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#019 - 📑 Journal Club 10


NICU journal club the incubator podcast

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


Characteristics and Outcomes of Women With COVID-19 Giving Birth at US Academic Centers During the COVID-19 Pandemic. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2782978


Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection. https://jamanetwork.com/journals/jamapediatrics/fullarticle/2779182


Timing of neonatal stoma closure: a survey of health professional perspectives and current practice. https://fn.bmj.com/content/early/2021/08/18/archdischild-2021-322040


Newborn Incubators Do Not Protect from High Noise Levels in the Neonatal Intensive Care Unit and Are Relevant Noise Sources by Themselves. https://www.mdpi.com/2227-9067/8/8/704


Cardiac Performance in the First Year of Age Among Preterm Infants Fed Maternal Breast Milk. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2783546


Race, language, and neighborhood predict high-risk preterm Infant Follow Up Program participation. https://www.nature.com/articles/s41372-021-01188-2


Is late treatment with acetaminophen safe and effective in avoiding surgical ligation among extremely preterm neonates with persistent patent ductus arteriosus? https://www.nature.com/articles/s41372-021-01194-4


Is it time to study routine car seat tolerance screening in a randomized controlled trial? An international survey of current practice and clinician equipoise. https://www.nature.com/articles/s41372-021-01167-7



 

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


SUMMARY KEYWORDS

babies, study, stoma, incubator, interesting, looked, acetaminophen, preterm, preterm infants, ligation, closure, cohort, unit, data, outcomes, women, thought, test, decibels, higher risk

SPEAKERS

Ben, Daphna


Ben 00:04

Hello, everybody. Welcome back to the podcast. I hope everybody is doing well today. Daphna. How are you feeling?


Daphna 00:47

I'm doing great. But I never get to ask you how you're feeling.


Ben 00:51

I am doing good. You know, I'm like a car with on fuel reserve. I don't know if you know, if you've had that experience. I'm seeing the miles trickling down and I'm like, I need to get to a gas station soon. So


Daphna 01:05

I'm sure you can. You can guess that I'm, I'm the type that drives pretty close to empty.


Ben 01:14

Yeah, like my


Daphna 01:15

cell phone battery. But it's,


Ben 01:17

it's a bit like me as well, right? It's always trying to find out how low can I go before I really, really need to stop.


Daphna 01:24

That's probably that probably resonates with a lot of people. Uh


Ben 01:29

huh. Well, you know, before we begin this episode of journal club, I mean, I wanted to give a shout out to Diana Montoya Williams, who was Dr. Diana Montoya Williams, who was with us last week. I think it was a great episode. And there's a lot of things that we're going to talk about today that are probably going to resonate a little bit between these two episodes. So thanks to her again, for being on and thank you to everybody who is helping growing the podcast community. We're getting more and more demands. And we're hoping to grow the podcast in different ways we can talk about in the future, but for now, should we choose who our next guest will be? Because I think it was a pretty big deal for us to have that person on. So next week, September 12, we will release an episode, which is an interview that we that we recorded actually yesterday with Eric Jensen, Dr. Eric Jensen from chop, we talk about a lot of stuff, ranging from BPD to research methodology and all that stuff. So it was a lot of fun. And we think you guys are going to enjoy that episode. Yeah,


Daphna 02:35

I think people learn a lot. I learned a lot. Yeah, no,


Ben 02:38

I mean, I'm, like really listening to the episode and taking notes.


Daphna 02:42

Yeah, we might have to have him back on to talk about some specifics, you know?


Ben 02:48

Yeah. Okay, so there's a bunch of articles that we could discuss this week. And I guess, I don't know, where do you want to start? Definitely.


Daphna 02:59

Yeah, no, I think it's reasonable, given all of the excitement about COVID. These last few weeks to start there.


Ben 03:09

Okay, so we have two articles that were published. One of them in JAMA, it's in the JAMA Network open and, and then the other one is published in Oh, I just lost it in JAMA peds so we'll talk to them in combination, because one of them is mostly an OB one. The other one is more for neonatology. But so the first one is called JAMA Network is in JAMA Network open it's called characteristics and outcomes of women with COVID-19, giving birth at US academic centers during the COVID 19 pandemic. first author is Justin chin. And I forgot this group is from Missy from the University of California, UC Irvine. So this was an interesting article, their objective was to examine the characteristics and outcomes of women who underwent childbirth with versus without COVID-19. And so they looked at women aged 18 years or more, who underwent childbirth from March 1 2020 And February 28 2021. And this, this cohort spent 499 us academic medical centers or community affiliates, and that was that was pretty amazing.


Daphna 04:29

I know.


Ben 04:32

Their follow up was limited to an in hospital course and discharge destination childbirth obviously was defined based on various codes and the diagnosis of COVID-19 was identified using the ICD 10 codes as well. So the main outcomes and measures that they were looking at the primary outcome was in hospital mortality. secondary outcomes included length of stay in admission to the ICU, requirement for mechanical ventilation and disk charge status. So briefly, obviously, since since this spanned almost 500 centers, the number of women included in the study was large, so 869,079 Women 18,008 18 to 19,000, of which were diagnosed with COVID 19. So that's represented about 2.2% of the over row population 850,000 and change did not have COVID-19. The women were aged 18 to 30 years, which makes sense considering childbearing age in the United States. And, and the proportion of of white women was 58.7% in the non COVID, cohort, versus 43% in the COVID-19 cohort. So interestingly enough, they didn't find any changes when it came to needing cesarean sections among women with COVID-19. However, women with diagnosis of COVID were more likely to have preterm birth, and that was 16.4% versus 11.5%. women giving birth with COVID-19 compared to women without it had significantly higher rates of ICU admissions 5.2% versus 0.9%. That was quite impressive. Requiring respiratory intubation mechanical ventilation that was 1.5% versus 0.1%. And in hospital mortality, were 24 women, which was point 1% versus 71. In the in the control, which was less than point oh, 1%. So that was that was very dramatic. This this data obviously was done retrospectively. But it highlights a little bit some of the of the issues that have been discussed in the public space about what should pregnant women do. There's a lot of anxiety, there was a lot of anxiety about potentially vaccinating women who were pregnant. I think there was a recent article in the New England that that reassured, I think everybody's saying that it was safe. And then you see that not only is it safe to get vaccinated, but I mean, there's significant risks when it comes to the patient herself. So that was very interesting. And then before we discuss this, I want to go into the second article, which was a bit more relevant to our practice. Sorry, one second. And so this was another article this time in JAMA peds called maternal and neonatal morbidity and mortality among pregnant women with and without COVID-19 infection. And that was the inter COVID multinational cohort study. Obviously, the list of authors is quite long. But that was sort of based mostly the corresponding author is from, from John Radcliffe hospital in the UK. So this, this paper not to and similarly from the other one was to evaluate the risks associated with COVID-19. And pregnancy. On this time, both maternal and neonatal outcomes, compared with non infected concomitant pregnant individuals, their cohort spanned 43 institution in 18 countries. So this time, we're talking about an international as we said in the title study, that's 42 institution 18 countries, and that ran from March to October 2020. And they continue to consecutive non consecutive non infected women were concomitantly enrolled immediately after each infected woman was identified. So basically, they identified each women with COVID-19. And then and then enrolled control at the same time. The primary outcome were indices of morbidity and mortality, maternal and neonatal perinatal, and then there's like a lot of individual components that that they've defined that we'll go we'll go into. So interestingly, I think if you look at the various outcome measures that they've looked at, everything seems pretty straightforward. We have preeclampsia, hypertension, health syndrome, and so on and so forth. You can look and they're fairly standard. The one I want to spend some time on because it's a bit less straightforward is something that they've defined as the severe neonatal morbidity index, and that will become important in terms of the results. This index included at least three of the following severe complications and they were not minor. It included BPD hypoxic ischemic encephalopathy, sepsis, anemia requiring transfusion Payton ductus arteriosus, requiring treatment or surgery intraventricular hemorrhage and necrotizing enterocolitis or retinopathy of prematurity diagnosed before hospital discharge. So remember that this morbidity index, including at least three of the following, so if you had for this index to be positive, you had to have pretty significant complications. So if we're looking at the results, there was a total of 706 pregnant women with COVID-19 that were diagnosed Post and they were able to sort of do a one to two ratio for controls. So they had 1400, about pregnant women without COVID-19 that were enrolled. And so women with COVID-19 diagnosis, they were at a higher risk of preeclampsia or eclampsia with a relative risk of 1.76. They were at a higher risk of severe infection, they were at a higher risk of Intensive Care Unit admission, they were higher risk of maternal mortality. And, and then talking about more now the perinatal stuff, they were a higher risk of preterm birth, the relative risk was 1.59. And they were at high risk of medically indicated preterm birth, meaning that their status was probably compromised to the extent that the medical team decided to deliver the patients prematurely. They were at a higher risk of severe neonatal morbidity index. This is sort of where we're going back to that index with a relative risk of 2.66 and severe perinatal morbidity and mortality index relative risk 2.1 For asymptomatic women with COVID-19 diagnosis remained at a higher risk only for maternal morbidity and preeclampsia. And among women who tested positive 54 of their neonates so that it was about 13% tested positive for COVID-19 as well. I want to I would like to refer the listeners to that table in the in paper, table one where you have all the different all the different morbidities and mortalities that are listed. And again, preeclampsia, eclampsia, 8.4% versus 4.4% infections 3.6 versus 1.1%. Admission to the ICU again, very impressive 8.4% versus 1.6%. maternal death, very similar to the US cohort 1.6 versus point 1%. preterm birth 22% versus 13%, medically indicated preterm to 18.8% versus pretty much 9%. And then this sort of severe perinatal morbidity and mortality index 17% versus 8%. And the other one, the severe neonatal, more morbidity index, which is the other one that's defined. So let me just clarify this. There's the severe neonatal morbidity index, which is the one that we spoke about earlier on that was 6.2% versus 2.3. And then they had something called the severe perinatal morbidity and mortality index, which basically includes any of the morbidity listed in the SMI, the severe, no more morbidity index, or intra uterine or neonatal death or neonatal ICU stay beyond seven days, and that was 17% versus 8%. So very impressive stuff. And, and it makes you make you think, you know, I mean, the numbers objectively made may not look impressive, in comparison to COVID Negative women, I think it's it's shocking. And if it was a loved one, I mean, you would not want to place your, your loved one in harm's way. I mean, you're thinking of all the things that could potentially go wrong when you're admitted to the ICU when you require mechanical ventilation. That's frightening. So yeah. What were your thoughts?


Daphna 13:10

Yeah, I mean, the percentages, and luckily, thankfully, both studies were pretty congruent, right? They showed the same things. And so I mean, for this, I mean, you talked about the percentages, but the relative risk admitted to ICU was five, and then maternal death. Does the number sounds small, but the relative risk is 22. And so that's not I mean, that's not insignificant at all. And it certainly shows a much higher risk propensity for these pregnant women. And then, you know, obviously, we care about the neonatal outcomes. And so those were significantly different as well. And something that, you know, doesn't even really trigger, for example, for the lay community, but the differences in low birth weight was was also not insignificant, and we know that has long term outcomes. And then certainly for moms, that development of preeclampsia we know leads to preterm morbidities. And for moms long term problem, so moms who have preeclampsia are developing chronic hypertension as well. And so it just, it just goes to show you there's so many things we don't understand about COVID Yet, particularly in pregnancy, and this is really the first study we've seen that she looked at kind of the fetal outcomes. So I'm really glad that we have this and I'm sure we're going to see more. Unfortunately, I think the next iteration with the Delta variant will look worse.


Ben 14:49

We'll see. I mean, that's the one thing that's interesting, right? I mean, I think there's a lot of uncertainty surrounding COVID I think rightfully so I think anybody that says we don't really know what the long term effects are of the of the virus there, right? And then on the other hand, even people who are questioning the efficacy of the vaccine saying, Oh, we don't know the long term effects, like, okay, let's have that discussion, even if you want. However, these studies are pointing something very interesting, which is, the outcomes that these patients are exposed to. So for example, preterm birth, lowest low birth weight, etc, etc. Those things we know what their long term outcomes aren't right? I spoke about that, like, for example, in the last episode, like we know that every week of gestation decreases the rate of autism, right. And so, yes, the long term outcomes we can always speculate on this data will, will thankfully come in. But at this time, yes, the long term effect, we can sort of know because if your baby is born, low birth weight preterm that has long term neurodevelopmental consequences, and I can tell you what those outcomes are, and that alone should help you in making a decision towards keeping your loved ones safe. So interesting stuff. Yeah,


Daphna 16:01

I mean, I think about pregnant people and the lengths they go to protect, you know, that pregnancy. And and this is a this is a big deal, unfortunately. Yeah. And then, like you said, with the with the vaccines, it's really just weighing the risks, the risks we do know, we for sure know, with the risks of the vaccine versus these risks of getting COVID While while pregnant. So,


Ben 16:29

ideally, ideally unvaccinated But ideally, I wish I'd never was placed in a situation where I needed to get vaccinated for a disease, right? I mean, it's just a fact of life where now we have to deal with this with this virus. And so like you said, we have to, we have to adapt. And that's, I guess, the strength of the human races and the species is that we adapt. And COVID, I think, was a good example of that.


Daphna 16:51

The one thing I was happy to see is really this impact on asymptomatic women, because that's the majority of women with COVID infections. Thankfully, unfortunately, we don't know which, which person is going to be asymptomatic versus which person is going to be symptomatic. So So that's, that's the clincher, right? We have to protect everybody because we don't know who's going to get really sick. And so far, we haven't been able to hammer down on the data to really outline who's at higher risk other than they're pregnant. But I was feeling thankful that the asymptomatic patients were not having at least these outcomes, I think there's still things we will learn. But that meant that made me feel hopeful. Yeah. So 100%.


Ben 17:41

Okay, we have a lot of articles to go through. And we could talk about COVID and pregnancy and for the whole episode, and I'm curious if if we maybe anyway, looking for maybe some guests that could could enlighten us on their studies and research. So we'll see about that. Anyway, what is the next paper you wanted to go over? Definitely.


Daphna 18:04

So I thought we should do this one on timing of neonatal stoma closure, admittedly, mostly because we're dealing with this in our own unit. Right now. We have a special patient. That's correct. So we have this timing of neonatal stoma closure, a survey of health, professional perspectives and current practice in the archives of disease. The lead author, Jonathan Ducey, and this is a study out of the UK. So really, this is a I mean, it's a survey study. They wanted to look at, not necessarily the optimal timing, but what is the perception of optimal timing, for stoma closures. They used an online survey, they sent it to all 27, neonatal surgical units in the UK, to look at what were the individual responses about, when is the right time looking at early closure and quote unquote, late stoma closure, and we'll talk about that. So they had a total of 166 professionals across those surgical centers 52 were from 52%, were from surgeons, 40% from neonatologist, 5%, from specialist nurses. And what they did is the survey looked at kind of these three domains. So the clinical role, which we talked about the current practice in the unit for timing of stoma closure, and then focused questions on what would make them potentially deviate or how they made those elections for when they're when their preferred time was. So overall, I think they got a big a big segment of their population so they got greater than two surgeons from a 24 out of 27 centers, so almost all centers and greater than or equal to two neonatologist from 24 out of 27 centers, so a lot of feedback. And so they actually didn't truly define early or later closure, but they let people self define for themselves. So the so they actually didn't define early or late closure, but they let the respondents choose for themselves. So they had 47% of respondents generally considered themselves proponents of quote, unquote, early stoma closure 28% of quote unquote leader stoma closure, and 25% were unsure so I thought that was really interesting. Welcome to the club. Very honest. So they also provided for different scenarios. Looking at what would the timing be different depending on the baby, so I'll read those briefly and we've all experienced them. But the first scenario as a 26 weaker, deteriorates clinically on the third day of life found to have an isolated perforation of the distal small bowel and they have both a stoma and mucous fistula. The second scenario preterm infant at 26 weeks gestation, clinical signs of neck at four weeks of age, the laparotomy confirms diffuse small bowel involvement. 50 centimeters of bowels resected a stoma mucous fistula are placed. Scenario three a term infant born with signs of distal bowel obstruction and failure to pass Lakonia simple meconium ileus and a micro colon are found a laparotomy stoma and mucous fistula are placed. The fourth scenario, a term infant is born with signs of proximal bowel obstruction failure to pass meconium they find a junella atresia, and a stoma and mucus fistula at that time are placed and the midget Unum. So, across the board, it looked like the most common time to closure was about six weeks. But there was variability between scenarios, which makes sense. So certainly for the preterm infant, more respondents favored a longer time interval between stoma formation and closure. And most of this was related to the weight of the baby. So most people were targeting a specific weight. So surely, if the baby required their first surgery very early in their admission, then they would wait longer to gain the targeted birth weight. And for most of the respondents, it looks like the targeted birth weight was about two kilos. The median was two kilos, and the mode was actually 2.5 kilos as their predefined weight for surgery. And that was really across the board for all the scenarios. The other thing that really looked like, would predispose to a later closure, or things that produced inflammatory pathologies. So bowel perforations with significant peritonitis and neck were considered to be justifications to extend the interval between procedures to allow for evolution of the guts Aquila, and abdominal quiescence. So letting that inflammatory response, pass, decrease of adhesions pass so that babies had a more optimal surgical outcome. And then they really had some qualitative questions to look at what would support expediting stoma closure, so things like growth, failure TPN dependence or not being able to advance feeds, and then certainly high output, stoma, so jumping, those were reasons that they would do an early closure. Other problems are skin breakdown, prolapse, granulation, and then certain social issues that would predispose to netic needing to get it done sooner, for example, for the term infants, doing it prior to discharge or coming back at a later date and being reconnected and then vascular access. So you know, difficulty of vascular access, which is what we're dealing with in our little, little babies. So the factors supporting delaying claim stoma closure, are obviously pretty much the opposite. So babies who are thriving with the stoma not having any dumping. Did babies have comorbidities that put them at risk for going to surgery at that specified time? And then like we said, the underlying gut pathology, so less inflammation, they were able to wait a little bit longer. And then unfortunately for this cohort, certainly the availability of going to the operating room specifically for COVID-19 limitations. So so much of our even our research is is being affected by COVID-19. So even when they wanted to take babies to surgery, and they were delayed because of COVID-19, for a number of reasons. So I thought this was an interesting study. Again, it doesn't tell us when is the right time to do it, but at least tells us the reasons why. Some people prefer to do it early. And some people prefer to do it later. What did you think, right?


Ben 25:22

I'm not sure. Maybe I got this wrong. But it seems like this is part of a larger study called the toss skin or tossin study, which is stands for the timing of stoma closure in neonates. So I don't know if that means that there's this survey that's coming out now. And that in the future, actually, this is just part of a larger study where they actually look at this in a more pragmatic way where it's not surveys, but they'll actually do a formal trial. So


Daphna 25:51

hopefully, you think so.


Ben 25:53

Okay, good. So then, so then then go to others. I don't think I misunderstood that. And it's interesting, because I'm going to be honest here. I mean, I learned stomach closure timing based on my fellowship training, right? So you go through fellowship, and you're like, right in my center, this is this is how the surgeons and the attendings do it. And then you move to your I mean, for me, I moved away from my fellowship training for my attending job. And so then you get a different approach. And you're like, Wait, why are they not doing it now? Because the baby is dumping or the baby is not growing or something like that. And then what you realize with this paper is that there's really no consensus. And I guess we have to be tolerant of our colleagues and our surgeons and not feel sometimes I feel like, Oh, this is the wrong thing, we should totally close this stump, this stoma, but then you realize, no, it's very variable. And there's no good evidence. So I think what's interesting, though, is that it seems that even if the timing is not completely agreed upon, there's certain metrics that everybody looks at very closely, meaning a higher birth weight is more favorable, obviously, to tolerate surgery to tolerate anesthesia, and all that stuff. And then obviously, growth and dumping and all these things and access or more practical aspect, where that might just shift your timeline. So I thought it was an interesting paper, just to note, I was very happy to see that at the end of the URL, the end of the article, before the acknowledgement, they listed the Twitter handles of some of the authors. And it's just giving you a glimpse as to the community shifting a little bit to a more modern, that was cool. I mean, again, when you think about what times are changing, when you think about what Michael narvi told us, when he said that when he started on Twitter, his his superiors said this is not something that you should do as a as a chair of neonatology, whatever. And now you're seeing this in articles. Clearly, this is a nice contrast. Anyway. Very cool.


Daphna 27:41

Very cool. You know, I want to talk about this noise level. In the ICU.


Ben 27:49

Yeah. Okay, so I'm gonna, I'm gonna try to, is it okay, if I go over the the article, and then you give us your thoughts? Sure. Okay, so it's a very interesting article. Because this is okay. Let me just Yeah, that's the reason why we have to pace ourselves because this is very cool. So this is published in children. And it's called newborn incubators do not protect from high noise levels in the neonatal intensive care unit, and are relevant noise sources by themselves. first author is tenger Reston. And this is from a group based out of dang it, I forgot where they're from. They're from Switzerland. That's right from Switzerland. And so what they did was very cool. So they basically used a an isolate in their unit. And they placed a microphone in it. And they measure noise levels. And they tried various different scenarios, opening the doors, lifting the top not doing anything, baseline noise levels, measuring noise levels, based on other things happening in and around the unit, and basically looked at those different measurements, the right so the study was done in Zurich. And so all in all, it added up to 60 measurements that they did, and this was a giraffe Omni bed, which is a very standard bed in the unit. I guess the one thing I wanted to start off with was, we're going to talk about sound pressure levels and decibels and all that stuff. And I think it's important to just clarify what are the numbers we need to have as reference points, and they're doing a good job in the background, saying that studies in the past have shown that preterm newborns may awake in reaction to some pressure peaks equivalent to five to 10 decibels right above background noise. And then they're quoting the American Association of Pediatrics, the AAP that recommends to maintain weighted sound pressure levels below 45 decibels in neonatal intensive care units, right. So that's a good a good frame of reference to then understand some of the numbers that they're going to describe.


Daphna 29:50

And if I if I can, maybe for people who aren't familiar with that literature, so 40 decibels is like quiet library sounds right. So less than that is like really whispering in normal household refrigerators about 50 decibels. Normal, our normal typical conversation is about 60 decibels. And you know, there's a lot of normal conversation happening in the NICU. And then 70 decibels is about a noisy restaurant. So just to give people some frame of reference while you talk about that.


Ben 30:23

Okay, so then let's just jump into into the results and see what some of the different measurements they collected, right. So the inside the incubator, the sound pressure levels, when the incubator was just running was measured at 34.7 plus minus point five decibels when the incubator was switched off. And 40.5 After the device completed, its startup procedure. That's pretty impressive. And so just the incubator running is already pretty significant. And then they did some some spectral signature of the incubator, which was kind of cool. It made me feel like of this submarine movie that I saw where every ship has a different signature, right. But they were able to do these things. And to be honest with you, I don't really understand how to read them. The one thing that's interesting though, is that in the spectral signature, you can see when they turn the fan of the incubator off, and you see the huge drop in terms of the amplitude of the of the of the noise level. So that's, that was kind of interesting. When they're looking at the transfer of noise into the incubator, I thought that was very interesting. They're saying that opening and closing of the one door added about 30 decibels while the closing of one door while another one was open, led to a 15 decibel increase in sound pressure level. Opening the incubator on one side as it is done for X ray evaluations evaluation I'm sorry, causes an the sound pressure level increase of 15 to 20 decibel and closing it of 38 to 42 decibels both during less than 0.4 seconds. They further found that the incubator watertank is an additional unexpected source of noise. Its closure causes a transient sound of approximately point three seconds duration with a sound pressure level exceeding wait for it 70 decibels. And I know opening and closing the top causes sound peaks beyond 70 decibels for for approximately point five seconds. And then they looked at the environment of in and around the incubator. And so they found that the average waited sound pressure level during acoustic evaluation at the NICU measured next to the incubator was 53 decibels. During more than half of the whole measurement time at the NICU. It was above 45 decibels during the recording at the NICU outside the Incubator we detected 194 occurrences of waited SPL sound pressure level exceeding 65, decibel, most of which were of short duration, and attributed to the opening and closing of the cabinet and the entrance in and out of the neck. So I am going to let you I skip to some of the some of their of their results because I wanted to focus on the on the main ones. But I think it's interesting rights to have this new perspective of the baby right from from the incubator and from the noise level. I thought that was a very cool study. So go right ahead.


Daphna 33:13

Yeah, so so we we know this. I mean, we have lots of studies that show that Nikki's are just too noisy. And we know that the incubators, while everybody thinks that their kind of closed systems are still too noisy. And in fact, there were some good studies that showed that when we do things inside the isolette, like our hands on care, opening packages, that the incubators, were actually amplifying the sound. And so I think we just it just shows how Cognizant we need to be about this. This was an interesting study, because it showed really, what does the incubator itself add to the equation. And I think it's terrifying to be perfectly. But that's not necessarily something we we can change, right? Hopefully, with newer iterations of the drafts and other beds that they'll get better, they'll get quieter. I also realized that I don't know when the fan turns on in the incubator, I have no idea how often a fan runs when and how that actually works. So that was something that gave me pause and how much time is spent doing that. And we know even this continual background noise noise is a concern even for full term infants. There's some been some good studies about those of us who are using sound machines around the clock for our newborns, and long term hearing loss. So, you know, this is something that we have to take very carefully, especially for babies whose brains are really just developing. I think the takeaways are what can we do in our unit right now, so I can't necessarily change the bed that I have or how the bed works, but we can test our unit and You don't know this, but we've been testing our unit about the noise levels. And our unit is very noisy. It's an older unit, the it's a single bay unit. So the nurses are frequently chatting together in the center. They don't know how they don't have another place to move and have their discussions. And in the evening time when we have thankfully, lots of families coming, I mean, it gets noisy even for myself. And as an adult, I sometimes feel like it's so noisy in here. So you can only imagine what's what's happening to the baby. So we can measure the units we can find out where are the noisiest parts in our units? Can we put the highest risk babies in the quietest places? We can educate the staff. So you have to tell them that like, oh, by the way, it's just too loud in here. Here's the studies. Here's what we know, here are the things that we do every single day for babies open the isolette. Do we have to put the side down? Or can we just use the portholes? Do we have to open the bed all the way? Or can we do some of our care without increasing increasing the noise, something that I found in our, in our unit. And this was new for us, right? Because we had previously been in places where the doctors worked in a separate workspace. And now we were right in the unit. So I think more than ever, we're noticing just how noisy it is in our practice. But the alarms so there's some babies who are always alarming. Low. Right. So those are the babies we really need to know about. But what I found in our unit is we have a lot of babies who are alarming. Hi there and 21%. And their, their upper alarm limit is 100. But we can we can stop that. Right? So those babies are doing okay, you know, we have a lower alarm limit. We can't change anything we can't we in the oxygen. So why do we have to let them alarm all day long. So I think those are things that we can everybody can institute in their units. Today. Obviously, we can specialize places for staff to congregate and talk. And then the next step is really, there's so much kind of noxious auditory stimulation, how can we encourage positive auditory stimulation. So if your unit is doing a lot of kangaroo care, that's awesome. Maybe the next step is for the right babies who are a little bit older starting to encourage humming, soft singing, reading to babies. So there are ways that we can dilute some of this harmful stimulus. So obviously, I did the paper, I hope our listeners go, you can get a decibel meter on your phone for free, you could download an app so you can start checking today.


Ben 37:38

And when I was when I was in medical school, we had a music therapist that would come to the NICU and and whenever she started playing the guitar with with those sort of slow and quiet sounds. Everybody would go quiet. Everybody, right, myself included. So shut up. Okay, so let's move on because we're running out of time and about appreciating these little comments of yours. Okay, so the paper I liked. I liked the paper on cardiac performance and breast milk.


Daphna 38:13

Yes. Magical.


Ben 38:17

Do you want to go over it? And should you want me to just run through?


Daphna 38:20

No, I can do this one. So again, this is another paper with a lot of data. And we still have a few other papers to get through. But this was a paper in JAMA. And so it's entitled cardiac performance in the first year of age among preterm infants fed maternal breast milk, the lead author of FEAF L. Qu. fosh. That's right, was a Twitter


Ben 38:45

friend of ours.


Daphna 38:46

So basically, what they did is they looked at this cross sectional study of cardiac and nutritional data at an academic medical center. In this specific cross section, they looked at ad, preterm babies and 100 of full term control babies. And these babies were all born between 2011 and 2013. And they looked at their 2d echoes, they looked at him at 32 weeks at 36 weeks, and then at a year corrected age, both in preterm infants and then their their full term cohort. So the full term cohort got it at one month of age and at one year of age. And so what they wanted to look at, were all of the echocardiographic kind of measurements of right and left ventricular strain, left ventricular mass and right ventricular area. So So basically, what they what we know about preterm babies as they have decreased cardiac parameters, even at one year of age, and so I thought that was a really nice review that they put in their introduction In, in throughout the paper, so I would recommend everybody can take a look at that just in and of itself. And so this is also part of a bigger study called the prematurity and respiratory outcomes program or the prop study through Wash U in St. Louis Children's Hospital. So we're gonna get a lot more data from this cohort. But so they that whole cohort has almost 700 babies. And then I told you, we have a much smaller cross sectional cohort. So And interestingly, they looked at the lot of the anthropomorphic parametric data, they looked at daily weights, they looked at links, and then they looked at their daily milk consumption of mom's no milk, donor human milk and bovine formula. And obviously, there are babies who get mixtures. And so they did talk about that. But let's go ahead to the data that they did get. So the preterm cohorts just so everybody knows had a medium birth weight of about 960 grams gestational age of 27 weeks at a median, almost exactly split split female to male. They did have a number of obviously maternal complications that are pretty similar for all of our preterm cohorts. And then again, they looked at what were the postnatal complications. So they had 61% of babies bronchopulmonary, dysplasia. Let's see neck 15%, ROP 36%, and ivh 20%. So it will say this is a this is a high acuity group, I think we could say, but then they looked at the echo data, and they were particularly interested in what happened at one year corrected age. So what they were able to do is really make these beautiful graph curves, which I hope we'll plan to post, but they looked at the left ventricular performance. So for each additional week of moms on milk exposure, there was enhanced left ventricular function there was they measured the left ventricular longitudinal strain, and they looked at the wall thickness, so it was decreased with each additional week of moms own milk. And then they looked at the right ventricular performance. So again, at one year, they looked at each additional week of mom's own milk exposure, there was enhanced, right ventricular function enhanced right ventricular strain, larger right ventricular cavity dimensions, and larger systolic and diastolic areas. Then they subsequently looked at the pulmonary hemodynamics, which I thought were particularly interesting. So again, at one year, each additional leak of mom's own milk exposure there was decreased right ventricular afterload increased coupling of the right ventricular to its afterload. And so basically, all of the cardiac parameters were improved in the babies who got mom's own milk, and it was dose dependent. So the longer you got milk for, the better your cardiac outcomes, were, they also looked at a subgroup of the cohort looking at the donor human milk exposure. And so interestingly, there was not a significant impact of exposure to donor human milk on the cardiac performance at one year. And so I thought that was interesting. Also know, obviously, we know breast milk is is magical, I would not have even thought to study this. Honestly, obviously, my area of interest is not in cardiac physiology, but still this, this association, I thought was unanticipated.


Ben 44:14

No, that's true. And it's it goes back to something we've said in the past on the podcast, which was if this was not saying breast milk, but said a random medication suddenly implemented in your unit. So it's fascinating, I think, in the when it comes to donor milk, I think they did a multivariate analysis at the end. And they showed that the HM donor human exposure, that each additional week of the HM exposure, they were increased measures of right ventricular function and morphology, even after adjustment for gestational age, but they didn't find there was no difference in the measurements of left ventricular function or morphology rvf to load or RV coupling, as you said, so it was even in donor milk. They had some benefits, even if If it was not completely encompassing of the for cardiac function, it's an interesting association, right? I mean, a thief in the paper in the introduction mentioned that there's nothing that has tried to link the two. And so they're making this attempt without really potentially understanding the theoretical basis for this. But just the fact that we're able to see this clear association is quite interesting, right. And the benefits of human melt, the list keeps growing. That's kind of cool. No, I don't have anything else to add. This is this is a fascinating people will post those those. We will post those, those graphs


Daphna 45:37

and then looking forward to seeing the larger cohort obviously.


Ben 45:42

That's right. Okay, which, which other paper do you want to go to next?


Daphna 45:47

Well, I think given our previous interview that we have to talk about this paper in journal Perinatology, about infant follow up. So you're absolutely right. It was it's called race, language and neighborhood predict high risk, preterm infant Follow Up program participation, lead author Yarden. Freeman. And so I thought this is just so serendipitous this came to us because I think this is exactly what Dr. Montoya Williams was talking about last week. So definitely, if you didn't get the chance, take take a listen. But basically, what they looked at is they have an infant Follow Up Program, which obviously helps to provide developmental surveillance for preterm infants after hospital discharge. And then they wanted to see what what were kind of the barriers, or what would be the factors that decreased that participation in that program. Because unfortunately, the participation was very variable. And I think a lot of us see this in our follow up programs. So they looked at race, they looked at English as a first language. And then they looked at something called the child opportunity index. And so briefly, what that means is it measures and maps the conditions, children need safe housing, good schools, access to healthy food, green spaces, and clean air, among another a bunch of other factors. And so we know that these conditions are not equitably available to all children in the United States. And certainly, minority children, black Hispanic, indigenous children, disproportionately live in neighborhoods that don't provide all of those optimal conditions. And though those neighborhoods are listed as a low child oper opportunity index. And those names interesting


Ben 47:46

because it they said that it was like publicly available census data. Yes. And


Daphna 47:50

so interestingly, everybody can look at their own communities, you can go to diversity data kids.org. And they have a map of the entire country to look at an mapped by the child opportunity index to look at, what does your community look like? And I think some people will be surprised even if your facility has great resources, you may still be in a community that once the babies leave have very low resources. And so it's important to know what kind of system you're you're functioning in. So I'll get back to the study. But I thought that was very interesting. And again, something everybody can do today is find out about what your child opportunity index in your community looks like. So they looked at 477 infants who are eligible for follow up at this level three NICU, and so then they looked at just what was the primary outcome, which is pretty much the the lowest threshold right did baby were babies seen in one visit to their follow up clinic. And then they looked at the factors associated with participation. So of the 477 infants 41%, so less than half participated in their outpatient follow up. The mean gestation age for this group were 29 weeks mean birth weight, 1.2 kilos, 20% with ivh, 13%, with BPD, home oxygen and set in 17%, and G tubes and 2%. So, you know, these were babies who were, you know, moderately sick, still having quite a quite a lot of needs. And so, when I think about my experiences, I think in general, those are the babies who are most likely to come to the follow up clinic. Those are also the babies who have a lot of other appointments, but we can discuss that afterwards. And so what they found was that the babies who were black compared to white race had lower participation. non English speakers have lower purchase dissipation. And then as they hypothesize those families in the very low childhood opportunity index communities have lower participation. And so, I mean, my takeaway from this is one I hadn't, I didn't know about the childhood opportunity index, I took a look to look at our community. And I think that will give me some information moving forward. And so basically, the data panned out exactly what their hypothesis was. But it just goes to show you that we can identify families that are higher risk for not having the resources post discharge. And then that's really where our interventions should be is, is how can we optimize some of those resources? For families?


Ben 50:46

Yeah, I think you're, you're the core of your neighborhood, and mine is identical. Yes. Sure. So yeah, I think it was an interesting paper number one, because of what you said, at the on the front end that it really ties in super nicely with what Diana spoke to us about, and how the data can can really uncover these types of disparities. I was interested in something in the discussion that they mentioned that I was thinking, could it could it be related to distance to the actual follow up place, but it looked at that and it was independent of distance, meaning, even if the people lived in the tree as far as each other, it didn't make a difference? And I thought, I guess there's nothing else for me to add on to what you say. Except that maybe when they spoke about like, for for people with coming from from the work, why sort of neighborhoods, what what increased their partisan participations were having like NICU comorbidity in like medical equipment at discharge, or so I thought, it's a crying shame that parents need to be so far on the end of the spectrum where their kids are so so sick that it that's all that's that's what it takes for them to actually come by themselves to the follow up programs, we should really emphasize, it means that we're not doing maybe such a good job at emphasizing all the other ramifications of the importance of these follow up programs for babies who don't need so much medical support. Right. So I thought that was interesting, as well as because it seems like from a sensitivity standpoint, right now, we're not doing a good job in it, the baby really needs to be really, really sick for for compliance or have to be effectuated. So we need to do a better job but to helping our families. And this is exactly the highlight that we posted on our Twitter account from Diana's interview, right? It's it doesn't matter, all the work you do in the NICU, if after they leave, then it's just there, into the ether. And nobody follows up after them. Right. I mean, all the work goes to waste sometimes. And so it's important.


Daphna 52:44

Yeah, and I, what I would have liked to have seen in this study, and I think will help all of us is, you know, a lot of these parents probably wanted to come right, and they just couldn't, because of the stressors that they have in their lives. And so, really, and again, that's going to be different. That's what she taught us is gonna be different for every community. And so we have to know what is what are the barriers in our own NICU in our own cities. So that's, that's something we can work on. For sure. That's right. I think we have to talk about these PDA papers, right?


Ben 53:18

Sure. Let's talk I mean, we can talk about this for


Daphna 53:21

a podcast with a paper about PDAs.


Ben 53:25

So this is a paper published in the Journal of parasitology. It's from a from a study group out of Canada, Toronto specifically and it's called is late treatment with acetaminophen safe and effective and avoiding surgical ligation among extremely preterm neonates with persistent patent ductus arteriosus. first author is Sally, Michelle Lee, and, as we said, from Toronto, so the objective of their study was to evaluate this the association between a late treatment with acetaminophen versus immediate surgical ligation with death or no other mental impairment among extremely low gestational age neonates alguns. With persistent PDA, the way this works is that their center gets a lot of referral for babies with needing PDA closures. And so they divided their study into two epochs, they had 2009 to 2012. This was epoch one. And during that time, basically, every baby that was referred to them underwent surgical ligation because that's why they were referred for now in epoch two, which spans 2012 to 2015. Babies were tried with oral a cinnamon, acetaminophen and and or referred to ligation right in the absence of improvement. And so they wanted to see in terms of the babies who underwent treatment with with Tylenol if if they had less that was their primary outcome really, a composite of death or no other mental impairment that 18 to 24 months, right. And so you should look at figure one because it's a little bit tricky. The reason why It's the reason why it's tricky is because it's a retrospective comparative epoch cohort study. Right? So I mean, it's, it's, they can't control for a lot of the stuff that actually happened, right. And that's where I think the study is suffering from its own design, because you wish that they could have control. So for example, in epoch one, they had 468 babies. And then 43 of those were referred for immediate ligation 31, that ligated 12 did not because either they died prior to surgery, or because the PA already had caused by that time. And, or clinically, they were doing better. But then an epoch two, they had 49 babies who were referred for advanced, I guess, management of their PDA, nine of which got ligated 40 of them received were put in the acetaminophen group. And in that group, basically, what ended up happening is that 19 of them ended up needing ligation and 21 ended up not needing ligation. So let's look at their at their their outcome they said so they hadn't. The summary of the results is that 92 alguns, with a median gestational age of 25.2 weeks, had a pagan PDA at the time of epoch, one in October, with a similar font exposed neonates receiving about seven days of treatment. That's also very important, I guess, the treatment the treatment modality was oral acetaminophen administered for seven days at a dose of 15 milligrams per kilo, Q six hours. And so alguns in epoch to have a reduced ligation with an adjusted or of point three. And that was basically the percentage wise it was 53% versus 72% Eating ligation, but it was no deep difference in depth slash NDI. And so their conclusion is that leads to treatment with acetaminophen to avoid surgery for PMDD is associated with reduced ligation but no difference down the road. It it's it's an interesting study, right? I mean, because at the end of the day, if you could avoid having to put a baby through ligation, I guess that's that's valuable. The question is, we're still struggling right with with the concept of leaving the PDAs. Open, right. And we we spoke about that in that pediatric study from a few weeks back where those PDAs can remain open. And what is the long term cardiopulmonary sort of consequences of that. So that I don't know. I guess what I'm taking away from this study is that I used to think that late treatment with acetaminophen was almost a waste of time, right? psychiatrists are so old, it's not going to work a Hail Mary. Absolutely. But then it shows that because some of their PDAs actually have closed, it's worth trying, right? For seven days. It's an insignificant, in my opinion, amount of time where you could potentially save a baby a procedure that has significant morbidity associated with it. So, so yeah, I thought that was I thought that was interesting.


Daphna 57:54

Yeah, that those are the questions right? Does acetaminophen work? And does it matter? You know, I don't think anybody can can answer the question yet does it matter but in in the PDAs, that we decide to close? It looks like acetaminophen works at least 50% of the time, even even late and we actually experienced that recently in two in two babies that we had that had failed ibuprofen therapy. So I definitely I think there's something to be said for that. Obviously, there are programs looking at acetaminophen as the primary medication. So maybe we'll be looking at more of that. But lots of people say I don't think anything Tylenol works at all, but I think this shows that it does again. So I agree it was a it was a there was a lot going on in the study. They they had a prophylactic indomethacin use in some of the babies. What else I will say about the Tylenol treated group is that those babies tended to be less sick. They had lower days of invasive mechanical ventilation and enrollment. Their first treatments for PDA management tended to be later than the not Tylenol group. So the groups were a little different at baseline. But the question is, if we give acetaminophen does it reduce ligations? And it did by 50%? Yep. So interesting.


Ben 59:34

Okay, we're coming to the end of the hour. I guess the last paper we can talk about, there's some other papers that we can potentially save for next time. We say that every week. It's fine. That's right. But it's a it's a good time, also with the guests that we'll have next week. So Eric Jensen spoke to us about this, obviously, that he likes to challenge the dogma. And so he has a paper that he first authored in the Journal of parasitology this month, called Is it time to study routine carseats tolerance screening in a randomized control trial question mark an international survey of current practice and clinician equipoise. How to Pronounce a Capote's. You got it? Yeah, we nailed it. So in the introduction, obviously, Eric mentions that there's not much evidence regarding the need and the the benefits of doing pre discharge carseat screening tolerance tests on on preterm babies. And so he went to hot topics, the annual conference in the US and started surveying neonatologist and participants about what their thoughts are on the pre discharge carseat testing. So I think there was 1300 registered conference attendees and he was able to get about 39% of them to return a survey 87% of which were physician. So and then, of those physicians, 70%, practiced in the US and 99% had provided intensive care to preterm infants. They were coming from 28 countries and six continents. So that's really exciting, because that will end up playing a role in sort of how we looked at the at the results. So the results were as follows the majority of respondents 75% indicated that pre discharge carseat testing is routinely performed in preterm infants at their institution. So far, I'm in that category. Most, most 66% believe that Carsey testing is medically necessary. And I guess, I feel I guess the same way. Routine performance, of course, the test was more common among us based the non US based respondents 96% versus 23%, as was belief that car seat testing is medically necessary 72 versus 51%. Among those practicing in Canada, 14% believe car seat testing is medically necessary, and 19% reported routine performance of car seat testing in preterm infants. So what was interesting is that the minority of respondents 42% had equipoise. So they had willingness to conduct a trial, right? And conversely, 75% indicated willingness in trial number two. So basically, what they did is that they offered them two types of trial. And I thought that was very interesting, because we'll put these pictures on Twitter and you can feel like, where do you learn? So the first trial that he offered them was saying half randomized to carseat and have randomized to discharge home without carseat. So you'll let have your patient go home without a car seat test. And in the full cohort, like the people who said no to that was about 60%. Like, no, I'm not letting half of my patients go home when that occurs. And when he looked, and then in the trial number two, which said, okay, all participant go through carseat testing, randomized one to one to either a restrictive or permissive criteria, which is like how do we define failed car seat test versus a past car seat test and we're coming at the end of the hour, we'll put these numbers in. So like, if there's an episode like which we consider positive here was 10 seconds 11 to 15. And so he has different criteria. And for that people were much more amenable to it. So I think about 70 percents, that there would be more more okay with with that type of trial. And so these survey, the discussion starts off by saying that the survey data suggests that routine pre discharge Carsey testing and preterm infant is common in the US and generally believed to be medically necessary among us based practitioner in contrast, less than one quarter of respondents will practice outside the US indicated carseat testing is routinely performed in their institution, and only one half felt it was medically necessary. And so what are your thoughts? I want to tell you a story about carseat testing before we close the show, but I mean, what were your thoughts on this paper?


Daphna 1:03:47

Yeah, I think, well, you talked a little bit about how the data was different depending on where respondents came from. And so I mean, I think that probably has something to do one with what does your system look like for for outpatient care? And, unfortunately, what does like malpractice and litigation look like in your country? And because we don't have the data, right, but you know, it feels like sometimes once something is in there, you just, you can't take away something that feels like a little bit of a safety net. And we've all had that experience, there are babies that fail the car seat and their babies who feel the car seat a lot, like many times. So I think that's interesting. I think it's an interesting study. Plan to see what do we do? I'm not surprised that there was more aqua boys for number two, where everybody's still getting a carseat test. But can we do it? Can we be a little bit more lenient with with the parameters, and it begs the question, you know, I hope he'll do it with some full term controls because I don't I've not seen that study, and I looked and what What happens to babies in car seats? Maybe Maybe it happens all the time, even healthy babies. So, that was interesting. And then the other thing that they did get some survey data on was what are people doing after the car seat failure? So, that was a range also. So, what is the most appropriate next step after cursey test failure? I mean 80% was will repeat the carseat test. But you know, there are other places where you well we discharged home anyways. So it says so


Ben 1:05:34

10% or 20% was like, yes. So this chart,


Daphna 1:05:37

and where I trained, we were discharging any failure home in the in a car bed, which in many communities is not, is not available. And then how soon after Carsey test failure should screening be repeated. And so this was a little bit of range, but 60% said, 24 hours, and that's what we do in our unit. We haven't talked about it, but that's just what we do. So I'm very, very interesting. So we'll see what comes of it when the studies roll out. But tell me your stories.


Ben 1:06:10

My story is that I did a portion of my training in Israel where the hospital I trained that was at the entrance of the desert. So we had a significant number, a significant proportion of our population was Bedouin, and the veteran population lives in the desert. They are nomads and live in tents, and they, they, they move on donkeys and camels and stuff like that. And it's very cool


Daphna 1:06:29

a lot of car seats.


Ben 1:06:32

But it's, that's the funny thing. The hospital when they came to deliver at the hospital, we mandated a car seat test, and they were like, I don't have a car seat test, like I came on to Dunkin. I'm gonna go home on a donkey. And the hospital and the administrator were like, We cannot let you go home without a car seat. So they had to go and get a car seat to get currency tested. And then you would see that I have I think I have this picture somewhere at home, where you would see people like leaving the hospital, mom, dad, the baby on a dunk holding the holding. And so and so it goes back to this paper about what is the necessity depending on the situation. Yeah, it's a good question to ask. Anyway,


Daphna 1:07:11

and, and the stressors we put parents through in the final days of discharge. Absolutely. Not so bad


Ben 1:07:17

that like the hospital was very inflexible about like, no, no, no, no, you gotta gotta do the car seat. They got into the car. So check that box, don't we? That's right. That's right. Anyway, thank you deftly. That was a fun journal club.


Daphna 1:07:29

Yeah, what I what I learned a lot today. I also learned that our journal article titles are getting longer as time. Yeah, I


Ben 1:07:38

don't think people are just not looking. I mean, it's funny when you read the literature, like from from way back when like, early 20th century they had zingers like, the titles that yeah, they took a lot of liberty and I kind of missed that, but it's okay. All right, definite. Well, see you next time. Guys. Thank you so much for listening. 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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