This week we are reviewing articles from a variety of Journals, including Pediatrics, Neonatology, Journal of Pediatrics, Pediatric Research, Journal of Perinatology and the famous Cochrane Library.

We touched on a multitude of topics. A paper from PEDIATRICS reviewed old data on the association between phototherapy and childhood cancer. It was fascinating to see that the association was really hinging on certain confounders and that once adjusted for them the initial association disapeared. We also reviewed a paper looking at the effects of intrauterine growth restriction (IUGR), which showed that being IUGR is a stronger risk factor for long term neurodevelopmental impairment than prematurity itself! You will surely enjoy this episode which also includes discussions on the effect of caffeine on preterm babies' sleep, a review of early corticosteroids for the prevention of BPD published by none other than Pr. Lex Doyle in the Cochrane Library. And finally a novel, and very cool way, to measure umbilical line position in preterm babies.

Article titles and links are timestamped below. Enjoy.

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

Update on Phototherapy and Childhood Cancer in a Northern California Cohort. Digitale JC, Kim MO, Kuzniewicz MW, Newman TB.Pediatrics. 2021 Nov;148(5):e2021051033. doi: 10.1542/peds.2021-051033. Epub 2021 Oct 29.PMID: 34716218

Hour-Specific Total Serum Bilirubin Percentiles for Infants Born at 29-35 Weeks' Gestation. Jegathesan T, Ray JG, Bhutani VK, Keown-Stoneman CDG, Campbell DM, Shah V, Berger H, Hayeems RZ, Sgro M; NeoHBC.Neonatology. 2021;118(6):710-719. doi: 10.1159/000519496. Epub 2021 Oct 28.PMID: 34710869

Neurodevelopmental Outcomes following Intrauterine Growth Restriction and Very Preterm Birth. Sacchi C, O'Muircheartaigh J, Batalle D, Counsell SJ, Simonelli A, Cesano M, Falconer S, Chew A, Kennea N, Nongena P, Rutherford MA, Edwards AD, Nosarti C.J Pediatr. 2021 Nov;238:135-144.e10. doi: 10.1016/j.jpeds.2021.07.002. Epub 2021 Jul 8.PMID: 34245768

Enteral Iron Supplementation in Infants Born Extremely Preterm and its Positive Correlation with Neurodevelopment; Post Hoc Analysis of the Preterm Erythropoietin Neuroprotection Trial Randomized Controlled Trial. German KR, Vu PT, Comstock BA, Ohls RK, Heagerty PJ, Mayock DE, Georgieff M, Rao R, Juul SE; PENUT Consortium.J Pediatr. 2021 Nov;238:102-109.e8. doi: 10.1016/j.jpeds.2021.07.019. Epub 2021 Jul 27.PMID: 34324880

Caffeine is a respiratory stimulant without effect on sleep in the short-term in late-preterm infants. Seppä-Moilanen M, Andersson S, Kirjavainen T.Pediatr Res. 2022 Sep;92(3):776-782. doi: 10.1038/s41390-021-01794-y. Epub 2021 Oct 30

Lung Ultrasound for Prediction of Bronchopulmonary Dysplasia in Extreme Preterm Neonates: A Prospective Diagnostic Cohort Study. Mohamed A, Mohsen N, Diambomba Y, Lashin A, Louis D, Elsayed Y, Shah PS.J Pediatr. 2021 Nov;238:187-192.e2. doi: 10.1016/j.jpeds.2021.06.079. Epub 2021 Jul 6.PMID: 34237347

Early (< 7 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants. Doyle LW, Cheong JL, Hay S, Manley BJ, Halliday HL.Cochrane Database Syst Rev. 2021 Oct 21;10(10):CD001146. doi: 10.1002/14651858.CD001146.pub6.PMID: 34674229

A novel and accurate method for estimating umbilical arterial and venous catheter insertion length. Tambasco CJ, Shabanova V, Peterec SM, Bizzarro MJ.J Perinatol. 2021 Jul;41(7):1633-1637. doi: 10.1038/s41372-021-01121-7. Epub 2021 Jun 8. PMID: 34103672

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

SUMMARY KEYWORDS

infants, babies, paper, study, nicu, iron, preterm, bpd, caffeine, birth weight, gestational age, looked, data, sleep, scores, weeks, point, high, hydrocortisone, iron supplementation

SPEAKERSBen, Daphna

Ben 00:39

Welcome Hello, everybody. Welcome back to the podcast. How's it going?

Daphna 00:48

I'm doing great. After some technical issues on a late late night recording. We are, we're back in

Ben 00:55

finally ready to go. Tonight. We're almost going to start I mean, almost getting close to 8pm. Now. Anyway, things are well, we're going to skip you. We're going to skip some of the details of what's going on these days things are good for us. But we have so many papers to review. I think we should just jump right into it. We have a few papers, dealing with phototherapy and bilirubin, and I think they're quite interesting. The first paper is called Update on phototherapy and childhood cancer in a northern California cohort. first author is Jean Digitali. And last author is none other than Thomas Newman. And you'll find out why this is so important. So the background of this paper is critical for you to read. I know that sometimes we say you can just skip the background, go for hypothesis and see how the methods are laid out. But in this case, it matters. The reason being is that they're referring to two prior studies, one of them by Thomas Newman that was published some years back, I think it was in 2016. And this study that was also published in pediatrics previously reported on the association between phototherapy and cancer using using billing data, right. I mean, they were using it they were looking at codes for cancer for different types of malignancies, I guess we should say, between 1995 and 2011. And they had reported that the study had reported that phototherapy was associated with higher rates of any type of leukemia and non lymphocytic leukemia in an an in the unadjusted model. However, when they did the propensity adjusted analysis that sort of went away there according another study by by agar and owl, who reported the association between phototherapy and childhood cancer, again, using administrative data from Quebec. And so in this report, what they're trying to do is to really do something that we don't see very often in in our field and in medicine in general, which is just repeating the study looking to see if they can confirm the data. And, again, they're making some tweaks, I think they're making improvement in the methodology. And so it was very interesting to see because obviously, the idea of associating phototherapy with potential malignancies is has has deep ramifications in terms of how we treat babies. Many physicians often put babies on phototherapy, before thresholds are reached, just to try to, quote unquote, keep the belly down. But if there's truly an association that that practice really has to be banned. So anyway, so it will be interesting. And so what they did is that they, they looked at data from the Kaiser Permanente collaborative, the KP and see I forgot what GPMC stands for actually doesn't matter. But you know what I'm talking about. And, and they looked at a group of pretty much 750,000 children, all born 35 weeks or older, between 1995 and 2017. So like I said, it takes back that data from the other paper and extends it by an extra six years. They categorize the children into neurotoxicity groups based on gestational age based on whether they're Coombs positive or comes negative, and compared all their total serum belly levels to the relevant phototherapy thresholds using the paper from the AAP published in 2004. The exposure of interest was obviously the weather they receive for therapy was very binary during birth, hospitalization or readmission. The outcome that mattered was codes for codes for childhood cancer in either inpatient or outpatient encounters. Something that they did there that can go unnoticed is the fact that they said we required at least two diagnoses of cancer from different departments or different days to reduce false part diagnosis. I think that was key, right? When you're doing billing data. You think about that and makes so much sense. Because if if that code appears only once and doesn't appear later, and maybe somebody either suspected or entered it by mistake, you really need that second or third, and so on data points to say, yeah, there was actually a confirmed diagnosis.

Daphna 05:20

When you when you think about how we how we write our notes, for example, there are so many, so many times where you don't have the rule out or suspected is the modifier and you have to use the diagnosis. Right? So absolutely.

Ben 05:35

And that's one of the many pitfalls of using of using coding databases. They did exclude cancers occurring before 60 days saying that the connection between phototherapy and the diagnosis probably was not really related. And they had a different they had a whole set of classification of the various type of malignancies. The follow up time was the time at risk and primary analysis was defined as as starting at the age of 60 days, and ending at whenever that first cancer diagnosis or censored at the age of the last encounter to date in that key PNC facility up until 2019. So let's look at their results because that's what we were all here for. And in the end, in these 750,000 infants 104 approximately 140,000 newborn had qualifying bilirubin levels and were included in the study of which 30% received phototherapy which is quite impressive. I mean, when you look at it in terms of these large numbers 30% wheezing for therapy is quite a large number. Infants who did and did not receive phototherapy differed in the expected ways, I'm assuming when it comes to the different risk factors and serum bilirubin levels and so on in unadjusted analysis, what they found was any cancer any human hematopoietic cancer, any and acute lymphocytic leukemia AML were associated for phototherapy. So sort of confirming, actually confirming the findings of the other two study. However, when they adjusted after adjustment for confounding variable using propensity score quintiles, none of the association remains statistically significant. And that's presented in the paper. The association between phototherapy and any cancer as well as any hematopoietic cancer was attenuated. The point estimate for the adjusted hazard ratio for non lymphocytic leukemia decreased to 0.72. Of note major contributor to the difference between this adjusted HR and the crude IRR were Down Syndrome and early hyperbilirubinemia. And I think that was obviously very interesting because these are obviously significant significant contributors to potential malignancies on down the road. In models that allowed for time varying hazards, similarly found no evidence for increased risk of cancer either before or after four years of age, defining the follow up period at age six years similarly revealed no evidence for increased cancer related to phototherapy. So I think that was that was very interesting, right? Because it's very rare that you see a group revisiting their own data, and really trying to make a conclusion that is, even though it's it's it's along, it's along those lines, but it reinforces the idea that when you actually look at the data a bit more carefully, that relationship that could have been there is actually not and so the main conclusions of the paper is that they did not and I quote, this, we did not confirm previous concerning association between phototherapy and adjusted risk of any cancer, non lymphocytic leukemia or brain and or central nervous system tumors in later in childhood. What do you think of that paper? Daphna?

Daphna 08:48

Yeah, I agree with you. I mean, it used to be the mainstay of academic medical academia is that you would try to replicate other people's studies so we can be sure of the work that you know, we were doing. And now, it's so uncommon, right for anybody to replicate anything, because you just want to find something new that hasn't been studied, but there is value to redoing studies or having other people redo the same study, to make sure that our conclusions are, are correct. So I think it was really great for them. It's a great reminder that when we look at our confounding variables that they, they change, they change the whole potential outcome. And and I agree with you, I think this is an important thing for us to look at, because you can imagine that there's a patho physiologic mechanism for this to be true for there to be an association. And so it's scary for something that we do, you know, we think is a pretty benign thing to look at that. So

Ben 09:51

that's the key. That's exactly what you're saying something that's benign, because we tend to call this physiologic hyperbilirubinemia. But when you look that in the unadjusted analysis We have kids who have Down syndrome, right, which is notoriously known to be a huge risk factor for malignancies down the road, right? Or babies who have hyperbilirubinemia within 24 hours of life, which, if you're doing board review, like it's the question that like hyperbilirubinemia, in the first 24 hours of life is not normal. It's a big red flag. So how can these babies be grouped with the rest of the cohort? And you see that when those confounders are accounted for suddenly that that that association that was initially found dissipates and that's and that's reassuring to see.

Daphna 10:35

I do think it'd be interesting to look at some of the extremes, right. So some of the babies who have very, very high belly ribbons who are on very, very prolonged phototherapy, it'd be nice to see some of that work. So we can put this to rest, but I'm glad they did it.

Ben 10:51

Yeah. So that leads us to our next paper. This one is not published in pediatrics is published in neonatology. And it's called our specific total serum bilirubin percentiles for infants born at 29 to 35 weeks of gestation. And this is a paper that can that has first author is Divya Jugurtha son, and it's coming from the group out of Toronto, I hope I didn't butcher the first author's name, some big names. In that paper, obviously, we note the presence of Brittany and Doug Campbell as well, who's a Twitter friend of ours. So this is something obviously that everybody is struggling with, which is that how can we have reference values for hyperbilirubinemia in babies who are not included in that AAP paper from 2004 and we're less than 35 weeks. So, this paper is trying to take a stab at this and the mentioned that the current study was undertaken to generate our specific pretreatment, TSB to low serum bilirubin percentiles, percentile curves among preterm infants born 29 to 35 and six weeks gestation, including by degree of prematurity, subsequent received from Sita phototherapy, and by influential factors such as enteral, feeding and laboratory confirmed abo incompatibility. So obviously something that will be the title you really craving to read. This is a multi site retrospective cohort study. And obviously, they included preterm between 29, and 35, and six. And interestingly enough, they excluded newborns who had RH disease. And so, so that I think is an important, it's an important detail to mention. Think they do in the in the method, they do explain this. So they do say that infants with RH disease were excluded as these infants are identified and managed prenatally through maternal bloodwork and prenatal screening, the current study focused on care provided to the infant postnatally. And so that's that's how they're, they're explaining that at that exclusion criteria. Infants who made the main inclusion criteria will further assess for completeness of their electronic medical records. So they looked at all different parameters, and the list is quite long. And you can you can take a look at that. So something I liked, obviously, is that the the they share their sample size calculation, and they said, using the methods for reference limits by Valera and Henley in order to obtain a 2.5% and 97.5% reference limit with a relative margin of error of 10%. For a Gaussian distribution, the minimum sample size of 448 preterm infants was required. They were able to collect data on 2549 infants, and they had who had at least one pretreatment Torossian bilirubin level available from birth to 72 hours of age. Obviously, these babies met the criteria for the gestational age, the mean gestational age, and birth weight of the study group was 32.6 weeks, and 19 115 grams, respectively. So for us Americans, says the French guy. But the bilirubin levels that are measured in the paper are in micromoles per liter. And I don't know, I'd be curious to see how many of our listeners are actually measuring bilirubin levels in Micromobility. But I do think most of us here in the US at least, are using milligram per deciliter, right. And so it's very confusing.

Daphna 14:36

Right, because you're thinking, well, in my practice, what do we do?

Ben 14:41

You know that from the kutani graphs and stuff that like, oh, like a belly of 20 milligrams per deciliter is exchanged level. And then here the like. Okay, so for the 40th percentile 52.3. It's like, Wait, what am I reading? So for, for the audience that's interested, the conversion rate between micro moles two per liter. Two milligrams per deciliter is a factor of 17. So if you want to go from micromoles per liter to milligrams per deciliter, you have to divide by 17. So all the values you'll be reading in this paper, just divide them by 17. And you'll get, you'll get the milligrams per deciliter. So that's just Yeah, because it could be quite discouraging to say, Ah, no. But basically, they were able to build very nice nomograms looking and highlighting the 40th 75th and 95th percentile. And, and I encourage what post some of these graphs on our on our Twitter account. The thing that were interesting to me was when they looked at their values by either degree of prematurity and by feeding type, so they had a total of 1120 infants were born between 29 and 32, and six weeks of gestation. And when they're looking at their total serum bilirubin rate of rise from birth, it was generally similar between the two jurisdictionally, the two gestational age groups that they looked at. So they looked at 29 to 32, and six, and 33 to 35, and six. What was interesting about the degree of prematurity was that the estimated total serum bilirubin level rate of rise from birth was generally similar between the two gestational age group except at the 95th percentile were the estimated Torossian serum bilirubin rate of rise was higher among the infants born at 33 to 35 weeks of gestation compared to those at 29 to 32. So it's interesting that that this is late preterm group actually has a higher rate of rise when it comes to those higher numbers. Another thing that was interesting is that pretreatments Billy level percentiles peaked earlier among the latter than the former. So they when they looked at babies who were born between 33 and 35, to 29, and 32. So the peaked the, the serum bilirubin peaked higher in the more premature group within the first 72 hours after birth, the mean pretreatment Billy level peed significantly earlier in the more preterm group 29 to 32 weeks, then those born later. Interestingly enough, one last point about prematurity. Furthermore, significantly more infants born at 29 to 32 weeks received for therapy than those at 33 to 35 weeks, I think we're still very much afraid of, of below high bilirubin level and extreme preterm. The last thing that was interesting is that they looked at Babies based on feeding type overall, among all infants, the mean, belly between birth and 72 hours was significantly higher in infants who were exclusively who was with who were receiving exclusively enteral nutrition than those receiving TPN, or a combination of both. I think that was kind of surprising, right? Because we tend to think enterohepatic circulation should do its job there. But somehow that is not what they found. So, again, it does not really answer the question as to what should we do with kids born 22 to 29. Right. But it's kind of nice to have normal grounds for babies between 29 and, and between 29 and 35. The normal graphs are really good. The X axis goes for every six hours. So you start that at zero hours of age, all the way down to 120 hours. That's really helpful.

Daphna 18:34

Yeah, I mean, it's a lot of great work, amazing data, very easy to use. But I think it would complicate my day to day life. Right? Because there are more details more factors when when really, the way we use Billy Rubin cut offs right now is, is quite simple. No matter what you're using. It's quite simple. And I wonder, you know, Are we under treating for for hyperbilirubinemia? I'm not sure that we are. But but having the data laid out? Is it is interesting to look at.

Ben 19:11

It's interesting to look at, it doesn't tell you doesn't tell you what the long term risks are, whether you're at the 40th percentile, or whether you're at the 75th percentile. Usually high intermediate risk is 75th percentile, I believe, is it? I think so. But when we look at our our current graphs, yeah, I think I think that that's what it is. Maybe Yeah, maybe speaking maybe it's Yeah, I think high intermediate risk is so anyway, yeah, cool paper. Check it out. Yeah. That's our summary.

Daphna 19:41

Summary. Um, well, I think we have a slew of developmental papers this month. This said a few weeks so I'll get started. We've got one and in the Journal of Pediatrics, and neurodevelopmental outcomes falling intra uterine growth restriction and very preterm I'm birth. Lead author. CHIARA Chiara Saatchi. I'm sure I've I ruined. This is a collaboration between the University of Padova and Italy and King's College of London in the UK. And the study represents actually secondary analysis of a previous study the evaluation of preterm imaging study, which was a randomized control trial that looked at MRI compared with ultrasound, and how does that change the care for babies preterm and their families, so they recruited infants less than 33 weeks gestational age, between 2010 and 2013. From the London perinatal network. They looked at term equivalent MRI and in the original study, they also were comparing two ultrasounds that the infant's had had. They looked at clinical chart data regarding the delineation for IUGR. And I actually thought this was quite interesting. So they looked at babies that were less than the 10th percentile for gestational age are typical definition of IUGR. But they also included babies who had anti natal abnormalities on fetal scans, including like their Doppler ultrasound. velocimetry. So I thought that was an interesting way to include more babies in the in the IUGR group. And because so much of the antenatal testing relies on size, we may miss some babies because we we, we assume they're a different gestational age based based on their size. So I thought that was interesting

Ben 21:47

that those are the absent and reverse diastolic first.

Daphna 21:52

And then they looked at, they wanted to see what does the term MRI look like? Are there difference differences involved? The volumetric studies of the MRI, and then they looked at some of the neurodevelopmental outcomes using the Bailey, our standard and the M chat. So people who aren't as familiar with that the modified checklist for autism and toddlers, which was performed at 22 months. If you're not familiar with using volumetric data, so there are a few, there are a few atlases for looking at brain volumes of the different structures in the neonatal brain, probably the most predominantly used as the North Carolina infant brain Atlas, which they used. And it helps map the parts of the brain based on larger data sets of brain volumes. So the current study sample had 314 participants born very preterm 49, delineated as IUGR. And very preterm and 265 babies who were appropriate for gestational age, still very preterm. The demographic differences in these two groups were really only in birth weight, the birth weight percentile, which is not surprising at that, that that we're looking at, and the total intracranial volume, which is interesting. So what they found is that very preterm babies who are also IUGR, compared with Infants who are born appropriate for gestational age, had smaller relative gray matter volume, particularly in the limbic component. So that is your amygdala, your hippocampus, a lot of your emotional regulation, but they had larger relative gray matter volume in the frontal insular, the temporal parietal and the frontal components. And so this is interesting. This mirrors a lot of other brain volume studies where some parts of the brain that are being utilized actually have they get over over connections of the dendrites, and some of them actually have atrophy. And so this mirrors those studies very well. In total, we had 90% of the whole cohort, able to do the follow up assessment, which, you know, week after week, when we do this, I'm surprised how they're able to do such great follow up. And there were no differences between those 10% who didn't follow up and the 90% who did follow up in terms of rates of IUGR or other demographic characteristic

Ben 24:45

that's something that people are starting to do which is if they do lose some follow up trying to look at who are the people who lost Yeah, did you lose the sacred ones to follow up with you lose the better ones better? One meaning more healthy. So I think that's kind of nice, very important.

Daphna 24:58

Yeah. Yeah. And so interestingly enough, the the toddlers, the 22 month, babies who were IUGR compared to those toddlers who were ajga also still born very preterm had lower Bailey scores. And they also had individual components that were lower cognitive motor and language. They were also more likely to score positively on the M chat. When they did the adjustments for sex. IMD, which is the, their index of Multiple Deprivation, which acts as like a marker for socioeconomic risk, gestational age and total intracranial volume, there were still significant differences. So lower scores for cognition, motor, and then more frequent M chat positivity, and those preterm group born IUGR. And then they looked at the were the cognitive were the scores associated with different brain volume measurements. So lower cognitive scores were associated with larger volumes of the frontal and occipital components, lower motor scores were associated with larger volumes of the parietal component, and no significant difference in size of volumetric components was found in those babies who screened positive or negative on on the M chat screening. So the babies who were at risk for autism or had symptoms consistent with, you know, early features of autism, they actually didn't have differences on the on the volumetric components. So I thought this was an interesting paper, we may not have talked about that I done. I was hand doing volumetric studies is a fellow and so this totally is up my alley. But I think what it speaks to is that that IUGR population, you know, we feel like they have increased risks for comorbidities in the NICU. But we should, you know, realize that they have ongoing increased risk, even even if they have a benign course in the NICU. In terms of neurodevelopment.

Ben 27:16

I think I think that was the key. Right, that was one of their key findings, which I think were very interesting is that there's showed that the being IUGR, in and of itself is probably conferring even more risk regarding long term outcomes than just prematurity alone. I think that was that was quite striking. And I think I think we often confound IUGR, which is being small and forgiving, being small, meaning your brain is also very much affected by that. So that's a good reminder, in terms of the M chat babies who were IUGR were more likely to have autism. Yes. Yeah. So it's right. So so they are, it's like what 40 44% Compared to 27%. Right, that was that was striking, especially considering that, considering that we don't know, the causes of autism, I think this is another piece to that puzzle, as to, as to what's going on in the brains of best, it's fascinating that we still haven't figured this out. Well, and

Daphna 28:17

I think so much of our counseling around neurodevelopment is really around intraventricular hemorrhage. And the fact of the matter is that there's so much more, it's so much more complicated than that. And so we you know, we owe it to families to do the studies, and we owe it to families to talk about some of these risk factors, because they are not insignificant about how they affect, like at home, like at school, and so making sure that we get them the resource. Yeah, and

Ben 28:45

this goes back. And this goes back to the potential meaningful uses of term equivalent MRI, which which, which, again, still are being debated as should we still do them not do them resources there. It's a it's, it's fascinating. Yeah,

Daphna 29:01

I wanted to also do this other paper in the Journal of Pediatrics and enteral iron supplementation and infants born extremely preterm, and it's positive correlation with neurodevelopment, post hoc analysis of the preterm erythropoietin neuro protection trial, the peanut trial, randomized control trial. So the Dr. Kendall, our German and so this was a post hoc analysis of the peanut study. So for those of you who aren't familiar with the peanut trial to was a multisite prospective, randomized, placebo controlled trial conducted to look at was there no protective effect of babies who are born preterm between 24 weeks and 27 and six, seven weeks of gestation, who got EBO and the associated iron components versus those babies who got placee though so we're not exposed to EBO. And to summarize, really, as their kind of preliminary findings were that babies who received EBO definitely had lower numbers and lower volumes of blood transfusions. So there was definitely an impact on anemia. But they didn't find differences between the EBO. And the placebo groups at 22 to 26 months of age in the primary outcomes of death or severe neurologic impairment, or in their proposed secondary outcome of death or moderate to severe neurodevelopmental impairment.

Ben 30:40

Yeah, so this was this was a huge paper, right, because we started using hippo. I mean, I had I was tasked with writing our protocol, right? And so the big question was, do we use it for anemia? Or do we use it for Neuro protection? And so that paper really answer that question, saying, Before anaemia and reducing blood transfusions? Yes, for using it for Neuro protection, at least at this time, there's no sign that this this provides any neuro protection. And

Daphna 31:07

so what was great as a group saw that there were maybe some signals that there was still something useful to look at here. And so what they identified was that maybe it's not the anemia specifically, or the lack of anemia. But is it something related to the iron load. And so what was actually interesting about this study is that use of iron supplementation was a part of the trial, but they didn't have really standardized iron dosing. And so babies in the trial got a range of iron supplementation doses. And so it really sets up this perfect situation to look at this spectrum of doses. And so now they've looked at the cumulative iron dose, and neurodevelopmental outcomes at two years of corrected age as assessed by the Bayley skills of development. Interestingly, I wonder what would have happened if they specify the iron dose for the EBO for the peanut trial?

Ben 32:11

That's a good point,

Daphna 32:11

the conversation for a different,

Ben 32:13

right, the problem is that there's no there's no strong data as to what would be the appropriate dose. And then there's and then for the people who are listening, the these trials have some some centers have a lot of options like providing IV iron to preterm neonates, which is, which is fine, but for the institution's we've been on for example, we've had difficulty getting IV iron for babies. And so it provides challenges. And so that's, that's, again, why the paper is so good, because these multicenter trials actually have to deal with the different parameters in each center.

Daphna 32:48

Yeah, the real world, right. So the group hypothesize that there will be a positive association between iron dose and the Bayley three scores, with a greater cumulative iron dose correlating with improved outcomes. So they had 692 infants in this kind of sub cohort, 355, placebo treated and 337 EBO treated included in the analysis, there are no significant differences between the maternal or neonatal characteristics. Not surprisingly, those infants treated with EPO did receive greater cumulative iron supplementation, because that was a part of the protocol.

Ben 33:28

And they could have gone up and they could go up as high as 12. Meg's per kill. Yeah, I know. So I remember when I was reading my protocols, like I'm not putting 12 I'm gonna get murdered by the staff.

Daphna 33:42

Well, when I mean, at almost every institution I've been at the fears is iron overload, and iron toxicity, which is what I think was a really valuable point of this paper, and we're getting ahead of ourselves, which we do sometimes. So there was a consistently positive linear relationship between the cumulative iron intake at day 60. And the Bailey three scores for both treatment arms. So the babies who got EBO and had more iron had better scores and the babies who didn't get EBO, but got more iron in their group still had better Bailey scores. And then they looked at a positive but statistically insignificant association between iron dose and Bailey scores, seen in kind of all infants when they lumped them together, and that the observed effect size was still greater in the EBO treated group. So the babies who got EBO and who also got higher doses of iron had the highest Bailey scores, but not significantly different from the effect among the placebo, the placebo treated neonates, and they even you always like this, they had an increase of 50 milligrams per kilogram of cumulative annual iron at day 60 was associated with a greater mean Cogley, we have score, increase of point seven, seven points highlighted and start. Sure it was like that then like that, which which is not a lot of points. But if you continue to add cumulative venture iron and you have cumulative point seven, seven points they start to add up. So that's exactly what they found when we adjusted for the cumulative IV iron, the positive impact of cumulative iron on Bailey three scores became stronger in magnitude. And so they looked at this across all of the iron doses and their figures are excellent. So we will definitely include some of those. And if they had this consistently positive linear association between the iron dose and the neurodevelopmental outcomes, they didn't even really have a fall off, as they describe it in the curve at the Greater iron doses. So trying to target that question is, is there a certain threshold where iron overload or toxicity is seen, and then we don't see any more of this positive effect. And they didn't see any of that. And then they also didn't see any flattening of the curve, it really is a truly, truly like linear, that they didn't, at least with these doses, find any saturation point. And so they looked at this at 60 days, and they looked at it at 90 days, and it had attenuated strength of association at 90 days. So certainly the early iron exposure seemed to have the most effect. They found that greater transfusion volumes was associated with lower Bailey, three scores, which was interesting. So is it that because they got less EBO? Or is it because the babies were sicker, requiring more transfusions? You don't know. But that's interesting to note. And then they took, I really impressed they took a stab at what should our iron dosing be based on their study. And so their recommendations were for eggs per kid per day, once infants are seven days old, and tolerating at least 60 ML is per kilo of enteral feeds. And then iron doses should be adjusted to achieve the ferritin and zinc protoporphyrin to heme ratio values within a goal of 76 to 400 nanograms per milliliter, which I've never used ever. So this is something that we can definitely evaluate in the future. But they're not saying just keep going up and up on the iron either. They're saying take a look at your individual baby, and what are their ratios? And could could they use more iron? So I thought this was an interesting study for sure. I am glad that they took a closer look at the data. And I think there's probably still more information in this study. It was such a big study, such an important study that I think we'll still we'll still be getting more information. What did you think?

Ben 38:07

I'm so happy that study came out? Number one, because when I don't know if you remember when we were pediatric residents that we did give iron supplementation to our toddlers, right? And we said this is very important for brain development for IQ. Premium. Exactly. And it's never it never was a question in my mind that iron supplementation to prevent anemia would have long term impact on their on their intelligence. So the fact that this paper comes out as a as a post hoc analysis of the Peano trials is great, because it actually makes the point that it's not all about reducing transfusion, but it's also optimizing iron intake. It also, I think, in my opinion, highlights something that's not mentioned in the paper, which, like we said, If you don't have access to IV iron, it means that you're gonna have to be committed to efficient feeding protocols, because you need to get to that 60 mL per kilo per day of enteral feeds to actually start giving Iren. And you can no longer be wishy washy about extending these NPO windows where kids are NPO for 10 days, and like you don't feed a kid like you're going to need to crank up the feet so that you can start administering the supplements.

Daphna 39:16

Well, and there's iron and there's iron in the food, right? That's right. Yeah, just in the diet.

Ben 39:24

No, and it's very surprising. That's one of the reasons why I'm working on this mobile app for nutrition is because we tend to underestimate how much iron is, is in the baby's formula. And if you do start at six, eight milligrams per kilo, assuming you're giving zero iron in your formula, you're gonna give pretty large amount of iron to the baby.

Daphna 39:42

To the converse, I think that we use certain formulas in in the unit and one in particular, that is almost deficient and I totally has no iron and so I think we can we all can't wait to see your mobile apps become optimal. eyes all over micronutrients. Right?

Ben 40:02

My my team was on vacation for Diwali.

Daphna 40:06

Well, they deserve it. They've been hard at work. Yeah. And where do you want to go next?

Ben 40:12

I want to take a little intermission and do this caffeine paper. I thought this was different paper. So this is

Daphna 40:18

a paper I've been I've been, I thought when I became an attending, you know, it wasn't a fellow anymore that my caffeine intake would decrease and no, the the opposite is true. In the last few months, my caffeine intake has become exponential. So I'm curious to see what it does.

Ben 40:38

I am wondering why you ever thought you definitely go down, they'd be your null hypothesis is probably this is a paper published in. In pediatric research, it's called caffeine is a respiratory stimulant without effect on sleep in the short term and late preterm infants, they're giving away some of the confusion in the title. That's a shame. The first author, this is a paper from a group out of Helsinki, and I'm going to butcher their name for others Maija, sepa, Moilanen. And, sorry,

Daphna 41:15

well, you know, our friend, Alberto is always saying that we should have a way to, to learn the author's name in the paper. And that would be particularly important for us. We're trying, we're trying to get some health.

Ben 41:33

And so the paper starts off by mentioning obviously, that's an adult and adolescent caffeine act as a CNS stimulant. And it alters sleep quality by reducing total sleep time and sleep efficiency, prolonging sleep latency and reducing subjective sleep quality. And in clinical practice, infants seem to sleep well, even when on high dose caffeine for apnea treatment. And so the aim of the study was really to investigate whether short term of caffeine on sleep in late preterm infants with polysomnography. So I think that was very interesting trying to see if, because we shook them up with caffeine, whether they're just just more more awake and really having difficulties.

Daphna 42:16

It doesn't keep me from falling asleep.

Ben 42:19

We give them very high dose for their weight. So that's, that's interesting. And we want to give them even more now to extremely low birthweight infants. So we'll find out so anyway, they performed polysomnography recording in 21 infants born preterm in the neonatal unit of Helsinki University, hospital and Finland. Basically, at the time of the study, the infants were clinically stable with no respiratory support or caffeine treatment. So that was very interesting yesterday, because we tend to start getting almost an admission if we suspect apnea of prematurity. But these are babies that were not on caffeine, and then were subsequently evaluated for apnea and then started on caffeine to study the infants.

Daphna 42:56

Some of them some of them were on caffeine, but had completed a caffeine course and then they will reevaluate had been

Ben 43:02

exactly the studied infants were considered by the clinician in charge to need caffeine treatment for opinions with the saturation or excessive periodic breathing, breathing. The study infants underwent four polysomnography studies to investigate respiratory events and sleep on day one. And so that's how they broke it down on day one, they had a baseline recording followed by the administration of caffeine citrate loading dose of 20 mils per kilo Kaffee, treatment was continued with a daily dose of five mils per kilo. And on day two after onset of caffeine treatment per second recording was performed. You can go into the methods when it comes to the polysomnography not a sleep medicine expert, but they do go over all the details of the EEG patterns and all the measurement they did. I think what's important is that arousal was defined as a period of three second or more with a sustained increase in chin EMG with, with or without changes in the EEG signal, because obviously, that's what they're looking at in terms of arousal secondary to the caffeine, and they determined that respiratory pauses of four second or more as apneas. So without much further ado, the results. So they were able to have 21 infants that were 4.7 weeks on the median The median age for gestational age was 36 weeks, and they were born at a median of 31 weeks. With a birth weight of with a median between 1.6 kilos, none of the infants receive respiratory support or supplemental oxygen directly before the study. 67% of the infants had previous caffeine treatment, as you mentioned, which was discontinued at a median of eight days before the study onset. I think that was important for them to mention because of HalfLife issue. So the caffeine acted as a short term breathing stimulant, it reduced the number of apnea the frequency of oxygen saturation, the saturations increased median SPO, two levels and decreased the high 95th percentile I'll end tidal co2 level. But caffeine did not show significant effect on breathing frequency. When looking at the sleep characteristic baseline polysomnography recording lasted longer than recording after the onset of caffeine treatment. But there was no significant difference in sleep efficiency. All the main sleep attributes remains similar in both study phases, sleep stages, distribution, frequency of sleep, state transitions, REM sleep latency and other characteristic of REM sleep showed no significant changes during caffeine treatment. That's pretty much it. And so the conclusion, the conclusion of the paper is that caffeine is a is it, it increases the arousal frequency to hypoxia, so that when the kids did get hypoxic, they they aroused quick more quickly, but it did not really act as a CNS stimulant, and affect their sleep quality. So that was cool, that babies can have a good night's sleep.

Daphna 45:55

That's right. You know, you know, I wrote I have a review article on neonatal sleep. They didn't cite my article, but I have. And in this is a really important study, there's so much we still don't understand about neonatal sleep. And the fact that they were able to complete a full gamut polysomnography on on these infants, I think is really valuable to show that we can do it, it's safe to do it. And in that we have a method to keep studying neonatal sleep. The other thing they talked about, which is kind of becoming a hot topic is heart rate variability. So looking at the beat to beat variability and heart rate. And so it, it kind of explains the interplay with between your sympathetic and parasympathetic nervous systems, it's a pretty good marker of well being. And so one might suspect that if you are highly caffeinated, that that might change your your heart rate variability somewhat, and they showed that it didn't. And so I thought that was also very interesting. And, you know, it's interesting, because we still don't really understand why caffeine works for babies, right? You know, we have we make some assumptions. And so I think more studies like this will help us understand that a little bit better,

Ben 47:19

because there's a paper touch on whether babies have dreams or not.

Daphna 47:23

It does not specifically touch on that talks more about the sleep wake cycles, where we can hypothesize that babies have dreams or not.

Ben 47:33

I think people have had, people have hypothesized that they do. They do. But that is the hypothesis, but we don't know what they dream about.

Daphna 47:43

I know I can't remember my dreams. That's what I know. So I don't expect the babies to either. And there are a few other really good studies. I wanted to talk about this study about lung ultrasound. Yeah, go ahead. Another paper from the Journal of Pediatrics, lung ultrasound for prediction. Dream preterm neonates, a prospective diagnostic cohort study, lead author Adele Mohamad. This is coming to us from Toronto, Canada. And so this was a prospective diagnostic cohort study conducted between July 2019 and December 2020. Recruiting infants less than 29 weeks at to tertiary care NICUs at Mount Sinai Hospital in Toronto and Health Sciences Center in Winnipeg. And so, what they did is they took this cohort a total of 152 invents, who were less than 29 weeks gestational age, they had a mean gestational age of actually 25.8 weeks. And they wanted to see if doing early lung, ultrasounds would predict the development of bronchopulmonary dysplasia. And just so we're all talking about the same thing. For definitions, their outcome measure of interest is BP as defined as the supplemental use of oxygen or respiratory support at 36 weeks of postmenstrual age or at the time of discharge. And they did it use the classification system mild, moderate and severe, using the NICU HD definition. So I told you the mean gestational age was 25 weeks, the mean birth weight was 923 grams, so pretty big group 44% male and 72% had received antenatal steroids, good for them. So what they did is for this group, they waited the first 72 hours because all of these babies were on their kind of neuro protection bundles. But on day three, the babies underwent lung ultrasound on day seven plus or minus one The day the baby's went, underwent a second one ultrasound. And on day 14 plus or minus two days, the babies underwent third lung ultrasound. And then they perform the lung ultrasound score by two separate people scanning for each zone of bilateral lungs. So for each baby, they had six zones total. And then they provided a cumulative score for the infant. And then for people who are invested in point of care, ultrasound, and how that still kind of a developing technology in the NICU, I think they did something that was really important that I wanted to highlight. So then they took 20% of the scans, and they reassessed them by other people so that they could really feel like they had good heterogeneity. Homogeneity scuze me about their definitions of the lung ultrasound score. So over time, 57% of this cohort was diagnosed with BPD, the lung ultrasound scores were significantly higher, and infants diagnosed with BPD compared with infants not diagnosed with BPD at every scan time point. So even at the three day long ultrasound, it predicted BPD, a score of greater than 10 at all three scan time points had a higher sensitivity, with specificity of 80%. And clinically relevant positive and negative likelihood ratios. And so they show their area under the curve for lung ultrasounds using all three scanning time points. And it shows an area under the curve of point nine, four. And so very highly predictive of BPD. And I think it just goes to show you some babies really are just from from the get go, our will, will develop BPD. And there are so many things we don't understand about which babies those are early on. I think that potentially no matter what we know right now, no matter what we do for them that they're developing BPD. But I think it's helpful, that potentially, we will treat babies different in the future based on their BPD. And this,

Ben 52:20

this is our way of getting as close as we can to potential histological sample, right. I mean, technically, we're not going to biopsy their lungs, technically, we're not going to put them through high resolution CT. And considering that BPD is a direct product of arrest in development, it makes sense that early ultrasound should start identifying some findings that could tell you that based on the degree of lung development, you can have, you can have severe BPD. Or you can have BPD down the road. So I think it shows a lot of promise. And yeah,

Daphna 52:53

absolutely. And the lung ultrasound score, which I don't know that we have the time to go all the way into but the lung characteristics, the eight lines, the B lines, those are things that are easily taught, right. And so I think this has a lot of value. It doesn't require any extra radiation. And the other point is that some people are really worried about scanning little babies in the first week of life. And I think at a minimum, this study showed that they they were able to do that safely.

Ben 53:23

Yeah, we're getting a nice ultrasound machine in our new hospital. Are we moving on Monday? So that's yeah, we're gonna start doing that kind of stuff. Let me let me mention this paper. Obviously, this is for for our listeners, I think this is one of the missions of the show is to keep you up to date. So there's, there's a Cochrane paper paper from the Cochrane Library that is out called early systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants. first author is like soil. There's a lot of famous author on this, on this on this on this paper, Brett Manley as well. So anyway, it's interesting because, as you mentioned, when the paper showed up on our folder of papers, reviews, it didn't we do something like that recently, and Lexol did write a very thorough review of the use of corticosteroids in the prevention of BPD and neonatology. So you can always go back to that episode or to that paper, but this is obviously a much more specific paper because it looks at early administration of steroids. And and it's interesting because they are looking obviously at the most common ones, because that's what most studies have looked at dexamethasone and hydrocortisone, they looked at primary outcomes of mortality, BPD death or BPD and long term outcomes, including blindness, deafness, CPE, and major neurodevelopmental disability. So they included a total of 32 states. These 21 studies use primary dexamethasone. And it's interesting because they said that the most common regimen and it's important to mention that it was point five mils per kilo per day of dexamethasone for three days, followed by point two, five or three days. Then point one two mils per kilo per day for three days followed by point 05 mils per kilo per day for three days. And then 11 out of 32 studies use hydrocortisone. The doses was very variable, some use almost physiologic doses. And some did not some were using it for management of hypertension, so it's a bit difficult to tease apart how hydrocortisone was used. But I think the findings were quite interesting what we'll go into them relatively quickly. But when it came to mortality, there was no evidence to suggest that early postnatal corticosteroid treatment reduced mortality at 20 days of life, or at 36 weeks of was menstrual age, or before discharge, or at the latest possible age to determine the outcome? When it came to BPD. It was very interesting because and, and we're not going to go too much into detail because the idea of corticosteroids preventing BPD, there's tons of data out there. But early systemic corticosteroids reduce the incidence of BPD, defined as needing oxygen at 20 days of life, and at 36 Weeks was menstrual age. There was a reduction in pediatric six weeks among survivors. Early systemic steroids reduce the need for later steroids, and among survivors. Let's what we'll go into, we'll skip ahead of the paper and look at some of the data that they presented when they looked at specific steroid types. And I think that's what's interesting. So when they were looking at BPD, they said most of the benefits of early systemic steroids in reducing the incidence of BPD was provided by dexamethasone with little effect of hydrocortisone, regardless of the definition of BPD benefits of reducing the need for oxygen at 36 weeks in survivors or of providing late rescue with post neurosteroids. We're also largely confined to the X medicine group. Strong evidence shows subgroup differences with low p values for interested find. I'll take that back. But so we know we know that dexamethasone is the one that is really, really effective, especially when compared to hydrocortisone. But then if you go through the paper, and you look at some of the other outcomes, it becomes a bit more tedious because when you're looking at complications, and you're looking at gastrointestinal complications, like intestinal perforation, and when you're looking at long term effects, such as cerebral palsy developmental delay, then those are also associated with dexamethasone. And so I think it's difficult to it's difficult to to provide a clear end point when it comes to the recommendations. And I think the implications for practice at the end of the of the paper quite summarized the dilemma that we're facing when it comes to deciding between dexamethasone and hydrocortisone when it comes to early cortical steroid use. And I'm just going to read you this and then we can move on to the next one because we're going to start running low on time, but they said benefits of early systemic postnatal steroids for preterm infants at risk of developing BPD may not repeat may not outweigh the real or potential adverse effects. Early systemic postnatal corticosteroid treatment resulted in short term benefits, including earlier extubation, decreased risk of BPD and of death or BPD at 20 days of life and at 36 weeks postmenstrual age, but was associated with a significant short term and long term adverse effects, adverse effects including short term risk of gastrointestinal bleeding, intestinal perforation, hyperglycemia, hypertension, as well as long term risks of abnormal neurological examination, finding and cerebral palsy. However, the methodological quality of studies determining long term outcome was limited in some cases, children versus predominantly before school age and no study was sufficiently powered to detect the important adverse long term neurosensory outcome. Therefore, given the risk of potential short term and long term adverse effects, versus potential short term benefits, the review supports curtailment of early systemic corticosteroids treatment for prevention of BPD. And, and here, I think, what and here we are, but they are saying that the findings from the studies on hydrocortisone, which are still in their infancy are showing I guess, quote unquote, promise. So this is why it is not

Daphna 59:30

easy answer is that there are probably some babies that are the right group to choose. And there are some babies that are probably the wrong babies to expose. We just don't know which group that is.

Ben 59:43

It's hard when you're looking at early administration of hydrocortisone, like they said, some of them give it for physiologic doses for BPD prevention. Some of them are doing it for hypertension, it's so hard to figure out how to how to interpret this data. So Yeah, I guess more More to come

Daphna 1:00:02

more to come. And we do know that there's probably this group of babies. It's probably not all of them that little babies, but there's probably a group babies that truly do have some degree of adrenal insufficiency. And so something about hydrocortisone as opposed to the other steroids, I think potentially has has promised, but we haven't identified which babies those are yet.

Ben 1:00:27

So we do one more, and close the show with one more.

Daphna 1:00:30

Um, yeah. Did you have one you wanted to do? I thought this Umbilical Catheter,

Ben 1:00:36

that's the one I wanted to do, especially because it was recommended to us by one of our Twitter followers. And I really wanted to make a point to address address that paper because it was it was kindly brought to our attention by one of our listeners.

Daphna 1:00:52

Let me to go. Yeah, go ahead. Yeah, I was I was just you were looking for the tweet.

Ben 1:00:58

I was looking for the tweets of the person that the person that recommended the paper is John Foster a neonatology Fellow at Stanford. So thank you for pointing out the paper. And the Yeah,

Daphna 1:01:11

recommendations coming. So this is in journal apparently otology, a novel and accurate method for estimating umbilical arterial and venous catheter insertion length, lead author, Christina Tabasco, this is out of Yale University. So I thought this was a pretty innovative, right, they took something that we do all the time, we've been doing the same way for a very long time, which is measuring deciding on the insertion depth of umbilical catheters. And so they looked at, they did a retrospective component review of infants from January 2016, to December 8 2018, who had successful umbilical line placements, and they in their unit, and most units, were using insertion lengths estimated by the shoe glue equations. With then we take the x ray, and we make changes based on where those lines ended up in the babies. And so particularly for our trainees, if you feel like well, gosh, I'm always having to reposition the line. I think the study shows that yes, that's in fact, true for most of us. And so much like most of us do, their target positioning was for a UAC catheter tip between the sixth and ninth thoracic vertebra. But they used an acceptable position is between the sixth and 10th thoracic vertebra. And then the optimal UVC position defined as a catheter tip measuring between point five centimeters below and one centimeter above the right hemidiaphragm medially, on on an AP radiograph. And so they looked at all of the babies in this retrospective review, and to see how frequently, the lines needed to be repositioned. And after using the equations that we were all used to using, and then they derived a model using their own data. And so they took the final insertion lengths, and adjusted them to account for basically the difference of the position that they found. They found the catheter minus T eight as a proxy for the midpoint of T six to t nine. And the final insertion lengths of uacs and UBCs. Were also plotted against birth weight. And then they made equations for line for trend lines, using statistical modeling and internal validation. And insertion lengths for discrete birth weight ranges were then derive by rounding outcome variables to the nearest point five centimeters for uacs. And point two five centimeters for UBC is to basically form data tables based on birth weight. Then they created a really cool mobile app. Did you download it?

Ben 1:04:15

I did. Yeah, I'm

Daphna 1:04:17

sure you did. It's called ambi Calc. It's super easy to use. It's free, and they also inputted this into their Epic EMR so that it would program the insertion length estimates automatically for both uacs and UBCs. When they when they made their procedure No. And then they took this model and they use a prospective cohort from June 2020 to November 2020. Where they either use the MB calculator or an OB Calc and or they use the Epic EMR to basically give them the right depth of insertion based on the birth weight. And then the umbilical catheters were advanced to the st made an insertion length. And then they wanted to see how accurate was the model. So were they able to get the line in the right position on the first attempt, and then they use radiographs to predict the final position. So there's a lot of math here, I know you dug this to about all of their math equations. They're all here. So for anybody who wants to replicate it, it's here. Or you can use the MB Calc. So they had 597, uacs, 629 UBCs, placed in 804 infants during that 36 month retrospective study period. And so, basically, what they found in the retrospective, so the first group of babies that the schugel equation successfully predicted acceptable insertion length, and 69% of uacs, and only 36% of UBCs. And in this group of infants, and so they had to do a lot of adjustments, which, which is, we all know the pain of sitting and waiting for the next X ray. And then, during their six month prospective period, where they use their own modeling and the aamby Calc, they placed 164 umbilical catheters in 112 infants, the median gestational age of which were 31 weeks, but ranged from 22 to 41 weeks and medium birth weight of 1650, but range from 490 to 4660. So big babies and little babies. And so basically, what they found is that their new prediction model provided correct insertion length estimates in 90%, of uacs. And 76% of UV sees on the first attempt, so improved success rates in all the birth weight categories, because then they looked at babies by gestational age, but also by birth weight, they were specifically interested in the smallest babies, where as we all know, it's it's difficult to keep the correct line position. And so even the smallest babies less than 750 grams, they had exceptional success rates in that group in, in particular, 81% of uacs, and 77% of UVC placements using the new equations, compared to 44% of uacs and 32% of UBCs, using our typical models, so I thought that was pretty cool.

Ben 1:07:32

Yeah, I think that was pretty cool. Number one, because it's a paper that usually they do these things, most of papers I've seen like they come up with a with a with an equation and then the app. And then the app comes later. But this was so nice that they had they had the paper the app every you could you can get everything the whole bundle right away. And I think it's something that's that's important to do. I also think that this type of papers specifically addressing umbilical line position is something that is direly needed right now. But I feel like once point of care, ultrasound is everywhere. We won't use calculations anymore, we'll just like put the probe and look at the position and call it a day. Until then I still need to use these these calculators. And the on Twitter when the discussion started around this paper, people said, Oh, let me I'm going to start using it. But obviously, I didn't want to start using it. I wanted to compare because I have a little app on my phone that use the, the, the chakra equation, right. And so I started plugging in different weights and trying to see how the to the to the to compare. And I have to say when you're looking at bigger birth weights, like closer to a kilo or pasture kilo, they're fairly similar. Both the the aamby, Calc and the Shockley equation. So I don't know if it's going to make that much of a difference there. However, when you go way, way down and the birth weights you started looking at like 600 grammar 400 grammars, you can see a gap in the in the output of these calculations. And if I think from memory at least this is something that has given me trouble in the past where an extremely low birth weight infant you calculate it, and then you press Blake, really I have to pull it even more and and you're like but it's already the UVC is already at five like you want. So I think this is going to be my go to especially when it's going to come to two extremely extremely low birth rate at less than 750 because I think this is where the sugar equation has given me more trouble in the past. So yeah, I mean,

Daphna 1:09:32

we we experienced that right? The big babies you rarely have to make any major adjustments but those little babies you feel like you're in out back a little bit and the next day doing the same thing, and it's it's critical right if we're trying to make our golden hour for example, waiting for a few additional X rays or finish or repositioning really prolongs the time that you know if it's the top open Yeah, the tops open and then

Ben 1:09:59

30 patience for the for the adjacent beds and it's really efficient for the staff. And also when you have to when you put it too deep and you have to pull there's there was anxiety of like pulling that UVC just a bit too much. And then it's suddenly low lying or falls into the in deliver and you're like

Daphna 1:10:16

well I'm you know, as a fellow, you know you Oh, as you pulled up your first extra, you know, the first extra, you're so proud. And the attending says what, Woody, what are you trying to catheterized the baby and the equation equation and I don't know I did the equation again and it's still where I would expect it. So anyways, hopefully they will save some tree trainees the embarrassment.

Ben 1:10:41

But the mechanic is super easy to use. You can find it on the app store. I think the icon is purple. It has like it's a it's like a you with some some gradation on it. So it's like a purple. It's a purple icon with a white you want it? Yeah. Great, great paper and super fun to play around with this app.

Daphna 1:10:59

Yeah, that was fun. Keep the recommendations coming.

Ben 1:11:03

Agreed. Agreed. All right. Anything else that for?

Daphna 1:11:07

Now? I think it's it's late night for us here.

Ben 1:11:09

I want to I want to just finish up the show by thanking everybody for downloading the episode with killer Jana. It's like this is I didn't know how this was going to be received to talk to a pharmacist. I didn't know if people were going to be as interested as we were to talk

Daphna 1:11:22

to pharmacists are people too?

Ben 1:11:24

I know, I know. But you never know this not not has not really been done before, as far as I know. And so it's so exciting. And so then I guess my my feedback to the audience's if there are other areas of the NICU and other people from the NICU that you want to hear from? Let us know, I think we have some plans to talk to speech therapy. But if you have any other ideas, keep them coming. We have

Daphna 1:11:53

lots of plans to talk to lots of people. But certainly we're happy to take recommendations. Kellyanne is like one of the coolest people I know. So you know that is

Ben 1:12:03

a standard. Very high standard for pharmacists, because she does so much but anyway. All right, definitely. There was fun.

Daphna 1:12:10

Thanks, everybody. Be well. Bye bye.

Ben 1:12:14

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 Daphna is at Dr. Duffner 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