#026 - Journal Club - Detecting bacteremia earlier, viral infections in BPD babies, quality of life for adult premies.... and more

As always, feel free to send us questions, comments or suggestions to our email: nicupodcast@gmail.com. You can also contact the show through instagram or twitter, @nicupodcast. Or contact Ben and Daphna directly via their twitter profiles: @drnicu and @doctordaphnamd. Papers discussed in today's episode are listed and timestamped below.

enjoy!
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02:12 - Health-Related Quality of Life from Adolescence to Adulthood Following Extremely Preterm Birth. https://www.jpeds.com/article/S0022-3476(21)00326-7/fulltext

12:45 - Low Birth Weight as an Early-Life Risk Factor for Adult Stroke Among Men. https://www.jpeds.com/article/S0022-3476(21)00632-6/fulltext

19:25 - Bloodstream Infections in Preterm Neonates and Mortality-Associated Risk Factors. https://www.jpeds.com/article/S0022-3476(21)00561-8/fulltext

31:01 - In‐Hospital Respiratory Viral Infections for Patients with Established BPD in the SARS‐CoV‐2 Era. https://onlinelibrary.wiley.com/doi/10.1002/ppul.25714

39:07 - Neighborhood Disadvantage and Early Respiratory Outcomes in Very Preterm Infants with Bronchopulmonary Dysplasia. https://www.jpeds.com/article/S0022-3476(21)00643-0/fulltext

47:57 - Family history of asthma influences outpatient respiratory outcomes in children with BPD. https://onlinelibrary.wiley.com/doi/10.1002/ppul.25603

50:23 - End-of-Life Care Related Distress in the PICU and NICU: A Cross-Sectional Survey in a German Tertiary Center. https://www.frontiersin.org/articles/10.3389/fped.2021.709649/full

As always, feel free to send us questions, comments, or suggestions to our email: nicupodcast@gmail.com. You can also contact the show through Instagram or Twitter, @nicupodcast. Or contact Ben and Daphna directly via their Twitter profiles: @drnicu and @doctordaphnamd. The papers discussed in today's episode are listed and timestamped on the webpage linked below.

Enjoy!

Transcript

Ben: 0:50

Hello, everybody, welcome back to the podcast. Dr. Barbeau. What's up?

Daphna: 0:57

I'm good. We've had an interesting week. We had some really hard things in the in the unit and these last few weeks. So that has been a reminder of why some of our initiatives are so important had, you know, taking care,

Ben: 1:15

to quote Jimmy Turner probably 10 times this week telling people hey, this week yeah, that's right. I'm telling them hey, listen, listen to the episode. He says so many cool things. That's right. That's right. That was that was

Daphna: 1:27

as a physician I know said exactly. So. But we have we have journals left to cover despite what's going on in the unit. How have you been?

Ben: 1:39

I've been good. You know, I'm taking this show on the road this week. And I'm recording from one of the study rooms at the medical school. So please, pardon our appearance if there's some some echoes and interruptions. But yeah, doing lots of working on lots of cool stuff. So I'm excited. And yeah, like you said, there's a lot of there's a lot of journals to cover this week. So maybe we shouldn't wait too much. Do you want to get us started?

Daphna: 2:05

Yeah, well, I think we have two articles on adults who are former former premiers. So I think we should start there.

Ben: 2:14

Let's, let's go right ahead. Sure. So

Daphna: 2:17

the first article from the Journal of Pediatrics is health related quality of life from adolescence to adulthood, following extremely preterm birth, and the lead author Yanyan me. And this is a collaboration between healthcare systems and psychology departments in the UK. And their objective was to look at self reported and parent reported health related quality of life and adults who are born extremely preterm compared to control participants born at term and to evaluate how that changes over time. And this was a follow up of the Epicure study, which we've actually talked about before on the on the podcast, but they've put out a lot of other papers.

Ben: 3:02

If somebody doesn't know the Epicure study, it's time to grill it,

Daphna: 3:07

especially for our trainees to take a look. But but the basics are that they looked at all births less than 26 weeks of gestation in the United Kingdom and in Ireland. And then they recruited participants who were born at term at about each six years of life. And then they followed, they followed them up. So in total, they have 129 participants born extremely preterm 65 control participants. And this study is looking at the follow up at night, the 19 year assessment as compared kind of to the 11 year assessment. Yeah,

Ben: 3:45

that was pretty cool. Yeah,

Daphna: 3:48

I think it was a neat study design. Just so we can just tell you a little bit more about the participations participants. They recruited between March and December of 1995. They had 812 infants admitted to neonatal intensive care units 315 of those survived to discharge and were followed. longitudinally, like I said it two and a half 611. And now 19 years, they're using the health utilities index mark three, or they call that the HEI three. So the Huey, I don't know if that's right. But it could be which covers eight basic attributes vision, hearing, speech, ambulation dexterity, emotion and cognition and pain. And then they look at function within each attribute graded on a five or six point scale, much like a Likert scale. And just of note that the Huey the normative values were defined from Canadian citizens They also looked at neurodevelopmental impairment determined at 11 years and it was defined as one of the following a cognitive impairment classified as a score greater than two standard deviations below the mean of controls using the Kauffman assessment battery for children, visual impairment or blindness, hearing loss with AIDS or profound hearing loss or moderate to severe neuro impairment, neuro motor impairment using the gross motor function classification system. So, let's get into the results. So 42% of both the controls and the preterm patients were followed up at 19 years. There was no significant difference in age sex, maternal education between the extremely preterm group and the control group. Participants born extremely preterm had significantly greater rates of cognitive motor and visual impairments at the 11 year mark than

Ben: 5:57

controls. That's not surprising, right?

Daphna: 5:59

No and and again, they've published on that in the in the past and so that is consistent with what we know about babies born extremely preterm. And then compared with the non assessed participants born extremely preterm, so the babies who did not return for follow up at 19 years, those assessed so the 129, the 42% have lower rates of cognitive impairment and in touch intellectual disability, greater developmental and intelligence test scores at the previous assessments. And and of note, they were representative of the original cohort in terms of sex, gestational age, birth, weight, maternal education, and overall neurodevelopmental impairment. So So again, those assess the 42% assessed had lower rates of cognitive impairment and greater developmental test scores. So they just wanted to mention that about the group loss to follow up. Participants born extremely preterm without neurodevelopmental impairment, again, that was designated at 11 years reported significantly lower scores at 19 years compared with controls. And those with impairment reported the lowest scores in comparison with controls or adults are extremely preterm without impairment. And similarly, those results were found when using the parent report. And then they wanted to go into that a little bit more granularly. So compared with controls, the participants born extremely preterm with impairment had significantly lower scores in speech, ambulation dexterity, cognition and pain, whereas those extremely preterm cohort without impairment reported only differences in speech and cognition. And then they wanted to compare those three groups to the parent report. So I'm Parent Report participants born extremely preterm with impairment have lower individual scores in speech, ambulation dexterity, emotion, cognition and pain. Compared with controls, and Parent Report differences for participants born preterm without impairment, were actually only found in emotion and cognition. Other interesting findings, both the self reports and parent reports showed that participants born preterm had more sub optimal attributes than controls, they had significantly greater proportions of moderate disability, and severe disability. Some of the other interesting findings between the parent reports and the participant reports is that parents reported significantly lower scores than participants did at 19 years. And that was also true at the 11 years. differences were found in ambulation, dexterity, emotion and cognition compared with self report. They didn't find any difference between parent report and preterm adults in vision, hearing speech, pain. And the last kind of interesting point is they looked at the change from 11 to 19 years of age, and they found that the scores decreased from point eight, seven to point seven, seven for participants born extremely preterm from one to point nine, seven, so still significant change for controls as well. And again, looking at the group of extremely preterm with impairment. They had the greatest decrease in scores from point seven to 2.55. And I just wanted to highlight so there's a lot of data in here.

Ben: 9:50

Yes, what do you make, what do you make?

Daphna: 9:52

particularly surprising so the lowest scores were in the group that was extremely preterm, who were noted to have some sick nificant impairment at 11 years, then the next lowest was a preterm group without impairment as compared to controls. And then in general, and that's been shown in other studies, parents reported lower scores than adults born preterm report for themselves. And everybody had lower scores, even the controls when they followed up between 11 and 19 years. And so, yeah, it's a tough, that's a time where everybody is transitioning and their health care from say, you know, pediatric, quote unquote problems to adult quote unquote, problems, they're on their own, potentially for the first time. So that I thought was really striking was that didn't matter which group you were in that the scores dropped, I think it's really important that we start really paying attention to adults born preterm, like when we had Juliette, on on the podcast, because they report different. What's important to them is not the same as what's important to their parents. And we know from data, it's not what's important to us as physicians, and then I just,

Ben: 11:12

yeah, when they looked. Now, I was gonna say, when they looked at the changes over time, right, they the findings you mentioned, were the pre terms on the median, and the you went down from point eight, seven 2.77. And then the control from one to point and seven, you mentioned that, but then the quantify that by saying that it was driven by decreases in vision, emotion and pain. So vision makes, it makes perfect sense to me, if you have any issues there, obviously, your quality of life could be directly impacted, but emotion and pain felt like such a dramatic, you know,

Daphna: 11:45

of all the things and those seem like potentially the most, you know, impactful of your of your day to day life. And I thought they just did a nice statement that it's clear that even those with without recognized impairments born preterm may have health related issues following extremely preterm birth that continue to exert important effects on quality of life and early adulthood. Medical services need to be aware of the challenges faced in adaptation to adult life and to recognize that ongoing support may be needed to successfully bridge this critical stage in development. Very well said yes, that I think sums it all up and, and particularly for those extremely preterm, particularly for those preterm with impairment, but it just shows that we were not even optimizing the transition for term people born term into adult care agree.

Ben: 12:42

So this leads us into our next paper published in the Journal of Pediatrics, the paper is called low birth weight as an early life risk factor for adults stroke among men. first author is Lena leisure. And this is from a group out of Sweden. So the interesting question that the study is posing is, is there an association between birth weight and the risk of adult stroke independent of BMI in young adult age among men in the background, obviously, they are mentioning that there is a knowledge gap between the risk of stroke and independent of bus body mass index in in men born preterm, so they're trying to bridge that gap. So that was very interesting. They're using epidemiologic data collected, thanks to the Swedish system on babies born between 1945 and 1961. So that was pretty neat. And if you're interested in how that data was collected, you can always look at the paper, they go over some of these identification techniques that Sweden has to track their population. And so they follow that, because these are large data sets didn't have much data to offer. I mean, they didn't have birth weight, they didn't have childhood, BMI, young adult BMI, but not much else. And they do acknowledge that the fact that they didn't have any information on gestational age and maternal smoking and things like that. So anyway, they're very upfront about it. So take it as you may, the group was very large, I mean, 35, almost 36,000 Children that were followed pretty much from the age of 20 years until stroke death, or if they left the country. And the group closed, I guess the study in December of 2016, meaning they didn't look at data past December 2016. They did calculate based on height and weight, the childhood BMI and the young adult BMI. So there's, there's a lot of interesting things in the methods but let's let's really look at the results. So for the patient population, the mean duration of follow up starting from age 20 years was 40 years. So that was, that was huge. The mean birth weight was 3.6 kilos, and they were able to record a total of 11 184 First strokes, 90 905 of them were ischemic. 234 of them were interested cerebral hemorrhages. And those obviously happen before the end of follow up. What was very interesting, obviously, is when they looked at the relationship between birth weight and stroke, they found that birth weight was inversely associated with the risk of adult stroke in a linear manner. Put it put even more interestingly expressed per kilogram the risk of adult stroke was reduced by 19% per kilogram increased in birth weight. And what was interesting is that this relationship was similarly found between birth weight and the risk of either ischemic or hemorrhagic stroke. They did a Cox regression model with multiple variables. And they really didn't find any difference, because even in the multivariate analysis per kilogram, the risk of stroke was reduced by instead of 19 by 21% per kilogram increase in birth weight, independent of BMI at age 20 years. So the relationship with BMI is is also an interesting one. In addition, BMI and young adulthood showed a direct association with increased risk of stroke. But childhood BMI, somehow was not significantly associated with the risk of adult stroke. So interesting that the BMI really plays a role in young adulthood. But childhood BMI did not really play a role when it came to the incidence of stroke. So then they were trying to evaluate the importance of low birth weight followed by overweight in young adult age, which I thought was very interesting. It really goes back to the Barker hypothesis. And this idea of if you're born small and and you your weight increases over time in the years following birth, does that really lead to problems down the road? So the way they approach this question is that they created I guess, tertiles is how we're going to pronounce this, they created three tertiles tertile. One included babies with lower birth weights tertile, two included babies with a regular on average birth weight, and her child three, were babies with high birth weight. So tertile one was 900 grams to 3.38 kilos, tertile, two was 3.38 kilos to 3.8 kilos, and tertile three was 3.8 to 6.63 kilograms. So individuals in tertile one, so lower birth weights followed by normal age normal weight at age 20. And individuals in total two and overweight at age 20, had significantly increased risk of stroke compared with individuals Interquartile to with normal weight at age 20. So just to rephrase those findings, babies with low birth weight, that then had a normal weight at age 20 are babies with a normal birth weight that when were overweight, had a high risk of stroke. But the interesting one was for individuals who have birth weight intertitle ones have lower birth weight, who with an overweight in young adulthood, they had an 81% higher risk of adult stroke compared with individuals entered out to where were normal wait at age 20. So I thought that was very interesting. And creating this relationship, and young men don't know, what did you think? Yeah, I mean, I

Daphna: 18:09

think it's, it's in line with the current. The current state of thought and in our nutrition matters, and our trajectory over time matters. And what it strikes me is that we don't do any, we don't do any anticipatory guidance about this specifically, you know, coming out of the NICU, and really even as a general pediatrician, when I was a general pediatrician, you know,

Ben: 18:35

I think I think it's even more pervasive than that. I think we should be wondering, how are we going to get this type of paper in front of our adult neurologist colleagues and adult Internal Medicine folks in order to incorporate the history of low birth weight as a risk factor for strokes? That's, that's, I think, is the question.

Daphna: 18:55

Yes. So much of your, really your birth history, your birth history just goes out the window, the minute you transition into adult that's, that's right.

Ben: 19:05

And then you wonder, are we going to ask people if they were born preterm when we're evaluating them for their risk of stroke? And that's should be the logical next step. Okay, but, okay, we spent 20 minutes and we have more papers to go so

Daphna: 19:22

well, let's move on. And okay. There's another article in the Journal of Pediatrics we wanted to talk about, entitled bloodstream infections in preterm neonates and mortality associated risk factors. Lead author, Michelle and the Belgian Basinski. Okay, so um, this is out of the Mount Sinai Hospital, University of Toronto and Sunnybrook Health Center Health Science Center. So what they wanted to look at was the association of early so they're saying early clinical and laboratory variables of Around the time plus or minus four hours of the onset of a positive blood culture, and we'll talk about that specifically, and to look at the primary outcome, which was the episode related mortality. So,

Ben: 20:14

death really shining a light on when the infection is discovered,

Daphna: 20:17

discovered, yeah. When you have a positive blood culture, what is what is the baby look like around that time and then again, the the primary outcome was death within seven days of the positive culture. So, they did a retrospective cohort study, looking at all neonates born in less than 35 weeks of gestation in these two tertiary NICUs between 2011 and 2016, who had a nosocomial bloodstream infection, and I told you about the primary outcome. So their definition of nosocomial blood stream infection was defined as blood and or CSF culture collected beyond 72 hours of age, positive for organism other than cons. So they chose that was important. Yeah, they chose not to include co ag negative staph. And since in their documentation, they felt like it was difficult to establish if it was contaminant or not. In general, they use only one blood culture, some units like ours, for example, it tried to draw two blood cultures so that you can say is this, is this a contaminant? You know, we redraw and can we compare, you know, are two positives versus one positive. So, knowing that, so is either blood or CSF culture positive after the first three days of life and not including cons. There were other exclusions as well, which I thought were important to note. And moving forward in other studies of sepsis and infection, we really do have to, I think, outline these groups, specifically. So they excluded babies if they were diagnosed with neck or an intestinal perforation on the same day, if they were transferred for surgical evaluation within seven days of the positive culture. So again, trying to rule out some of those potentially intestinal translocations if the antibiotics were discontinued, less than five days, so feeling as though the team thought that this was a contaminant. We're if the baby was already on antibiotics at the time of culture, which I thought was interesting, where they, you know, the baby had two positive cultures where they're going to count them twice, but they they've excluded those babies. And then they told us about what they were looking for. So that they looked at the following clinical and laboratory

Ben: 22:39

that was important for them to look at the patient population. So selectively, right. I

Daphna: 22:42

mean, that was very selective. Yeah.

Ben: 22:45

And that that makes it interesting, because at the end, do you have a patient population that is not really contaminated by all these other diseases like NEC, and so on, and the data ends up being maybe a bit narrower, but extremely, extremely well put together and clean I guess, right? I mean, that's, that's the goal.

Daphna: 23:03

Yeah, I agree with you. And I think they were really trying to categorize like the sick baby. No, real true, you know, are markers of sepsis. So, and they had a lot of data based on, you know, the kind of clinical findings. So they looked at between the four hours before and after somebody decided to get the culture that became positive. So they looked at the highest heart rate, the lowest systolic diastolic and mean blood pressures, the highest fraction of inspired oxygen, the highest mean airway pressure needed, the lowest white blood cell count the lowest platelet count and the highest base deficit, highest and lowest blood glucose values, and urine output, which I thought I was glad that they included. So for their results, they included a total of 142 neonates, the mean gestational age was 26 weeks, plus or minus 1.9 weeks and mean birth weight 833 grams, plus or minus 261 grams included during the study period. So she really is a small group of premature babies, the median age and weight at disease onset so that positive blood culture were 16 days of life, and 800 893 grams. So they had 70 episodes. 49% of the bacteremia was from gram negative bacteria. 62 of the episodes 44% were from gram positive bacteria, six infants grew both gram positive and gram negative and four had a bloodstream infection with a Candida species.

Unknown: 24:48

Yes, that's, I know. Yeah, that's that's something

Daphna: 24:55

totally the most common bacterial isolates in order prevalence number One E coli and a 52, group B strep and of 31 and then Staph aureus and of 24. The rate of bloodstream infection related mortality was 14%. So 20 of the infant's died within the first seven days of that blood culture, five and I thought this was useful granularity of the data. It's right five infants died within 24 hours of disease onset. So getting that blood culture 11 died between 24 and 48 hours of disease onset so fast and then the remaining four died between days two and day seven and 16. Of these 20 patients mortality was from severe unresponsive cardiopulmonary failure, and then the remaining four it actually resulted from withdrawal of life support for a range of factors intractable seizures, and in severely abnormal neurologic status in conjunction with being acutely ill. Some other details neonates who died from a bloodstream infection were of slightly lower gestational age at disease onset, the incidence of meningitis and indwelling central venous catheters were higher than those who died.

Ben: 26:14

However, it's funny how I highlighted the exact same passages as

Daphna: 26:18

what you thought was interesting. Absolutely. However, the differences did not reach statistical significance. And again, it was a small group. So definitely things for us to worry about when we get our lines out. Not surprisingly, the neonates who died had lower blood pressure, lower platelet counts, lower blood glucose levels, and higher respiratory requirements based deficit and incidence of oliguria. I thought this was interesting only for infants who died out of the 20 Were you thought it was interesting to look at that passage? We're receiving Iona troops within four hours of the disease onset and none were receiving steroids. The last thing I highlighted was that evidence of post Bloodstream Infection severe brain injury. So findings of intraventricular hemorrhage of grade three or higher or periventricular, leukomalacia was similar between neonates who died and those who survived. The other findings about the labs, they did a lot of a multivariable analysis demonstrated that the lowest mean blood pressure and highest base deficit within four hours of disease onset, were independently associated with mortality. But when you put them together, they had the highest kind of predictive value. So area and have an area under the curve of point nine. One

Ben: 27:38

that was that was insane.

Daphna: 27:41

Very, yeah, very, very important to note. And then looking at, again, other lab values as a single measure the base deficit of greater than 6.9. So minus 6.9, or greater was the best cut off with 89% sensitivity and 71 specificity, 71% specificity for mortality within seven days of a bloodstream infection onset. So those babies who were not having acidosis, who began to have acidosis, obviously, that was really a harbinger for for mortality. So there's more data, but those were the big picture. I thought, what did you think?

Ben: 28:20

No, I agree with everything you said. And I think it was nice of you to go over the different mortality time points, I think this was something that I took away from the paper is that when you see mortality at two to seven days, often you think that if I can get antibiotics on board within 48 hours, then then I'm safe. We're in the safe. That's right. Yeah. And and then you're not I mean, babies could still die this far out into the infection. So reminds me of being vigilant. The other thing that I think was really cool in this paper for the people who are going to check it out is that they developed a score, right? Where they're using the highest base deficit, and the lowest mean blood pressure. And the score, I mean, I can go over it is a constant times the highest base deficit minus another constant times the lowest mean blood pressure. And with the test is defined as positive if the score exceeded a cutoff of minus 1.27 and negative otherwise. And what was interesting is that when they combine these two values, a positive test would have 82% sensitivity and 94% specificity for bloodstream related infection mortality. And so I think, I think that was really interesting, too, for the for the group to put themselves out there and to provide a score that people could use, and I still have to play around with it, to be honest, but I think this is really neat. And for the people who are going to check it out, they give you everything basically and it's

Daphna: 29:52

everything right. Yeah. And I think they went a step further and talking about okay, well, how can how can we really hone in on which babies are at highest risk. And they talked about some of the other things we've talked about on the podcast and sofa score. Can we use that with the clinical findings and the laboratory findings in the sofa store does use some laboratory findings in it, but to better, especially some of these clinical features, to better predict which babies are at risk for dying, so I thought it was interesting. I thought that having that really narrow group defined was valuable. So I learned something for sure.

Ben: 30:36

Yeah. Same here.

Daphna: 30:38

Shall we talk about BPD?

Ben: 30:40

Oh, yeah,

Daphna: 30:41

let's go your favorite topic?

Ben: 30:42

Yeah, I could I could read a BPD papers all day. This is just such a fascinating topic.

Daphna: 30:49

And we have them every week. That's right. That's right. And

Ben: 30:51

that's just because I'm restraining myself to put even more papers in our article folder. So yeah, you're welcome. Okay, so and the paper I would like to start with is published in pediatric pulmonology. It's called in hospital respiratory viral infections for patients with established BPD in the SARS cov. Two era. first author is our Twitter friend, Matthew kilt. And some of the folks at Nationwide Children's some of our friends from the BPD collaborative, including the notable leaf Nealon. So they're asking a very interesting question, which is, during the SARS cov, two era, has there been any changes in the positivity rate of RV is right respiratory viral infections? And I think people call them different things, right? I mean, they could call them RPPS, RSVPs, bio fires, I mean, at the end of the day, they are these PCR panels that we send to look for viral pathogens. And so the question was, because of COVID, has the rates changed in terms of positivity. And so that's something that I've been wondering myself. And so let me go over some of the methods because these are very interesting. The study was retrospective. And this was done at Nationwide children, which is very well known to have a large BPD center, they use the definition of BPD, from Dr. Jensen's paper from the neonatal Research Network, right. And you, the paper goes over the different criterias, which we should probably all know at this point. And babies born at more than 32 weeks of gestation, were excluded. RVI testing was abstracted from the electronic health record. And so that's that's where they got their data from. Interestingly enough, they outlined a lot of their policies for their unit. And I think this is very instructive for anybody interested in how nationwide runs their VPD units, because obviously, they're one of the top centers in the country and in the world. So there's a lot to learn for us there. So they say our unit policy is to screen former Serbian nasal swab on all patients admitted from outside hospital at the time of admission. So that was interesting. However, they are following very strict protocol when it comes to checking for viral pathogens. And they do not do routine Mersa or viral pathogen surveillance cultures, right. I mean, some some units do do that. They go over some of the restrictions that were applied in their units. And they talk about the different use of PPE, droplet precautions, so on so forth, even talk about some of the way they were able to accommodate a social distancing on rounds, and the number of people on rounds, and so on and so forth. So I thought I thought, I thought that was interesting, too. But the interesting part, obviously, related to the COVID era, is the different restrictions on visitation. So they they're talking about that the end of their methods, and they say lastly, nationwide, Children's Hospital developed a hospital wide policy of limiting family visitation to only one family member at the patient's bedside for 24 hour period, and only two family members to visit the entire duration of the patient's hospitalization. Obviously, these are hospital wide restrictions. And I don't think they're making the case for this being something that was specifically designed for their BPD babies, I'm sure that if if they had their say they would have liked as much interaction with the family as possible, right. I mean, that should make sense. So in terms of determining when they were doing these viral panels, that was very interesting, because they did have practice guidelines, and they're sharing those practice guidelines with us. They're saying that it's difficult to make to the diagnosis of our VI is difficult, right? Because BPD patients have so much variability in their, in their care and in the natural progression of their BPD that it can be difficult. So they're following and so they're ordering respiratory viral panel when three conditions are met, basically, if there's a fever without a clear source, number two if there's deterioration in respiratory status that cannot be explained by BPD alone. And three if there's recent exposure to sick contacts, nasal pharyngeal swabs were taken for babies born intubated. Tracheal aspirates. were taken from baby who were intubated. Their bio fire panel included 22 Viral pathogen and the primary outcome of the study was a positive RVI write a positive test result. So without much further discussion into their mythology, let's get into the results. So they had 402 patients that met inclusion criteria 44% of whom underwent RVI testing. In general, the members of their cohort were born extremely preterm and had low birth weight. 57% of them were treated with invasive mechanical, mechanical ventilation at 36 weeks and reached the status of grade three BPD patients who underwent RVA testing and the SARS cov. Two era were more likely to be born via C section when compared to patients who underwent RVA testing before the SARS cov. Two era. So what was interesting is that when the immediate the median number of respiratory viral tests performed per patient per month, was not significantly different in the SARS cov. Two era versus in the pre SARS cov. Two era which I think I think was interesting, right? Because at the end of the day, you wonder if because there's been in the news so much talk about the fact that other viral illnesses are in the on the decline because of restrictions and lockdowns, maybe people were less inclined to order them. But it turns out that no, they had they had this similar number of tests in both cohorts. These are the main findings in the pre SARS cov. Two error 30% of viral panels were positive compared to six during the SARS cov. Two era and that was I mean 30% versus 6%. Is is pretty significant. P value is 0.0000. And, and so they go over the different results of their RVI. Which pathogens were more likely, and so on and so forth. But I guess definitely, really the big question of this paper is should we restrict even more visitations?

Unknown: 37:06

Well, so I'm just Yeah. I'm sorry.

Daphna: 37:09

No, but that's it. That's a very interesting point. So we restrict a lot, right? We all across the world, we have the restricting parent interaction with the babies. Right, but, but baby she way more people than their parents on a day to day basis. And I haven't seen a single study that looked at who who was the transmitter of infection, right. And it could just as easily be the nurses and the doctors and the therapist as as a parent. So my answer is no to that. But Will Will we ever go back to these decreased mitigation strategies when we shouldn't be

Ben: 37:50

misrepresenting the paper on purpose? I mean, that's not what they were trying to say. They didn't say that they're not trying to say that we should restrict visitation in the NICU more to prevent the spread of viral illnesses. I think, right, the main point of the paper is that as lockdowns have been in place, and there's less congregation, viral illnesses have spread less in the community, and by default, right in the NICU as well. And I think that's what they're trying to document and doing it very elegantly. So

Daphna: 38:19

well. And I mean, that's super important, right? I mean, having viral outbreaks and then ICU of medically complex babies is really a problem. And then we just have to, you know, what, what happens when finally things are in a low again, which I hope one day they will be always, what do we do about the mitigation strategies and weighing the risks of developmental, you know, interrupting some of that normal development? And wearing masks? I don't know. Yeah, I don't know where we go from here. We'll see.

Ben: 38:58

Yeah, we'll see what we do. And there was an interesting paper answering an interesting question. Shall we move on to other papers?

Daphna: 39:05

Yeah, we've got a few more. That's right. The next

Ben: 39:09

paper that is also related to BPD is published in the Journal of Pediatrics and I was very happy to see this paper because it comes from my hometown of Marseille, France, and God knows there's not a lot of NICU papers coming out of my hometown. So the paper is called neighborhood disadvantage, and early respiratory outcomes in very preterm infants with bronchopulmonary dysplasia. first author is Juliet ditional and study out of France. And so the objective of this study was to use a French regional dataset in order to determine whether neighborhood disadvantages influenced the risk of respiratory related hospital admission in the year after discharge from the NICU in a population of very preterm infants born with one with BPD I guess I don't know if they're born with DPD, who developed BPD. So the way they selected their patients, they looked at babies that were born less than 32 weeks Sub gestation between September 20 2006 and December 2014. BPD was defined as a need for oxygen or ventilators support that 36 weeks postmenstrual age. So not really one of the common definitions that we use in the US but fairly typical for other papers published from friends who are dealing with BPD. And so they obviously are benefiting from the French socialized medical system where they have a good tracking of their patients good follow up. And so they're they're talking about this BPD follow up clinic where pretty much 82% of their of their babies usually follow up within their first year of life. The study was done prospectively, and babies in attended follow up BPD clinic in the first year of life, every three months, infants discharged on supplemental oxygen received regular home nurse visits, and were seen every month until oxygen was discontinued. Interestingly enough, a paid parental leave program was offered to parents who postponed their work activity and stayed at home with their infants for six to 12 months after neonatal hospital discharge. So that's kind of the perks of socialized medicine, I guess that the defined this SDI, right, the socio economic deprivation index, and basically I'm not really going to go too much into it, it has various components that involve something like, median household income, percentage of people, but 15, who failed high school who failed to graduate from high school, percentage of single parent families, so on so forth, the bottom line is a high number is not good. So if you and so it goes from one to five, one being a good index and five being terrible. And yeah, so that's, that's

Daphna: 41:48

the and of course, they came out of it, all the babies had universal health care. So all of their medical health care costs were covered.

Ben: 41:55

That's right. That's an important point to mention as well. So when when they were looking at respiratory related hospital admission, they define that as a at least one overnight stay in the hospital during the year following discharged from the neonatal intensive care unit for any sort of respiratory causes. And they included in that upper respiratory tract infections, lower respiratory tract disorders that include like bronchitis, etc, wheezing, asthma, according to the ICD 10 codes that they found in the chart, something that was not so good, but I was happy that they acknowledged it in their methods, considering the effects of maternal smoking, and because of the high rate of missing values, they had to perform multiple imputation. But they were missing that 41% of their data concerning maternal smoking, which I think for respiratory related illnesses and health care utilization. That's an important point. And for the people who may not be aware of this in Europe, and specifically, in France, smoking is quite prevalent much more than here in the United States. So let's go into the results. And the study ended up including 423 infants, the mean gestational age of the study population was 27 weeks, and their mean birth weight was 940 grams of those 51% lived in a disadvantaged area. So let's look at some of their results. 76 infants 18% were hospitalized for respiratory causes. In the first year after discharge from the neonatal intensive care unit, we're counting for a total of 96 hospitalization, and the breakdown was not very surprising. 62% were for bronchitis. 12% for pneumonia, 10% for asthma, you are i Where 9.4% And then they had 5% for BPD decompensation. I think that was probably just a catch all if they couldn't figure out the diagnosis, I guess. RSV was tested in 41 of the 60 bronchial lights, events. So that was about like 70% and 55% of them were positive. So that was really interesting, right compared with the non hospitalized infants. The hospitalized infants were more premature at birth, not really surprising, were born more frequently during the winter season, and lived in urban areas. So we'll get back to that. And I have some things to say about that. The other findings were that the hospitalized infants lived preferentially in disadvantaged area with an SDI high level in 68% versus 47% of the babies that have the controls. hospital readmission rates were approximately three times higher in infants living in disadvantaged area from 8.8% at the SDI low levels to 24% right at the SDI high level, as expected. And I quote, maternal high school education level and breastfeeding rates declined as the SDI level increased. So obviously, as you reached, right, as you reach more disadvantaged neighborhoods, the level of education was not as high and the rates of breastfeeding were lower. I wanted to go back to this finding definite before before before you give us your opinion on the paper. Compared to the non hospitalized infants that hospitalized infants were more premature at birth, fine. Were born more frequently during the winter season and lived in urban areas. How interesting was that? I feel like we don't tend to ask enough, right? I mean, we don't really go over this with the parents, when it comes to Don't Ask the type of the type of home they're going back into unless they're going back with medical equipment. And this really becomes an issue. But otherwise, it's something that we should probably focus on a bit more. The other interesting thing is, do we tend to think about the date of birth of the baby and what season where they're born in? And how does that affect it? How does that affect the season of the year at the time of discharge considering their hospitalization? I think these are things that we could think about now, when we're looking at our patients, both on admission and on discharge. So anyway, I know you like that paper very much. And so I'm curious to hear your thoughts as well.

Daphna: 45:57

Well, I think the first thing that was striking was actually compared to some of the data that we've looked at hospitalization rates are are pretty low. Right. Right. And so I think that speaks to the good follow up care that they have, and specialized care VPD babies good access to regular RSV vaccination. And yeah, thing and

Ben: 46:24

I forgot when which Journal Club, we talked about that. But we did discuss that if you had good outpatient follow up your healthcare utilization after discharge was low, right way,

Daphna: 46:32

way down. Absolutely. But the fact of the matter is, even I that's what I thought was so striking about this, I'm not surprised in our health care system where your health care is tied to your work and your very much your socioeconomic status, that that the healthcare utilization is higher, especially in emergency visits and hospitalizations. But it was striking to me that even when, you know, health care, expenses were were the same, right. So that was a stressor that was removed. Babies in high SDI. So socio economic deprivation areas, were two to three times more likely to be hospitalized as compared to those living in affluent neighborhoods. And it's just a reminder of the things we've been talking about in the last few episodes is that there are so many stressors on families that that interfere with their, you know, ability to stay healthy. That, you know, we really have to look at what what does, what do our housing situations look like? What is What are the baby's Child Care look like? You know, so many things that we gosh, can't even begin to start to account for at discharge, but we can try.

Ben: 47:54

Right, right. And to that end, I want to briefly mention that we're again, we're always short on time. But I wanted to mention this article that was published in pediatric pulmonology. And it's called family history of asthma influences outpatient respiratory outcomes in children with BPD. This was first author is Julian maglin. And this is from the Division of Pulmonary and Sleep at the Children's Hospital of Philadelphia. So I'm not going to go in depth when it comes to this paper, but I will give you a little bit of what they were trying to do and some of their main outcomes. So what they were trying to look at was the family history is family history of asthma, a risk factor for more severe BPD, as well as, as well as higher rates of acute care usage and respiratory symptoms in preterm infants and children with BPD in the outpatient setting, so really looking at that family history of asthma, and see how that affected babies with BPD. And the results were quite interesting, right. Children with family history of asthma had higher odds of emergency visit, emergency department visits. Since the use of systemic steroids, nighttime respiratory symptoms, and activity limitation. There was no association between family history of asthma and BPD severity. And so the conclusion of this study is that children with BPD and family history of asthma were more likely to have respiratory symptoms acute care usage in the first three years of life and their family history of asthma was associated with a lower socioeconomic status. Family history of asthma could predict an increased likelihood of both Edy visits and need for systemic steroids in infants and children with BPD followed in the outpatient setting. So another topic rates that parents often ask us about when it comes to asthma.

Daphna: 49:33

Yeah, and they frankly they ask a lot, right? Parents are always asking, Is my baby going to have asthma and and we are going to we should take a better family history so that we can do better anticipatory guidance about which babies are more likely to develop, you know, asthma type symptoms, then then then others and what can we do? How can we get engaged in our communities to help with some of these other factors that make a difference for long term outcomes and health care utilization.

Ben: 50:02

Yeah, I agree with you. I mean, we may not be able to change all the external circumstances of our patients, but there's a way for us to be aware of them and try to mitigate them one way or another. So yeah, that was definitely interesting.

Daphna: 50:15

We are getting close to the end of time, but I thought that it would be pertinent to talk about this study end of life care related distress in the PICU and NICU, a cross sectional survey in a German tertiary center. So this comes from the open access journal, frontiers in pediatric frontiers in pediatrics. Lead author, Lars Garten, again, this is coming from Berlin, Germany. So they wanted to look at and compare the perceived care related distress and experiences in both NICU and pick you nurses. So it was a single center, and they used a cross sectional survey design and anonymous self report questionnaire. Again to study this quote, unquote, moral distress and caring for neonatal and pediatric patients, specifically in the end of life. So they had 49 NICU nurses, 24, PICU, nurses, and the NICU nurses came from two large NICUs and the PICU nurses came from one med surg pick you and one he monk pick you. In Germany. Interestingly, they were almost all female, all but one participant that responded, were female. Yeah. And majority, though, had I thought this was very interesting, had greater than 10 years of ICU experience. And so I thought that might change how people answer these questions. 50% answered, Yes, to quote unquote, religion. So I took that to me, and, you know, religion or faith was a was an important part of their lives, but they didn't specify that. Yeah. And the majority were caring for about one to five end of life patients per year. So that tells you kind of what their population looks like, right? This survey was an 18 item questionnaire written in German contain four types of questions, yes, or no questions, multiple choice questions, scaled Likert questions, and then an open ended kind of free response. So they were looking particularly at these 22 potential sources for distress. And there's a wide range here, I'm not going to be able to read them all. But I get to kind of the meat of of the results that the number one source of distress in end of life situations for both the PICU and the NICU nurses were staffing shortages, unfortunately. And so for the NICU, that was about 65%, for the PICU 100% of nurses, staffing shortages, to be one of I think it was their top three that they had to pick

Ben: 53:04

some of the adding to the craziness of the picture, right?

Daphna: 53:07

Can you imagine? You know, we see this every day, we don't always maybe feel it as much as the nurses do in these situations. The other things that were at the top of the list for the NICU nurses included especially close relationship with the child, especially close relationship with the parents or relatives, and extended duration of the care assignment. So you were on that he was kind of primary care team, it seemed all at identical rates of about 59% of respondents. The pinky Nurses also rated their quote unquote own expectations of terminal care not being fulfilled multiple deaths within a short time, so within a week, and observing co workers being in distress, so all of those were about the middle 66% of respondents as frequent sources of distress. Then they were asked to self report their top five sources of distress. And the three most frequently reported distressing factors for NICU nurses were one lack of clearly defined and agreed agreed upon therapeutic goals, pain and dyspnea. And for the NICU, the PICU nurses, again insufficient time and staffing, pain and dyspnea. And then lack of clearly defined goals, which was a number one for the NICU nurses was actually only named by one PICU nurse. So I thought that was interesting. I will come back to that. They also looked at distress related reactions or symptoms in the healthcare worker, again, using a Likert scale and the most frequent distress related reactions or symptoms for NICU nurses were excessive self criticism. I feel that one emotional exhaustion are symptoms and speech listeners. So I mean, they really even had trouble putting their thoughts together. Together. The PICU nurses identified also emotional exhaustion or symptoms Sleep difficulty upsetting dreams and irritability is most frequent distress related reactions or symptoms. And really all of those even individually or taken together I mean can really interfere with your work but also your your personal life obviously. Then they did also look for 15 helpful mechanisms for potential coping. And the top of the list for helpful for coping by the NICU nurses were discussion time before the patient's death, almost 90% team support almost 90% and discussion time after the patient's death almost 90%. The PICU nurses identified compassion, almost 100% team support and personal and private life, hobbies and discussion time after the patient's death, all nearing 90% as as hopeful as helpful coping mechanisms. So I took a few things for this for the Ninos, at least because that's where we work. I think that yeah, defining our goals of care with patients and families, helps patients but it also helps providers and caregivers. And can we target pain and dyspnea that's something that neonatologist are not very good at doing in the end of life, but it is affecting our patients, but also our caregivers. And then easily discussion time before and after death that include the bedside nurse. So we are are having those conversations, hopefully most of the time with families, but they don't always include the nurse. And so I think that's something we can do. So there's less discrepancy about what what the what the plan is, and and the whole team has to know what the plan is. And we can't we can't leave the nurses. Right. Right. Yeah, dark about that.

Ben: 56:51

Yeah. And it feels like you almost need a period of time to just decompress and the staff or maybe just get together and just go have a bite to eat. Right. Yeah. And and just be able to talk this over and talk about how they feel. Outside of the code. I feel like there's a lot of pressure that after a code, it's alright, next patient, right. It's just nonstop and goes back to some of the things obviously, that we discussed with Dr. Turner on on our last episode. But yeah, definitely an interesting paper.

Daphna: 57:20

Yeah, I think, you know, lots of hospitals are finding ways to do a quick debrief or a pause or a moment, just to give people the time to just sit with the weight of that. And we're finding that nine, it doesn't even have to be that long. That we can do that. The other thing I thought,

Ben: 57:40

right, but these are very technical, it's about what did we do? Right, what we could have done better. So yeah, that's different than this, right. And we need something to talk about how we are feeling after a traumatic event, I believe.

Daphna: 57:54

Yeah, and sometimes, the most effective ones I found are not even really word, your didactic, it's just saying like, let's just take a second and say like, this happened to this family to this patient, but but to all of us, we're all involved in this care. So let's just like take a moment to breathe and reset before we have to rush off to do all of those other things we have to do. The only thing that I think I can start to do in my day to day care is this pre brief, right? So if we know that the end of life is near, we just bring together the team,

Ben: 58:30

you're gonna end up being the Grim Reaper if you start doing that. I don't

Daphna: 58:33

think so. I don't think here's the data, the data says pre breeds pre briefs help. So we know that studies show that we are nurses are having distress, much like we are describing and that doing good interventions. For ICU staff for emotional here, they have emotional physiologic physical harm by optimizing institutional support. And these interventions, not only optimize the providers, but they optimize the quality of care of the dying ICU patients. So even if we don't do it for ourselves, we should do it for patients and families.

Ben: 59:18

Do you think we have time for another paper?

Daphna: 59:20

Well, I mean, I think we're, we're, we're over time already. We're over time already.

Ben: 59:26

So So then let's do it. Let's do it. Twitter highlight. Yeah. Okay. So this Twitter highlight comes from Katerina piatek, I think from from Finland, and I hope I'm pronouncing this correctly. She posted a tweet saying I've just given a talk about neonatal medicine podcasts for my hospital, which again, it's in Finland, and I'm not going to butcher the name of that of that poor hospital. And for my hospital colleagues, I told them about my favorite episode of the incubator of two peas in a pod the BMJ podcast I also mentioned webinars from newborn brains and 99 NICU. So yeah, thank you, Katerina, so much for highlighting our podcast, and for mentioning us to your colleagues. That was very thoughtful. Yeah. Thank you also to all of our listeners for continuing to download the episodes in a large volume. We're very impressed by the growth of our community. So thank you. We're humbled. And we're really working very hard to provide you new content and opportunities that I think will be very exciting. Daphna, anything else you want to talk about.

Daphna: 1:00:34

I guess that's all. Have a good week, everybody.

Ben: 1:00:38

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, Nicu 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 Dafna 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