less than seven days, the classifier correctly identified 16 out of 18 failures 89% sensitivity specificity and an A confidence interval between 74 and 100% compared to 17 out of 26 in the late extubation group. So the model did very well for the for the younger baby. The performance of the classifier decreased when re intubation less within the within seven days following extubation was used as his definition of failure. So the 73 balanced the accuracy of the model was actually took a significant hit if you said Can they get reactivated within one week of being excavated. Indeed only 11 which is 50% of infants reintegrated between 72 and 168 hours were correctly classified as failures. Finally, some some mortality stuff three infants died within hours of following and electively planned extubation. The cause of death were massive pulmonary hemorrhage minutes after extubation withdrawal of life sustaining therapy. I know withdrawal of life sustaining therapy after a diagnosis of great for hemorrhage made seven hours post extubation and fulminant. Neck diagnose less than eight hours post exhibition in all these patients were correctly identified by the classifier as extubation failures.

Daphna 28:28

That's interesting. I know, that may be the most interesting feature.

Ben 28:33

That's what we're here for we try to present to you guys interesting stuff. So in the discussion, they mentioned that the final classifier that they design, improved identification of extubation failure at the expense of misclassifying, nearly 1/3 of infants who were successfully excavated, and they're saying making it not suitable for clinical decision at this point. So that's, that's very honest. Notably, notably, the classifier performed best among infants who were excavated before seven days of age identifying 70% of success and 90% of failures. 89% of failure I'm sorry, the APEC classifier performed with a balanced accuracy of 73%. We mentioned that and then the apex classifier alone in clinical practice, would correctly identify three fourths of infants who would go on to have successful extubation while misclassifying as failure about two infants that could have been otherwise successfully excavated. The conclusion of the paper is that the combined use of clinical data with automated analysis for cardio respiratory signal by using machine learning algorithms may provide an adjunctive tool to improve prediction of extubation outcomes, but still require further refinement before adoption into clinical practice. As an automated and objective method that requires no human intervention Apex requires further investigation in larger populations from various settings to understand its effect on patient outcomes, safety and generalizability thoughts.

Daphna 30:00

Yeah, I mean, it's not perfect, right. But we learned so much. I mean, data is data out. Right. So maybe we're not giving it the right information to make the right predictions? I don't know. So, and they talked about that, that, you know,

Ben 30:17

yeah, I think they touch the touch on that very cleverly in their discussion where they're saying, as, as a standalone tool without human inputs, it will not succeed. And I have a feeling that nothing related to machine learning algorithm will succeed without human input as well. So that's interesting. I thought the other interesting thing was that the machine algorithm did very well, in the first seven days, which I think probably hints at the fact that when the number of variables is lower, maybe it's maybe it's easier to predict. Yeah, yeah. But it's interesting. And unfortunately, for the people who are I'm sure people are going to ask this question is, there's no such thing as like a web app that you can test the apex classifier, there's not like a mobile app that you can download. It's a it's basically not something that they were intending to let people play with. So no, I tried to see, not yet. But for example, there's other extubation calculators if you want to say that are available out there based on certain research papers, in this case, I can you can save yourself the trouble I looked?

Daphna 31:21

Well, you know, there are a lot of units, who maybe have a ton of variability between providers, and this is potentially the perfect still opportunity for a unit like that, I think to reduce variance.

Ben 31:35

I think what's interesting, though, is that maybe we're not making the most use of machine learning algorithms. And maybe we should pick many, many, many, many more variables, right? I mean, when you're saying that the outcome of interest is just, is it really going to remain activated for 72 hours? Yeah, maybe maybe we can potentially stress these systems a bit more and see what they do with many, many more variables. That'd be interesting. Okay. You're next.

Daphna 32:00

Okay. So yeah, the my next article is daycare attendance is linked to increased risk of respiratory morbidities and preterm children with bronchopulmonary dysplasia, lead author Sharon McGrath, Morrow and senior author, Joseph collabo. This is in the Journal of Pediatrics. It's coming to us from chop with support funding from the NIH, the AAP and the Thomas Wilson Foundation, so a well funded paper. So what's the question? So they wanted to test the hypothesis that daycare attendance among children with known bronchopulmonary dysplasia is associated with increased chronic respiratory symptoms and or greater, and like healthcare related utilization for in particular respiratory illnesses during the first three years of life? And at face value? It seems like, well, obviously, because because all children have increased respiratory infection infections when they go to daycare, but it was it was it you know, parents ask us this question all the time. Like, is my kid safe to go to daycare? So I thought it was a definitely a valid question. study design, it's mostly in kind of an observational cohort study. Participants were drawn from the BPD collaborative outpatient registry. So this includes nine centers across the United States. And they were looking at this cohort between September 2018 and February, February 2021. So the inclusion criteria were a diagnosis of BPD. At least one clinical visit prior to three years of age and documentation of daycare attendance, or non attendance prior to three years of age. So it had to be documented somewhere that the baby that the child definitely did not go to daycare or definitely did go to daycare. So that was all from kind of chart polls. Of note the BPD definition used was the 2001 consensus statement. So the intervention, so again, snappily an intervention, the team was looking at associations between exposure to daycare and chronic respiratory symptoms. In addition, they wanted to do regressions for outcomes, adjusted for certain covariates that may affect the ability to attend daycare, so they wanted to look at age. At the time of the clinic visit age at hospital discharge, presents a pulmonary hypertension, and then any respiratory support in particular tracheostomy and home vent. So baseline characteristics a minority of subjects 18.8% of the group were reported to attend daycare at least on one clinic visit prior to three years of age. Daycare attendance varied across the tertiary centers from three point 3% At one center up to nearly 35% of subjects at a given center. And of the 64 participants who attended daycare 41 attended only in home daycare, which that was 64%. So the majority of the participants who went to daycare we're at an in home daycare 22 patients so 34.4% attended some sort of center daycare only. And then one participant 1.6% attended both locations at different time points. So they went to both home daycare and some sort of center. Daycare attendance at the time of recruitment was higher in 2018 to 2019. Compared to those recruited between 2020 and 2021, which given the COVID pandemic, there's, that's not a surprise. So into the data, there was no significant difference in age of recruitment, gestational age or birth weight between either groups, those who attended daycare, and those who didn't. The mean gestational age of the group is 26.8 plus or plus or minus 2.4 weeks. The mean birth weight was 906 grams plus or minus 356 grams. There were no differences between the two groups in public insurance coverage supplemental oxygen use tracheostomy presents ventilator use feeding to presents human milk intake or number of children living in the home between the two groups. But I will tell you there was actually a trend to more babies with tracheostomy and home ventilator use in the no daycare group, which isn't totally surprising. So I'll tell you those numbers, though.

Ben 36:46

But that's going to matter in terms of the

Daphna 36:48

correct a study. Exactly, exactly. So it wasn't statistically significant. But tracheostomy there was 9.4% to any daycare and 15.9% No daycare, and there was approaching significance point oh six, home invasive ventilator use any daycare 6.3% No daycare 12.3% approaching getting to significance point oh seven. But they were they were not so was the primary outcome. So again, was acute care utilization. It was higher and children who attended daycare, children attending daycare were more likely to have emergency department visits and odds adjusted odds ratio of 2.81. More likely to have systemic steroid use adjusted odds ratio 4.23. Children who attended daycare were more likely to report activity limitation adjusted odds ratio of 4.03 more likely to have trouble breathing, adjusted odds ratio 2.66. And more likely to be using rescue beta agonist, medication and odds and adjusted odds ratio of 7.38. And so again, these babies were really less likely to have trach or home vent. But I told you about the significance. Yeah, and the secondary outcomes. So they looked at chronological age as a risk factor for respiratory morbidities. And so they did this by doing these age stratified groups, they looked at six to 12 months 12 to 24 months and 24 to 36 months to look at these kind of five outcomes. So they found that daycare attendance during infancy so the six to 12 month group was associated with a higher likelihood of hospital admissions, systemic steroid use and activity limitations. They didn't observe any specific associations in the 12 to 24 month age group. But they did observe that daycare attendance during this early childhood period, the 24 to 36 months, was associated with a higher likelihood also of hospital admissions and activity limitations. They also wanted to look at the specific subgroup of babies who had respiratory support. So either supplemental oxygen, ventilation and or tracheostomy at the time of the clinic visit, and did it influence these associations between daycare and respiratory outcomes. So they did find associations between daycare and emergency department visits and daycare and nighttime symptoms, only really in the group on respiratory support. So being in daycare and on respiratory support, obviously, was the highest risk categories. They saw association between daycare and rescue medication, actually only seen in the group off of respiratory support. And then associations were seen in both groups for systemic steroid use and activity limitations. So being on respiratory Support wasn't the major factor there. So I thought this was an interesting study, I think I actually learned got more out of it than I expected. Obviously, the limitations are not insignificant. It's chart review required good documentation of daycare utilization. And over that three year time period, especially during the COVID 19 pandemic. I mean, kids may have been falling in and out of child care situations. But it's, it's interesting nonetheless.

Ben 40:35

Yeah, it's, it's actually fascinating because the, I don't know if we reviewed this paper on the podcast, but I had read a paper, I want to say was in frontiers in pediatrics, I don't have it at the top of my head. But I remember vividly that babies with BPD who attend daycare have better neurodevelopmental outcomes. And so now you have this paper that says, Well, which one? Are you going to prioritize? Because on the one hand, yeah, rest, like respiratory morbidities are very dangerous. God knows, you know, if if one, influenza infection or pneumonia can literally push a kid over the edge, and they have so little reserve and how dangerous can that be for a baby? And like you said, babies were tracheostomy were less likely to be in daycare. So can you even imagine if they're even more fragile, right. And on the other hand, if you decide to protect to quote unquote, protect your baby and say, I'm not going to send them to daycare, because I don't want them to get sick, then you're saying, on the other hand, missing out on the socialization aspect of the baby is going to reduce their northern mental outcomes. Ah, which one do you pick?

Daphna 41:42

Yeah, I think it's just I mean, it's just a reminder of how many stressors we think like, oh, they're they graduated from the NICU. This stress is so much better, but what how much stress that our families go home with and making these hard decisions that they're hard even if you don't have a baby who is in the NICU and they are hard if you have a baby who doesn't have chronic lung disease? So yeah, it's just a stark reminder the realities, ongoing realities of our, of our families.

Ben 42:19

Yeah. And it's and it's also trading off normalcy. For for this, this, this getting more and more stuck in this in this rut of of medicalization of the child, that that's not pleasant. If you can normalize your baby. By letting them do things that are normal, they go into daycare, that that's kind of that's kind of good. So anyway, all right. We cannot we can talk about this all day. I have. Okay, I'm gonna we're running short on time. I have maybe two articles I want to go over. The first one I wanted to go over is a very interesting one. It's called Supraglottic Supraglottic airways compared with facemask for neonatal resuscitation a systematic review. First author is Nicole Yamada. And it's basically from the International Liaison Committee on resuscitation, neonatal life support Task Force, otherwise known as Al Khor. Right. I don't know if people call them alcohol, alcohol. I call it IO core sounds. Yeah, it sounds very cool. So and they and they're, and they're an international entity that publishes a lot of recommendations. They have their own website. So yeah, and the paper is published in pediatrics. Okay, so the background is very interesting. They're mentioning a lot of stuff that we know from NRP that 85% of term infants achieve the transition after birth without assistance, but that 10% do need respiratory support in response to two symptoms, and 5% receive positive pressure ventilation. ventilation of the newborns, infant lung is the single single most important component of neonatal resuscitation, something that's often also tested if you're studying for the boards, and determining the most effective interface for administering PPV as a research priority. During neonatal resuscitation, face masks and the tracheal tube are the most frequently used interfaces, but both have limitation. And they're dark. They're saying that although most clinicians can achieve achieve proficiency with training, face mask ventilation, the skills required to deliver ventilation through the face mask declined rapidly. And the efficacy of the face mask ventilation can be compromised by leaks in and around the mask or upper airway obstruction option and resulting in adequate tidal volume. And God knows that we've all seen when you're handed, just let's let's just not even talk about technique. You're handed the inappropriately sized map slightly too big so slightly too small, terrible for effective ventilation. Yeah,

Daphna 45:03

I mean, it's one of the major skills, right that learners have to learn, you know, to be proficient that, you know, it changes your resuscitation, right, you either go, maybe success or maybe kind of this you know, so false. Right,

Ben 45:24

right. Right. And so they're mentioning that Supraglottic airways, which you can also know as, as LM A's, right? I mean, they're, they're the same thing, right? They're these tubes that you can just shoved down into baby's throat, that eventually

Daphna 45:38

occluded check for him in gently please.

Ben 45:42

Yeah, but without any technique, basically, you don't need to, you don't need to visualize anything. You just push it down. And it occludes the esophagus and then ventilation is being delivered to the other outlet that's there, which is the trachea. Yeah, yeah, of course Dental. Yes. And so the goal of the of the systematic review and meta analysis is aim to compare the use of the LMA or the supraglottic airway, with facemask as the initial device for administering PPV during resuscitation immediately after birth. And to determine if the use of an LMA would decrease the probability of failing to improve during the initial PPD. You may ask, isn't that a bit of an overkill? Should we compare LMA to et tubes that has been done already by the Alcor NLS Task Force, and that's been published before. And they've shown that they've shown that the LMS do just as well. Now what's interesting, right, that's which is huge. But now, this is actually very interesting, because you can say, Oh, isn't anatomy kind of a bit aggressive compared to just using a face mask. But it's interesting because, and we can give people a bit of a sneak peek as to what we're working on these days. But we've been in touch with a lot of groups in Africa, we're going to try to do some work with and collaboration through the neonatal network with people in Africa. And the skills to train people to bag mask baby is difficult. It's not simple. And remember that we are thinking sometimes like neonatologists, or pediatricians, and we say, Well, isn't that part of our job, but in many instances in the world, it's a midwife who has to resuscitate the baby, or it is, it's people who technique technically are not pediatricians or trained in pediatrics, who are ancillary staff in and around the birth of the baby who have to step up and help these babies through the first few steps of transition. And so that's where

Daphna 47:37

I don't know about the cost. I don't know if they, we can

Ben 47:41

talk about that afterwards. You're absolutely right. We absolutely right. And that could be a component. But it is true that an LMA erases a lot of the technique, difficulty that could be seen when you have to put a mask and appropriately on the face and deliver consistently good pressure. So this was a this this. This review was done where they basically were looking at randomized controlled trials, quasi randomized controlled trials and non randomized studies. All these were included in the included in the in the potential search. They were looking at newborn infants that were born before 34 weeks of gestation, receiving intermittent positive pressure ventilation during resuscitation immediately after birth. The intervention was the use of a supraglottic airway. And the comparator was the face mask. So what were some of the outcomes that they were looking at the primary outcome was failure to improve with the assigned device as defined by the study authors. And we'll get into that in a second. The because that that obviously, right, that obviously can create some some variability. But the secondary outcomes really took care of that in terms of they looked at Babies requiring intubation during the initial resuscitation, they looked at the time to heart rate above 100. From the start of PPV, during the initial resuscitation, they looked at the duration of PPV for the duration of the resuscitation or time to cessation of PPV. They looked at the need for chest compression, the need of epinephrine. They looked at soft tissue injury, as defined by the authors in the various studies, obviously, that they will include admission to the NICU pneumothoraces survival to hospital discharge and neurodevelopmental impairment at 18 months or

Daphna 49:33

very thorough. Yeah.

Ben 49:37

But it's always the same, right? I mean, that's, that's what they want to include. And then you'll see which studies include what and sometimes the outcomes cannot be determined because there was not well assessed, so you can I mean, it's a very, it's the Alcor Task Force. The methodology is very sound, the editing they were able to find 21 for text art. called they were assessed for legibility, and nine were included in the final review. The systematic review included five randomized control trial, one quasi randomized control trial and two retrospective cohort studies. The total number of babies that ended up being included in this review was 2075 newborns. All studies used the size one LMA, so I think that's important to know. And to RCTs use the LMS with without an inflated inflatable cuff because obviously, there's some that don't have a cuff some of them have a cuff. So in terms of the primary outcome of which was failure to improve with the device, it was reported in all six randomized in all six trials in all six randomized trial and quasi randomized control trial, and the outcome was available in 18 123 newborn infants. The meta, the meta analysis showed that using an LMA, compared with a face mask for PPV, immediately after birth, decreased the probability of failure to improve with the assigned device with a relative risk of 0.24. In terms of secondary outcomes, and to tracheal intubation during the initial resuscitation was reported in four RCTs and quasi randomized control trial. The meta analysis revealed that PPV delivered through an LMA compared with face masks decreased the probability of intubation. And that, to me is probably the only one outcome where it's kind of unfair, because you are much closer to being intubated if you have an LMA in than if you're just bagging considering that the esophagus technically is occluded when you're using anatomy. So

Daphna 51:40

yeah, I wouldn't it's not fair. That's the point. I guess it's the point

Ben 51:45

but I'm not surprised. I'm not like, oh my god, this is amazing. It's like Right. However, the other ones are interesting. The duration of PPV, during the initial resuscitation was reported in for RCT and quasi RCT. And they reported a shorter duration of PPD using an SMA. So that's that, to me is very interesting. The main analysis also showed no difference between the groups for the probability of receiving chest compressions or epinephrine during resuscitation, the relative risk of air leaks, which is the one I really wanted to find out could not be estimated from the RCT because no event occurred in either group. In the two studies that reported this outcome. That's great. Yeah, yeah. And no difference in the incidence of soft tissue injury. That's another one. Technically, we were just joking about that. Right. That's like, if you shove it in, like if you're not.

Daphna 52:38

Yeah, I think I think when you say what, what's the major risk? Right? That's it.

Ben 52:43

So yeah. Yeah, so a no difference in the incidence was found in a meta analysis, and no difference was found in the probability of admission to the NICU. So the other outcomes obviously could not be determined based on the studies that were selected and the outcomes that were reported. So the discussion is very interesting. Let me see how much time do I have left? I went over already great. But they looked at at a lot of stuff that they're quoting in the discussion. So it's a very interesting read. And it's this, they were saying, so I'm going to quote you a few things. So it's interesting. They said in a simulation study involving experienced clinician providing face mask PPV. With the term mannequin, the median leak was 71%. And obstruction was observed in 46% of inflation's, among birth attendants, in a resource limited setting mask, least mask leak was nearly 90%, something that we were mentioning a bit earlier. And and it's it's really the risk of, of the mask wear. And it's interesting, because we were friends with Alex Stevenson, who, who if you're not following on Twitter, you should follow who works in Zimbabwe. And I was asking him about that. And he says, it's, it's not so straightforward to get all the stuff that needs to be trained to do proper facemask ventilation. And he was expressing the need for alternative ways to deliver positive pressure ventilation without requiring too much techniques so that it could be delivered effectively and consistently, to help reduce mortality, which is obviously something that they deal with much more than we do in higher resources settings. So the results of the review and meta analysis suggests that in late preterm infants who require resuscitation after birth, ventilation may be more effective if delivered by an supraglottic airway rather than face mask and may reduce the need for endotracheal intubation. Moreover, the results suggest that the supraglottic airway can be successfully inserted by a wide range of clinician with brief training using mannequins. And they talk about that in terms of the number of minutes and time that needed to actually train somebody. And the a lot of these studies were like one session like they were able to train providers to introduce the element. So interesting. You're very interesting.

Daphna 55:00

Yeah. And it's got a lot of attention on Twitter and I think one of the major things is like, it's not just for resource limited settings, right? Like, you know, say say you've got a difficult intubation. You know, that's something we have to think about, you know, it's in our hectic to keep in our toolkit.

Ben 55:19

So, Agreed. Agreed.

Daphna 55:22

All right, my turn. I'm going to do maternal acetaminophen use and cognitive development of four years the Ontario birth study, lead author Jennifer Lai, and senior author, Ray rejean. This is a pediatric research is coming to us from Toronto. So the question is there an association with maternal acetaminophen use and neurocognitive disorders. So there have been some studies that showed decreased cognitive scores in older children than in this cohort and other studies that showed an association with decreased behavioral outcomes. So, if you're not familiar with the anterior birth study, it was initiated in 2013, as really this giant prospective pregnancy and birth cohort. So women who seek prenatal care at the Mount Sinai Hospital in Toronto, are recruited between 11 and 14 weeks gestation. And then participants are basically asked to complete this series of questionnaires at 12 to 16 weeks and 28 to 32 weeks gestational age, and at six to 10 weeks postpartum. So, I mean, they're really trying to find all these associations based on survey data. They still have ongoing recruitment. And so this paper reports on clinical and lifestyle data that were collected. It's not this many participants in this paper, but from 1900 55 pregnancies from 2013 to 2019. So they already had this cohort of, of pregnant people who enrolled. And then basically in a few years ago, they started enrolling this orient or Ontario birth study, child group. So anybody who had previously enrolled, were asked if they wanted to be a part of the child study. So participants are asked to complete questionnaires when the child is age 24 and 36 months old, as well as at four years of age when children are then asked to complete the NIH toolbox for assessment of neurologic and behavioral function, early childhood cognition battery, so that's the kind of outcome measure at four years old for this current study. So they looked back at information on prenatal acetaminophen exposure, which was collected from these participants using the prenatal questionnaires. Participants were asked about the frequency acetaminophen use within the three months prior to pregnancy, quote, unquote, early pregnancy, which was the first 12 to 16 weeks and later pregnancy, which was three months prior to the Second questionnaire. So this was administered at 28 to 32 weeks, so they basically asked for the second trimester, so quote, unquote, use was considered if there was at least one day per month during that period. So they, the they're basically they had sent invitations to a four year follow up to just over 1000 participants. The number of children who completed the four year follow up was about 616. They had some missing data, and so they finally analyzed 436 children. I told you the primary outcome was NIH toolbox early childhood cognition battery, which was administered via tablet at that kind of four year mark. They also wanted to look at a number of potential covariates and a secondary analysis. And in addition, they wanted to look at the differences. For those people who reported higher quote unquote acetaminophen use, so at least one day per week, as opposed to one day per month, baseline characteristics the overall acetaminophen use was very common 69% reported use which is not so surprising because it's really like the only medication that you know your left you that you can use. So that's why this study is such a big deal. And studies like it are such a big deal because if you take away it's what's left 38% reported use before pregnancy 36% in early pregnancy, and 43% in this late pregnancy respectively. High Frequency and may the same acetaminophen use was less common, but 36%. So over a third reported high frequency acetaminophen use fewer mothers reported use before pregnancy 8% of this high use 16% in early pregnancy, and 18% in late pregnancy. So in this cohort, though, for the primary outcome children born to mothers who reported acetaminophen use did not perform significantly differently on any cognitive test, except for the Picture Vocabulary Test where they actually performed slightly better than those who are not exposed at the late pregnancy time point. So that was the three months prior to 28 to 32.

Ben 1:00:44

That's my smiling when she says that, by the way, because for the people listening on the

Daphna 1:00:49

the secondary outcomes I told you, they looked at all of these potential covariates, Elektra, maternal BMI, maternal fever during pregnancy, maternal smoking during pregnancy, antidepressant use in mid pregnancy, depression and anxiety symptoms in mid pregnancy, antibiotic use among pregnancy, child gestational age of birth, ethnicity and household income. And there was no significant differences in the secondary analyses of these covariates. And I told you that we're going to look at the higher acetaminophen use as a separate analysis. And there is no significant difference in those Infants who are born to parents classified as higher acetaminophen use, either. So I suppose that's good news. But it does contradict previous studies. So question goes unanswered. Obviously, this is a small sample size, they're young children, right? So we're only looking at four years. There didn't really look at exposure past 32 weeks, and especially when we're talking about this higher use group, right, because the the regular use group was only once a month to trigger kind of that group. But even the higher use group once a week, they were just not as many participants in that group. So raining on the party. I know. I'm just just saying with that information, what you'd like.

Ben 1:02:19

Yeah, no. All right. I think you've said everything, your turn. Okay. My last paper for today is something that caught my eye, the title was like something. The title of the paper is effects of semi upright swings. And NICU infants. first author Sue Haji Kadakia, University of Maryland, in the United States of America, this is published in paediatric research. So they're talking about a lot of stuff they're talking about in the background, the fact that these actives, the I like how we all call them differently, and then the people who have to write the paper have to actually find the find the proper term. So active setting devices, such as semi upright swings, bouncers, are increasingly used in the hospital to suit babies and at home as well. They're citing something important that the American Academy of Pediatrics does caution against sitting device in general as sleeping environments and warns against its use in infants under the age of four months, and those who are at risk of falling over suffocation and or airway obstruction.

Daphna 1:03:29

So, so all the babies in the NICU?

Ben 1:03:32

Right, I mean, technically, I think we The key here is that we don't we rarely let them sleep. Maybe they fall asleep and then they get moved to the bed but it's strongly

Daphna 1:03:44

disagree. That is that is not a finding. i i implore all of you even with policies about not sleeping in the image chairs to go and look at the babies in your unit or not. The people are not taking those beat those sleeping babies.

Ben 1:04:05

But I mean, they get in the in the swing, awake, usually. And then they fall asleep snappy intention, just it's not the intention and end to the credits of our NICU there on the continuous monitoring monitor. Yeah,

Daphna 1:04:16

of course. Of course. I'm just I'm just of note, I'm just saying.

Ben 1:04:21

So the question of the paper is that they sought to determine whether the placement of an infant in a swing results in discernible changes in vital signs. And they explored a bunch of stuff including heart rate, respiratory rate, apnea, Brady, and the saturation. So this was a within subject prospective observational study of infants from October 2018 to October 2019. What they mean by within subjects is that basically each infant served as its own control. Before and before and after moving out of the bed into the swing and vice versa. They included any inborn or app born infants corrected to at least 34 weeks of gestation, they excluded babies who were on In invasive respiratory support, who had heart condition, genetic condition, HIV, and in general who did not meet local guidelines to put the baby in a swing. So they were using the mammal rule, right, which is a commercial commercial product that can be purchased. But I thought it was interesting to mention which swing the babies were tested in. And if you don't know what the mamaroo is, it's basically a swing that can move either up and down or side to side. While the baby remains relatively constant at a at an angle of about 30 or 45 degrees. From each infant enrolled in the study, data was data were collected 24 hours apart from to position, a semi upright position in the swing and the supine position in the conventional crib serving as his or her control. None of the infants were placed in the swings during feeds, that's important and multiple clinical and demographic variables were collected, I don't want to really go into all the things they collected, because you can just see it in the paper, they did do a power calculation, calculating that a sample size of 65 was calculated for the detection of a case of small to medium effect size for the difference in average oxygen saturation between the two positions with the power of point eight and a type one error of point oh five. The results of this study are as follows 65 infants were then included. And their baseline characteristics are presented in the paper 45, which is 70% met the criteria for low birth weight. The average birth weight was the birth weight was 1900 grams, so yep. And what else did I want to mention there, Apgar scores were on average six and eight at one and five minutes. The gestational age at birth was about 32 weeks. So they were not particularly like micro X micro preemies or so. And the gestational age at the time of this study was about 39.8 weeks. In terms of the respiratory support, these babies were on 60% Were on straight room air 20% on low flow 9% on high flow 9% on CPAP and 2%, on Nia PPV. So the amount of data collected averaged was an average of 160 minutes of recording and each position, the mean, auto saturation was 95.7% in the supine position compared to 95.55 in the swing, so no real difference. The mean heart rate was 151 beats per minute, versus 150.9 beats per minute in the supine and swing respectively. The respiratory rate 54 breaths per minute in the supine versus 54.5 breaths per minute in the swing, again, pretty much the same. There was no significant differences between the two position for the proportion of time spent with pulse oximetry recording below 95%, whether it was between 90 and 9485, to 85 to 89%. And below 85%. Infant placed in the swings we're more likely to have slightly greater frequency of the saturation events, which was 3.6% of the total recording versus 3.3% of the total recording in supply in. In the swing versus supine. The exploratory analysis of temporal trend in oxygen saturation and heart rate showed that infants placed in the swing experienced reduction in heart rate over time, as shown in some of the figures. So you can see it's very slight, but it is it you can you can definitely see it. There were no other significant overall changes in the in the groups, there were no apneic events in infants in the swing or the crib, five bradycardic event were documented. And in the swing that required stimulation, while none of the infants experienced any apnea, three of these infants experienced bradycardia and and all five of them had actually the saturation as well. And out of these three had spontaneous resolution, one required stimulation and another one required repositioning, no oxygen supplementation was ever required for any of these infants. And there was no consistent predictors of these events that were identified. And so to conclude, I mean, you get the gist of this paper, semi or upright swings are increasingly being used in the NICU. And according to their to their data. It's not associated with any discernible changes in vital signs supporting the relative safety of the use of these swings in the NICU. While it was not really a primary outcome of the study, a slightly higher rate of the saturation events and sporadic bradycardia in the swing, especially amongst what were low birth weight infants, warrants further Institute investigation and then They really make a point that we've discussed in the background that these babies are babies in the NICU, that these babies are being monitored continuously. And so none of these results apply to the home environment.

Daphna 1:10:12

Well, you know, I love I love swings positioners you know that. So I think I'm glad to see the results. And that obviously, it depends on the baby. And we have to individualize care and make sure baby's ready. Ready to do those skills to sit up? A little bit, but I'm hopeful it will give people some competence. It there are some units that don't use any swings. So

Ben 1:10:45

I mean, there's a cost. Oh, yes.

Daphna 1:10:47

Especially the mama Roo. And that's one thing I wanted to mention. The Mama is probably the most horizontal of all the swings the least angled. So this is a different than putting babies and putting a baby in, you know, bouncer for typically developing near right, you know. So. Okay, do we have time for one more? Are you sure it's through? Okay. Yeah. Okay. All right. My last paper is an influence of maternal and Perinatal factors on macronutrient content, a very preterm human milk during the first weeks after birth, lead author Christina badass Novell. Senior author, Isabel Yglesias Flatus. This is a journal Perinatology. And the authors are from Spain and the UK. So the question, Does breast milk composition change in relation to certain neonatal and maternal factors? I thought this was fascinating. So, is it a valid question? And absolutely, I mean, we're always looking for ways to modify and optimize nutrition. And if we don't, so many times, we don't know what we're starting with. So I thought this was valuable. So it's an observational prospective, by centric cohort study. The inclusion criteria was that the team was enrolling lactating mothers with infants at 32.0 weeks or less gestation between January 2018 and January 2020. exclusion criteria were mothers of newborns with congenital malformations known chromosomal genetic or metabolic anomalies are low chances of, quote unquote, short term survival as per judgment of the attending clinician. So these lactating people provided one to two MLC times eight pumps for 24 hour period. So basically, what that means is they pumped, they were asked to pump eight times in 24 hours, and collect one to two MLS at each pump. It was like a 24 hour breast milk collection, basically, in weeks 124, and eight after delivery, or until discharge, whichever came first. In addition, on weeks, 356, and seven, and they were asked to deliver a single morning sample. So they took these poll, these pooled, not collectively pooled but pooled per participant samples of milk. And they took two males to do this milk macronutrient analysis. And they mentioned that the first study sample was collected between days seven and 10 of lactation. So then they wanted to look at the overall composition over the force first four weeks of life. Using these daily pooled samples. They did a lot of data pulls from the maternal obstetric charts and the neonatal clinical data. And some of the things that they looked for was IUGR, which they defined as weight under a percentile, a third percentile, or under the 10th percentile with placental dysfunction. They were also very interested in the hypertensive disorders of pregnancy. So maternal blood pressure higher than 140 over 90, and or evidence of damage to a target organ. They looked at delivery modes, and those were the major things hypertensive disorders, delivery moods, lactation history, sorry, was the other one. And then they wanted to look at a variety of neonatal characteristics. So let's just get down to business so they recruited 129 lactating people 117, provided quote unquote, valid sample, so overall, they had 625 valid samples. 38.8% of participants were over 35 years old. That was interesting, and more than half 56.4% were On prime MIPS, and in relation to maternal body mass index, they had 9.4% of mothers were underweight. 21 17.9% were overweight and 14.5 obese. Obviously, when we talk about nutritional content, that's why they stratified them by weight. 9.4% had gestational diabetes. There were 17% were multiple gestations. 17% suffered from hypertensive disorders or pregnancy 19% were diagnosed with intrauterine growth restriction. The mean gestational age for the group at delivery was 28.7 plus or minus 2.3 weeks and the mean birth weight was 1100 67 grams plus or minus 380 grams. 53% of the neonates were male, to the kind of primary outcomes. And I think none of this will be surprising to people who have recently studied for the boards or who are studying for the boards. Across the group protein and lipid decreased over the first four weeks, carbohydrate increased over the first four weeks and calories decreased over the first four weeks maternal conditions. So then again, they looked at macronutrient by the maternal conditions. So advanced maternal age was related to higher milk protein concentration, and without differences in calories. There was a weak positive correlation between maternal age and the week one and week two milk protein concentrations. I thought this was interesting this next part because this I think there's mixed this is mixed in in previous studies, but overweight and obese mothers had higher protein, fat and energy content in the mature week for milk, but no differences in overall composition over the first four weeks. So looks at pregnancy characteristics nutritional content was lower in the milk of mothers delivering multiples, both in early lactation, mature milk, and they had decreased average protein and energy content over the first four weeks. Those with hypertensive disorders of pregnancy produced early milk with lower fat and energy content. But the contrary was true regarding weak for protein which was higher in those with preeclampsia and eclampsia than those without in terms of those parents with IUGR babies, the protein concentration was higher in in milk, both at week four. And over the first four weeks of lactation, there was actually no difference between those that had and had not experienced gestational diabetes. I told you they looked at delivery, there were no differences in milk composition between those who underwent C section and those who did not regards to lactation history, average protein content over the first four weeks of lactation was actually lower in those that had previously breastfed. And then they wanted to look at the neonatal characteristics. So gestational age was negatively weakly correlated with protein content on week one, and week four, an average protein content during the first four weeks.

Ben 1:18:24

What does that continue? So through that,

Daphna 1:18:28

so the the older the baby, the less protein content? Does that make sense? They were negatively correlated,

Ben 1:18:38

negatively correlated, right? Because that's something that always trips me up. So that means that as the baby as the weeks of gestation progressed,

Daphna 1:18:47

the protein content decreases, decreases, okay? It was also negatively weakly correlated with fat, and energy. So same findings on

Ben 1:19:00

nature nature corrects for prematurity, right,

Daphna 1:19:02

it's trying, it's beautiful. It's awesome. And and they did look at gender and there were no differences according to gender. They did perform this multivariate analysis and the only independent predictors of early milk protein and energy. So this week one samples were gestational age and having a hypertensive disorder of pregnancy, Protein Concentration at four weeks was independently influenced by multiple gestation, maternal pre pregnancy, BMI and the presence of labor before birth. And then when they looked in terms of energy content on Week Four was related to both maternal overweight and obesity and hypertensive disorders of pregnancy. So, you may not have caught all that you may have to go back and look at it. But I mean, this just begs the question of, you know, individualizing our nutritional components based on put potentially some some phenotypes

Ben 1:20:02

100%. And we have the technology to test the breast milk now and it's still not readily available at the bedside. But sometimes, you know, I like I like this paper because it has good graphs, it has great tables, and sometimes, FEM families have a hard time understanding what we're trying. We're doing exactly with the complex nutritional management of babies born preterm, late preterm. And it's kind of nice. Many families are very well educated and they can interpret data. Well, you know, and so, it's nice to have these tables knowing that they're in a paper where you can actually go back and say, This is what it looks like, in terms of, especially that that graph about the average protein associated with the gestational age, I think, I think that's interesting. So that's kind of cool. I really liked that paper.

Daphna 1:20:53

Yeah. All right. We did it.

Ben 1:20:56

That's it for Journal Club. Very, very cool. This week, we will have an episode of Tech Tuesday, where we talk to Russ Summers, who is the founder of first day healthcare, he talks to us about his bilirubin app. He talks to us to us about his system for wireless monitoring of babies after discharge home from the NICU, very cool stuff. And yeah, you have CME credits available on the website, we are working very hard on getting the incubator translated in more languages. So it looks like French and Portuguese, we have Spanish that is being released slowly, but surely we are in our first few episodes, but that's going to become more consistent. French and Spanish are coming as well. French and Portuguese are coming as well. So this is a lot of fun. And we have two projects that we need to talk to the audience about, which will do at some point. One of them is the NICU or life in between, which is a photography project, which we'll talk to, we'll have a guest specifically on to talk about that. And our very own conference, so stay tuned.

Daphna 1:22:01

Stay tuned. All right, buddy.

Ben 1:22:05

I'll see you later. Definitely take care. Bye. Bye. Thank you for listening to the incubator podcast. If you like this episode, please leave us a review on Apple podcast or the Apple podcast website. You can find other episodes of the show on Apple podcasts, Spotify, Google podcasts, or the podcast app of your choice. We would love to hear from you. So feel free to send us questions, comments or suggestions to our email address NICU You can also message the show on Instagram or Twitter at NICU podcast or through our website at WWW dot v dash incubator that org This podcast is intended to be purely for entertainment and informational purposes and should not be construed as medical advice. If you have any medical concerns. Please see your primary care professional. Thank you

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