The articles covered on today’s episode of the podcast can be found here 👇
Neonatal MIS-C: Managing the Cytokine Storm. https://pediatrics.aappublications.org/content/early/2021/10/19/peds.2020-042093
Randomized clinical trial investigating the effect of consistent, developmentally-appropriate, and evidence-based multisensory exposures in the NICU. https://www.nature.com/articles/s41372-021-01078-7
Association of Increased Seizures During Rewarming With Abnormal Neurodevelopmental Outcomes at 2-Year Follow-up. https://jamanetwork.com/journals/jamaneurology/fullarticle/2784930
Randomized Trial to Increase Speech Sound Differentiation in Infants Born Preterm. https://jpeds.com/retrieve/pii/S0022347621010283
Language function following preterm birth: prediction using machine learning. https://www.nature.com/articles/s41390-021-01779-x
The bacterial gut microbiome of probiotic-treated very-preterm infants: changes from admission to discharge. https://www.nature.com/articles/s41390-021-01738-6
Prioritization framework for improving the value of care for very low birth weight and very preterm infants. https://www.nature.com/articles/s41372-021-01114-6
The transcript of today's episode can be found below 👇
babies, infants, nicu, paper, seizure, hospital, sepsis, intervention, higher, study, looked, talk, gestational age, language, discharge, data, probiotic, cool, group, neonatal
Hello, everybody, welcome back to the podcast Daphna. How are you today?
I'm good. It seems we're both a little sluggish today, but we're gonna we're gonna get it together.
That's right. That's right. We know, it's just people don't know we this. This is right. We rescheduled this twice.
Yeah. You know, it stays like this where, where I realized why the podcast is so useful, because who has the track? That's right, an extra all nighter to review articles.
reconsider your life choices, right? You say why am I doing this? Why am I doing this
now? But all joking aside, we were this is this is good was fun for us.
Yes, it is. And it's cool to get to record. It's fun. All right. Anything exciting going on?
Well, I mean, the Incubator has some exciting things coming up. We don't really have the time to talk about him right now. But we're aside from recording and journal reading and interviews. We, we've been very busy. So I'm excited about those things.
Yep, yep, yep. Yep, we have what we have our neonatal trainee and global, our global neonatal trainee and physician network. That's that's taking shape. I'm working on a mobile app for nutrition stuff. You're working on a set of books. We're going to start I guess we should start like, teasing a little bit some of these things on the podcast, because it's like I said, we keep saying like, Hey, we're doing like some cool stuff. But maybe it's time to actually divulge a little bit of some of these things. So anyway, yeah. So I've been meeting with my team of developers. I'm talking beta, functional beta naught beta. It's like
so it's a whole different lingo.
It's a whole different lingo. Not something that taught me in med school. No, but it's, it's okay. And we have some
we're moving hospitals soon.
So we're Yeah, yeah. Or we're busy. Our hospital is actually closing down to open in a brand new building. I guess the healthcare system thought it was cheaper to just instead of renovating to just build a new device. So yeah, listen, whatever. I'm not gonna pretend like I understand how money works. But that's what they decided. So we're moving to a brand new place. It's really, really exciting. It's actually this time we're actually on the university campus. So that's very exciting. Yeah, it's, but it's,
there's a lot going on. So let's just jump right in.
Let's just jump right into it. We have we have a bunch of just cool articles. I think, one article that that is a game changer when it comes to practice, like the HIV paper. I think this is one of the papers where it's directly we all have to probably change some of the things we're doing. But the other ones were fascinating stuff. So I'm going to start this week with a case report published in pediatrics, and it's a paper coming out of India called neonatal mhsc. Managing the cytokine storm. Authors are submitter submitter Saha and last author is Dr. Deep. Mukherjee. The reason it's interesting is because this is a as the title hinted is a case of neonatal COVID. And, and it's I don't know, I'm this is me talking out of my butt right here. But I feel like we've all heard of like, the babies with COVID. And like, I haven't been able to really I've been craving the case to see like, what
did it look like for sure. And, and specifically this baby COVID. But I mean, really misc and so you know, there's still potential that we will keep, you know, we will see this even in the next you know, in months after COVID infections. So I thought it would be I agree that it's useful for us to hear the case. Yeah.
Yeah. So I'm gonna go through the case because I think it's interesting because there's a lot of little things in this case that are It can't be peculiar. So it's a term infant girl. And anything that we're revealing, by the way about the patient is whatever is coming straight of the, it's like we don't have extra access, extra pH i that I'm revealing breaking HIPAA here. It's all in the paper. So it's a term infant girl, antenatal history that says on an eventful and she becomes febrile on the eighth and develops a rash, generalized fleeting rash with facial sparing and there's actually very nice pictures that were taken out and they're available in the Yeah. So they they do what probably all of us would have done, they just watch for a few days. And after two days, as the fever really doesn't, doesn't wane, they bring the baby to the hospital, they hospitalized the baby obviously, number one on their list of diagnoses are sepsis. They start the baby on meropenem and me caisson, I don't want to really have to talk about antibiotic choices. This is a different country with different resources. I am
well even two years just to your point, right, a fair brow baby a date where we practice I mean, would be would have gotten a full sepsis work would have gone
before sepsis workup, some broad spectrum antibiotics. But I this is not the point. The point is not to talk about the management of sepsis. But anyway, so they do it for sepsis workup, CRP, blood culture, all that stuff. The blood culture reveals co ag negative staff, which I think was interesting, right? Because you read that and you're like contaminants, maybe, especially since you read the title, and you're like, right, this is this has to do with COVID. So meropenem was discontinued teicoplanin was added. And within 48 hours, she was noted to be a febrile and the rashes and the rash had subsided. The cool thing about that is that they do give you lab values, right? So you see that, that you can see the trend of the different values. Now, she received a single dose of IVIG, one gram per kilo after two successive days of platelet transfusion, because of platelet count persistently below eight. And that drop was quite impressive, I think, on I don't know if it's admission, but the first platelet count they report is 105. And then it goes down to 10, then five, and that's like oh this is followed by a progressive rise in platelet count. And you see that it went up from like 5000 to 110,000 They did an echo that was normal. They did an ultrasound of the abdomen that revealed some hip megali with a minimal Mercedes. And she had clinical improvement and was on roughyeds day of life. 17 So far, pretty standard type of course on day 24 The fever comes back. It feels like an episode of Dr. House. It's
very this kind of recurring scenario
so that the fever recurred with a rise in sepsis markers. And that's something that very, very impressive. So day of life 17 The baby CRP was like, I think nine day of life 24 It went up to 44. disseminated erythematous maculopapular skin lesions were noted that's also in the failure. There were sparing of the face involvement of the neck, elbow and knees and the necrotic lesion the left one they repeat the blood culture and it did not grow anything and the patient gets transferred from that hospital to the hospital of the authors on day of life 25 I think the baby I think the baby and ended up going through three hospitals. So there's so because I think I missed the first transfer baby gets sick in the first hospital it sort of becomes a bit hectic. So they move to the patient pushed into another hospital. And now the baby has moved to a third hospital which is the hospital of the authors. Okay, on the life 25. So on admission that to that to the third hospital, she's febrile, pale tachycardic, Harvard 180 to 200 hepatosplenomegaly, greenish, watery stools hemodynamically stable and on minimal oxygen two liters per minute on a nasal cannula and maintaining good sets the change the antibiotics to several pair zones. So back so back then, and flucloxacillin and clindamycin. Considering a differential diagnosis of staphylococcal or Pseudomonas sepsis,
especially that little necrotic lesion that's quite quite impressive in the pictures.
Yes, yes, absolutely. You're right about that. Yep. So then they do something that we've all started to do, which is they do routine COVID-19 screening on admission to the hospital and they find out that the baby is COVID-19 Positive. overnight. The documented rapid deterioration, progressively increasing respiratory distress, mixed respiratory and metabolic acidosis on arterial blood gas, and then she needs to be intubated and placed on mechanical ventilation to her chest X. re reveals pulmonary edema and cardiomegaly. And the echo revealed a significant Systolic Dysfunction with an ejection fraction of 40% and mild pericardial effusion. They start to be on adrenaline and continued for three days with high grade fever multi system multi systemic involvement, and as well as high inflammatory markers elevated CRP, elevated ferritin, elevated pro B and P D dimers. They make the diagnosis of Multisystem Inflammatory syndrome, which is also in children also known as mis C. And they start the baby on IVIG to gram per kilo over 24 hours along with methylprednisolone. And noxa. Perrin was also started at therapeutic dose, which was subsequently changed to prophylactic dose because of the D dimers. Improving you think you're out of the woods, right? I mean, through the reading of this article, you're like, oh, it's gonna get better now. Poor little girl on
seventh, the terrifying part of the whole thing.
Right on the 27th. She has a short seizure. She started on Phenobarbital, and at the end of the day, I'm going to spare you the detail, but it was a clinical diagnosis of seizure that was then she was weaned off phenobarbital afterwards, based on seizure cessation, and there's no documentation of any EEG at any point. She gets an MRI on day of life 43 No abnormality. I'm assuming it has right. They don't specify what kind of MRI I'm assuming brain. That was my assumption. Right. On the same day, she has pulmonary hemorrhage cardiac arrest, knees, resuscitation and post resuscitation develops acute kidney injury. She has a normal kidney function. The ultrasound of the kidney reveals renal parenchymal disease. With normal Doppler flow in the renal vessels. She's conservatively managed with albumin and fewer ossified. Her anemia is, I guess, intermittent but corrected with PRBC as the patient gets excavated to high flow nasal cannula after five days and the feeds are initiated again, she has a bronchoscopy which shows Klebsiella and Bronco alveolar lavage. And she is her antibiotic regimen is adjusted. She gets a high resolution CT of the thorax that reveals that electrolysis of both lower lobes of the lung and the rapid the repeat COVID-19 RT PCR results is negative at seven days, seven days from the initial one. So repeat echo at day 30 suggests normal cardiac function ejection fraction is now 64% Steroids are stopped after five days. So you think you're done. So you think that's it right? So she developed then feeding intolerance and her status deteriorates again five days after extubation has to be re intubated. They repeat an echo now showing moderate Left Ventricular Systolic Dysfunction and generalized left ventricular wall hypokinesia ejection fraction is now down to 35 to 40%. She has a second rise in third in ferritin and milrinone is started methylprednisolone is also restarted. After that she shows clinical improvement over the next few days. She's excavated to high flow nasal cannula on day of life 37 She's febrile yet again, and showing still Klebsiella and Bronco alveolar lavage, which is now sensitive to meropenem for which he's on for like a couple of weeks. And they were able to reestablish feeding after that sepsis marker and we will function improved over the next few days. IV methylprednisolone was given for five days with followed by oral prednisone, and she's eventually discharged home and they have like 50 on tapering doses of prednisone, subcutaneous low molecular weight heparin and vitamin supplements. She they actually even document follow up saying that she had no further recurrence. So in the end, it's a happy story. Yeah, but my oh my the fright of this case and the roller coaster that documents the ups and downs. Very, very frightening. This cardiomyopathy was impressive. Yeah, I thought it was cool.
Yeah, I think that's one of the scariest this kind of relapsing, recurring kind of picture. how significant this really myocarditis was, and that it improved, and they got worse again, I thought that was interesting. Yeah. And then what I thought was also interesting, it's a good reminder for us, when people can take a look at the pictures. I mean, the rash is impressive. And to, to think the rashes just was just the start. Right? So wasn't like, you know, it was a it was really a harbinger for what was to come for her. So I was an interesting case for sure. I hope we don't see a lot of them.
Right. You wonder also about whether these bacterial infections were super infections, contaminants that clouded the picture. What was interesting is that in the discussion, they mentioned that the mother did test negative for COVID that new family members had symptoms of COVID and she wasn't to different hospitals previously that she could have, they say that she could have gotten COVID there as well. Right. So it makes, which by the way, it's not about making an indictment on the other hospital. But considering that there's no family history, the question is, is this a baby that what started first? Was it the chicken or the egg? Was it a bacteremia that then led way to COVID infection or COVID infection that led way to bacteremia? I think this is interesting.
Yeah, or right. I mean, there, there are a few pathogens, but I mean, superimposed bacterial infection as well described in the adult population. So, you know, it's, it's hard to say, but if we look at her kind of Cardinal signs and symptoms, I mean, she meets the criteria for for MSC and, you know, they they have that here, I think it's potentially useful that we go over them, just so everybody has them kind of in their mind. The CDC definition is a little different than the who, but for both of them, there are some standard criteria that must be met. So pediatric basically. So for CDC age less than 21, for who less than 19. They must have clinical presentation consistent with Nic so prolonged, documented fever, cardiovascular changes, either in vital signs or by echo or arrhythmia, respiratory signs, so pneumonia, ARDS, pulmonary embolism, renal findings, neurologic finding seizures, stroke, hematologic specifically coagulopathy, gi findings, liver enzymes and the dermatologic findings. So they must have have some greater than or equal to two of those organ systems involved. And then laboratory evidence of inflammation, which certainly had no alternative plausible diagnosis, which again, this this baby did have some bacterial and there were some alternate, that's true could have been, and then evidence, obviously, of a COVID. And if COVID infection, like a positive test, which he which he had. So I think it was an interesting case, at least to to recall what that what that looks like. And it you know, it mirrors you know, Kawasaki following lots of other viral infections. But obviously, the presentation can be even more severe. Do you wanna go next? Sure. We gotta get into some of the heavy hitters, but I wanted to do a light paper. I had been looking forward to seeing this data on the sense program.
I cannot say that I didn't think that this will be tickling your fancy over there?
Well, as you know, we've started the sense program in in our unit, which I had a lot of hopes that of what the data would show. But let me let me tell you what it shows.
So can you I was thinking maybe to take the opportunity, because of the paper, I don't know what you're going to say about about the study, but maybe inform people by the sample that actually is
absolutely so I was gonna tell you, but I was gonna do it the other way. But this is fine. Well, we'll talk about it to pique your interest. So the the sense program is supporting and enhancing NICU sensory experiences. And so it really is a kind of multimodal sensory program to really increase parent engagement in the NICU and in developmental care. And so basically, the kind of hallmarks of the program are that for every week of postnatal age, they have a descriptor for all of the senses, smell sight, hearing touch, to see how parents can engage with their babies. So I think that is super valuable. You can find it at their website, the sons website, and you can get the kit. It's not too expensive yet, and have it for your unit and print them out and leave them at bedside. I think it's really a neat thing for parents, but also for the team to say, you know, how can we get parents involved in developmental care. Other components of the program are that they have an app, they have a lot of features for documenting it. And they've kind of provided a minimum dose necessary for some of those things like kangaroo care and breeding. And so I think that's an interesting thing for people to go and look at and learn about. So then they studied it, to see what they would find. And hence this article randomized clinical trial investigating the effect of consistent developmental The appropriate and evidence based multi sensory exposures in the NICU. This is the journal Perinatology, lead author of Roberta Ponyta. It should be noted that they did a pilot study for the sense program before this randomized trial. And it was related to increase parent confidence on the maternal competence questionnaire, better infant neuro behavior with less asymmetry on the NICU network, neuro behavioral scale, and higher scores on the Hammersmith, neonatal neurological evaluation. So that was in their pilot study. So then they said, well, let's randomize babies to our routine care or to getting the sense program. And specifically they randomized babies who were in the single individual rooms because what they found is that their babies in general when they switched from a large pod openbay to individual rooms, that they saw some changes in the kind of neurodevelopmental outcomes of their neonates, based on kind of their routine in unit testing. So they were specifically interested for those babies that were now in single patient rooms. So they recruited 70 Parent Infant dyads, a very preterm infants born less than 32 weeks. They were recruited within the first week of life at St. Louis Children's Hospital between August 2017 And June 2018. They excluded infants with suspected or confirmed congenital anomaly or babies, like I said, who were in the open Ward because they were really looking at these babies in the private room. Their primary outcomes, we're looking at term equivalent age, excitability subscale score on the NICU network, neuro behavioral scale, and the ASQ at one year corrected gestational age because they were specifically interested in looking at language development. They also looked at sensory processing using the sensory profile too. They looked at a variety of markers of maternal mental health, and those questionnaires included the STI the state trait Anxiety Inventory, the Edinburg, postnatal depression scale, the life stress subscale of parenting Stress Index, and the perinatal Post Traumatic Stress Disorder questionnaire. They also looked at the parents stress or scale, the MCQ, which is the parent maternal competence questionnaire, infant care questionnaire, and then at the one year, they went ahead and use the Beck Depression Inventory. So I'm really impressed by the amount of data they were able to collect on these families. And I think it's useful to go over some of these inventories because they are the most frequently used set or a combination of them, they really did the whole the whole cohort of deaths. But in looking at kind of parent stress in the NICU, they also use
and I appreciate you naming them and not using the abbreviation, right? Because it's it gets so it doesn't mean any EPDs and the psi and the Q and the PPS, and it's just like,
oh, yeah, individually. What's neat about these, because I've used them, they're short, they're easy to use, they and they each target something very different. And I think that's why they went ahead and used so many of them. They also assessed medical risk defined as infant having any of these factors during the hospitalization, inotropic support PDA neck, parenteral nutrition greater than 21 days mechanical ventilation greater than seven days BPD cerebral injury. And obviously, they wanted to see because those things affect long term outcomes. I appreciated that they didn't keep those kids from being in the study. Because I think that's a group that's a population, our sickest babies, we keep taking out of neurodevelopmental studies. And so we're not really following them. They also looked at a social risk score to assess family environment after the NICU. So they took 70, infant dyads and randomize them. Three expired, five withdrew 10 were transferred. So 52 infants, were able to be evaluated again at the term gestational age. Well did not complete the one year assessment. So leaving 39 infants the one year follow up. So what they looked at is the groups were homogenous with their demographic factors, except that there were younger mothers lower household income, and more social risk observed in the census group. So I actually think that's pretty important. Some of those differences are significant in terms of long term neurodevelopmental outcomes. There were more sensory interventions conducted with infants in the sense program significantly, which makes sense because they got a lot of education about, you know why that's important. They had the documentation. So parents were really engaged in the program, with a much greater percentage of infants receiving 100% of the doses as defined in the sense program. So some of those were difficult to achieve. So I think that's really impressive that they were able to do that. So when they looked at their outcomes, they were looking at the neuro behavioral score, specifically the B excitability component, which was not different. But these babies had more, quote, unquote, lethargy on the scale, even after controlling for medical and social risks. Infants who received the sense program had significantly higher communication scores on the ASQ at the one year corrected age, but unfortunately, this relationship failed to reach significance after controlling for medical and social risk, and really on the other parameters of like maternal mental health, they really didn't have any differences, which I guess is a good thing I would have liked to see improved maternal mental health. So my thoughts about this were I was disappointed that it didn't show greater changes. However, I want
to ask you a question, I want to ask you a question. What do you think that's the one thing that I took issue with was the language assessment at one year, right.
So that's what I was gonna say, I think that potentially had they used different different markers, they would have had different outcomes, I think the NS is an easy thing to use, we don't have a lot of good. We don't have a lot of good tests for evaluating babies just at corrected gestational age. And this is kind of really just their tolerance to kind of hands on for lack of a bit of a short description. And then again, using the ASQ as the verbal definition, at one year of age, I think there are better tests to evaluate language at one year,
right, then it's and it's not, I'm not saying this, because there's it's not a proper assessment, it's just that there's so much less to assess at one year. And it's so much difficult to get an accurate representation of what language development will be like a 2430 36. And then eventually, three years of age, it doesn't seem to be giving, they don't seem to be giving themselves the best tools to assess language at one year, I think it's just so restrictive. Yeah, I totally agree.
And hopefully, they'll follow the group, but they're already down to 39. And so I think finding a difference at this point is going to be tough for them. So all that is to say that, you know, there have been lots of studies about developmental interventions during the NICU stay, and many of them have come up much like this without much change. But I think we've all experienced those babies who are getting really good developmental care really engaged parents, they, I mean, they are different at discharge than the babies who don't get those those interactions. So I just, I think we're just like you said, we're just not good at measuring yet, unfortunately. For anybody who's not
and distance program is really, really good. That's why there's so
thorough This is the project I wanted to do as a fellow didn't have a lot of support to get it done. So I didn't get to do it, but they did it and they did a really nice job. It's super easy to use. So if you haven't learned about it, if you never heard of it, I would go just look on their website and take a look. It's just so easy to use. And I think anybody can learn from it. Even our most experienced attendings or most senior physicians, you know, you may learn something that you never even thought about when engaging with a baby developmentally. So I think I think it's useful. I don't want people to see this negative study and say, Well, I guess we don't need to do it, because it is a lot of work to implement something like this. But I think there's some intangibles that we just couldn't measure here. Where do you want to go next?
Well, we have a lot of cool papers on language development, but if you want to get the this, the seizure paper out of the way, fine. Okay, so that it's about people that don't want to get out of the way, but it's a very, I think it's very important paper. So this paper is published in JAMA neurology. I was made aware of this paper thanks to our Twitter friends, and it's called the association of increased seizures during rewarming with abnormal neuro development outcomes at two years follow up a nested multi site cohort study first author is Lena shellac. And it's basically a bunch of very famous people from the Naval Research Network who are all on this paper. Most notably senior author is Wally Carlo and rosemary Higgins. Okay, so what are they trying to show? They're trying to determine whether you can detect electrographic seizures, and whether they are more likely to occur during rewarming compared with the preceding period, and whether they are associated with abnormal outcomes in babies who have HIV, receiving hyperthermia therapy. And I mean, the background introduction is interesting, right? They're basically shining a light on the fact that the reward, the rewarding period is this black box that we're not really paying too much attention to. And they're saying we're not really sure what's happening there. And, and they're highlighting that a lot of the studies that we have currently on therapeutic hypothermia, the outcomes are not great yet. I mean, we still have a lot of neurodevelopmental impairment down the road. And they said, so there's room for improvement there. And why not look at rewarming the rewarming period, it's a bit tedious right as to what this study is because it is what they call a nested trial. So it's data from a larger, larger trial. Right. So the smart SMA RT was a nested pre specified prospective study conducted by the neonatal research network between 2011 and 2013. Within the OSI for neonatal HIV randomized clinical trial, OC standing for optimizing cooling, so it's a trial within a trial. And the idea that you need to know is that this bigger trial actually was just looking at randomizing neonate, to either to temperatures to cold temperatures for hyperthermia, but most importantly, to two different types of duration for hypothermia, 72 hours versus 120 hours. You can you can definitely look up that paper. And and you can we're not going to go too much into that.
No, but so we should mention at from that study, they didn't see, we should just discuss that they didn't see benefit with low with lower temperatures, 32 degrees or with prolonged cooling 120 hours, and in fact, trended to having kind of some worse outcomes. So that's why we're not doing it. Thank
you. So in terms of in terms of the of the outcomes that they're looking for, obviously, is the change in electrographic seizure on an amplitude integrated EEG between two consecutive 12 hour interval either prior to the rewarming. And during the rewarming. Let's let's look at so in within the paper, right, they talk about these groups right today. And, and obviously that has to do with the way that the trial was designed. So Group A refers to the patients who receive 72 hours of cooling, Group D were the ones who received 120 hours. So they were able to enroll, the domain trial had 364 infants and over these 194 were screen 10 declined, and 120 met or predefined inclusion criteria. And then of these, they were able to get 90% follow up data on death and disability. And this data was analyzed in 2018 to 2020. And okay, the I'm not gonna go too much into the intervention. Basically, they just monitor the EEG status during rewarming. But the main outcomes, and then the main, the main results, so, so they had a total of 120 newborns that were enrolled, mostly like 7070 of them were male, so that's 50%. And the mean gestational age was three, nine weeks. So more infants had electrographic seizures during the rewarming epoch compared with the preceding epoch. So for example, in Group A, which are the babies who are being cooled for 72 hours only, and again, we don't really care, the difference was 27% versus 14%. So a huge increase of about 13% During the rewarming period, and in Group B, it went up from 10 to 21%. adjusted odds ratio for seizure frequency during rewarming were 2.7 for group A and 3.2. For Group B, the composite death or moderate to severe disability outcome at two years, was significantly higher in infants with electrographic seizure during rewarming. The relative risk was 1.7, after adjusting for baseline clinical encephalopathy, and seizures, as well as center. So I think the reason this and the graph is the figures are pretty impressive. But the bottom line is this is now I think, a landmark type of paper that puts the puts a finger on the fact that we should monitor EEG monitoring during the rewarming period to prevent seizures that are more likely during that that period, especially considering that the long term outcomes are actually significantly impaired by the presence of seizure during rewarming. Fascinating, fascinating paper.
Yeah, yeah. And they mentioned that this the the neonates enrolled in the smart trial this company on it were actually less sick overall compared to the original cohort. So they were less likely to pulmonary hypertension, and less severe HIV less requiring INR troops nitric ECMO, and the hospital mortality for this group happened to be less than the full cohort. And so these weren't even the sickest babies. So one would venture that if we looked at the sickest babies, we'd see even more incidences of of seizure in the in the rewarming. Time. So yeah, those were my take home points that we need to monitor, we need to keep the the EEG or amplitude EEG on and look for seizures. It was interesting that there was no difference really in the seizure burden or the seizure change in the longer cooling group. So some people say, Well, if a baby's having seizures, should we call? Should we call them longer? Should we call them shorter? And this this car starts to answer that question. But it didn't show a difference. And so that's interesting to note. The other thing they showed is that obviously b Not surprisingly, I should say not obviously, but that babies were more likely to cease during that time if they had seized before. And then the other thing is, obviously, for all of our babies with ha that our clinical seizure tends to underestimate the total seizure burden. And that's really what they showed here to that who are having electrographic seizures and not not that many clinical seizures. So very interesting. For sure.
Yeah, that was that was a very interesting paper. So okay, it's your turn.
We don't have to tip for tat here. But I think you know, probiotics are a hot topic these days. So
let's let's deal with language. That. Yeah, I mean, there were there were two papers on language. There's one that predicts language, at long term follow up using artificial intelligence. And then there's that cool study from nationwide. Can we? Yeah, the reason why I didn't want to let the give you attorney because I'm afraid that you're going to you're going to talk about the paper I wanted to talk about, which in the end is fine. But anyway, so this is a paper it's a pre proof in general pediatrics, it's called randomized trial to increase speech sound differentiation in infants born preterm. first author is Selena deja, which I'm assuming is French or French descent. And last author is Natalie Lumet, which are Natalie Medcom. Sorry, which, which is, has published in the past, they're from nationwide, and it's a very, very cool study, what they're trying to look at is speech, sound differentiation. And if you are not familiar with brain development, and when it when it comes to speech, differentiation, the background is actually very informative. And he talks about the fact that, that the auditory function began at 23 to 25 weeks, and that this is an ongoing development for this type of neural network to develop in the baby's brain. Now, they they do a lot of definitions, right, so they talk about phonemes. And, and things like that, which are these units, the smallest parts of a sound, right, which are really essential for for words, meaning, but what's interesting, right, is that they talk about this specialization of our brain to to focus on a single language, and that we have an ability to differentiate various different sounds. But as time goes on, we specialize and we're only sort of experts in in one single language. So they conducted a pilot clinical trial to test the hypothesis that active learning using infants directed foreign language in the NICU would increase speech, sound differentiation, with specificity for the intervention language, meaning you teach them, teach them Mandarin, and they'll know Mandarin, was a great idea for it. And this foreign language intervention would not decrease differentiation in response to English, meaning it would not impact their ability to differentiate words spoken in English. So first of all, I read this, this objective, and I'm like, how, like how, first of all, how do you come up with that type of hypothesis? And second of all, how do you go about doing this? So the study is very cool. So they did a prospective randomized trial between 2018 and 2020. They enrolled babies that had a post menstrual age of 36 to 52 weeks, they were medically stable, they had normal obviously ADRs. And they took, obviously, babies whose parents only spoke English, they really wanted to make sure that when they introduced the foreign language, this is not something that the baby had been exposed to prior. And then they they randomized the babies into three groups. The first group is English enrichment. The second group is French contingent, and the third is Chinese contingent. So what do we mean by that? that infants in the English enrichment control group were exposed to paths were exposed passively to American English, infant directed, recorded lullabies and reading. So this was just like basically English, English lullabies and the stories being played in the background. The other two were using something that I had I didn't know existed, which I had to Google and it turns out it's a thing. So it's, it's, the infants were exposed by actively sucking on the sensor equipped pacifier to infant directed French lullabies, and reading or Mandarin lullabies and readings. So what is that? Basically the there's a pacifier? I seem to know about this or not. I was not, I was not expecting you not to know about it. But right, so it's a, it's a pacifier right, then the baby sucks on the pacifier. And during the sucking it activates the sensor, which then starts the playing of whatever music or whatever it is. So in this case, it would have been French lullabies, and reading or Mandarin lullabies and readings. And when the baby stops sucking and falls asleep, then it just stops. So it's, that's why that's why it's
so they're kind of rewarded. The sucking is like rewarded with this kind of positive input. And for them, that's it. That's the different input, right? It's the less commonly heard language. It's neat.
Yes, and there's data on that on that device, looking at the ability to actually reach for feeds faster. And so it's a very neat device. We're not sponsored by this. Just FYI, we could be we could be and that's why I'm clarifying that we're not it just sounds cool, because it is cool. Compared with so then they go into again think this is important compared with adult directed speech. Infant directed speech is characterized by a slower rate, higher vocal pitch, simpler sentence structure, variable prosody, and elongated vowels. Infant directed singing is characterized by a slower tempo, higher vocal pitch gliding between pitches and elongated or sustained vowels. Obviously, they had a board certified music therapist to review all the recordings making sure it was appropriate. And the intervention with this pacifier activated lalbhai device was 20, twice daily, 15 minute session for there were at least three hours apart over the course of two to three weeks. And so then how do you test for foreign language in a small baby. So basically, what they did is that they did EGS looking at looking at event related potentials when exposed to the various languages to to assess speech, sound perception, and vowel and consonant discrimination. So the methods is pretty easy as the very cool pipe, but the results are in court. So 45 subjects were recruited. And unfortunately, they couldn't recruit more because of COVID. Right. I mean, they said that they had so many restrictions that they just had to stop, which is another way that just COVID makes our life difficult. The 45 subjects were divided 15 went into the English group 13 into the French and 13 into the Chinese contingent group, the median gestational age at birth was 34 weeks. And what they found was the pre intervention mean, event related potential amplitude for English. Contrast, French contrast and Chinese contrast, were not different between the two groups. So at baseline, they were they were identical, which I think is very important to establish, however,
which is kind of cool, right? Because the babies do here predominantly English just in the unit.
So I'm gonna make you which I mean, that can be so interesting, because you think about our units where we do have a few staff members work, we'll speak speaking Spanish speaking, it'll be interesting to know how that infects effectively any. So post intervention, they looked at the in the event related potential ERP. So they found no post intervention differences in ERP, two pairs of English speech sounds across the three groups, regardless of signal location, meaning, the ability of the babies to respond to English spoken words was not affected, which is what something you would expect him to control because they were not exposed to anything else. But it was important for that to be mentioned in also the French and the Mandarin speaking groups. However, post intervention differences in French sound differentiation were present in the French contingent group compared with the Chinese contingent and English arrangement group. And similarly post intervention, Chinese sound differentiation was present in the Chinese contingent group, compared with French contingent and English enrichment group meaning. The sound differentiation was present for Mandarin and the babies who were exposed to Mandarin. It was there for French for the babies who were supposed to French and that was compared to the other two groups who were not and and this is just this is just very, very cool. I think it's in the discussion that he talks about this neural commitment that I was mentioning earlier, and that the fact that we have an ability to affect that in the NICU is mind blowing, I'm going to stop talking because it's already like for
now, it's totally cool. And I mean, that's why, you know, this is the evidence, right? That developmental interventions in the NICU can work, we just have to, we just have to study it right. You know, this would be a great study, to use functional MRI, gosh, I hope we will start using more and more of that it's just so expensive and hard to find. But this is the perfect study for that. And it reminds me that my daughter was born. Every day I picked a different station, a different language for her to listen to,
we listen to you speak multiple, you do speak multiple languages in my
house, and in that was the goal. But she still she still didn't learn anything. But that's my fault that herbal, but in that in that early in the early period, her newborn period,
if you had, if you had plugged her up to an EEG you would have I would have ever known. I would know, you would have had the RPS for sure.
But every day was something different. You name it, we listen to it all day long. So anyway, she's quite the talker, but only in English. I thought you were gonna do the language, the machine learning.
So I'm just going to talk about this one it's in its in which this was in general, apparent intelligence,
no SPR. Society to pediatric Yes, yep.
Yep, pediatric research. That is right. So this was called language function following preterm birth prediction using machine learning. It's a very cool article that looks at can we predict language development at two years corrected gestational age based on a bunch of clinical factors. And, and again, this is the they take into consideration a lot of different clinical factors and including brain MRI. But basically, all you need to know is that based on their algorithm based on the variables that they've included the model that was that the design was able to achieve 91% accuracy 86% sensitivity 96% specificity for language delay a two years corrected. So they have, we can go over these variables quickly on the brain MRI, the increased value for something called PSF A, which is the skeletonize fraction, anisotropy I guess, it's which is again, found in MRI, radial diffusivity, and axial diffusivity, derived from the MRI, were some of the variables and then twin status, any complete or incomplete course of steroids, antenatally. And breastfeeding, and being a female was actually protective of any language delay. So I think I think this is very important when we understand how pivotal language development for for babies and children are to have as many tools for us to use. And I feel like the papers this week are kind of interesting, because they provide like a lot of different ingredients for both assessing intervening monitoring. So it's a nice combination of papers to look at that at that topic. Because again, the ability of a parent to interact with their child also has an augmented effect on the development of the baby's brain. Anyway, I don't want to spend too much time. Sorry. I ramble on.
I think the takeaway home point, the take home point is that we got to keep talking to babies was basically so we I mean, we're, we've done a lot, but I think we have to get to this probiotic paper and also this cost utilization paper. So that's where I will go. This is another another paper in pediatric research the bacterial gut microbiome of probiotic treated very preterm infants changes from admission to discharge. Lead author Jacob Westaway, and this is coming from the Townsville Hospital and Health Services NICU in Queensland, Australia. And so what's interesting about their group, all babies less than 29 weeks born in North Queensland are referred there so they have a lot of little babies, and it is standard of care in their unit for all babies to get probiotics, so they get the influent product and it has Bifidobacterium bifidum and lactobacillus acidophilus. So their inclusion criteria were babies born in less than 32 weeks. And, again, they got one capsule, the probiotic daily. And then they looked at a lot of things. We don't have time to cover all of the data that they did, but as a reminder, this wasn't a randomized study. It wasn't looking at Babies who got probiotic and who didn't get probiotic. It was looking at all babies who got probiotic and what were their different features. So So it included both maternal data which looked at antenatal antibiotics anti natal infections like choreo, prolong membrane rupture, preeclampsia, diabetes, and then infant data sex mode of delivery diet, gestation at birth, neck sepsis, days and timing of antibiotics death ROP birthweight and then discharge wheat. So let me tell you some other variables about this baby, these babies just so you know a little bit about their cohort. So they had, I want to tell you how many babies so they, again collected samples from babies less than 32 weeks and less than 1500 grams. That underwent sequencing, we had 71 admission samples and 63 discharge samples. So not all babies had both samples. The probiotic started on day one and discontinued at 34 to 36 weeks. So the group 44% Male 30% received exclusive formula, almost 50% exclusive breast milk and the rest got a combination. The cesarean delivery rate for this group was 66%. So obviously we have to think about that when we talk about microbiome. The neck rate was 9%, sepsis, rate 6%. And then, interestingly, the neonatal antibiotic rate was 94%. So 94% of the babies got an antibiotic. So it's definitely something for us to consider, and that the chorio rate was 43%, which is also pretty high, which may explain their antibiotic rate. So they wanted to look at the diversity of microbes, and then subsequently the taxonomy associated by these clinical variables. So what they found was that there was a significant significant change in the type of microbes they saw between admission and discharge. They saw staphylococcus much higher admission, and enterobacteria, lactobacillus, Clostridium and veillonella. Higher a discharge. And if you had to look that up, I had to look it up. It's an anaerobic gram negative tipple Gex.
I'm so happy you picked that paper because the names of the bacteria were really frightening for me.
I did it I mailed. So certainly the average species diversity increased from admission to discharge. And again, that's interesting given how much antibiotic use there was, but again, the babies are received probiotics. They did see differences in diversity for diet, sepsis, and ROP, also for Korea. And differences in taxonomy with choreo, preeclampsia, sepsis, neck, ROP and diet. Only diet had a significant impact on the gut microbiome with mode of delivery, not reaching significance for diversity, which is interesting, because that's something that has been well described in the literature. They looked at diet, like I said, infants who are fed only breast milk had significantly higher Bifidobacterium and Klebsiella and lower veillonella, relative to those that were only formula fed, but only at discharge, and those fed only formula had significantly lower lactobacillus. So again, healthiest bacteria at discharge. And infants whose mothers were diagnosed with choreo before during labor staphylococcus, significantly higher admission. And those moms with preeclampsia, there was no differences admission but lower ecoli and Shigella discharge, which is a good thing. They looked at a lot of the neonatal complications, but only ROP neck and SubSys were found to significantly modified the developing preterm gut microbiome. So both sepsis and ROP significantly improves diversity. Those infants diagnosed with sepsis had significantly lower diversity. And infants diagnosed with sepsis had significantly lower Pseudomonas. And then hydro factor in combination was significantly enriched Bifidobacterium. And then they were specifically interested in our op. It's one of the few studies that looked at our op in relation to microbiome found differences at admission between infants who are diagnosed with the disease and those who did not. And staphylococcus significantly higher and infants diagnosed with ROP. The last thing that I think is important, we can't talk about microbiome without talking about neck is that the Bifidobacterium was significantly lower and those infants diagnosed with neck so this was really just a descriptive study to talk about how does diversity change from admission to discharge based on clinical factors? And it's another? Is it the chicken or the egg? Is it? Do they have? Do they end up with the disease because of what they have? Or is their microbiome changed because they had certain diseases? And I mean, we need more information, basically. But their neck rate, you know, one of the things we look at are in these very preterm babies is the sepsis and the neck rate very high when they're treated with probiotics. And I think their rates are pretty consistent with other rates reported in the literature. What did you think?
Well, I thought it was interesting, as you said, right, I think what's cool is to see the shift right from the Arabs to the anaerobes. Right, starting with staff and then moving to more anaerobic sort of colonization. I printed this article in black and white. So these nice graphs of all the different bacteria are all great are all great for me,
makes it much harder to read.
Write, because they all have the same color. And I cannot tell anything, but so I suggest that when we put out the link, you go on the website, look at the diagrams. The histograms are beautiful. But yeah, don't print it in black and white, like the stupid person I am. And no, that's that was I think, I think it's like you said it's not really looking at any intervention. It's looking at the the descriptive study, and I think that's helpful, I think. Yeah, yeah. Yeah.
So I we have time for a few more, I really want to go over this article prioritization framework for improving the value of care for very low birth weight and very preterm infants in the Journal of Perinatology. This month, some big names on this study.
Yeah. All our all our buddies are on there.
So we'll be we'll be tagging them on on Twitter.
Yeah, Brian King is the first author Ravi Patel is on there. Nick Bomet is on there. Matthew Hall. I mean, they're they're all out there.
Right? That's right. So and this study was presented this year at PHS. It is a multi center study, coming from the Pediatric Health Information System database, so hospitals, Children's Hospital Association, Emory, Stanford trop, and nationwide, the database uses data from 51 tertiary care centers, and it includes de identified data on demographics, diagnosis and procedure codes using ICD nine and ICD 10 codes, and daily resource utilization. So the goal of the study was to provide kind of an objective measure of priority setting for where to focus our improvement efforts. And so they wanted to look at the inner hospital variability of CTS, clinician driven tests and treatments among these facilities, and they looked at the relative weights as a ratio, looking at the mean length of stay for each DRG relative to the overall length of stay among all infants admitted to NICUs, included in this database. Then they took those values, and they really tried to kind of normalize the data. So they took out the extremely high and low outlying values, replace them with the 95th, and fifth percentiles, respectively. And they again, to further eliminate extreme outliers, they took out the Nicki mortalities. And so they looked at data on cost on what was the most frequently used CTT. And this is what I think is most valuable. That's what this paper adds is that they use the they looked at the inner hospital practice variation. So to me that says if there's a lot of variation, then we haven't really decided what is the standard of care for that CTT or clinician driven test or treatment.
Can you go into details about how they calculated the variability index, please. You don't want me to do that. Do you want to do well, the Euclidean distance, right between exposure and utilization variables, right? I mean, this is the type of paper where it's like yes, I'm, I'm the one with mild neurodevelopmental impairment, like I did not it flew over my head. And I understood what they meant by interhospital variability, understand what they meant by exposure variability, utilization variability, but when they go into like, Oh, how did you calculate that? And it's like, oh, yeah,
there's a lot of math. There's a lot of math there's Yeah. For for
right. Yeah. You did a good job of explaining it, I think because it's it's easy to get drowned in his paper and to put it away. But the the findings are so so important. Yeah, it's good that we get to talk about
Yeah, you have to work your way through the methods and I had to look a lot of things up. And we don't have time to discuss it all right now,
I looked at some stuff. And the thing that came up was this paper again,
that's circular. So I'll get I'll give you a little bit more of that information. So it was a again, retrospective cohort, they looked at 26,000 infants less than 1500 grams, so less than 32 weeks between 2012 and 2019. Across eventually 40 Children's Hospital, contributing 1,373,883 Total NICU days, they did exclude certain things, critical congenital heart defects, but did not exclude PDA or ASD. They didn't exclude congenital malformations and excluded any hospital with less than 100 neonates. So again, there's a lot of data here about how they accounted for variation in the charges across the hospitals.
And you can you can you can, I think it's, you would do everybody a disservice by trying to describe one and look it up. No, but I think I think it's, it's, I think the result is really what we should spend time on. And it's, I think it's difficult to even to when you sit down, when you sit down at the table, and you read this through and you have all your your things next to you, it's hard to understand, if you do it, I'm assuming people are listening in the car or something. I think we're gonna we're gonna lose some some some audience members, because it's so it's so tedious. Just look it up. But the results are fascinating, fascinating. I think they did tremendous work. Yeah,
I'm not gonna go into the specifics. But I think it's important that people realize that, you know, all that hospitals had different billing systems, and so that they did provide a way to account for that by using standardized costs across all the encounters. And just, you know, what does it mean exposure to one of those clinical tests or treatments was defined at least one charge for any component of that on at least one day during the NICU stay. So in addition to reducing the variability in the billing practices, they looked at, again, the hospital hospital variation, they used a random hospital effect to account for NICU patients at the same hospital. So they looked at babies at the same place and other hospitals, I told you about removing the high and low cost outliers, and then they created this variability index. And so it uses two types of inter hospital variation variation in the number of patients exposed to a type of category. So exposure variability, and variation in utilization among those exposed. So for baby who got it, how much did they How much did they get? I think that's enough of a descriptive piece. We can all get to this would be a whole journal club, potentially, to look at how they how they did the statistics, but let's get to the results. So on multivariable, logistic regression analysis, decreasing gestational age, male sex, black race, outboard admission, and the higher NICU severity of illness score, were all associated with significantly higher odds of a resource intensive NICU stay. And
which, which, which is surprised Right, right.
Right. Yeah, it's like, yeah, and the way they define resource intensive NICU stay was a hospitalization that was in the top 10% of the CTT related costs. So none of that, I think, is
no, if you're small, and you're 300 grams, it's gonna require a lot, it's going to cost a lot to bring you to destroy fun,
and interesting way mortality and self pay insurance were associated with lower odds of a resource intensive NICU stay.
Ahead, I didn't know what to do, right? Because obviously, mortality means that the hospital stays cut short, I guess, maybe that truncates the cost as well by default. And then I'm assuming that the self pay thing, right is always something that's interesting, because I've had patients like this where they cannot, they don't have insurance. So everything has to be really accounted for and so on and so forth. And you don't know how the hospital bills them either to try to just make sure that they can actually pay something. Yeah. So I don't know what to make of that. Yeah, money and medicine, because we don't, we don't treat them because we don't treat them differently. Right. Right. We don't we don't withhold interventions or diagnostic tests, because they're self pay and we can pay for the kids just going to good luck, right, right. No, no. So but because it's billing you never know.
When they excluded the NICU severity of illness score, the odds of a resource intensive NICU stay increased as the birth weight category decreased. Again, not so surprising. Six hospitals 15 Plus that were outliers in the total CTT related costs. Most of these costs were in pharmaceutical therapies. And they were the same six hospital outliers and overall spending. So I thought that was an important point because it just shows how expensive the medications we give our TPN or parenteral nutrition chemistries, and the anticoagulants which they specified some of that were was for if you had the headlines, yeah,
just yeah, like like the heparin and the fluid havia that was considered anticoagulant
were the costliest CTT categories responsible for a combined total cost of 111,373,888. Wow. And together, those three were 40% of the cumulative cost of all the categories, including the that's more than by just a little bit. A little bit. Chest X rays were the costliest imaging CT, but ranked fifth and total cost across all billing groups are give you a little bit more data, you guys have to take a look at these scatter plots. I thought they were so useful, and I think it will help elucidate some of this data. When you guys can see it, we'll post
them on the Twitter account as well.
And then looking at the inter hospital variability index, which again includes the exposure variability and the utilization variability. anticoagulants again your central line, Heparin, glucose monitoring and hematology lab tests were the most variable overall, the imaging CT with the highest interhospital variability was abdominal X rays. So taking all those things together, which ones are the costliest, but which ones also have the most variability. And that's where they came with the highest prioritization scores. So they came up with parenteral, nutrition anticoagulants and hematology testing, which together were responsible for 33% of the cumulative costs of all included CTT categories. So the most expensive but also the ones with the most variability. So indicating that maybe we have room to standardize how we use some of those things. Obviously, it's a large data set relies on billing practices, there was a lot of I think, needed manipulation of the data. But I thought having that variability component is really, really helpful. Because it shows that we just don't have one correct practice.
I think it was very smart, right? That they looked at the variability, where it's like, if other hospitals, if there's so much variability in the intervention itself, it probably means that either one, some of them are doing it too much, maybe some of them are doing it too little. But there's room there to actually find a good middle ground. And when you look at the actual interventions that came out, came out of the data. It's true, right? The TPN, the anticoagulant is a bit shocking, because you're like, Wait, I don't put my babies on a target. But when you understand it's kind of intertwined with PPN. Right, although a lot of the TPN 's are actually getting some heparin. It's interesting, right? I mean, we had a patient, we had a patient in the unit, right, that had a history of NEC, right that needed that had to get ostomy replacement. And then the question becomes right to you, when you do your replacement that you use TPN. And then what if you ordered TPN that comes in the that night, right? And the baby didn't have so much output? Like, oh, I wasted a bag of TPN? Well, when you take into account these types of costs, if I felt very guilty about ordering, I think there was one day where I ordered TPN for this poor child, and there was no output and we ended up wasting a bag of TPA. And this paper made me feel like crap. Or, or or the Oh, it's Monday, we need to check an h and h, right? It's like, it's not because it's Monday that you should check NIH, NIH, maybe maybe do you have other ways to make a proper assessment and time your labs more carefully. So congratulations on on this group. For put the mean, you read the methods. First of all, it's not really surprising the methods when you look at the names on paper, you like the methods? These are like, brilliant, brilliant physicians. And so yeah, you're like, fine. But it's good, though, that if you like you said, don't worry about the methods like, just hop onto the results, you'll understand the paper. Also, it's not completely out of reach. But the methods just goes to show how difficult it is to actually get substance out of the data. But, but they had all the tools and the brainpower to do it. So that's, that's, that's really cool.
Yeah, and again, the graphs are amazing. I think it really helps to describe the the dataset,
and even that table, that table was kind of cool with all the different intervention that was table two, with all the interventions, the different ranks, the variability, the actual the the actual index So the that, that they had defined the prioritization score, that's what I was looking for. I thought that was very interesting. So yeah, that was a great paper. All right. I think this is it for us. I'm
sure we have time for any more.
No, I don't think so. It's yeah, I don't think we have time for any more. And let me see. No, I guess I guess we can save some for next time. You
always try to squeeze a few in at the end.
What's funny is that on the list today, there was one from before that didn't make the cut and who's also not making the cut today. Poor paper, but we'll
get there. We'll keep it on the list. We'll keep
it under this. It's going to be Yeah. All right, Daphna. Do you want to talk about who's coming up next week? Because I think this is kind of exciting. So we're changing things up a little bit next week. This is not going to be a neonatologist or physician coming to us, it's going to be Kelly Anna O'Meara, right, who is a pharmacist. So this is really, really exciting. Because we we live and die by the skills of our pharmacists. So it was so good to get to talk to her. And yeah, I think I think people will enjoy that episode. And
yeah, yeah. You know, Kellyanne is so charismatic. She is a clinical pharmacist who's just an everywhere she's worked is just kind of intimately ingrained in the units where she is. And so it's just, it's just a reminder that a multidisciplinary approach is possible. And I think it's possible
and she also highlights how the other work being done by the pharmacist right with the I think the EMR has created this barrier between the US and the pharmacist and it doesn't do justice to the volume and the and the precision that's required of them. Constantly. That was that was something that I took away anyway, we're not gonna tease too much of the episode,
but I think people enjoy it makes anyway the other perspectives in the unit.
And I think the episode this episode today is getting released on Halloween. Correct. So Happy Halloween to everybody be safe out. You know, I didn't grew up celebrating Halloween, or something. No, we didn't celebrate Halloween in France. So as like, I mean, I've I'm getting routinely getting knocks on the door for a trick or treat. And I have
I forgot because it's not like on my calendar and no,
I'm first generation so my parents didn't grow up trick or treating either. So they just they still don't understand Halloween. They just asked me this week. Was it fun knocking on doors, and I was like, yeah, yeah, I think it was.
I have to Amazon Prime some candy so that I have something for Sunday. Anyway, all right. All right. That
was a good one.
I'll see you next week. Take care. 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 email@example.com. You can also message the show on Instagram or Twitter at NICU podcast. Personally, I am on Twitter at Dr. Nikki spelled Dr. NICU. And Daphna is at Dr. Daphna 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