Hello Friends 👋

We hope you enjoy this week's Journal Club. Unintentionally, this week's episode has a strong infectious disease feel to it. We talk about using oral antibiotics in neonates with suspected infections, bacterial colonization of OG vs NG, the implications of drawing blood cultures from both central cathethers and peripheral site, and epidemiology of neonatal COVID in the US. We also reviewed other very intersting articles. Please make sure to collect your CME credit for this week and we hope to see you Monday for another week of neonatology review podcasts

Have a good sunday !

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

Blood pressure values and hypotension management in extremely preterm infants: a multi-center study. Peeples ES, Comstock BA, Heagerty PJ, Juul SE; Preterm Erythropoietin Neuroprotection (PENUT) Trial Investigators.J Perinatol. 2022 Sep;42(9):1169-1175. doi: 10.1038/s41372-022-01425-2. Epub 2022 Jun 17.

Associations Between Maternal Antenatal Corticosteroid Treatment and Psychological Developmental and Neurosensory Disorders in Children. Räikkönen K, Gissler M, Tapiainen T, Kajantie E.JAMA Netw Open. 2022 Aug 1;5(8):e2228518. doi: 10.1001/jamanetworkopen.2022.28518.

Epidemiology of Neonatal COVID-19 in the United States.Devin J, Marano R, Mikhael M, Feaster W, Sanger T, Ehwerhemuepha L.Pediatrics. 2022 Oct 1;150(4):e2022056297. doi: 10.1542/peds.2022-056297.

Age at First Extubation Attempt and Death or Respiratory Morbidities in Extremely Preterm Infants. Shalish W, Keszler M, Kovacs L, Chawla S, Latremouille S, Beltempo M, Kearney RE, Sant'Anna GM.J Pediatr. 2023 Jan;252:124-130.e3. doi: 10.1016/j.jpeds.2022.08.025. Epub 2022 Aug 24.

Dual-site blood culture yield and time to positivity in neonatal late-onset sepsis. Coggins SA, Harris MC, Srinivasan L.Arch Dis Child Fetal Neonatal Ed. 2022 Sep;107(5):475-480. doi: 10.1136/archdischild-2021-322844. Epub 2021 Nov 9.

A comparison of bacterial colonization between nasogastric and orogastric enteral feeding tubes in infants in the neonatal intensive care unit. Vongbhavit K, Salinero LK, Kalanetra KM, Masarweh C, Yu A, Taft DH, Mills DA, Underwood MA.J Perinatol. 2022 Nov;42(11):1446-1452. doi: 10.1038/s41372-022-01452-z. Epub 2022 Jul 15.

Efficacy and safety of switching from intravenous to oral antibiotics (amoxicillin-clavulanic acid) versus a full course of intravenous antibiotics in neonates with probable bacterial infection (RAIN): a multicentre, randomised, open-label, non-inferiority trial. Keij FM, Kornelisse RF, Hartwig NG, van der Sluijs-Bens J, van Beek RHT, van Driel A, van Rooij LGM, van Dalen-Vink I, Driessen GJA, Kenter S, von Lindern JS, Eijkemans M, Stam-Stigter GM, Qi H, van den Berg MM, Baartmans MGA, van der Meer-Kappelle LH, Meijssen CB, Norbruis OF, Heidema J, van Rossem MC, den Butter PCP, Allegaert K, Reiss IKM, Tramper-Stranders GA.Lancet Child Adolesc Health. 2022 Nov;6(11):799-809. doi: 10.1016/S2352-4642(22)00245-0. Epub 2022 Sep 9.

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

Ben 1:00

Hello, everybody. Welcome back to another episode of the incubator. Journal Club episodes. Right?

Daphna 1:06

That's right. That's right.

Ben 1:10

Very odd hours, isn't

Daphna 1:11

it? This isn't our first time doing this.

Ben 1:13

I know. I know. We're recording very close to release though. That's it's something that we haven't done in a while. Have you been definitely I'm good.

Daphna 1:22

I'm good. Long call lung overnight. But it's okay. Yeah, it's service week. Right. But you forgot you forgot about that. I forgot about I think things are things are stable as we as they say.

Ben 1:38

How about you? Oh, about to go on service. That's right. When trading? Yeah. So I'm all amped up and ready to go.

Daphna 1:46

So so. So we're recording on our one day where neither of us have their answer.

Ben 1:53

That's correct. Tomorrow, which is Monday, we'll have our neonatology review podcast that will be coming back this week, we'll be talking about extubation readiness, and we're very excited to have our first guest host for this series. Dr. Lindsay Clinique is going to be hosting this week, we'll be there as well, obviously. And it's it's a great series of episodes, we hope you really enjoy it. And so stay tuned for that.

Daphna 2:23

And we've got some other guests lining up. So that's,

Ben 2:28

that is correct. If you are interested in in presenting a topic on the neonatology review podcast, reach out to us and we'll, we'll see where we can fit that in. And we're we're just very excited to give people an opportunity to share their voices and their expertise. It's a lot of fun. But on to journal club, there's so many articles as usual, so we should not waste too much time. Do you want to should they start to do you want to start? Yeah, you

Daphna 2:54

start you always start?

Ben 2:56

Fine. I'll start then. I wanted to begin with this paper that was published in The Lancet. And I wanted to give credit actually where credit is due on because despite having two faculty appointment at two different universities, I still didn't have institutional access to that paper.

Daphna 3:17

It's a problem. It's a big problem that I mean, not just for this paper, right, like it's

Ben 3:24

not just for that theory. That paper is just a good example of this. So I had to reach out to our friend on Twitter, Dr. Atul Malhotra and asked them to if you could share the PDF with me. So a tool Thank you. Thank you. This this episode of journal club is partly sponsored by you then. The paper, the paper is called efficacy and safety of switching from IV to oral antibiotics, amoxicillin clavulanic acid versus a full course of intravenous antibiotics and neonates with probable bacterial infection infection. This is the Raine trial. It's a multicenter randomized open label non inferiority trial. Quite a mouthful of this is still the title, by the way.

Daphna 4:06

But a hot topic, right? Yeah,

Ben 4:09

very interesting. Actually, I was very curious to read that paper, the first author's flu cage, and this is from the coming from a group in the Netherlands. So the background is very interesting, obviously, because it says a lot of things that we probably all already know. The initiation of antibiotics of antibiotic therapy is based on an assessment in which there's some maternal risk factors and neonatal clinical symptoms are considered and we'll make a decision. And once we start antibiotics, usually we tend to stop at 36 to 48 hours in most cases, if there is enough evidence to reject the suspicion that the baby is infected. Now switching from IV to oral antibiotics is quite common in older children in PD in more mainstream pediatrics, as we probably all know, from our personal training, but the as the authors highlight. It's rarely used in neonates, and mostly because of concerns regarding drug absorption and subsequent exposure. Now, what's interesting is that they're recording a few large clinical trials in low income and middle income countries that have shown that simplified antibiotic regimens, including oral antibiotic are not inferior to parenteral administration and that this treatment strategy has already been recommended by the who, in cases where hospital referral is not feasible. And it's another great example of how high income countries I guess, or countries with with more resources could potentially learn from experiences in low income and middle income countries. Because the question is, can we evaluate whether this is feasible even in countries that are not LMI? See, like low and middle income. And so the group aimed to evaluate the non inferiority of IV to oral antibiotics which therapy with augmentin, basically right amoxicillin clavulanic acid in neonates with probable bacterial infection compared with a complete course of IV therapy. So I know this is sort of talking about the design of the study, but the bottom line is these are not kids who have positive cultures are positive and right I mean, we're not saying like you're going to treat bacteremia sepsis and meningitis with Po, but it's all these suspicions where it's like, you don't really have anything to go on. And so so this is where we lead the rain trial is trying to provide some answers. So the the rain study is a multicenter randomized, open label non inferiority trial participants were enrolled at 17 teaching hospitals in the Netherlands. The inclusion criteria were neonates with a postmenstrual age of 35 weeks or more, the postnatal age of zero to 28 days, and they had to have a body weight of at least two kilogram. And these were babies who were intended to receive a seven day course of antibiotics for, quote, probable bacterial infection. And these were the kids that were eligible for enrollment. And neonates had to be clinically improved and tolerate oral feeding at the time of inclusion. Now, what does that mean? Probable, right. I mean, I think that's what we're always like, right? We all have different definitions. But in this case, probable bacterial infection was defined as the presence of maternal risk factors or clinical symptoms, and elevated inflammatory parameters, whether it's like CRP of 10, or more elevated or elevated procalcitonin. And despite having negative blood cultures, no mentions of Ben de Mia or things like that on the CBC because I feel like sometimes it's it's the situation I find myself in where you have, you have a baby with a maybe elevated CRP, the bends are high culture is negative, and you're like, am I gonna do a full course not a full course. But regardless the excluded on neonates who the infection suspicion was rejected after 36 to 48 hours of antibiotic. All neonates with a cultural proven bacterial infection or severe clinical sepsis also were excluded. And the additional exclusion criteria were failure to collect a blood culture the presence of central venous catheter, severe hypermobility and major congenital anomalies. So how did they do this switch? Right? How did they transition tickets, so neonates were randomly assigned at 42 to 78 hours after the initiation of IV antibiotics. When the blood culture remained negatives, they were randomly assigned to on a one to one fashion to either an intervention group which was oral antibiotics, or the control group, which was continuation of IV antibiotics. After randomization, neonates allocated to the intervention group switch to an oral suspension of amoxicillin and clavulanic acid given daily in three doses so Q eight hours basically augmentin Q eight hours. But where this this, this study holds a lot of promises, because these neonates who are on augmentin, which is Po, a bit like in the pediatric inpatient for a word then discharged home once they had been shown to tolerate the oral suspension and had no other reason to remain in the hospital. And so suddenly, the baby that needs seven day treatment can continue the last 3434 days of treatment at home. Both groups were treated for seven days. Follow up for the participants included telephone interview on days four and 14 by a member of the study team. And then they had some digital questionnaire. They had a an outpatient clinical visit on day 35 etc. Anyway, so what are they looking at? So they switch these kids and what is the outcome? So the primary outcome was cumulative bacterial reinfection within 20 days after treatment completion, which is sort of what you you're worried about, right? You You're not really treating the infection if they it's they're assuming the worst case scenario. Kids are actually infected, they need the treatment and then they get re infected. So how did they define a bacterial infection? It was clinical symptoms of infection such as fever, hyperthermia, elevated inflammatory markers. And that was it. They didn't really have to have a positive culture or a positive urine culture or positive CSF culture, just having fever, temperature instability, elevated inflammatory markers, and needing another course of antibiotics was enough. I think I forgot to mention that with a need for prolonged data. And that's

Daphna 10:24

interesting, too, right? How do we how do we decide who needs it? Pro more antibiotics, right. But

Ben 10:32

and I think that this was because it was a non inferiority trial. They were very strict. Like, you know, what, if a patient needs antibiotics, and we've we're going to consider it we feel secondary outcomes were clinical deterioration during the study intervention, with symptoms, possibly related to either new or ongoing infection, the duration of hospitalization, readmission rate, they had some quality of life questionnaire in the first month end adverse events. And they had other they have other additional secondary outcomes, and and some of these will be released in the upcoming studies. And I think that's it, that's what I'm gonna talk about, let's let's keep moving on. So, from 2018 to 2021, they were able to have 510 neonates that were randomly assigned, and after excluding a few, the group were 252 infants in the augmentin group, and 252 infants in the IV antibiotics. They had both an intention to treat analysis set. And they also had a protocol population. The median gestational age was 40.3 weeks. Again, we said that in the inclusion but it's it's meant for full term babies, right? We're not looking at pre terms. 97% of the 400 of the 504 neonates received antibiotic treatment for suspected early onset sepsis that was presenting before 72 hours of life. The majority of neonates were treated according to the National Guideline and received penicillin and gentamicin IV for the first 48 hours of life, which is sort of what we all do. We or at least it was we both to here as well. 39% required respiratory support in the first 48 hours of life, which is not insignificant, right? I mean, you always wonder, are these kids just transitioning or Are they sick? CSF and urine cultures were not routinely performed. Patients allocated to the amoxicillin clavulanic acid group switched after a median of seven after seven days of IV penicillin, antibiotic after 7am Sorry, not seven days, what am I saying? I was I knew I was reading this wrong. Sorry. So the patients were switched to the augmentin after seven IV penicillin antibiotic administration, which is about like two three days basically. The oral suspension was generally well tolerated. Over the available data 2% of the 244 neonates in the augmentin group did not complete the full course with 49 of them. So with 49 of them of the width 49 of the which is 20% of the kids in the ivy group who did not complete their course either. These were considered protocol violations. Yeah. So let's talk about some of the primary outcomes. So the cumulative reinfection rate at day 28 was similar between the groups. It was one of 252 neonates in the augmentin group versus one of 252 neonates in the IV antibiotic group. And these really only, as you recall, only included probable bacterial infections only. So these two neonates because it's only two of them were actually referred to the hospital with fever, clinical signs of infection and elevated inflammatory markers two weeks after treatment completion, which to be honest with you, many people would say, could be even related to the initial bacterial and viral tests remain negative. Very important. I think that this was mentioned. Both neonates received the full course of antibiotics and both episodes were consequently considered the primary outcome. What else interestingly enough, they had a few late preterm neonates, babies who were like 35 to 37 weeks, and they were included in the study in the study, the occurrence of the primary outcome was low and none of the cases occurred in late preterm infants. So that was also interesting to see. Obviously, in the intention to treat a population the median duration of hospitalization was significantly shorter in the PIO antibiotic group, the amoxicillin clavulanic acid group, compared to the IV group. It's 3.4 days versus 6.8 days and that was significant. There was no the occurrence of serious adverse event and the readmission rates were similar between the two groups. And regards to quality of life. The in the intention to treat population there was no difference in exclusive breastfeeding rates and or sleep quality observed in the first month after treatment completion in both groups. But another last important point patient in the IV group had a median of two additional intravenous cannula reinsertion attempts during readmission during admission. So that's that's a big deal. I mean, IV infiltrates needing an IV is not a benign. And so in conclusion, the conclusion of the article is that early IV to oral antibiotics which therapy with amoxicillin clavulanic acid is not inferior to a full course of IV antibiotics in neonates with probable bacterial infection. We found no increase in adverse event in association with the use of oral antibiotics. And neonates receiving oral treatment can be discharged home earlier, which might help improve their and their parents wellbeing and potentially reduce healthcare costs. So love that paper.

Daphna 15:47

Yeah, I mean, obviously, right? Well, we'll, we'll play the the ad the, as I say, the devil's advocate here. I'm sure there's some people who say, well, probably a lot of those babies didn't need antibiotics anyways. Right? And if you could put them on oral and send them home, then then do they really need the antibiotics. But we've all been there, right? Where there's a baby that you just feel worried about taking off the antibiotics. And maybe this is a

Ben 16:16

it provides. It provides a another option that sometimes we don't have there. Sometimes there's a baby. Because here's here's the dilemma that I had, I had these discussions actually with with one of my senior residents in pediatric residency where the discussion is, you start the antibiotic because you're worried, right? You have very little information in the beginning, and you're like, you know what, I can't I can't jeopardize this baby's health. So I'm going to start antibiotics. And then you accumulate more data, the baby doesn't look as sick maybe. And you say, Well, did I did I just jumped the gun a bit too much. Nothing is growing. But now, but now I'm still treating this original picture, right? And then you could have, like you said, devil's advocate, who says, well, could the kid look so good, because the antibiotics are working? Right? And it's like, and then it's like, ah, because if it is, if it is in vivo,

Daphna 17:06

you were worried and now the baby's better. But the baby's been

Ben 17:10

better because you're doing something. And so I felt like sometimes you're like, I don't feel comfortable, just stopping. I also don't feel great about continuing IV antibiotics and keeping the baby in the hospital for seven days. So I feel like having that option is phenomenal. Phenomenal. Yeah,

Daphna 17:24

I think it also there's also that group of babies, right? Where you're close to the end of the course, in the IVs Fallout, right? Or they go bad or whatever. And so then you could say, Yeah, let's let's proceed with oral and I imagine I imagine it in our lifetime in our careers that we will potentially be finishing even some courses for you know, culture proven sepsis with

Unknown Speaker 17:52

with a kid easy see,

Daphna 17:54

we'll see. We'll see. I'm okay being wrong. That's what

Ben 18:02

I'm trying to get people on board. That's why I was so I was tiptoeing around the facts like it's for suspected. I was like, I don't want to get like we I don't want to get a slew of emails saying like, we should be doing this, but maybe hopefully.

Daphna 18:17

All right, I have an interesting paper. This is a comparison of bacterial colonization between nasal gastric and orogastric enteral feeding tubes in infants in the neonatal intensive care unit. This is in a journal Perinatology. Lead author, Connor Carr Vong, Bobbitt, and senior author Mark Underwood. This is from University of California Davis. So what's the question and they really wanted to evaluate the difference between the associated biofilms in orogastric tubes and nasal gastric tube like, what are the bacteria that exist? Is there a difference? So, the inclusion criteria were basically all babies during the study period in their unit with an orogastric or nasal gastric tubes were all able to be included in this study. So the intervention so babies had routine care and when the tubes were removed on the regular schedule as anticipated for that baby, the team cut the tube into Fringilla, esophageal and gastric segments based on you know, the length of the tube for evaluation in this study, they're describing the pharyngeal segments because they want to, that's probably the segment most likely to be affected by whether it's OG or and gene, and then the DNA was extracted and evaluated. So for their baseline characteristics, it was a small study, obviously, they had they it's interesting in the table, they say they had 14 infants with OG tubes and 27 with infants with NG tube. So that's 41 babies, but down here in them methods it says they had 97 feeding tubes collected from 47 infants. So obviously some infants had multiple tube placements. But I, maybe somebody can help us find out why there's a difference in that number. Regardless, there were some differences between the groups. major differences were that the OG group was much earlier gestational ages and mean gestational age was 27.5 versus 34 weeks, and a median postmenstrual age. The time of the collection was also much earlier in the OG group 31 versus 35 weeks. More babies in the OG group had antenatal steroids and intrapartum antibiotic prophylaxis. And infants in the NG group, are more likely to have had antibiotics on the first day of birth. That that was interesting. So then they wanted to look at what bacteria were present. So the most abundant phyla identified in the samples were Proteobacteria, firma cuties. And then Actinobacteria bacteria, bacteria, DTS cyanobacteria, fuser bacteria to generic cuties and Thermae were also detected. And then they get into what was found were so mean relative abundance in Ng and Og tubes. So the predominant bacteria, like I said, was Proteobacteria in both, but 49% in Ng and 59%. In OG, then the firm acuities 32% In Ng, and 22%, in OGS, and Actinobacteria, and 8% in en Gs, and 6% in OGs. And so I wanted to see did didn't want to one site have way more bacteria than the other? Not necessarily, so a total of 15. And then they looked at the bacterial families. So total of 15 bacterial families were detected with mean relative abundance greater than 1%. So, enter bacteria were the most abundant in both feeding tubes 27% In NG tubes, and 38% in OG tubes, then they had more x more Accela 14% and staphylococcus 11%, more abundant in NG tubes than OG tubes, and then in the OG tubes, and they had more abundance of streptococcus guy and the Syria which is pretty consistent with the colonization in those regions. We looked at some of the other less abundant bacteria. We had Karina bacterium, streptococcus leukocyte looted, I don't know. And Pseudomonas were more abundant in OG tubes than NG tubes. And in contrast, Enterococcus, staphylococcus streptococcus, Neisseria, homologous pair, influenza and Pseudomonas were more abundant in NG tubes. Pseudomonas was most abundant and infants receiving antibiotic treatment on the first day of life. And there were no differences at the genus level between preterm and term infants mode of delivery, duration of feeding tubes and milk type of feeding, which I thought was very interesting, I thought there might be a difference by helping and then they wanted to look at the secondary outcomes first, for anybody who does microbiome research. Obviously, these definitions are very familiar to you. But for people who don't, it's a reminder, we've we've looked at these before. And we have these cool colorful scatter plots of the bacteria on on the graphs. So they look at alpha diversity, which is a measure of microbiome diversity applicable to a single sample. So we look at a within sample analysis, and then the beta diversity is a measure the similarity or dissimilarity of the two communities. So let's look at the Alpha diversity. So the NG tubes had higher alpha diversity than the OG tubes, by one measure that Simpsons index but not by the Shannon's index. There was no significant differences in alpha diversity in all feeding tubes are in the subsets and G versus OG based on the variety of clinical variables, preterm versus term mode of delivery, dwell time, antibiotics, milk type, or history of neck or sip. And then they looked at the beta diversity. So microbial communities between samples collected from Ng and Og tubes are significantly different based on their insertion roots of the feeding tube, and G versus OGs. And they looked at a variety of different I guess their their Beta diversity tools. So this suggests that the NG and Og tube communities were significantly different. I also thought it was interesting, I think, potentially some of the most interesting results were that antibiotic administration duration of feeding to placements influenced some measures of beta diversity, but again, that the milk type did not. So the overall study takeaways if you totally got lost, what bacteria was where was that there is a difference between Ng and Og tubes and relative abundance of several taxa at both the family and the genus species level, and in the alpha and beta diversity. And some of those differences are probably related to the differences in the gestational age or birth, the steroids and intrapartum and postpartum antibiotics, because they were a little different between the two groups. But it's, it's interesting to note at this doesn't change my practice at this time, but I think it'd be nice to see larger studies and maybe is one is one safer than the other. Does it matter if you know, there if the feeding tubes are colonized? I don't know. And obviously, this was a very small study, but the findings are interesting nonetheless.

Ben 26:30

Yeah, I agree. I mean, I think that these these two plots, these two box plots were interesting with Shannon, with the Shannon Shannon's diversity index and the Simpsons diversity index. I'm not a microbiome person. But I remember Shannon's diversity index as the one that I have seen before. And that was not significant, as you said, but the Simpsons diversity index difference was different between the NG and the OG, like you said, I think it's it's shining a light on a problem that I had never thought of before. And I'm curious to see,

Daphna 26:58

and, you know, because we, I mean, at least in our unit, and many units that I've worked in huge kind of non discriminately, placing them based on and they've talked about that respiratory support is the baby feeding or not. But, you know, maybe we shouldn't be making one decision over another if we have the opportunity.

Ben 27:19

Right, right. And so, like you said, I don't know if this is going to change my practice today. But I'm curious to see if people continue to look at this if they actually can see if the effect of duration placement and all that stuff on certain specific outcomes that are very interesting in the future. But I'd like people thinking outside the box. Okay. All right. What am I going to go through next? Listen, we're doing a lot of work doing a lot of ad stuff. And yeah, and so I'm gonna keep going then. Okay. So my next paper is called dual sight, blood culture yield and time to positivity in neonatal late onset sepsis. First

Daphna 27:59

off, I was very interested in this paper, I must say, I mean, they're all

Ben 28:03

very first author is Sarah Coggins from chop in Philly in the US. And the, the background of the paper is an interesting one, right? The idea of blood culture number and sites that need to be collected are unknown, particularly among infants with indwelling vascular catheters. We also know that clubs is central line associated bloodstream infections are important contributors to hospital acquired infection in the NICU. So obtaining blood cultures from Central vascular catheters is controversial, as you may induce false positives or contaminants, and then you can inadvertently also cause Catterick contamination. And then if that's the case, and then you consider these central line infections, the repercussions are significant. Now, among adults undergoing clubs evaluation, the current Infectious Disease Society of America, the IDSA, recommend sending blood cultures from both the catheter and peripheral sites prior to antibiotic initiation. The NICU at a chop which is obviously caring for a very high acuity group of patients and a very varied mix of of patients has a policy that they they follow this guy, this IDSA guideline when initiating a workup for late onset sepsis, and they actually culture the line. So the question that they're asking is, can we determine whether bacterial yield organism and distribution and time to positivity differ by culture source and what they did was that for patients who were more than 72 hours old, who were being admitted at the Children's Hospital of Philadelphia between 2007 and 2019, they looked at the sepsis evaluation that they carried out, and they identified all episodes Of late onset bacteremia, in which concurrent peripheral source and catheter source blood cultures were obtained during the sepsis evaluation. They first identified a broad cohort which included all bacteremia episodes regardless of antibiotic treatment duration, and then they created sort of these narrowed cohorts which included cons bacteremia episodes only if receiving systemic antibiotic therapy for more than five days, within these cohorts, then they group the bacteria episodes by site and by the site of the cultural growth. So, for example, they had like the C plus p which was like the group where they cultured both the catheter and peripherally, then they had the C group which was catheter only, then they had the P group which is was just the peripheral culture only. And so the the the you have to follow the flowchart of how the patients were organized because they had about like 2000 positive blood cultures. Among 687 infants after 72 hours of life. They excluded about 500 of these kids 1600 positive blood cultures were identified 813 Positive cultures among 590 sepsis evaluation, and then 179 episodes with both catheter and peripheral blood cultures. And then they looked at which one got which did they get both sides cultures only one and then they looked at that and then of those then they removed the the ones that they thought could potentially be contamination because the bacteria could the bacterial cultural group cons and the baby did not receive a full course of antibiotics. The recommended blood culture volume was one milliliter which was collected in pediatric aerobic culture bottles. Time to positivity was defined as the hours elapsed from the culture receipt in the mitral microbiology lab to notification of culture, which are both time stamped in the EMR. So is an interesting question as to when does culture begin as soon as blood hits the bottle, as soon as it's incubated? All that stuff is up for discussion, but that's how they did it. Okay, so what did they find in the results, they look looking at the culture yield by sight. So among 179 episodes of bacteremia in the broad cohort 67% demonstrated growth from both the peripheral and the catheter blood culture. So that was very interesting. How, however, 17% of episodes grew only from the catheter site with a negative peripheral blood culture, and the remaining 16% grew only from the peripheral site with negative catheter culture. And looking at the demographic factors among those three groups, there was no significant differences between them. The gestational age in weeks was about like 31 weeks for all of them a bit smaller for the peripheral site only where it was 29 weeks. And that was not statistically significant. The corrected gestational age at the time of culture was about they were almost almost all around term, 40 weeks for the catheter and peripheral and 40 weeks for the catheter only 37 weeks of peripheral only when you can look at the rest of these of these parameters. between groups, there was no difference in catheter days, meaning there was not the duration and the duration for which the catheter had remained inside the baby had been different. The catheter and peripheral group had a higher frequency of persistent blood culture positivity within 48 hours following initial culture growth 66% compared with 28% in the in the catheter only, and 3% in the peripheral group only. And I feel like we've all experienced this, that the baby that grows both from frontline and peripheral tend to be be more difficult to clear compared to other forms. coagulants and coagulase negative staph cons back to remain was proportionally more common among episodes of single site culture growth, accounting for 62% of the Catholic group episodes and 66% of the peripheral group, the peripheral. So I think it doesn't the paper doesn't get into much more than that. And And their conclusion is that among episodes with your site cultures, and at the time of sepsis evaluation, the majority grew from both sides, right, we said 67%. However, they mentioned that a minority of episodes had a pathogen grown from a single site only suggesting potential continued utility to our current practice of obtaining both catheter and peripheral blood culture among neonates with central line undergoing late onset sepsis evaluation. And I think and I think it's interesting, right that when, when both I mean, yeah, I mean, I think it's interesting data. It's just interesting that I mean, we are specifically looking at this in our unit right now. And so, yeah, I'm wondering, what do you make of this right so six So the when you In summary, right this this group, they had about almost 200 kids and they and they they had 67% of the group grew from both peripheral and and the catheter 30. I mean, I don't have the shoot, I don't have the monopod. And then it was like 1767. And then it was 17% for only the catheter site and 16% only from the peripheral site. So yeah, interesting question. I

Daphna 35:32

agree with you. I don't I don't know what to make of, I don't know what to make of the data. But it's just interesting. So I was especially curious to see what the cons data with would look like break is where I was, you know, hope hopeful that we can, we can get at maybe a cons that we can, you know, get into this is a contaminant and not a true infection, but it was equivalent, getting them from peripheral. And from the central line. I thought that was interesting. So,

Ben 36:04

yeah, I think the big question to me is, we're very worried about accessing the central catheters, but then, but then you look at this, and you're like, there's 17% of kids who only grew from the catheter. So, if those kids never had the catheter cultured, then you would get how would you know? Right? You wouldn't you would not know. Exactly right. And that's very scary. Because on the one hand, for the people, I don't know how it is outside the US, but in the in the US, a club Z, or a central line associated bloodstream infection is a disaster. Like, there's all these root cause. And it's like, it's a big, big deal. So so so it's, it's not something you

Daphna 36:45

know, when what I was gonna say, one thing we don't know, from the data is right, those are positive cultures. But I mean, some people feel like they're, they're not. Some of these, some of these catheter associated may not be true infections. These are babies who got cultures, presumably because they were unwell. And maybe you got something positive. So it's hard. It's hard to ignore. Right. But that's, that's the argument and some other data is that that

Ben 37:14

you could, you could argue that defining a contamination as as cons requiring less than five days of treatment could be restricted. There's other weird bugs. I mean, I've had bugs that grow from the library, like there's no way this is a real infection. This is like some very, and then even the lab will be like, yeah, that's, that's, that's a contamination. So you're right. You're right. But I think this is interesting. Seven, that what I took away from this is, if you culture the site versus not you remember 67% 16 and 16. That's interesting data that keep in mind.

Daphna 37:45

Yeah, totally agree. Okay, more infectious disease today. So this is a paper out of Pediatrics, about the epidemiology of COVID-19. And, and this, they were looking specifically about how has COVID-19 affected neonates. So I left your wheelhouse Yeah. Lead author Joan Devin. Senior Arthur Lewis, who were her mu. Her MUFA. Me I have even practiced that one before. Okay. So the study design, yeah, you know what, wow, we're, we're pretty COVID cautious in my house. I was definitely interested to read this paper. Study Design over 1 million neonatal encounters at 109 us health systems, because they were using the Cerner real world database. So the CR WD is a large if you're not familiar with it is a large fully D identity database collected by Cerner corporation that consists of EHR agnostic data from over 120 US health systems. It consists of clinical data that has demographics, encounters, conditions, labs, and clinical events. And they use the 2021 q3 version, which of note included more than 153 million patients and 1.5 billion encounters across all care settings and ages. So that was not all of that's not all of the sample, but it's all the records they had access to. So a really large database and they were looking at the time period of March 2020 to February 2021, obviously, the kind of height of the pandemic, at least in the States. And then, interestingly, COVID-19, diagnosis was assessed using either the laboratory tests or the diagnosis codes, but not necessarily both. The inclusion criteria they extracted data on neonates aged less than or equal to 28 days at the time of hospital admission, with a positive diagnosis of COPD. Would 19 Between March 1 2020 And February 28 2021. They also looked at cases of vertical transmission of note, they were defined by timing and the tests using descriptions and other studies about the kind of vertical transmission window period, and so they basically use a 12 hour window for neonatal diagnosis. Because a lot of the most of the records were not linked to the maternal records, right, because it's all de identified, so they couldn't confirm maternal COVID-19 status. Okay, so there's a lot of data here, I think it's an interesting thing to read. I am going to focus on the more severe cases, especially since they tend to include a lot of the preemies and babies with congenital anomalies. So COVID-19 was diagnosed in 918, neonates or point 1% of encounters. And of these 71% or 7.7% had what was classified as quote unquote, severe infection and I'll tell you what that is severe illness was classified as cases that met at least two of the following three categories. The first category is any of fever apnea, cough to kip Nia respiratory distress, supplemental oxygen requirement, vomiting or diarrhea. The second category, any of the following a low white blood cell count less than 5000, a low lymphocyte count less than one, sorry. That's correct, or raise CRP greater than five milligrams per liter. And the third category was an abnormal chest X ray, or a diagnosis for pneumonia, which was used as a proxy for abnormal chest X ray. A little bit of about the demographics 55% of neonates with COVID were male. The study population had 36.7% Hispanic or Latinx 27% non Hispanic white, 7.6% non Hispanic, Black or African American 1.7% non Hispanic American Indian or Alaskan native and 1%, non Hispanic, Asian. The most common type of insurance for babies with COVID was Medicaid or other government sponsored insurance 37.4%. More about the time course and median age of admission to the hospital was 11 days for all neonates that range from one to 22 and 15 days, so actually little later for those with severe COVID 19. But it also range from one to 22. The median time to diagnosis was 14.5 days from birth. And I told you there were 918, neonates and a positive laboratory test in the D in the data was documented for for 440. neonates, the remaining cases were identified using diagnosis codes. One neonate was diagnosed with COVID-19 within 12 hours of birth, suggesting possible vertical transmission or perinatal colonization. The most common signs of infection Not surprisingly, were to kip Nia and fever, neonates otherwise, were generally asymptomatic at initial presentation to hospital. But number three,

Ben 43:50

and that was hyperglycemia. Three for meaning ticket you said you said the most common one, where where were ya to give me an symptoms, symptoms. And then in the they have like this figure one where they have severe versus non severe COVID. And then the severe the, maybe the second or third was fever and pneumonia. But in the non severe hyperglycemia was pretty common. Frightening. I was like,

Daphna 44:18

Yeah, I mean, think about how many of those views really have a risk factor for hyperglycemia. But they're here with hypoglycemia. You know, you're thinking back in the last. Don't you feel like we had a bunch a whole whole lot of that, you know,

Ben 44:31

so it's this is I can't be doing that. I can't it's kind of it's terrorizing.

Daphna 44:36

All right. Let's see. I told you neonates are generally asymptomatic and initial presentation a hospital with no reported signs of infection and 63.5%. So I, I wonder if those were babies whose families were sick, they got tested, and then they tested everybody, I don't know. Pneumonia was diagnosed in 28% of those with severe infection. So in this Severe group, those with severe infection were more likely to receive respiratory support 50.7% versus 5.2%, of course, and in this group, there was a much higher proportion of low birth weight so less than 2500 grams or premature neonates in the severe category than in the non severe category. comorbidities were more likely in this category. So among patients with severe COVID 19 46.5% had at least one comorbidity, but they're varied those comorbidities and the most prevalent being a congenital anomaly which again, varied wildly 38% had a congenital abnormality, cardiac abnormalities excluding PDA accounted for 17% of comorbidities, obviously one of our highest risk populations. Suspected sepsis was observed and 24%, jaundice and 28%, and anemia requiring transfusion and 7%

Ben 45:53

average on the spikes for everything so

Daphna 45:55

that's right, of course, and in this time period, there's jaundice, right? And those with severe COVID-19, were more likely to have a higher CRP median of two milligrams per liter, versus a median of zero milligrams per liter. They're more likely to have lower albumin levels and decreased platelets. Now severely ill neonates received a range of therapies 38% received analgesia 33.8% received antibiotics. I actually thought that was surprising. I thought more of them would have antibiotics, anticoagulants and 32% steroids in 26%, remdesivir 2.8% and convalescent plasma 1.4%. interment minute ventilation masari mechanical ventilation was needed for 11% and the majority of patients requiring mechanical ventilation were premature had congenital anomalies. An additional 36% of neonates with severe COVID-19 received other forms of respiratory support that did not require intubation. A total of 93.6 infants were discharged home 1.1 transferred to another hospital out of the system and discharge disposition unknown for 5.2%. One neonate 2.1% With presentation suggested of the multi system inflammatory syndrome and children are the the MIS see died after 11 days of hospitalization. Yeah. And then they did share some data based on geographic regions. The highest rate of total neonatal COVID-19 cases occurred in zip code region zero Connecticut, Massachusetts, Maine, New Hampshire, New Jersey, Rhode Island, Vermont, with 77.1 out of 100,000 encounters, this represented 8% of total cases. Region, one Delaware in New York, Pennsylvania had the lowest rate at 22.5 out of 100,000 cases the highest rate of severe neonatal COVID-19 cases occurred in region three our region, ama, Florida, Georgia, Mississippi, Tennessee 9.6 out of 100,000. region three also had the lowest cumulative COVID-19 vaccination administration rates, which we know to be true. Anyways, for people who are wondering how COVID-19 it has presented in neonates, I thought it was a good review. Obviously, cases are backup, especially in our region region three, so

Ben 48:43

don't call us region three.

Daphna 48:46

Now, I know region three based on the Cerner database. So that's that.

Ben 48:54

All right. Okay, we're running short on time.

Daphna 48:57

So we always we always do,

Ben 48:59

but I wanted to get into maybe one and a half more papers. So the one on one and a half to whenever we're going to talk about is obviously one that we're going to discuss a little bit this week, which is called age at first extubation attempt and death or respiratory morbidities in extremely preterm infants. first author is we some shadow leash. last author is Dr. Year Miss Santana from the University of Montreal, who will be on the show this week in the unit. Oh my gosh,

Daphna 49:28

that was such a that was such a fun episode, I hope and I will listen to

Ben 49:34

briefly Well, it's there's a well established link between mechanical engineering, mechanical ventilation and increased mortality and morbidities. Infants requiring more than seven cumulative mechanical ventilation days are at increased risk of BPD and need for supplemental oxygen at discharge from the NICU. The need for reintegration prolongs mechanical ventilation by 10 to 12 extra days, which is in and of itself, increases the risk of death slash VPD. The question that the group asked is, is the timing of the first exhibition attempt in the in their cohort of extremely preterm infant. Any any indicator of relationship is there any indication of relationship between that the age of its first exhibition, exhibition outcome and death slash respiratory morbidities. So this was a secondary analysis of the multicenter observational cohort study called the apex study, which we reviewed on the podcast before these patients were enrolled from five tertiary NICUs. In Canada and the United States from 2013 to 2018. infants were born with a birth weight of 12 150 grams or less with no congenital anomalies. They were enrolled if they needed mechanical ventilation anytime after birth, and were undergoing their first their first planned extubation. During the study, the apex was a pragmatic study. So all the decisions related to the timing of the extubation the timing of the intubation, the timing, reintegration, all that stuff was determined by the clinical team, there was no protocol in place. Moreover, there were no specific criteria mandated for either extubation or reintegration. during the study period. The participating centers did not practice insure or Lisa, which Lisa may be insured also, whatever. The age at first exhibition was divided into either early within seven days from birth versus late days, eight to 35. And then the extubation outcomes were divided into reintegration within seven days, which is called failure versus no reintegration during that period, which would be called success to create four extubation groups, early success, early failure, late 60s, late failure, the primary outcome of the study was a composite of death or moderate to severe BPD. defined as the need for any non invasive respiratory support and or supplemental otoo at 36 weeks postmenstrual age. secondary outcomes were BPD and survivors and cumulative days on mechanical ventilation on any respiratory support. And on supplemental oxygen. So the results of the study was that 250 infants who received mechanical ventilation in the first 24 hours of life were included. And the first extubation occurred on the following days. So 52% were estimated in the first seven days, another 37%, between days eight and 35. And then 11%, beyond day 35, the highest peak of extubation was in the first 72 hours of life, followed by a smaller peak around the fourth and fifth postnatal week. So if you can activate them early, it's usually a good sign. Yeah. Now the probability of extubation failure was 26% 31% 40. Okay, I'm going to say that again, because this is not going to be conducive to an audio format. So the probability of extubation failure was 26%, on days of life, one to three. So in the first three days, 31%, day 47 40%, day eight to 21 34%, day 22 to 35 and 21%. Beyond day 35. So interesting that in the first, in the first three days, odds are a bit lower, and then they

Daphna 53:25

like a bell curve, right? Yes, yes, which which, which fits the clinical, you know, schema you have in your head.

Ben 53:33

And then figure three in the paper is quite interesting. It's the proportion of infants in each gestational age group with successful extubation, failed extubation, or never excavated in the first week of life. And what you see is it's a, it's a, it's a superimposed bar graph with three colors, you have yellow, which is not activated, you have orange, which is failed exhibition, and then you have blue, which is exhibition success. And then the 19 kids were 23 weeks, there's no exhibition success, then there's a bit more exhibition success, maybe, I don't know, maybe like 10% in 24 weeks, and then close to 20% or 25 weeks. And you can see that that blue bar of exhibition success increases progressively with each additional week of gestational age at birth. Sure. When compared with infant experiencing an early failure, infants with early success had a greater gestational age and weight at birth, and lower mean airway pressure, and oh to need at extubation. And you can look at that. I mean, the those four categories are interesting, early success, early failure, late success, late failure. It's not in incredibly high number early successes. 93 infants, early failure, 36 infants, late success 59 infants and late failure 34 infants. When you're looking at the gestational age 30 success, the gestational age was 27.4 weeks compared to 26.3 in the early failure, and then the late success, it was 25.4 weeks compared to 24.6 weeks in the late failure. And then you can look at the PMA extubation, you can look at the PAH all that stuff is is quite impressive. What's interesting also, is that they were not reckless, right, if you look at the FIU to extubation, on average was about, like, for the early success, it was 21%. But the early failure was 23%. So it's not like these kids 140 5% You know, and then for the for the late failure, it was only 26%. So, and the co2 is, in the late group was like 51 to 5351 for the late success 53 for the late failure, which which is not bad, which is really not but the pH 7.3. Foreign delayed success 7.31 In the late failures, these are these are very much X debatable numbers. Talking about some of these main outcomes, the proportion of infants with death slash BPD was 31%. In the early success 83% In the early failure 66% In the late success 91% In the late failure. So quite, I mean, quite impressive. If you were able to successfully excavate early 31% risk of death or BPD in a in a in a 12 150 grand more or less baby, which I mean, there's rates of BPD is insert institution that is much higher than that in good institutions, right. But knowing that if you have an early failure, it jumps to 83%. Geez, infants with early failure had significantly greater risk of death, or BPD BPD duration of mechanical ventilation, duration of any respiratory support and duration of oxygen supplementation, compared with infants who were successfully excavated early. And, yet, so and the if you want to tease those two apart, because we're talking about death and or BPD, but BPD alone, early success was 29%, early failure 81%. So not that far off, and death was 3% in the early success versus 11%. In the early failure. What else similarly, infants with late failure had significantly rate greater risk of the same respiratory morbidities compared with late success. However, there is no significant differences in rate of respiratory morbidities when you're comparing early failure and late success, except for a greater crude number of well, I'm going to talk about that in a second. So that's important, right? So we're going to see that again, there's no significant differences in rates of respiratory morbidities, when you're comparing infants with early failure, and late success, which means try it. Except for a greater crude number of deaths in the early failure group for deaths compared with none. And I'm not going to we talked about that during the weekend. It's frightening. And if I go into this, people are going to be afraid people are gonna be afraid to extubate early. There were no significant differences in respiratory morbidities when comparing infants in the early failure group with infants in either the late success or late failure group another very important point. So and they have a very nice graph as well about the probability of death or BPD, which we'll put on the Twitter page. In conclusion. Exhibition in the first week of life was achieved in 52% of infants, but only conferred improve respiratory outcomes when the attempt was successful. And although early extubation remains the priority, future research need is needed to develop and validate predictors capable of promptly identifying infants ready for extubation and those at the high risk of failing intubation. extubation I'm sorry, in the first week of life, which is the topic of tomorrow's neonatology review, podcast. So yeah, that's a great tease for next week's episodes, for this week's episode.

Daphna 58:59

Yeah, it's kind of, you know, the group I wonder about, is it a chicken or the egg right? Or are they more likely to fail? Because they were they're just more likely to develop BPD or, you know, is fit, does failure set you back so much that you're more likely to develop BPD than you would have if you hadn't been? Trial? You know, there's they're sort

Ben 59:23

of trying to answer that question in the background by saying, Well, this has been shown that yes, it's not just Yeah, it's it's these interventions, whether the intubation the reintegration, the exhibition failures, they're in and of themselves independent risk factors.

Daphna 59:38

And we know that right yeah, we've all had the baby where you tried and then they were way worse off than when you when you attempted Yep. And and the data still supports trialing early extubation today.

Ben 59:55

Yes, ma'am. Yeah, okay.

Daphna 59:58

But the this this, this is special. group these little little, teeny Chinese earliest babies are still a very special group, right that we haven't totally figured out yet.

Ben 1:00:10

Do you want to do you want me to do the last paper I have? Or do you have anything else?

Daphna 1:00:14

I have one more that I can do pretty quickly. And I actually think it's kind of interesting because we, we reviewed a paper recently that had similar findings. So this is out of the JAMA Network open entitled associations between maternal antenatal corticosteroid treatment, and psychological developmental and neurosensory disorders in children. Lead author contrary, Raikkonen senior author, Eero? Could John T.

Ben 1:00:46

Raikkonen is the first author like the famous driver,

Daphna 1:00:51

yes. Hey, love. Okay, I thought this was an interesting study, because it was done using the Finnish national registry, which is obviously an enormous population based registered linkage study, which looks at all singleton live births in Finland, and their study time period was between January 1 2006 and December 31 2017, followed up until December 31 2018. They also did a sibling comparison but in the for the sake of time, I won't cover that. They did provide what their treatment guidelines are for antenatal steroids so they recommend beta methadone 12 milligrams, administered twice 24 hours apart throughout the study period. Like here in the in the States until 2009 treatment was recommended until 34 weeks and zero days of gestation, or 32 weeks in zero days in the case of premature rupture of membranes. And then after 2009 treatment was recommended until 34 weeks and six days of gestation. And in the select cases even later, like certain indications fetal hydrops or maternal disorder warranting C section, repeated treatments were not recommended before 2009 2009 And then after 2009 Like here in the States, and they started with a one repeated, you know, like the rescue course could be a considered when the risk of respiratory distress remained Thai. And then the primary outcomes and they have you know, pretty good follow up of their cohort. The primary outcomes were specific developmental disorders of speech and language, Scholastic skills and motor functions, pervasive developmental disorder, other unspecified psychological developmental disorders disorders, vision and hearing and epilepsy and CPE. So, again, they used all of the register ICD 10 codes. Then they looked at a whole bunch of covariates known to be associated with developmental disorders, to do kind of a multivariate analysis. So, to baseline characteristics, the the total cohort 670,009 670,097 infants 2.2 were exposed. That was just under 15,000 infants and then of the exposed children 45% were term 54% were born preterm of the non exposed children and 97.8% were were male as compared to 53.9%. In the in the treatment exposed 96.9% were born at term and 3.1% were born preterm. There were some differences between the two groups, obviously, because some of the nonexposed babies just didn't meet criteria for the therapy. So compared with a non exposed children treatment exposed children in the entire population were born earlier had lower birth weights more often admitted to the NICU more often received a diagnosis of major congenital anomaly, and were more often delivered via Cesarean birth mothers of treatment exposed children, more and more often prime MIPS had premature rupture of membranes, gestational diabetes, hypertension and pregnancy. Also had any mental or behavioral disorder. I ear disorders, nervous system disorders, and were more likely to have smoked during pregnancy. All of those are independent risk factors for things like prematurity. So I'm not actually going to go over the total entire cohort because again, I don't think that describes the group that we're looking at right babies who maybe could have gotten treatment but didn't so looking at the age groups. I think what's really interesting in general in the entire cohort that treatment exposed children had significantly higher adjusted hazard ratios than the non exposed children for almost all of the primary outcomes. But again, that included a big discrepancy in the majority of the treatment exposed groups were much more premature premature smaller birth weight. So I think it's interesting to look at the groups like by gestational age, so, in the term born group, compared with non exposure, so babies born at term who got antenatal steroids treatment exposure was significantly associated with higher adjusted hazard ratios for the following specific development disorders of speech and language specific developmental disorders of scholastic skills, specific developmental disorder, motor function, pervasive developmental disorder, and other unspecified disorder of psychological development, also epilepsy and cerebral palsy. And then if you looked at the pre term group, the pre term treatment exposed children and did have higher cumulative incidence rates of all psychological developmental and neurosensory disorders than the nonexposed preterm children. However, when you looked at the multivariable models, none of the adjusted hazard ratios were statistically significant after adjusting for some of those other covariates. So this is consistent with the other study that we reviewed and that people are really interested in, and that, you know, in general, for the preterm baby, the benefits outweigh the risks, but in this this term group of babies who are getting antenatal corticosteroids, that there is a, there is a risk of developmental disorders. So

Ben 1:06:51

do you think we're going to start seeing less less babies being born with antenatal steroids on board?

Daphna 1:06:59

I mean, I mean, hopefully not in the pre term, because, I mean, I think the data is clear that, you know, the benefits outweigh the risks. You know, Atla, our, our group, for example, has pretty stringent criteria, right? So they're, they're really not giving antenatal steroids in that in that older group. So,

Ben 1:07:22

we'll see. Yeah, this is. Yeah, I mean, I mean, it makes sense when you when we say it, right. antenatal service will only be given to the babies that you really feel like I need to be delivered. But I mean, for our OB, ob colleagues, it's hard to to determine which one of them is imminent and give yourself with enough enough, what is it 24 hours that you need, at least to give those two doses? So tough?

Daphna 1:07:47

Yeah. Because Because what they were trying to hammer out in in that in that other study, and I don't have the I should have pulled up the citation. But they were looking at the time of exposure, and whether you're ended up or being born preterm, or you made it to term. They we don't have all of that, you know, fine granularity in this finished study, but

Ben 1:08:16

okay, well, we're over time, but I just wanted to mention one paper that was published in the Journal of parasitology. And it's called the blood pressure values and hypertension management in extremely preterm infants, a multicenter study, it's from the peanut investigator first authors, Eric peoples. They basically took the data from the peanut trial, and they wanted to see the primary goals of the study was to use that data to estimate modern BP norms for extremely preterm infants, and to evaluate the variability in BP management between 19 sites that participated in the peanut trial. And it's interesting because they have data on babies who did not receive any hypotension treatment, babies who receive pressors baby who received hydrocortisone babies received both. And they're publishing these normal grams of normal blood pressure values with systolic diastolic mean arterial pressures, and then they also have the lowest mean arterial blood pressures by day of life for the first 14 days of life. And without getting into too much into it. I guess. The few things that are that I was interested in is that I think ovvero was one recently on Twitter asked like, Where is that thing coming from where, where the map is supposed to be equal to the gestational age. And when you actually look at these graphs, it's not that far off from jurisdictional age, but it still shows that the expected mean arterial blood pressure increases with each gestational age and decreases progressively over the course of the first 14 days of life. The only thing that we're Is that I thought was very interesting is, obviously we are. On the one hand, we're not, we're treating sometimes too many babies for hypotension when the effects of this what we suppose is hypertension on the baby's hemodynamics. And all that stuff is not very significant. However, they did something where they compare the infants who were surviving at day 14, who were not treated with any pressors. And they found that the average lowest mean arterial pressure was lower for those surviving infants who received hypo antihypertensive therapies, meaning that the babies who were treated who had low blood pressures, even after treatment was started, they didn't meet the same blood pressure as the controls were not being treated. So we're not even correcting to what they perceive to be the control, which made me really puzzled because on the one hand, I always feel like we're over treating, but now it looks like when we are treating, it's not enough. But in any case, I don't want to take too much time out of the podcast, too, and do a disservice to this study. But it was very interesting. The peanut trial was very rigorously conducted. And they're just publishing their their data from the blood pressure. And at the end of the day, this ends up being probably one of the largest studies, there's not a lot of studies on measurements of baby's blood pressure, and they end up having close to 1000 Extremely low birth weight infants enrolled, I think 936 is the exact number. So it ends up being a very valuable data set.

Daphna 1:11:38

I mean, it just makes sense, what we say, what's the right blood pressure at well, why wouldn't we use norms in preterm infants? Like we use norms everywhere else? Right, we use them for children and adolescents and adults. So, um, I think it's very bad.

Ben 1:11:52

I think the data on the babies being treated with vasopressors is interesting. However, again, the peanut trial was not really looking at that. Right. This was erythropoietin administration. So you could always argue,

Daphna 1:12:03

and it was right. They didn't have a protocol. To my knowledge on you. No, no, sir. Me?

Ben 1:12:09

Yeah, absolutely. And even then, like, these babies are thought to be hypertensive because they receive treatment. They were not looking at that. But even if only for the babies who did not receive any pressors, that graph of babies who were not being treated for anything it provides, it provides data normative data, correct. And that's what they're highlighting in their conclusion. That, that this is this is a study that provides the highest and lowest daily BP values for the largest contemporary cohort of extremely preterm infants to date. And, yeah, so.

Daphna 1:12:43

Yeah. And I mean, if if you're following along on twitter, I mean, this discussion comes up like, weekly right. presser management is a whole nother.

Ben 1:12:54

Absolutely. And they're making the case for the fact that because of the HIPAA trial that we've mentioned, with Gabrielle altered that we've, we've talked about before, but we're not going to see data coming around very, very soon. It's difficult. So we have to take whatever we can and that's pretty good. So I wanted to give a shout out to that group.

Daphna 1:13:15

Okay, buddy. All right. That was good. Another week, another journal club.

Ben 1:13:18

Yeah, we're being very consistent. I'm very proud of that.

Daphna 1:13:22

Well, thanks, everybody for listening. Have a great week. You too. Bye. Bye.

Ben 1:13:28

Thank you for listening to the incubator podcast. 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 podcast, 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 or through our website at WWW dot v dash incubator.org. This podcast is intended to be purely for entertainment and informational purposes and should not be construed as medical advice. If you have any medical concerns. Please see your primary care professional. Thank you

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