Hello Friends 👋

We are happy to bring you a new episode of Journal Club, with new articles and studies fresh off the press. This week, we review the latest publication from the New England Journal of Medicine about the effects of DHA supplementation in preterm infants and neurodevelopmental outcomes at 5 years. We have so many more interesting articles and we hope you enjoy listening to this episode as much as we enjoyed recording it.

We are also very excited to introduce to the show a new member of the team, Priya Patel PharmD. Priya, in the past weeks, has taken an active role in the production of the show and with other initiatives carried out by The Incubator team. We are happy to see our team expand and we have no doubt that Priya will be a positive addition to the show.

Have a good Sunday!

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

Delayed Surgical Closure of the Patent Ductus Arteriosus: Does the Brain Pay the Price? Lemmers P, Vijlbrief D, Benders M, Alderliesten T, Veldhuis M, Baerts W, Koopman-Esseboom C, Groenendaal F, van Bel F.J Pediatr. 2023 Mar;254:25-32. doi: 10.1016/j.jpeds.2022.10.010. Epub 2022 Oct 12.

Association of Antenatal Steroid Exposure at 21 to 22 Weeks of Gestation With Neonatal Survival and Survival Without Morbidities.Chawla S, Wyckoff MH, Rysavy MA, Patel RM, Chowdhury D, Natarajan G, Laptook AR, Lakshminrusimha S, Bell EF, Shankaran S, Van Meurs KP, Ambalavanan N, Greenberg RG, Younge N, Werner EF, Das A, Carlo WA; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.JAMA Netw Open. 2022 Sep 1;5(9):e2233331. doi: 10.1001/jamanetworkopen.2022.33331.

Predicting the likelihood of lower respiratory tract Ureaplasma infection in preterms. Viscardi RM, Magder LS, Terrin ML, Davis NL.Arch Dis Child Fetal Neonatal Ed. 2023 May;108(3):250-255. doi: 10.1136/archdischild-2022-324192. Epub 2022 Oct 19.

Neurocognitive Outcomes at Age 2 Years After Neonatal Hypoglycemia in a Cohort of Participants From the hPOD Randomized Trial.Edwards T, Alsweiler JM, Gamble GD, Griffith R, Lin L, McKinlay CJD, Rogers JA, Thompson B, Wouldes TA, Harding JE.JAMA Netw Open. 2022 Oct 3;5(10):e2235989. doi: 10.1001/jamanetworkopen.2022.35989

Cannabis use during lactation may alter the composition of human breast milk. Josan C, Shiplo S, Fusch G, Raha S, Shea AK.Pediatr Res. 2023 Jun;93(7):1959-1968. doi: 10.1038/s41390-022-02315-1. Epub 2022 Oct 4

Characterizing the Language Used to Discuss Death in Family Meetings for Critically Ill Infants. Barlet MH, Barks MC, Ubel PA, Davis JK, Pollak KI, Kaye EC, Weinfurt KP, Lemmon ME.JAMA Netw Open. 2022 Oct 3;5(10):e2233722. doi: 10.1001/jamanetworkopen.2022.33722

Neonatal Docosahexaenoic Acid in Preterm Infants and Intelligence at 5 Years. Gould JF, Makrides M, Gibson RA, Sullivan TR, McPhee AJ, Anderson PJ, Best KP, Sharp M, Cheong JLY, Opie GF, Travadi J, Bednarz JM, Davis PG, Simmer K, Doyle LW, Collins CT.N Engl J Med. 2022 Oct 27;387(17):1579-1588. doi: 10.1056/NEJMoa2206868.

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

Ben 0:54

Welcome. Hello, everybody. Welcome back to another episode of the incubator. It's Sunday we're doing Journal Club Daphna. How are you?

Daphna 1:03

I'm doing great. We've been busy. I feel like we always say that, you know, that is something I'm going to get on my soapbox for a little bit I just came to me is a culture as a society, we just say we're busy. We're busy. We're busy. We have been really fortunate to have a lot of opportunities this week is what I wanted to do that came out wrong. We're very

Ben 1:27

excited today, because we have a new member of the team that's joining us on the podcast. And please join us in welcoming Priya Patel to the show. How are you Priya?

Speaker 3 1:38

Good. Thank you, Ben. And Daphna, such an honor to be here.

Ben 1:41

Well, we've known Priya for some time. We've worked with Priya before. And so we're very excited. We think she's tremendous and that she's going to be a great addition to the show. She's she's going to she's been a huge help in terms of there's a lot of preparation. I mean, I know it sounds like a very casual conversation when we get on the show, but we actually prep intensively for these episodes. And Priya has been helping us in the background with prepping and logistical stuff. And she has a unique background that we think is would allow her to join us on these episodes and share some some wisdom. So Priya, tell tell the audience about yourself and who you are. And yeah,

Speaker 3 2:21

yeah, thanks actually been I'm trained as pharmacist so I did residency after pharmacy school. And I worked 10 years as a NICU clinical pharmacist or pretty busy NICU, and then transitioned sort of into industry. And I've been in industry for about six and a half years, recently took a new position that's working in pediatric ultra rare disease. And really, you know, my love and my passion is neonatology. So I'm grateful to be here.

Ben 2:49

Yeah, I guess I want to be very transparent with the audience. This is something that we're very, very much dedicated to. So for. I think people may even find this out in the future. So I want to just get it out in the open, you used to work for our primary sponsor, Casey. And that's sort of the work that you were doing when you're talking about working in industry. And obviously, I think this wouldn't really have happened unless you had moved on. So you're no longer working with Casey so that so. So that I think is also very important for us to not have, I think it would have been very different if if a company is sponsoring some of the things that we're doing would have had a representative on the show, it could have been misconstrued but that's no longer the case. And so if people are not up to date on the latest, Priya Patel, latest magazines at the at the checkout counter and see what she's up to

Speaker 3 3:41

appreciate that Ben, but also, I have to put the disclaimer here that these really are my opinions based on my experiences, and not of those of my previous or current employers. It's just me, that's who you're gonna get.

Ben 3:53

That's who we are. Okay, so let's, let's get into Journal Club, because we have a ton of articles. So we're recording this on Thursday, October 27. So we usually record these episodes pretty close to the release date, so that we can be as up to date as possible. And as I was finishing the preparing touches on the on the articles that we're presenting this week, my wife like tells me Hey, have you seen the paper that dropped in the New England and I'm like, god dammit. I thought I was done. But I guess this is where I would like to start because anytime when you need a paper comes out in the New England Journal of Medicine, it's something that everybody really wants to find out exactly what this is about, and, and and what is what is the new evidence that just came out. So I'm going to start with that one and the paper is called neonatal, docosahexaenoic acid, DHA, and I'm no longer going to try to pronounce that it's going to be DHA for the rest of the review in preterm infants and intelligence at five years. The first author is Jacqueline Gould. It's in the New England and it's data out of Australia. So I really enjoyed the Background section of the papers. It does provide a refresher on a lot of high yield stuff about DHA. It mentions how infant born at the earliest gestational ages are deprived of the placental supply of DHA that normally accumulates in the brain during the final trimester of pregnancy. So many things like that are being disrupted because of early delivery. And they also mentioned that DHEA makes up approximately 30% of the lipid content of the brain and is integral in the synaptic ZOMO structure during neuronal development. Now, preterm babies born before 30 weeks of gestation have reduced DHA concentration in neural tissues, which may be a contributor to some of the poorer cognitive outcomes that are seen in that specific patient population compared to full term babies. The current feeding practices in preterm infants is to provide approximately 20 milligrams of DHA per kilogram of body weight per day, which is the level naturally present in the milk of women who are consuming a typical Western diet. And I think that was important that they quantify that which is still lower than the estimated in utero requirements, that would be closer to 60 milligrams per kilogram per day, so about like three times that number. And they were mentioning how there's really mixed data on how DHEA supplementation can improve cognitive cognitive function later in life. And the late the largest trial that they were referencing is showing potentially a benefit when it comes to language at 18 to 22 months correct age. So what they were embarking on in this study was to evaluate the general cognitive functioning of infants before born before 29 weeks of gestation, who had been part of a very large trial that involved 1200 1300 infants. And that evaluated the effect of providing the estimated requirement of DHA during the neonatal period as compared with a standard practice for the prevention of BPD. And so that was the original trial that they that they had conducted. Now they took the data from this trial and wanted to assess intelligence at five years corrected age in a subgroup of these children. Now, for the people who are curious, well, what about BPD? I'm not going to go into we don't have time to go into that other paper. But that other paper is published in the New England as well. And for reference, when they looked at the outcomes of physiologic BPD, clinical BPD, actually, the DHA group, abs had worse BPD than the control. So that's why you're probably not giving DHA for BPD prevention. But it doesn't mean that the data can be used to look at the effect of DHA on long term and neurodevelopment. So this was the Nero trial and three Oro trial, which is a multicenter blinded, parallel group randomized control trial that evaluated the effect of DHA feeding on bronchopulmonary dysplasia, or originally, it recruited infants from 2012 to 2015 2015. The infants were enrolled if they were born before 29 weeks of gestation. The trial was included 1273 infants across 13 centers in Australia, New Zealand and Singapore, the patients were basically randomized one to one to either receiving their after their first enteral feeds to either DHA or control substance. All infants in the trial received the 20 milligrams of DHA per kilogram per day from the human milk or preterm infant formula as soon as they will receive one zero feed. So that remained the baseline right. Now, the intervention was the emotion provided 60 milligrams of DHA per kilogram per day, from the time of enrollment, as were the control, we're not really getting that that extra DHA that we perceive might be more equal to what the baby would have accrued during the third trimester of pregnancy. The trial emotions were administered three times per day, so on a on the data, so q q eight basis, right, starting at enrollment for at least seven weeks, the administration of these emotions stopped at 36 weeks of postmenstrual age, or discharge home, whichever occurred first. Remember, this was a trial that was designed for BPD. So that's sort of why that time point I think was was chosen. Now this study only involved the centers that participated in the original study from Australia. You remember I said it was Australia, New Zealand and Singapore, this was only for Australia. The infants were followed up at five years of age. And the primary outcome, what they were looking at was at the five year follow up was the full scale intelligence quotient, assessed at that, at that time, point, corrected age with the Wechsler Preschool and Primary skill of intelligence, fourth edition, so very standard tools to assess to assess that some of the secondary outcomes involved other indexes from the Wechsler from the Wechsler tool as well as mild and moderate to severe intellectual impairment, or other cognitive impairment, were pre specified secondary outcomes. Other secondary outcomes included pre specified things like executive functioning, represented by the fruit Stroop interference score, which is basically a score where the higher you score, the better the performance, they also looked at height, weight, head circumference, Z score, for corrected age, sex, neurological and physical diagnosis or disability. The analysis was done an intention to treat bases and whenever they had missing outcome data they did they perform a multiple imputation system. So far, so good guys. Got it. Okay, so what are some of the results right? So of the 702 children who had been enrolled in the initial Nero trial at the five centers that they were looking at 656 survived to five years corrected age, and 652 were eligible to participate. There's a lot of complicated exclusion multiple imputation. The bottom line is 656 children were entered into the final cohort 323 into DHA group 333. In the control, the baseline characteristics were similar between the groups. So what are some of the results, the mean, FS IQ, so Fs IQ when you see that in the paper, it's the full scale intelligence quotient at approximately five years of age was 95.4 in the DHA group versus 91.9 in the control group, and that was statistically significant. So the babies in the DHA group did better. Technically, the estimates of treatment effect on other indexes of the Wechsler and the fruit Stroop interference core generally did not support the result of the primary outcome. Now, the percentage of children with a clinical diagnosis of autism spectrum disorder, attention deficit hyperactivity disorder or other behavioral or neurological disorders were below 7%. And we're similar between the two groups. Likewise, the growth Z scores were similar between the two groups. And in terms of adverse events. In the follow up study, they were similar between the two groups. So the conclusions of the article is that they're an enteral emotion of DHA at a dose of 60 milligram per kilo per day, was associated with modestly higher, full scale intellectual quotient scores at five years of age among infants born before 29 weeks. These results support this is some of the conclusions from the author. These results support the current recommendation that preterm infants born before 29 weeks should receive approximately 60 milligrams of supplemental DHA per kilo per day, in addition to the DHA available from human milk or preterm infant formula in order to approximate the fetal required ratio. Twitter is abuzz Martin Shire? Absolutely. Everybody is weighing in. I think, to me, the the point that has been made by by many people, I think, I think a psychologist even mentioned that on Twitter is, is that difference? Is that three point difference in the IQ that you're seeing? Are you are you going to notice that in any way clinically, that's going to be a significant change. Right. And, and even though the numbers as we've said, the numbers technically are different enough that statistically you reach significance is a 95 versus a 92. That big of a difference? That's a very interesting question. And so I'm curious to hear what what you think.

Daphna 13:47

Well, for me, I mean, DHA has always been very promising, right? Because we're using it prenatally. We're some recommendations to use it in the pediatric population. So why not examine it in in neonates? And I think for me, who has an interest in kind of neurodevelopmental outcomes, it's like, like when we do BPD bundles when we do you know, it's a cumulative effect. So if you can amass three points with everything that we do, then I think you're, you're you're gearing up for a big change. I think we also need some more data,

Ben 14:23

right? You wouldn't really know if if all the interventions would be additive, though. I think that that could be Yeah, but

Speaker 3 14:33

yeah, yeah, and one thing I was gonna say is I'm really impressed with the final number of kids that got followed up versus the initial that's a high rate of retention there that's that's really good.

Ben 14:47

Yeah, and Kenny Martin on on Twitter has has written extensively and she's responding to people about the basically what you were talking about definitely maternal dietary intake, how that how How important is that? And how much does that contribute? And she even read a reference to paper in JAMA with the maternal DHEA supplementation on BPD. Free survival in preterm infants. So definitely, yeah.

Daphna 15:12

And that brings up a good point, which we've talked about some of the other nutrients that maybe, maybe if you got enough of it prenatally, maybe it doesn't make a difference what you get postnatally right. But we, we, we can individualize the medicine, or we can make recommendations for everybody. But you know, if we're not, you know, if you're at a deficit already, depending on your prenatal accumulation, or lack thereof, you know, maybe makes a difference for you. Right, so.

Ben 15:41

Yep. So, we're hoping that we're trying to stay on top of these different publications as they come out. So we were very happy that we were able to cover that for you guys this morning. And yeah, so who wants to go next?

Daphna 15:57

I'll go next. Okay, I'm gonna take it in a totally different direction. I've been looking forward to reviewing this paper. Actually, I am doing two papers today that I was very much looking forward to. But this is entitled characterizing the language used to discuss death and family meetings for critically ill infants. I just think this is such an important topic. I lead author Margaret Bartlett and trilling author, Monica lemon. This is in JAMA Network open. Pediatrics is coming to us from Duke in North Carolina. So what's kind of the background necessary if you're, you haven't been reading the literature in this space. So there consensus guidelines about how we communicate with families versus comes from adult literature, which is like trickle down to pediatric literature. Now, we're moving into kind of perinatal care, but it really it emphasizes the importance of clear communication. And in particular, avoiding euphemisms where we use different words to describe what we actually mean. Because what we actually mean to say is a topic like death, which is uncomfortable for us, or we feel like it is uncomfortable for family. And so we have seen beating around the bush. That's exactly right. That's exactly right. And there are many ways to do that, which I'll tell you about shortly. So what did they want to look at? They wanted to look at family meetings and see like, what language are we using to discuss death, and family meetings between parents of critically ill infants in the clinical team. So they enrolled families of infants with neurologic conditions. So this is this is like, you know, kind of a subset of our population. But I think the information is useful regardless, you had a plan family meeting for kind of goals of care, were enrolled from September 2018, to September 2020. And this was a longitudinal observational study that they transcribed the family meetings over the course of the infant stay. So some infants may have had many goals of air discussions. And they looked at, again, the language around death. So inclusion criteria of age younger than one year, diagnosed neurologic condition hospitalized in the neonatal pediatric or pediatric cardiac intensive care unit, at their study site, and that they had a plan family meeting to discuss either the prognosis, or starting not starting or discontinuing life sustaining treatment, exclusion criteria as parents were not enrolled, if they were younger than 18 had some speech or hearing impairment, which I think is really interesting that they included this. And because that is a population that we ignore, or we don't really talk about in our in our study. So I think that was really valuable and required translation to read or interpret, required interpretation to converse in English another. Another population that gets left out of our communication literature.

Ben 19:09

Yeah, there were a lot of articles recently in pediatrics about outcomes in children of parents with disability and, and we didn't get around to reviewing these articles, but they were really, really good. So I encourage people to go check that out in pediatrics. I think it was maybe a month ago.

Daphna 19:28

The primary outcome was again, what was the language use to reference the term death during family meetings between parents and clinicians. So they screened all of these family meetings for the discussion of death, but they were looking really for the following either mention of an infant potentially dying owing to a current medical problem or a diagnosis, or either not starting or discontinuing life sustaining treatment. mention of a prior near death event like the baby had had a code previously mentioned have a high hypothetical future near dere Near Death Event like anticipating bradycardia.

So baseline characteristics, they had a total of 68 family meetings involving 36 Parents of 24 infants, and discussion of death was present in 49% of the family meetings. And you know that all of the meetings were supposed to be talking about prognosis that's already. Oh, that's already an important fact. Okay, I didn't realize the 33 family meetings that included discussion of death involve the care of 13 of the 24 total infants, so 54% and 56% of parents. So for these 13 infants, one parent identified as the infant's mother, hold on a third for all 13 infants, there was one one parent, identified as the infant's mother for seven infants, or 54%. Another parent was enrolled, who identified as the infant's father. Among the 13 infants death was discussed in a median of three meetings, a range of one to five meetings, and family meetings that included discussion of death, the 13 infants being discussed had a median length of hospital stay of 86 days, the median gestational age was actually 37 weeks. But remember, these are babies with neurologic diagnoses, seven, or 54%, were female 46% were male 92% received mechanical ventilation 46% required chest compressions 38% had to do not a do not resuscitate order placed, and 15% or two of the events died during admission. So I think you can understand this pretty sick cohort, right? So definitely babies who should be having goals of care discussion. There was some data about the family, the parents, but in the interest of time, I'm not going to get into that. So the primary outcome, the words, die, death, dying, and stillborn in some situations were used a total of 32 times in 406, references to death, only 8%. And they were present in 15 of the 33 family meetings that included discussion of death. So in, that's 45%, so the words that you know, the actual words die, death dying, we're only used in 45%. Alright, most words, during discussions of death were spoken by clinicians. So 73% family members that were were responsible for, were responsible for most uses of die death, dying or stillborn. 59%. When referencing death, family members were more likely to use die death, dying or stillborn then were clinicians. And among family members, mothers were more likely to use die death dying or stillborn and 89% as compared to the fathers, among clinicians, palliative care clinicians, were most likely to use these terms. 54% Not surprising. And interestingly, many uses of die death dying or stillborn by clinicians followed a parent's request for clarity. For example, they document one of these exchanges. The they may say took place after clinicians 350 word description of bradycardic episodes in an infant with a congenital brain anomaly. The mom, what you're saying? I mean, I want you to actually say it in the intensive care fellow. So I'm going to say it, I'll say it, I'll just say I'm concerned that at some point, her heart rate may go all the way down, and not come back up and she'll die. So they there was a lot of this beating around the bush until parents said like, I really need you to clarify what you mean. clinicians and family members replaced die death dying and stillborn with a euphemism most of the time. 374 the total references are 92% but different in the types of euphemisms that they use. And they identified four different types of euphemisms that people were using instead of those code words. So medical jargon accounted for 36% of references to death, and the majority of medical jargon was used by clinicians. medical jargon took two major forms. In the first death was described using technical words or phrases, with connotations that are not clear to clinicians to non clinicians. To this included shorthand for other events such as an episode a code and arrest are phrases such as ultimately fatal, a guarded prognosis or let's redirect care to comfort measures. And the second form of medical jargon was kind of what they call it physiologic circum location in which a concrete description of death was given without interpretation. And this sometimes overlapped with with other terms. So for example, they'd say, if if your baby were to code, which parents don't always understand will not be providing chest compressions. So they indicated that the baby would die, but they didn't actually say it. Or with her condition, there's always a possibility that sometimes she can stop breathing. So for us, we know that means babies will die but families don't, don't have the information to carry that step out. The next most type of most common type of euphemism was cloak cloak, colloquialisms, in which death was replaced with some sort of figurative language. And this accounted for 26% of references to death, and were the most common type of euphemism used by family members 34% There were multiple different types of colloquial colloquial isms, death was abstracted using a variety of metaphors, a journey to the afterlife losing a fight or battle running out of time, the most common were to pass away or to not make it. The next most common type of euphemism was pronouns and vague nouns which accounted for 22% clinicians and family members reference death using pronouns at similar rates. And most of it, most of those were, yes, it's using like it, what this or something will happen. For example, the clinician might say, yes, it's really hard for us to predict when it would happen, family member might say, I know what would happen at any I know what would happen at any time. And if that does happen, I would rather it happen knowing that we got a bond. So they people indicated they understood that death was a possibility or likely outcome without actually saying, and the final type of euphemism was survival framing, 19% clinicians and family members referenced death using survival framing at similar rates. So it's really talking about life in a reference to death. So the statements were kind of a denial of the opposite or double negatives, such as, don't live or not survive, or we don't know how long she may live or his life is going to be short. And decisions that they they also want to talk about statements that left the potential for death implied to decisions that might result in death, such as discontinuing life sustaining treatment, or placing a do not resuscitate order were discussed without any reference to death. So they were talking about these real concrete goals of care without you know, even saying that using them or without them, baby may die. This type of language is used in 21 of the family meetings 64% and was most often initiated by clinicians. In 52% of these meetings, there were no uses of die death, dying or stillborn, even though they were asking parents to do something like withdrawal of life sustaining treatment, or putting in a DNR. And in encouraging parents for death statements often spoke about logistical arrangements or doing memory making, enjoying the time they had left. This type of language was used in 48%. And again, typically initiated by clinicians, in 38% of these meetings, there were no uses of the words die death, dying or stillborn. And hoping or planning for a different outcome speakers often made statements about what they wished is true, which actually in palliative care is a useful tool, if used correctly. So they might say, for example, we always join you in hoping for a miracle. And in palliative care, you learn that we always join you in hoping for a miracle. And I'm worried that might not happen or, and that's not what I see happening for your baby. And so this type of language occurred in 30%, of meetings. And in 60%. Again, there's no use of die death dying or stillborn. And so there are a few more data points. And I was glad that they gave us this great table that showed some actual quotes from the discussions. But I think that this is really important for us to think about the words that we use in general, and parents want us to be concrete about what we say. So there's no real confusion about it. I think what was really a salient point for me is that when the words were used. And they were more often used by families. So I think that is a signal that those are the words, we should be using the family's

Ben 30:10

thoughts. I saw that paper, I was like this, I didn't even start reading it, I sent it to you because I was like, this is because for people who may not know you are our palliative care specialists in our unit. I want to highlight the fact because also, I think sometimes you could misinterpret the data. So you because sometimes, you know, I will do this very often, where if there's too many things to discuss with the family, you will, you will sit with them like twice in a day, you know, you're like, I'll just break break one thing first, and then we'll have a discussion. But these meetings were conducted by the attending physician 97% of the time, so so they were not, quote unquote, dumped on a trainee that doesn't have experience. The palliative care was present 73% of the time. So so these are not like, you know, okay, this is not like the the curbside where, ya know, these are these are meetings and meetings. Yeah. And what's interesting is that if you had asked me before the article, what, I'm sorry for the noise, they're doing some, some event planning next to the office, but the colloquialism like your child will pass away, I would have thought would have been okay. Right? Because I'm like, it is it is, I mean, passing away we culturally, it means your baby is not going to live. But it was interesting that it had to be the word had to be sort of set. And I had an attending in residency, who used to say, did you say the word and if you did not, you have to go back. And it's something I'm trying to teach my medical students also about, like delivering bad news, because that's, fortunately, medicine has gone a long way we no longer are having to disclose a patient's died. But we have to always disclose these difficult situations where patients are, quote, unquote, dying. And so it's very difficult to have these these conversations. So no, it was great. And the inverted pyramid was great. We're going to put that on our social media accounts. So yeah. Agree. Agree. Agree. Thoughts? Yeah,

Daphna 32:13

I think we just want to say more thing, I think we owe it to parents. We can be hopeful, like, like they were trying to express in some of these meetings, we should be hopeful. But we owe it to parents, when we feel like their babies might die. So they have the opportunity to do some of the things that were recommended and discussed. But parents may be like, Yeah, but why do I have to do that.

Ben 32:39

And it's exactly what you're exactly right. Meaning we don't avoid the word because we're just malignant, it's so uncovered, we don't want to, we don't want to have to say the way that's just painful to us too. And I think that's something that, we just have to unfortunately, accept that and just just just, you know, take the leap, and just face the challenges that are gonna follow from from bringing that into the conversation, but it is ourselves as well, I see this with the medical sense, like, I don't want to tell people that they have cancer, I don't want to tell people that their kids dying, I just don't want to do it. And it's because it hurts me. Like it hurts me, it's not that like, I'm just a girl, if I mentioned it, they're going to keep me waiting for like another 15 minutes cuz they're gonna have so many questions, I want to believe at least that most of our colleagues are not like that you don't go into neonatology with. So I totally

Daphna 33:23

agree. And I think one of the most valuable things I did in these additional palliative care, you know, training that I did was I think everybody who works in our community has to take some time to think about their own relationship with death and dying. And what about it is so uncomfortable for them? Is it something you talk about with your family, with your partner, with your children, and and you really have to first become comfortable with it yourself before you can be comfortable with it for families? So I think a reflection exercise is fine.

Speaker 3 34:03

Yeah, I think that this just highlights the article highlights that we do need to focus on this and make it more comfortable, whether it be for trainees or even people who are mid career that this is, you know, maybe we need some more education. Not everyone has this expertise or this, you know, comfort with the conversation and the topic.

Ben 34:26

And it's funny because I remember this, I'm gonna take things to a lighter note now, in the TV show scrubs, which is my favorite medical TV show. There's a there's a moment where the main character says we're friends with basically they're saying like how they're friends with death, because it's like death is in and around the hospital all the time. And so as a physician, you're like, and then the show there's like the character representing death walking around, and they just basically are saying hi to the doctors as if it's like another co worker in the hospital. And so what aside from from the joke there, it's just the fact that despite the fact Were surrounded by mortality and death in the hospital, it still doesn't make this any less comfortable and uncomfortable. And I think and I think that's something that as, sometimes as a critical care physician, especially when you have friends who are not in medicine, you're like, I see death every single day or I see shadows of death in in the unit and that, and that really, really messes you up. Pretty big time. But yet, still, it's nice to see in that paper that there is that that sensitivity remains there where people are just not they just don't want to say you just don't want to say the word. It's just very good. In my opinion.

Daphna 35:33

I think it does also highlight the value of data, dedicated palliative care teams. I think a lot of times in the NICU, we talked about this all the time, we're so siloed we're on this bubble. And we're like, you know what, we got this we can handle it. And like you said, we deal we quote unquote, deal with death. But you know, there's a subspecialty trained to just have these conversations. And so for units that haven't maybe embraced that, and I hope that one sheds light on

Ben 36:03

the one thing that exactly right, and I think that the palliative care can come to relieve a little bit the sense that I'm talking for myself your way when you do have to bring up the word. It's even though it's not a failure on your part like to write always, it always feels like have I failed, like is the baby dying because I have failed as a physician. And that's very tough. And I know it's completely irrational. And it's it's not true. But still it's like I have maybe have failed and I don't want to admit to my to my failure because it's painful. This episode is proudly sponsored by Wreckit. Me Johnson. Recommend Johnson is dedicated to the research and development of nutrition products that help support baby development at every stage, including an extensive Enfamil portfolio for premature and low birth weight infants learn more at HCP dot meet johnson.com We need to keep going because we're going to because All right, so Priya, you wanna you want to? You have a very exciting paper so I'm excited for the review.

Speaker 3 36:58

Yeah, I was gonna say it's exciting topic. So the title of this paper is cannabis use during lactation may alter the composition of human breast milk. The author first author is Chipman deep joson. And it was published in the pediatric research journal. And the authors are from McMaster University in Canada. So I felt like this was a really interesting and relevant topic and given you know, the increase in legalization of cannabis not only in the US, but really worldwide. And I think as a pharmacist, we're often consulted to review meds for breastfeeding. So this one really hit home for me. And so the authors really tell us that you know, cannabis is used by women to manage symptoms of morning sickness during pregnancy and postpartum stress and anxiety. The use during pregnancy has been found to negatively influence growth. And postnatal exposure through breast milk has been associated with decreased infant motor development at one year of age. So what we know about cannabis is it does cross the placenta into the breast milk. And there's a thought that maybe there's this long term storage of cannabinoids and a slow release back in to the breast milk during lactation. We know that the ACOG recommends discontinuing during pregnancy and lactation. And interestingly, there's a Canadian survey of pregnant moms and they asked them you know, do you understand the risk factors? And greater than 90% of these pregnant mothers said, Yeah, we do understand the risk factors. Despite this, though, there is an increased use of cannabis. And the self reported prevalence is anywhere between two to 11.3% in pregnancy.

Ben 38:39

Yeah, I was what I was wondering if that's even I don't know if that's true. I mean, right. Well, that's what they said. That's what they say. And I'm sure I'm sure the data is correct. I'm not questioning the data, but it's like, I feel like even in medicine, we barely know. Right, right. It's like, like, if you ask the doctors like, what are those like? You have to think? I mean, I think people want to be left alone. Maybe that's once a year. Yes. Right.

Speaker 3 39:01

Yeah, the reporting is definitely I feel like under reported probably especially know the connotation and the thought that you know, this, we know it's bad. Am I going to tell my doctor, it's bad? Because it's bad. So anyways, the question here was, what are the changes in lipid protein carbohydrate, lactose, and secretory. immunoglobulin A, which I'm going to call S IGA from now, levels in the milk of cannabis users and non users and this S IGA really is the predominant immunoglobulin and colostrum and mature milk. It's been shown to be essential for immunity. So really, they wanted to look at this and they said that, you know, they've heard of reports, there's obviously a lot of data out there, but this is the first actually looking at these in, in, in the breast milk and the composition of the breast milk. So the study design was pregnant and recently postpartum partum women who were either using cannabis or not using any substance that was our control group were recruited out of prenatal and antenatal OB GYN clinic and birthing units. at McMaster, the participants provided verbal and written consent, and they completed a questionnaire via the REDCap system. So their medical information was taken from the time of delivery from patient charts. And they provided milk samples between six to eight weeks postpartum, it was two ounces of milk that they were asked to provide, which was stored frozen, and they were paid $25 for participation. One thing that I felt that was missed here was the study period, I went back and looked several times to say, Okay, how long was this study? For what years? I think it would have been important. So I did read that, you know, in 2018, this was legalized in Canada. And so that reference and timeframe would have been important.

Ben 40:56

They announced and that's something else that's very important is that for the people, because that was not familiar with that, but any in Ontario, which is where the study is taking place, any person 19 or older can buy us possess and grow recreational cannabis within the legal limits. So that's important, too, that it's that recreational marijuana is legalized.

Speaker 3 41:17

Yeah. So they did look at the metabolites. So a cannabinoid analysis, they looked at THC, carboxy, THC, 11, oh H THC, CBD and CBN. And this was studied based on previous research, they actually have an analysis method that they developed and validated at McMaster. And what they do is they use this protein precipitation method, then they follow it with a lipid Removal Step and then evaluate VMFS back and look at the peak area measured. They also use human, a human milk analyzer to measure the macronutrients. So energy, fat, carbohydrates, and protein. And then the milk samples were defeated via centrifuge, and then recent reviews. The aqueous fraction of that. And then the IGA was looked at via the Elisa, and lactose was looked at via the lactose assay kit. So for the results here, so they had 78 women that really provided consent to be contacted. But of those 78, they recruited 18 non users and 22 users that were enrolled and 17 non users and 19 users completed the study. So and the reason why there was a drop out there was because there was little or little to no milk supply was the major reason for the difference in the numbers there. So the demographics, I thought were really interesting. So cannabis users were younger, but they're also really well educated. So 50% in both groups went to college university, there was a lower percentage of breastfeeding in users and I you know, 86.4 is still high versus the 100% non users. And there's a reported lower levels of milk production at weeks one to four and six compared to non users and the authors related this back to a previous study that said that these patients could probably have lower prolactin levels, but they did not look at that. So 91% of the cannabis users used in the six months prior to pregnancy, at 2% During pregnancy, with most in the first trimester and less each subsequent trimester 44% reported using during the entire pregnancy, and then 55% used post to delivery so of our users only 55% reported using post delivery. The author's looked at the type of cannabis the frequency was reported most smoked, and use daily for both pregnancy and post delivery. They also looked at cigarette use alcohol consumption and patterns by partner or roommates. So they looked at those reports to when looking at the milk samples. So we had 5014 milk samples collected from 13 cannabis users. And they presented detectable levels of cannabinoids. It's interesting because there's a table that has a nice breakdown of the min and max concentrations of each of these metabolites and also the range, but the THC was higher and daily users and they had one user who had the highest THC level and that was the only sample that showed the detectable CBD. So it also goes to show here that these metabolites are not all the same, that they don't present the same. So I thought that that was interesting, an interesting analysis. The macro news nutrient levels were not different from the milk of non users versus users, where they did see some differences where lactose levels were higher in users. And also users as pregnancy and then postpartum were combining them both. But they really found no difference in the pregnancy only users. So lactose levels were also higher when you adjusted for maternal age. The importance with lactose is that it's the most abundant carb, 90 to 95% in breast milk. So you would expect to that you would see a difference in the carb levels, but there was no difference there. And they said that they the sample size was just too small to determine that affect the s IGA was significantly lower in users, but no difference in pregnancy only users. And then obviously, the speculation here is that these low s IGA concentrations could impact the immune profile the milk, as IGA would levels were significantly lower in the milk of cannabis users who did not report cigarette smoking. So then you also wonder, is there some sort of protective effect with the use of both, but then, you know, they say postpartum specific stress has been linked to reduced s IGA concentrations. It really is important for us to understand this relationship is it cannabis use? Is it stress is it both? They didn't, you know, really analyze stress in the study here. There was positive correlation with carboxy THC and crude protein a negative correlation with 11 Oh H C, THC and carb levels. So when again, when we're looking at user versus non user, really no difference in the BMI of these moms, the CO use of cigarettes plus cannabis, how to lower carbohydrate but greater crude and true protein levels. And hypothetically, the you know, there's previous studies that show that lower protein levels with cigarette smoking, it's hypothesize that this ko use disrupts the process that decreases protein levels, from colostrum to mature milk, no effect on of alcohol co use. And when we looked at the birth weight of the babies born, the mean adjusted birth weight was lower by about 213 grams on average, but it was not statistically significant. So some of the limitations of this study is that, you know, they didn't really look at the amounts and frequency of the cannabis. They weren't recorded in detail, these milk samples were only collected at a single time point. And this really could have provided us further insight into the accumulation and the effect of cannabis on the milk. The conclusion by the authors are again, this really is the first study reporting the effect of maternal cannabis on breast milk composition. And that they report the maternal cannabis consumption during lactation is associated with the presence of several cannabinoids, including the metabolites of THC and attenuated IgA levels in the milk of users. And this may impact the infant's health due to a direct cannabinoid cannabinoid exposure and altered milk consumption. And as as with every study, we further studies are needed, we need to look at, you know, infant health outcomes, specifically neurodevelopmental and behavioral outcomes, as well as body weight and growth of infants exposed to cannabis through breast milk. And this is so that we can inform our mothers and also, you know, know, for ourselves what this what the impact is here. So I'll open it up to you guys for your thoughts.

Daphna 48:53

Yeah, I thought it was an I thought it was an interesting paper, right. We talked about this all the time, about quote, unquote, is it safe or not? And, you know, what, what is what is safe or not safe about it. And I think this is particularly important, these preterm infants, where we know that moms own milk is so valuable, right. But they're also the babies at highest risk for neurodevelopmental borne or developmental outcomes. And I thought this was an interesting take by looking at what it does to the nutritional components of of milk. I'd like to see more work I'd like I think, especially looking at what's the what's the trade off, right? Getting mom's own milk and NAC or, you know, versus these some of these outcomes to that's where I'm at with it, and that we're gonna see more and more marijuana use in this country as well in the United States as well. So we got to start learning about it.

Ben 49:53

Yeah, I mean, the numbers were small. It's difficult to draw conclusions from this and I think, but it does, it does. I mean, to be honest that I I was really appreciative of all the bar graphs that they created. Because these are things like I said, you can always pull and bring to the bedside and show parents and say, well, it wouldn't make that much of a difference when it comes to that and it will reduce for example Secretory IgA Yeah, the cigarettes stuff. very puzzling. I mean, that's just very, I would, I would be curious to see. It sounds like a European study that's going to need to be done where everybody smokes cigarettes. But, but this was no this was very interesting and, and it's not benign. I think again, as we always say, it's very important in the public consciousness that conscious consciousness that legalization doesn't mean that it's it's healthy and that there there is there are side effects and I think I can't I'm trying to pull up this paper. I can't seem to find it. But there were data about some effect on on intelligence in babies who were breastfed in mothers who were using marijuana, but I'm not sure I can find the paper now. So now I'm now hesitating in any case, I will I will find it and try to bring it up in any case, yeah. Okay. Okay, have you have a few more paper to go through? I'm gonna start with this one if that's okay, right. Definitely. Okay, if I go? Yeah, please. Alright, so this is a paper on antenatal steroids. It's called the association of antenatal steroids exposure at 21 to 22 weeks of gestation with neonatal survival and survival without morbidities. first author is Sanjay Charla, it's in JAMA open, lots of good articles this time, this time around in JAMA open, and it's coming from the NICU, the neonatal Research Network. We've talked a lot about all these papers that have come out on antenatal corticosteroids and how they may have some deleterious effects long term in babies who end up not, for example, not being delivered preterm. So I thought it was very interesting to review some data that might reassure us that you know, steroids actually have have a positive effect. So, in the background, they mentioned that the administration of antenatal steroids to pregnant patients at risk of develop of delivering between 24 and 34 weeks is associated with lower mortality, lower risk of reduced RDS neck ivh. And I quote this a for clinicians caring for pregnant patients are 22 weeks gestation, at risk of preterm delivery, the value of antenatal steroids administration at 22 weeks or younger remains unclear. They do mention this shift in the recommendations from the ACOG to to conduct shared decision making at these types of gestational ages with family about the administration of antenatal steroids. And the question they're trying to ask is, what are the rates of survival and survival without major neonatal morbidities among infants born at 22 to 23, and six weeks, were either exposed to antenatal steroids at 22 weeks or younger, versus infants who were not. So it was a retrospective cohort study using prospectively collected data from the NI CHD neonatal Research Network. The included infants were born between 2016 and 2019 at a gestational age of 22 to 23 and six weeks. The excluded infants were born at a outside outlying hospital, who had major congenital anomalies who had received whose mother had received antenatal dexamethasone and they were saying it was too rarely used to create its own category. So they excluded the few patients that were in that category. Received antenatal steroids at 23 weeks or received more than one course of antenatal steroids all these patients were excluded. Infants who died within 12 hours without receiving postnatal life support were also excluded. So that means babies who I guess received what we call comfort care. Right after birth, the intervention basically classified everybody in three groups either no steroids are you had a partial course that you got one dose and then mother delivered or a complete course you got two doses and then delivered. Many maternal and infant variables were collected. Resuscitation that delivery is something that they defined as either you needing chest compression or epinephrine. The primary outcome was survival to discharge secondary outcome were severe survival without severe neonatal morbidities including ivh PVL, surgical NEC severe BPD, severe ROP requiring treatment. Okay, so let's get into the results. Because we are short on time there was a total of 431 patients the mean gestational Ages was 22.6 weeks. It 54% were boys and they included 110 patients who received no steroids. So that was 25% of the cohort at patients who received one course like just one dose, not one course one dose that was 18% 18.6% of the court, and then 241 infants which is 56% of the court who received the full two doses, differences in the maternal and infant character sistex were present among groups for maternal education, magnesium sulfate exposure, antibiotic exposure, clinical correo histological correo, premature rupture of membrane mode of delivery race, gestational age, Medicaid insurance and Apgar scores at one in five minutes. So a lot of different variables that they're going to have to account to in some of these analyses down the road. The earliest antenatal steroid exposure was at 21 and two weeks just going to let that sit. Okay. So, let what are some of the results among the infants exposed to complete antenatal steroid 54% survive to discharge compared to 37% with partial course, or 35% with no antenatal steroids and I'm going to pose these bar graphs because they are impressive. Yeah. among infants exposed to complete antenatal steroids 27% survived without major morbidities compared to 12.8% with partial steroid course, and 10% with no antenatal steroids. Two more points compared with infants without antenatal steroid exposure. infants born after a complete antenatal steroid exposure had significantly higher adjusted odds of survival to discharge with an AOR of 1.95 and their survival without major morbidity with an AOR of 2.74. interesting findings, which I want to mention, they say and I quit when looking in at individual morbidities, the risk of sepsis was higher in infants born after complete antenatal steroid exposure compared with those with partial antenatal steroids exposure. Not exactly sure if other factors play a role. I haven't really looked and want to be honest with the audience haven't looked if these patients specifically had prolonged ruptured memory? I don't know. I don't know that stuff. The conclusion of the paper is that among babies were born between 22 and 23, and six who receive intensive care exposure to a complete course of antenatal steroids at 22 by 22, and six weeks or less, was independently associated with a greater odds of survival and survival without major morbidity. This data suggests that the use of antenatal steroids in patients at 22, and six weeks or less could be beneficial when active treatment is considered. I thought it was a phenomenal data. I just wish it wasn't really telling you why the babies ended up being delivered early, right, which is something I would have liked to know. But other than that very interesting, and I think a lot of the papers have come out recently can make you squeamish as to should we give steroids as much as we're doing it. But to see that evidence, especially in the most preterm, if you are pretty sure that these mothers might deliver early. It's definitely a strong, valid thoughts.

Daphna 58:05

No, I think you've hit the major points. I think the data speaks for itself. I guess I certainly I agree with you looking at all those figures. If that was valuable.

Speaker 3 58:17

And one of the things then maybe I missed it is did they talk about repeat courses? I know this comes up like when you give the course and the babies really?

Ben 58:25

Those babies were excluded. Okay, so if you had like the rescue the rescue course as as we call it, that you were not included in the trial.

Daphna 58:36

But I think you bring up a good point. And what why didn't they complete the course. Right? Was it you know, is it precipitous? Right, it's precipitous labor, most likely, which could be related to another a number of things, was it infection was it you know, what, you know, so that the phenotypes of the babies, as we say, are very important. I had a paper I wanted to touch on, I'll just do the main highlights because we are really short on time. And I have and you have more.

Ben 59:08

I have technically two more, but I'm going to just quickly go over one of the results. And that's it.

Daphna 59:12

I was excited about this paper because I think that we will be seeing more information about ureaplasma and infections in previous you know, I'm always looking for ureaplasma in the taking that one for you. But that's partially because we had such great collaboration at the University of Florida with obstetrics and when you heard how much mycoplasma ureaplasma was, is is recovered from the flora of mothers who are born preterm. You're like it's gotta be it's gotta be related. Why aren't you paying more attention to and so the studies are coming. This title, predicting the likelihood of lower respiratory tract ureaplasma infections and pre terms. Lead author Rose Marie the sqrt, senior author Natalie Davis has an archives of disease child and fetal addition, coming to us from the University of Maryland in Baltimore. So they really wanted to inquire about how you could predict which infants would have ureaplasma or not. So they actually had data from five different published cohorts with enrollment dates from 1999 to 2016. So that's just something to take into account. The cohorts had different gestational ages and respiratory criteria, but all the inputs were less than 33 weeks. And the analysis is kind of based on the fact that they collected the same demographic, obstetric and neonatal variables from each cohort. And basically what they did is they looked at tracheal, aspirates and nasal pharyngeal aspirates obtained from an intubated infants, and if they had an endotracheal tube, and then not nasal pharyngeal aspirates, from non intubated infants. So that was different across the cohorts. And there was congruence most of the time for tracheal, aspirates, and nasal pharyngeal aspirates. So that's details that if we had more time, I think we should go go over, but they were really looking at developing risk models for ureaplasma carriage in these infants. So they used three different models, which I'll talk about, and in general, they're enrolled 637 infants. And when you looked at their status in in 65%, of infants, and they had tracheal, aspirates, without nasal pharyngeal aspects, but had confirmed available for culture 32%, and they had confirmed ureaplasma and 68%. And so I thought that was, I thought that was pretty high. And then in babies who had paired nasal pharyngeal aspirates, with concordant, tracheal aspirates, that was 85%. So that potentially nasal pharyngeal aspirates could still be useful. So there's a lot of data here, I'm just going to jump to the really the models they had three predictive models and all the area under curves for the three predictive models had very good predictive accuracy. So area under the curve, point seven, three 2.77. And I'll just talk specifically about the highest achieving model that was our model number one, with an area under the curve of point seven, seven. And the variables they included were sex, race, multiple gestation, maternal age, P, prom, rupture, membrane duration, antenatal steroids, maternal antibiotics, choreo, route of delivery, birth weight, gestational age, the app gar, me included admission, white blood cell count, and ANC. And so the big differences between the models is that model one included the gestational age per week, the duration of the retro membrane is greater than 72 hours, and the admission white blood cell count. And so when all 17 predictors were included in the regression, it was really the gestational age, the rupture of membranes and the admission, white blood cell count were the predominant kind of selected predictors. And so they were they have a, an equation there, if you want to plug everything in for risk stratification. But they commented in the discussion that potentially the infant's risk could be simply classified at the bedside and to low risk and high risk by using gestational age. And so I'll haul I'll highlight that it was really those babies born less than 26 weeks that had the highest risk for ureaplasma. And, and then admission, white blood cell count less than 9600 or greater than 9600, which is actually I think, a pretty low. So count. So if you if you don't have the admission information, just antenatal using the gestational age and the rupture membrane duration gray that is 72 hours to be used for simple risk classification. So I think that's a lot of babies. So that's

Ben 1:04:17

interesting that like, it's, it's, it's leukocytosis

Daphna 1:04:20

That's right. That's greater than nine equal to or greater than 9600. Which is not that high.

Ben 1:04:29

Yeah. I feel like like 90% Almost all the babies. Yeah, because technically, I would have thought because I was looking at the equation and it's not like it's a it's, it's a direct relationship, not a not an inverse relationship. So on, but so yeah, okay, so hi. leukocytosis very interesting.

Daphna 1:04:46

Hi leukocytosis, the rupture of membrane duration greater than 72 hours, and the gestational age highest in those babies for less than 26 weeks.

Ben 1:04:56

My friends have well versed in grammar, I didn't mean to say hi leukocytosis This I apologize. It's fine. Fine. It's been we've been at this for some time now. And. Okay. Yes. All right.

Daphna 1:05:09

So you finish up here.

Ben 1:05:10

Okay, I'm going to finish up fine. So there's two papers I wanted to mention. The first one is also published in JAMA open. It's called neurocognitive outcomes at age two years after neonatal hypoglycemia in a cohort of participants in the H PODD. randomized trial. first author Taegan Edwards in from New Zealand. super interesting. I mean, we deal with hyperglycemia all the time. And the question they're asking is, is there an association between neonatal hyperglycemia and neurocognitive outcome at corrected two years in late preterm and 14 neonates born at risk of hypoglycemia, without evidence of an acute neonatal illness, what they basically did is that this was like a, this is the h h pod trial, which basically looked at babies and the identified risk factors for potential hypoglycemia. And it didn't really let them get hypoglycemic, they just give them feeding and dextrose. Gel before, almost the before the first measurement, and then they were trying to see if that would have that would reduce the incidence of hypoglycemia, or if it would have any immediate short term outcome. So we can link that paper. The bottom line is that it didn't have it wasn't really recommending giving, prophylactic prophylactic glucose gel, but they were able to include I'm gonna skip a little bit some of the some of the of the result of the of the methods. But they were able to enroll a 1321 infant. They assess them at two years of age. And yeah, and so basically, what are some of the results I'm gonna actually just pull up the abstract because I wrote down so much stuff. Yeah, and I realized I'm gonna not abide by my word. So fine. So 52% were male compared with the norm the normal glycemia group children who experienced hypoglycemia were more likely to have neurosensory impairment. 23% versus 18%, particularly if they experienced severe episodes, in which case it was 28% versus 18%, but not recurrent episodes. So the severity the presence of hypoglycemia, or it's a very had a significant impact on the neurosensory impairment. However, if after that you had more recurrence, it didn't really translate into worse numbers down the road. The risk of cognitive language or motor delay was similar between groups. The children who experienced hypoglycemia had lower barely three composite cognitive, and motor scores. And so the conclusions of the article is that children born at risk of hypoglycemia, but otherwise, well, those who experienced hyperglycemia were more likely to have neurosensory impairment at corrected age, two years with higher risk for severe episodes, further research is required to determine causality. Sure, but this was to me a paper that was very interesting because it's terrifying, because you get the data.

Daphna 1:08:08

And the data is, I mean, it's not new data, right? But it is just the hammers home the point like this, we can't just like sit on this hypoglycemia.

Ben 1:08:17

You can't sit on it, but also like they give them prophylactic dextrose. Yes. Right. Right. So it's like, I mean, yeah, but it's definitely something that the frequency is not an issue, but the severity of the episodes. So that's something I feel like we may have the ability to impact on so Okay, last paper I wanted to mention is in the Journal of Pediatrics, it's called delayed surgical closure of the PDA. Does the brain pay the price?

Daphna 1:08:43

You left this one for last?

Ben 1:08:47

I was supposed to open with that one. But then the New England decided to drop the bomb with a DHA paper. So now here we are, but I'm leaving this for last because I'm going to okay, it's first author, Petra, Lammers, Journal of Pediatrics, the data from Utrecht in Holland. This is another paper that had a lot of attention on Twitter. So you're going to be able to go on Twitter. And I think it's Abdul Razak who, who tweeted about it and there's a lot of interesting discussion with FFL cool, fresh weighing in and so all these guys, again, if you're not on Twitter, you're you're missing out, but I am finishing it off just finishing off with this one because I feel like people will be able to continue the discussion on Twitter. So the objective was to investigate the relationship between hemodynamic significant PDA cerebral oxygenation, MRI determined brain growth and two year northern mental outcome in a cohort of preterm infants whose duct was closed surgically. So the design is that preterm infants were born at less than 30 weeks who underwent surgical closure between 2008 and 2018. were included in this observational study. They monitored cerebral oxygenation saturation using near infrared spectroscopy during an up to 24 hours after ductal closure that used the Bailey three assessment at corrected age two years, and all infants also had MRI at term equivalent. The result is that 90 infants fulfilled the inclusion criteria, the days of a PDA ranged from one day to 41 day and the multivariable linear regression analysis show that duration of a PDA negatively influenced cerebellar growth and motor and cognitive outcomes at two years of correct age. And the conclusion is that prolonged duration of a PDA in a surgical cohort is associated with reduced cerebellar growth and suboptimal neurodevelopmental outcome. The big point of discussion on Twitter if you want to go and network I can sort of prime if you're listening, I can prime you for what people are talking about is the the nutritional information on these babies, obviously, as to especially when we're looking at MRI findings. And what was that but actually, interestingly enough, one of the authors Daniel fish visual brief, who's the second author of the paper is actually active on Twitter and actually is also participating in the discussion. So please, go take a look at that. However, I do have to say that this data is aligned with other data that has shown that prolonged exposure to a hemodynamically significant PDA does have negative long term outcomes, especially on neurodevelopment. If if I think if if Elko fashion mentioned that as well. So yeah, that was another interesting paper, you may have questions about, How did you decide to perform surgical closure? What was hemodynamic all that stuff is in the paper, I actually wrote it down in my notes, but I just we just don't have the time. So trust me, it's there. And if you're that passionate, it's there for you as well go read it.

Daphna 1:11:51

And like you said, this is the if you've been hesitating to get on Twitter, just I mean, this is the time, you can follow. You know, when we post this, it's already on fire on Twitter, but when we post this discussion will definitely continue. So follow us do and you'll get in on the conversation.

Ben 1:12:08

Absolutely. And I mean, can I can I just mention one more thing, right? I mean, if I'm actually going to pull this up right now, so Abdul Razak, who is one of the who's who's one of the social media editors for EB Neo, and who wrote a bunch of Cochrane Reviews is publishing that article, right? If you fail to finish, who is a world experts on the topic of PDA? Is there weighing in? Or very good friend Gabriel alternate from Montreal? Right? who is an expert in hemodynamics? is they're weighing in Nick and Bolton, Kenny Mauryan. Dr. Gautham, right. All these guys are having a discussion. And I forgot in the midst of all that we have obviously the the author of the paper who is interacting. So to have this degree of excellence like this, this roundtable with all these experts, in one place is freaking phenomenal. So

Daphna 1:12:59

yeah, I feel like if you're a trainee, if you're a fellow and you're, you know, the PDA is a hot topic, right? You got faculty on one side on both sides, you know, you there's conflict in your unit. I mean, you come join the conversation as a voyeur. Just look, just just watch to see what people are talking about. So you so you can bring it up on rounds.

Ben 1:13:20

Absolutely. So to close out the show, please remember to send us your stories of how the podcast has impacted your day to day life in the NICU. Oh man, first of all, I want our heart and some of them are phenomenal. And we're very It gives keeps us excited to keep doing this. We'll have a way to incorporate that in our end of year giveaway. We have board review podcast starting tomorrow on abdominal wall defect. We're having the pleasure of having as our expert, Dr. Nora Scrl, who's going to talk to us about what does life look like for these babies within phallus yield and gastroschisis. And remember to, I guess, yeah, that's it. We're going to give you more information about the Delphi conference as as registration opens, it's going to be limited seats. Unfortunately, we we don't know how to do this. So we planned for a certain number of people right. Now, and so we plan for a certain number of people, because if we cannot afford, we're learning we're learning. So next year,

Daphna 1:14:21

you know, we want to make it a really special experience.

Ben 1:14:24

We don't want to drop the ball. We don't want to drop the ball. So we've decided we're starting to set the scale. So when the registration opens, please make sure to register and we'll talk to you more in the coming weeks about the NICU life in between which is our photography project with Richard Doty. So stay tuned for that. There's lots of stuff going on. So yeah, stay tuned. Daphna. Priya. It was fun. Great job on your first Yeah. All right, guys. Thank you for listening to the incubator podcast. If you'd like to sip So 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 Nikki podcast or through our website at WWW dot v dash incubator. Dat 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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