#308 - đ Journal Club - The Complete Episode from May 11th 2025
- Mickael Guigui
- 1 day ago
- 41 min read
Hello friends đ
In this special anniversary edition of the Journal Club, Ben and Daphna celebrate four years of The Incubator Podcast while diving into a compelling lineup of neonatal studies. The episode kicks off with a review of a phase 2 multicenter trial on the safety of furosemide in preterm infants at risk for BPD. Despite widespread Lasix use in NICUs, data on dosing and safety have been lackingâthis study finds no significant increase in serious adverse events but emphasizes the need for larger trials to better define its role. The team then explores a study from India comparing 7- vs. 14-day antibiotic courses in culture-proven neonatal sepsis, showing that shorter courses may be safe and effective in select populations.
Additional discussions include a randomized trial from Australia evaluating âsigh breathsâ during high-frequency oscillatory ventilation and their effects on lung volume and oxygenation, a study examining how kangaroo mother care boosts breast milk intake, and a large Japanese cohort study detailing neurodevelopmental outcomes of infants born at 22â31 weeks. Finally, a meta-analysis on prenatal cannabis exposure underscores risks of low birth weight and preterm birth. With depth, humor, and clarity, Ben and Daphna guide listeners through evidence that shapes neonatal care.
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Weâre celebrating four incredible years of The Incubator podcast! As a thank-you to our amazing global community of listeners, weâre hosting a special giveaway packed with awesome prizes. Entering is easy â just take a super short 2-minute survey about your experience with the podcast. By filling it out, youâll be automatically entered to win incredible prizes including a MacBook, Bluetooth headphones, Bluetooth speakers, Incubator merch, books, tickets to the Delphi Neonatal Innovation Conference, and so much more. Your feedback helps us grow, improve, and continue to serve the neonatal community. Thank you for being part of this journey â and good luck! Click here to enter
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The articles covered on todayâs episode of the podcast can be found here đ
Kono Y, Kusuda S, Nishida T, Mori R, Toyoshima K, Sasaki H, Yonemoto N, Uchiyama A, Fujimura M; INTACT Study Group.J Perinatol. 2025 Mar 26. doi: 10.1038/s41372-025-02268-3. Online ahead of print.PMID:Â 40140596
Monnelly V, Nakwa F, Josephsen JB, Schmölzer GM, SolevÄg AL, Rabi Y, Wyckoff MH, Weiner GM, Liley HG; International Liaison Committee on Resuscitation Neonatal Life Support Task Force.Arch Dis Child Fetal Neonatal Ed. 2025 Apr 29:fetalneonatal-2025-328577. doi: 10.1136/archdischild-2025-328577. Online ahead of print.PMID: 40306761
Martinez TA, Remmer E, Mardakis S, Leone M, Boyer J, Lv S, Beltempo M, Sant'Anna G, Shalish W.J Perinatol. 2025 Apr 12. doi: 10.1038/s41372-025-02291-4. Online ahead of print.PMID:Â 40221609
Lo JO, Ayers CK, Yeddala S, Shaw B, Robalino S, Ward R, Kansagara D.JAMA Pediatr. 2025 May 5:e250689. doi: 10.1001/jamapediatrics.2025.0689. Online ahead of print.PMID:Â 40323610
Sinha B, Mazumder S, Thakur A, Devi S, More D, Ashorn P, Sommerfelt H, Kurpad A, Bhandari N.Am J Clin Nutr. 2025 May;121(5):1109-1116. doi: 10.1016/j.ajcnut.2025.02.006. Epub 2025 Feb 11.PMID: 39947481 Free article. Clinical Trial.
Hough JL, Jardine L, Hough MJ, Steele M, Greisen G, Heiring C.Arch Dis Child Fetal Neonatal Ed. 2025 Apr 17;110(3):297-302. doi: 10.1136/archdischild-2024-327445.PMID:Â 39406472Â Clinical Trial.
Dutta S, Nangia S, Jajoo M, Sundaram M, Kumar M, Shivanna N, Gathwala G, Nesargi S, Jain S, Kumar P, Saili A, Karthik A, Tripathi S, Bandiya P, Dalal P, Ray P, Randhawa VS, Saigal K, Radhakrishnan D, Venkatesh V, Jagannatha B, Sharma M, Nagaraj S, Malik M, Dogra S, Mittal S, Saini A, Makkar N, Dhir M, Chandramohan A, Pragati RA, Srivastava T, Mukundan L, Benakappa N, Shukla A, Rasaily R.Arch Dis Child Fetal Neonatal Ed. 2025 Apr 25:fetalneonatal-2024-328232. doi: 10.1136/archdischild-2024-328232. Online ahead of print.PMID:Â 40280737
Greenberg RG, Lang J, Smith PB, Shekhawat P, Courtney SE, Hudak ML, Moya F, Iyengar A, Eldemerdash A, Bloom B, Go M, Hanna M, Rhein L, Aliaga S, Lewis T, Febre A, Kiefer AS, Bhatt-Mehta V, Khoury JA, Selewski D, Anand R, Martz K, Payne EH, Zimmerman KO, Benjamin DK Jr, Laughon M; Best Pharmaceuticals for Children Act â Pediatric Trials Network Steering Committee.J Pediatr. 2025 Apr 28:114629. doi: 10.1016/j.jpeds.2025.114629. Online ahead of print.PMID:Â 40306549
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Watch this week's Journal Club on YouTube
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The transcript of today's episode can be found below đ
Ben Courchia, MD (00:00.76)
Hello everybody, welcome back to the incubator podcast. We are back for an episode of journal club. Daphna, how are you?
Daphna Yasova Barbeau, MD (00:06.734)
I'm doing well buddy. I've got everything pulled up here. Trying to keep the computer quiet so we can have a nice seamless episode.
Ben Courchia, MD (00:16.558)
Um, this episode is going to be released in the podcast, obviously, but also on YouTube. We're trying to do a lot more video stuff for you guys. Um, and, um, yeah, that being said, we're at this point of the year where we're celebrating the anniversary of the podcast. so May 4th was the first episode, 2021. And, um, it's now been four years that we've been doing this. Um, we, we've been
Daphna Yasova Barbeau, MD (00:37.207)
Oof.
Yeah.
Ben Courchia, MD (00:46.454)
It's truly been four years. We haven't missed much.
Daphna Yasova Barbeau, MD (00:49.272)
No, hardly a week, I think in four years.
Ben Courchia, MD (00:54.41)
And so we will roll out this week on the website our annual giveaway to celebrate the birthday of the podcast. So we've talked about it on this YouTube video and we will repeat it here. We're going to do the same thing we did last year. It's a very short survey. We take that information. It helps us make the incubator better. And then if you submit the survey, you automatically enter to win one of our many prizes.
We have an Apple computer this year. So that's very exciting. We also have some swag from our shop. We also have tickets to Delphi. We have books. hopefully, I don't know, we have a big audience. I don't know if everybody's going to get a prize, but at least you should feel like you have a high chance of walking away with something. So we are happy about that. So we'll put it on our brand new website on the top banner.
Daphna Yasova Barbeau, MD (01:42.894)
High chance we like to give stuff away.
Ben Courchia, MD (01:53.356)
It will be one of the featured sort of pages and then you can go fill out the survey. It'll literally, it will take you five minutes and then you're entered. You don't need to do anything. We used to do a lot of these like, tweet, you repost and you hold one hand up and one feet down and then no. Go to that survey. You're done.
Daphna Yasova Barbeau, MD (02:05.332)
much. Do a handstand. Yeah, and I really appreciate when people fill out the survey because we have always made changes. Yeah, we read every single comment. We make changes. We've always made incremental change based on the feedback from the community. And I mean, as we do this fourth birthday thing, you did a nice job on the video, but it's really,
Ben Courchia, MD (02:15.618)
We read every comment.
Ben Courchia, MD (02:25.314)
Yeah.
Daphna Yasova Barbeau, MD (02:33.75)
In part to everybody who tunes in and listens and engages with us. And we're so grateful for people who, who have been along for the ride or are joining us now or sharing with a colleague for sure.
Ben Courchia, MD (02:48.204)
Yeah, whenever we hear that this works for you all, not that we need to hear that it works for you all, but when we hear that what we're doing actually makes a difference in your day to day, it gives everything we're doing meaning the meaning that we're hoping for. that being said, Journal Club doesn't wait for no man or no woman.
Daphna Yasova Barbeau, MD (03:00.344)
for sure.
Daphna Yasova Barbeau, MD (03:10.638)
All right, you go.
Ben Courchia, MD (03:12.142)
Alright, I don't know what to start with. I have...
Daphna Yasova Barbeau, MD (03:14.156)
I know you're very excited about this group of articles.
Ben Courchia, MD (03:17.356)
Yeah. I'm going to start with something that is probably on everybody's mind all the time. And this is a paper that is published in the Journal of Pediatrics and it's called, Furosemide Safety and Preterm Infants at Risk for Bronchopulmonary Displasia. First author is Rachel Greenberg. It's a very, very interesting paper. Taking a look at furosemide, Le6. And we know that Le6 obviously is used
Daphna Yasova Barbeau, MD (03:29.518)
and
Ben Courchia, MD (03:44.302)
in so many units, half of all preterm infants under 1,000 grams in the NICU get Lasix. So it's always that stat that keeps coming back with every furosemite paper, but it still every time blows me away. And we still don't have a good idea on how and when to use it. it's interesting how our field is. Now, the idea in this paper is the idea of, obviously, it's always simple. We try to treat pulmonary edema. We try to improve gas exchange.
And for many, there's this belief that can we reduce BPD? Can we reduce the incidence of BPD? Until now, we've only really had small trials, maybe database review, retrospective reports. And there's not a lot of pharmacokinetic data available out there. And the result is what we are encountering, massive variability. Now,
This particular study is important because it's going to be the first sort of multi-center randomized placebo-controlled dose escalating trial of furosemide in this particular population of preterm infants. So I was very interested in reading this paper. It's a phase two trial that was conducted between 2015 and 2018 across 17 NICUs in the US. They included babies based on certain eligibility criteria. They had to be less than 29 weeks of gestation at birth. They had to be 7 to 28 days.
postnatally at randomization, and they had to be on some form of respiratory support, CPAP, high flow, or mechanical ventilation. Their exclusion criteria included like diuretic exposure, electrolytes, or renal abnormalities, hemodynamically significant PDA, meconium aspiration, or known diuretic allergies, which, yeah, I've never thought of that before.
The intervention is an interesting one. They basically randomized kids in a three to one ratio of furosemide to placebo, and they divided their furosemide group into three groups. so bear with me here. They had the first cohort, which was a low dose. They give them one mc per kilo IV every 24 hours. They had a load and they did also offer enteral, but the conversion was basically double. So they had this pharmacokinetic assessment that basically determined that if you were using one milligram per kilo IV,
Ben Courchia, MD (05:57.838)
based on the absorption and so on, would probably need to be 2 mg per kilo and to roll. So every dose will be multiplied by 2. Then they had a cohort number 2, which was a medium dose. And that was 1 mc per kilo IV given every six hours. And then they had a cohort 3, which was the planned high dose. And planned is the keyword here because they were supposed to give 2 mc per kilo IV, 2 mg per kilo IV, Q6, sorry, or 4.
per kilo Q6 entirely. But they never really initiated because there were some safety concerns. So we'll get into that. The infants in the study all received the drug for up to 28 days. And whether it was going to be given IV or oral was left at the discretion of the team. didn't really influence that decision. They monitored the labs for these babies pretty closely, electrolyzed sodium, potassium, bicarb, BUN, creatinine.
and phosphorus and they checked at least twice weekly following dose escalation because obviously they didn't really, they started these kids on lower dose and escalated. I say BUN. Do you say bun? I've heard people, I've heard you're muted. I've heard people say both and the first time I heard bun, was like, what is that? Yeah.
Daphna Yasova Barbeau, MD (07:11.956)
No, B-U-N. What's a bun? B-U-N.
Ben Courchia, MD (07:19.414)
So the primary endpoints were obviously it's a phase two trial. that was safety measured in the form of adverse events or serious adverse events. But they also had some key outcomes that included death before 36 weeks, moderate to severe BPD or death, electrolyte abnormalities, hearing loss, and then renal complications like nifrocalcinosis or nifrolethiasis. So let's get into some of the results. They ended up having about 82 infants randomized. 62 went into the furosemide groups.
and 20 went into the placebo group. AD completed the study. The median gestational age was 26 weeks. The median birth weight, 798 grams. And the median postnatal age at randomization was 21 days. 93 % in the furosemide group.
reach their max dose. I'm not going to get too much into that, but basically for the kids in the higher dose, they basically did a dose escalation process where they started them on lower doses and then eventually started escalating the dose, checking electrolytes and so on and so forth, making sure that this was well tolerated. So it's important to know that 93 % actually reached their max dose. And there was some open labeled diuretic use in the study, like 24%. So take that as you wish. So in terms of adverse events.
Surprisingly, even the placebo, was a lot of reported adverse events, 293, which corresponds to 93 % of adverse events. I just want to check in my notes that I didn't... Because this is such a high number of infants. So 93 % of infants, including...
including 223 adverse events among the infants who received furosemite, so 92%. And they reported 70 adverse events, 95 % in the infants who received placebo. So there were adverse events in both groups, but basically, most of them were very mild or moderate. And there were 14 serious adverse events in 20 % of infants in the furosemite group.
Ben Courchia, MD (09:37.974)
and only 11 % in the placebo group. Now of these 14 severe adverse events in the furosemite group, two were deemed by the site investigators as at least possibly related to the study drug. definitely something that to me doesn't seem particularly striking and speaks a little bit about maybe the safety still of furosemite. And we'll talk a little bit more about that.
When it comes to some of the secondary endpoints, let's talk about mortality and BPD. On adjusted analysis, they found no significant differences in the combined outcome of BPD or death between the groups with an odds ratio of 0.97 for cohort one compared to the placebo and then an odds ratio of 2.59 for cohort two.
versus placebo. yeah. In terms of serum electrolytes, obviously they found one or more serum electrolytes adverse events that occurred in 83 % of the AD infants, 84 % of the cohort in the low dose of Le6, and 93 % of the...
the babies in the cohort with the moderate dose of Lasix. On adjusted analysis, the odds ratio for having any serum electrolyte abnormality was 4.46 in cohort one compared to placebo and 7.89 for cohort two. Again, the medium dose versus placebo.
Another interesting outcome is hearing loss. They found that hearing loss prior to discharge was seen in 14 % of the furosemite-treated infants and in 22 % of the placebo-treated infants. And so as you can suspect on the adjusted analysis, they found no difference in furosemite potentially increasing the risk of hearing loss, which was kind of surprising because we know that auto toxicity is something that we always learn about furosemite.
Ben Courchia, MD (11:53.07)
Could it not have an impact in babies this small? Maybe. And the authors do talk about that in the discussion. In terms of nifrocalcinosis and nifrolithiasis, nifrocalcinosis was diagnosed on renal ultrasound, and it was seen in 23 % of the furosemide-treated group compared to 29 % in the placebo. So again, not something that was found to be.
statistically significant. The niphrolithiasis also no significant difference, but the numbers were very, very small in that case. So they're having some issues, obviously, reporting on that and making it sort of more of a generalizable result. In terms of BPD or death risk, which is also like kind of an innovative thing that this study did, where they didn't just look at the outcome of BPD, as we mentioned earlier, but they also looked at the potential trajectory. So using the BPD calculator that is available,
on the Neonatal Research Network website. So if you go on the Neonatal Research Network website, you can actually go to the tools and you can get the outcomes estimator for your prenatal console, but you can also get the BPD risk calculator. And so the BPD or death risk, because obviously death is one of the outcomes that is measured in the BPD calculator, decreased from baseline to week four, regardless of the study drug. And on adjusted linear regression analysis, the treatment estimate for cohort one
versus placebo was minus 2.7. And for cohort two, it was minus 1.34. The overall treatment effect was not found to be significant with a p-value of about 0.6. Now, in terms of the third dose, the third cohort with the very high dose, now the trial was basically terminated after an unmasked review of cohort one and two interim safety and efficacy data.
The FDA concluded that the risk benefit assessment for the third high dose group was not favorable and directed the study team to remove the high dose cohort, which was what they did. So in summary, this trial of preemies shows that Lasix furosemide administration at doses of one through four mpq per day for 28 days was not associated with an increased incidence of adverse events.
Ben Courchia, MD (14:03.15)
It was not associated with an increase in hearing loss and nephrocalcinosis or nephrolithiasis and future larger trials are needed to better define the optimal use of Lasix in preterm infants with developing BPD. Now these trials will likely need to include management of electrolyte as part of the trial design with amelioration of the electrolyte abnormalities. These trials may be able to safely administer higher doses of furosemide to determine the risk and benefits of prevention of BPD. And I think that this is obviously something that in retrospect feels a little bit obvious that yeah, like Lasix is going to mess up your electrolytes, but
Obviously that cannot be sufficient to exit the trial because then you're going to have issues again trying to test these much higher doses. So I thought this was interesting. I don't think it changes very much. I'm not a big advocate for Lasix in general, but it's kind of data that needs to be reviewed if you're a neonatologist. It is after all a phase two randomized trial. Like it's a multi-center trial. Like it's important data. Should be familiar with that.
Daphna Yasova Barbeau, MD (14:57.538)
Mm-hmm.
Daphna Yasova Barbeau, MD (15:01.558)
Well, and I mean, this really kind of, there was a big pendulum swing on diuretics in general, right? And so revisiting this is interesting. It's a lot of lasix, right? So here we are, like, should I do a three day course, a five day course? Can the baby get the one dose, you know? And they're doing 28 days. So it was interesting to say the least. I was also quite impressed by...
how much nephrocalcinosis there was in the placebo group.
Ben Courchia, MD (15:32.546)
Yeah, yeah, exactly. again, maybe showing that I think that's always the big fear that we don't know the effectiveness of Lasix, but what about the side effects? But to me, to see that hearing loss was not as prevalent as I would have expected. Neither are kidney stones. I think that's quite good. We've spoken to Nick Bammett from CHOP at Hot Topics about specifically that he had published some work with using the pediatrics database on Lasix. Again, showing that number one,
Daphna Yasova Barbeau, MD (15:48.834)
Yep, he has very strong feelings about...
Ben Courchia, MD (16:01.142)
Lasix remains one of the most used medications in the NICU. So we should have a conversation about Lasix. But again, advocating for what you were saying, that it probably has a place, but it doesn't have a place for an indefinite sort of type of treatment where kids can be on it for weeks and weeks and weeks with no end point in sight. So yeah, interesting data.
Daphna Yasova Barbeau, MD (16:03.054)
Mm-hmm.
Daphna Yasova Barbeau, MD (16:20.462)
Yeah, very interesting. All right, I have one for you. I have some international papers this week. You put this one into the folder, seven day versus 14 day antibiotic course for culture proven neonatal sepsis, a multi-center randomized non-inferiority trial in a low and middle income country. So this is coming from India.
Basically, the study was looking at is seven days non-inferior to a 14-day course, even then the face of culture proven infection. So this was a multi-center randomized non-inferiority trial, one-to-one allocation ratio, and the outcome assessment was felt to be blinded. This is part of kind of
an ongoing study. This is like a sub study. but they enrolled neonates that were zero to 28 days old with a birth weight of greater than or equal to a thousand grams. So not the smallest group of babies, but still quite small and suspected sepsis. So antibiotics were initiated by a neonatologist after sending a blood culture. So this is a group of babies that were screened.
But inclusion criteria required a positive bacterial blood culture, receipt of at least seven days of quote unquote appropriate antibiotics. So the pathogen was unambiguously sensitive to and clinical remission of signs of signs of sepsis by day five of this appropriate antibiotics. So then on day seven, so the baby had to be basically improved while appearing.
and have had these seven days of antibiotics. So then on day seven, you hear the dog? She's being very annoying. good. Okay. Then I've been, she's only bothering me. So basically on day seven, then they were randomly assigned to either receive the seven days, which was the intervention to be done. Yeah, to be done at seven days.
Ben Courchia, MD (18:15.222)
Actually, she's not bothering me today. So I can't hear her. We have good microphones now.
Ben Courchia, MD (18:30.734)
So there would be like no further treatment.
Daphna Yasova Barbeau, MD (18:34.286)
or seven more days for a total of 14 days, which was the comparison arm for antibiotics. They had some exclusion criteria. So the growth of contaminants, they excluded staph aureus, interestingly, or fungi. If there was ambiguous in vivo antibiotic sensitivity, infections that would have felt to necessitate more than 14 days of antibiotics like meningitis or life-threatening malformations. A lumbar puncture was performed on all participants.
CONs were considered coagulase negative staph was considered contaminant if they grew after 48 hours of incubation or if repeat cultures were sterile despite resistance to the empiric antibiotics chosen. So they, I told you they randomized the babies, but they also randomized, they stratified the randomization by center and birth weight category. So a thousand to 1500, 1501 to 2000 grams and then greater than 2000 grams.
They felt that weight would be potentially an important determinant of postimmune response. Okay, they enrolled the babies and they monitored them weekly for at least 35 days post-randomization. So the outcome variable they were looking for primarily was this composite of a definitive or probable relapse within 21 days after antibiotic completion. So did we treat it or did we only partially treat it and it came back?
A definitive relapse was an episode of sepsis caused by the same species as the original infection with an identical antibiogram. And a probable relapse was adjudicated based on clinical signs and laboratory parameters with a sterile blood culture. So they had a definite relapse or if the baby had these new signs and symptoms, but they couldn't prove the same species.
after treatment. Sorry. I forgot. I didn't know what I wanted to say there. Okay. I think that is it. All right. I think we'll have to get into it. So they recruited participants from February, 2019 to December, 2022. So they actually performed an interim analysis after 261 patients were enrolled.
Ben Courchia, MD (20:34.649)
Yes
Daphna Yasova Barbeau, MD (20:58.094)
126 in the seven day and 135 in the 14 day groups had completed their follow-up. So actually at that time, after the interim analysis, the data safety monitoring board recommended to trial termination as they felt the non-inferiority was demonstrated using two-sided 99.5 % confidence intervals. So about the...
About the study, the baseline characteristics were pretty similar between the two groups. In the 14-day arm, 10 participants clinically deteriorated during the eighth to 14th day of antibiotics. So they were on the extended course of antibiotics, including two with a new culture positive sepsis epices. One died and one was transferred. Six participants were excluded from the...
follow-up analysis. One from the seven-day arm because that baby was enrolled despite probable meningitis, so that was one of the exclusion criteria. And five from the 14-day arm because four were lost to follow-up and one had an incomplete antibiotic course. In the 14-day group, one infant required ventilation and inotropic support, one required a packed red blood cell transfusion. None in the seven-day group required ventilation, inotropes, or blood products after randomization.
Two participants in the seven day arm and six in the 14 day arm experienced the primary outcome with a risk difference of minus 3%. Sorry, and the confidence intervals, I didn't tell you the confidence intervals, but they cross zero. So as the upper bound of the confidence interval was well beyond the net below the non-inferiority margin, again, there was a recommendation to stop the trial.
In the modified intention to treat analysis, they included three additional participants whose outcomes were known, one lost to follow-up but later identified, one whose 14-day course was incomplete and the one enrolled despite meningitis. Three others were excluded from that analysis because then they were lost to follow-up and could not be tracked. But the risk differences for the primary and secondary outcomes supported the non-inferiority of the seven-day antibiotic course.
Daphna Yasova Barbeau, MD (23:17.528)
They did a sensitivity analysis for many outcomes. I will list them for you. That was the definite or probable relapse by 21 days, mortality or definite or probable relapse or secondary sepsis by 21 days, definite or probable relapse by 28 days, mortality or definite or probable relapse or secondary sepsis by 28 days, definite or probable relapse by 28 days.
They use those post-completion and post-randomization. So they had duplicate sets here. But basically, all of those sensitivity analyses favored the non-inferiority of the seven-day course. The median durations of secondary outcomes were significantly lower in the seven-day arm, and adverse events did not differ significantly between the two groups.
So I think this is interesting. We're always talking about antibiotic exposure. And I think that's true in a lot of facets of medicine. We don't know how much antibiotic is enough and we are reducing antibiotic courses for lots of things. It would be nice if we could use shorter courses in our small babies. I'm not saying people should change what they're doing. I'm just saying, I'm glad people are looking into it.
because hopefully we'll get to a place where we can use shorter courses.
Ben Courchia, MD (24:43.138)
Yeah, I think.
I agree and I think that it's going to come from low and middle income countries where resources are definitely thought of a little bit more carefully. maybe they will be able to bring about the reassurance that a shorter course, even in culture proven sepsis can actually be valuable. yeah, definitely, definitely interesting. Okay. I am next. I have definitely two papers that I want to bring. Maybe I'll leave this fun one for last.
Daphna Yasova Barbeau, MD (24:50.861)
Mmm.
Ben Courchia, MD (25:15.34)
The other one that I wanted to review is a paper that was published in the archives of disease and childhood called intermittent sigh breaths during high frequency oscillatory ventilation in preterm infants or randomized crossover study.
I feel like it's an ongoing question. don't know where some of our listeners are practicing, but side breaths on high frequency is always a point of discussion. Should we go up? Should we go down? Should we even have it in the first place? my God, yes. And so we know, but we know that the reason it's a topic of conversation is because ventilator induced lung injury is always a concern.
Daphna Yasova Barbeau, MD (25:41.038)
Even in our own unit.
Ben Courchia, MD (25:57.07)
And one of the goals with high frequency is to maintain adequate and expiratory lung volume while minimizing barotrauma and value trauma. Now, the side breaths are kind of widespread and it's been used obviously for patients who are on high frequency jet ventilation, but there's a growing interest in combining brief conventional side breaths for high frequency oscillatory ventilation to facilitate lung recruitment without interrupting the high frequency pattern.
And this paper is actually here to test this idea in the form of a randomized clinical trial. So this study basically aimed to answer the question using electrical impedance tomography or EIT. And I don't know if our listeners are familiar with EIT. I started to learn more about it for the past like 12 months. It's a fascinating tool where you have a non-invasive basically bedside tool that can track changes in regional and global lung volume, including
and expiratory lung volume by measuring impedance across electrodes placed on the chest. So the kids wear like kind of a belt around their chest and you get these sort of diagrams of long volumes and aeration. It's quite interesting. So this was a randomized double crossover trial conducted at the Mater Mother's Hospital in Brisbane, Australia. It's a short, it's a small study, 16 preterm infants, all less than 36 weeks gestational age were enrolled.
They were all on high frequency oscillator, and they had to have their FIU2 between 25 and 70 % to maintain SATs above 90. Major congenital lung or heart anomaly, obviously, were considered exclusion criteria. So they randomized these infants basically into two groups, some of them receiving high frequency oscillation with a side breath, some without. The side breaths were delivered three times per minute, so the rate was three.
Each psi used an inspiratory time of one second and a PIP of about 30 centimeters of water. The psi frequency was chosen to limit interference with CO2 clearance, maintaining the gas exchange strategy. The primary outcomes were changed in end-expiratory long volume, ventilation distribution measured through the GI index, and secondary end outcomes looked at the SATs, the heart rate, the blood pressure, and other ventilatory parameters.
Ben Courchia, MD (28:17.624)
So the results are very interesting. The infants in the study had a median gestational age of about 25.5 weeks and a median birth weight of about 700 grams. Truly like small babies. So that was kind of helpful. So what the team found was that the addition of side breaths significantly increased global and expiratory lung volume. This increase was especially notable in the posterior or the dependent lung regions.
And that was found to be statistically significant and also in the left lung. Over time, the increase in global and expiratory lung volume, right and left, and the GI index improvement were all statistically significant. There was a trend toward increased impedance amplitude, suggesting possible tidal volume benefits as well. Now, from a physiologic standpoint, the oxygen saturation was significantly improved on the group that received side breaths. The mean airway pressure was not significantly altered.
And if anything, map set points were actually lower in the group that received side breaths. The relationship between SATs and FiO2 showed no statistically significant improvement, but the overall direction seemed to be positive. There were no other significant changes in hemodynamic or ventilatory parameters between the two strategies. So in conclusion, the authors are saying that side breaths during high frequency oscillation ventilation improves end-expertory lung volume.
ventilation distribution and short-term oxygenation and that these findings are physiologically sound and clinically promising. However, the study is very short in terms of the number of babies that are enrolled. It's not looking at long-term outcomes and it's definitely not powered for neurodemental outcomes. we don't have the safety data on extended side-breadth usage and its effect on outcomes like BPD and ventilator days. And so that's why they're recommending obviously longer and larger trials. But I that was interesting. It's a topic. I I saw the title and
reminding me, like you said, to our discussions in the unit. So yeah, definitely brought that back to the table.
Daphna Yasova Barbeau, MD (30:12.834)
Yeah.
Daphna Yasova Barbeau, MD (30:20.012)
Yeah. You could see how potentially over time that may be helpful, but yeah, we'd have to balance it with those, you know, adverse events and things like that. Neat. Okay. You wanted to do another one or you want me to go? Okay. I actually have another study from India, which I'm just going to, just do kind of briefly, because I think it's a value, but their practice is very different than ours.
Ben Courchia, MD (30:26.348)
Mm-hmm.
Ben Courchia, MD (30:32.485)
you can go.
Daphna Yasova Barbeau, MD (30:45.366)
So this is in the American Journal of Clinical Nutrition. It's called Effect of Kangaroo Mother Care in Low Birth Weight Infants on Human Milk Intake, a Randomized Control Trial. So basically what they did is they wear American Journal of Clinical Nutrition. So the study participants were part of another
Ben Courchia, MD (30:58.83)
Where was that published? Yeah, which journal?
Ben Courchia, MD (31:05.281)
Okay.
Daphna Yasova Barbeau, MD (31:14.446)
primary trial, but they use this same, just like a sub study to look at eligible babies in terms of kangaroo care. So basically they took newborns weighing 1,500 to 2250 grams and their mothers and screen them from enrollment within 72 hours of birth in the first trial. So in the sub study,
They were able to consent moms and their infants aged between days three and seven after birth. So they have a group early on from 2015 to 2018, and then they even enrolled more babies from 2017 onward. So basically what they did is they had an intervention group and they had a control group, the Kangaroo Mother Care Intervention Group.
comprised of promotion and support of continuous skin to skin care and exclusive breastfeeding. So basically the intervention delivery team would visit the infant mother dyads allocated to the intervention arm. And most of these visits were occurring in their homes, even in this cohort of babies, 1500 grams to 2250 grams. And so basically they were going and supporting kangaroo mother care with the dyad on days one, two, three, five, seven, 10.
14, 21, and 28 after birth to really just help them manage with this continuous skin-to-skin care. So they were counseled to practice skin-to-skin care for as long as possible during the day and the night, and they basically trained the other family members to help assist this mother. So they wanted to really look at the mean daily infant human milk
intake, and they wanted to look at some other composition of breast milk markers, nutritional biomarkers. So this was kind of interesting. They use this, I hope I'm saying it right, deuterium dilution dose to mother technique. So basically the mom was given this measurable drink of
Daphna Yasova Barbeau, MD (33:34.894)
deuterium at their homes. And then they basically were able to pull it from the saliva in the moms and the babies. So that's how they measured like what, how much milk transfer. Okay. So they were using kind of this mean daily water transfer from mother to infant during a 14 day period. Okay.
That's kind of where we are. So they had 550 eligible infants and their mothers were enrolled and they wanted to look at milk assessment. among the 550 participants, infant human milk intake assessment was completed in 85 % in the control arm and 86 % in the intervention arm. The median age of enrollment was day five in both arms. The median
Infant weight at enrollment was 2.1 plus or minus 0.2 kilos. Baseline characteristics were similar across the arms for the maternal factors. Place of birth, like home births, was thought to potentially be a potential confounding factor. was unequally distributed. So 18 % in the control arm.
and 13 % in the intervention arm delivered at home. In both study arms, 64 % of the included infants were born preterm. There were no significant differences in the baseline characteristics of the infants when those data was available. So in the control arm, so not the intervention arm, asked to do skin-to-skin care, 8 % of mothers reported practices skin-to-skin care and the mean duration
of skin to skin practice was two plus or minus seven days with 0.5, so 30 minutes plus or minus two hours per day. In the intervention arm, all the mothers reported practicing the use of skin to skin care. The mean duration of skin to skin practice was 28 plus or minus two days with a mean duration of 12 plus or minus four hours a day.
Daphna Yasova Barbeau, MD (35:53.006)
The mean human milk intake in infants over the 14 day period from enrollment was 331 plus or minus 144 in the control arm and 368 plus or minus 135 grams per day in the intervention arm.
So compared with the control arm, the mean difference in infant human milk intake in the Kangaroo Mother Care arm participants adjusted for place of delivery was 37 grams per day or 12 grams per kilo per day. And on the basis of multiple analysis, the mean daily intake of human milk was 331 grams per day in the control arm, 370 grams.
per day in the intervention arm, yielding a mean difference of 38 grams. In the subgroup of infants born preterm, the adjusted mean difference in the human milk intake was 45 grams per day compared with 20 grams per day in full term infants. the effect was greater in those babies born preterm. Among SGA infants, the adjusted mean difference in human milk intake
was 40 grams per day, whereas in appropriate for gestational age infants, it was 31 grams per day. So again, a bigger effect in the SGA infants. The mean concentration of carbohydrates in human milk for mothers in the control arm was 50 plus or minus six. In the intervention arm, it was 51.2 plus or minus six. The mean difference was 1.0.
to the mean concentration of total protein in human milk was 16.3 plus or minus four. And then the intervention arm was 15 plus or minus two. The mean difference was minus 1.3. The concentration of fat was similar in the control arm and the intervention arm. They did not find any differences in the mean concentration of the human milk amino acids, IgA concentrations, and lactoferrin in the study arm.
Daphna Yasova Barbeau, MD (38:09.302)
So I thought this was interesting because, well, it's a good reminder that in many places of the world, moms are doing 12 hours of skin-to-skin care a day. This could potentially improve milk output and it had a bigger effect for preterm babies and SGA babies.
Ben Courchia, MD (38:28.75)
Now it's always sort of these types of studies where you're mostly not surprised, right? You're mostly not surprised, but you're like, yeah, but you're like, yeah, yeah, yeah, like sign me up. But it's interesting also to see how other, like, I think that we all have resources, constraints when it comes to resources and leveraging these very cheap
Daphna Yasova Barbeau, MD (38:42.114)
Yeah, that's fair.
Daphna Yasova Barbeau, MD (38:56.942)
I've
Ben Courchia, MD (38:58.786)
low tech tools could definitely help you achieve outcomes that go beyond that. I think that's the interesting part. All right. We don't have a lot of time left. I'm going to do my paper and then not my paper, the paper that I've enjoyed reading the most this week. And then we'll see, I have another one, but if I have time. So this is a paper that I found in the Journal of Perinatology and it's called...
Daphna Yasova Barbeau, MD (39:05.176)
Mm-hmm, for sure.
Ben Courchia, MD (39:25.762)
Interprofessional perspective on non-invasive respiratory support practices in extremely preterm infants, a Canadian survey. A lot of the team members, I'm actually on good terms with Dr. Mark Beltempo, Dr. Guillermes Santana. And so I was curious to read this paper just because they wrote it, but also because of the title. So we all know that non-invasive respiratory support is critical for us in the NICU, but while it helps us avoid intubation and...
and associated complications, its application is far from straightforward. And it demands bedside attention. You have to maintain it. You have to monitor. You have to troubleshoot. It's a lot of work. And failure of noninvasive respiratory support is not a small deal. You have both short and long-term morbidities that are associated. So the authors were asking the following question. Can we better understand the barriers and the variability that is associated in practices related to noninvasive ventilation?
And they did so by listening to the frontline workers, physicians, nurses, and respiratory therapists. So basically what they did is that they sent this survey nationally to Canada. They identified 32 NICU, so they sent it to their 32 NICU directors. They sent it to 13 fellowship director, to 32 nurses manager, to 32 respiratory therapist educator, who then circulated that survey with their teams. It had 19 items.
three categories, the perspective of people on non-invasive respiratory support devices and management strategies, the monitoring and management, and the failure and improvement strategies possibly for non-invasive respiratory support. They were given like a clinical vignette to sort of put a context to all that and sent the survey. they got like 381 responses, 61 physicians, 173 nurses, 147 respiratory therapists. They represented about
23 tertiary NICUs across Canada and 24 % of the group had zero to five years of experience, 22, six to 10. But most of the participants, 54%, had more than 10 years of experience. perspective on devices and strategy. So let's start with device exposure and usage.
Ben Courchia, MD (41:42.382)
So CPAP was the most commonly used form of non-invasive respiratory support reported by 69 % of providers, typically usually at pressures of about up to eight centimeters of water. NIMV was followed at 21 % and usually using peak pressures of about 20 centimeters of water with an IQR of about 18 to 24. Now what's interesting is that they asked how people felt about these pressures. They're like, is it high? Do you feel like you guys are using high pressures?
And there was some interesting interprofessional differences there that nurses were more likely to feel unsure or feel that CPAP and NIMV level were too high, especially when the pressures were 10 or higher, or that you reached 22 or more on NIMV. Now, so for interfaces, the dominant strategy reported by about 70 % of groups was to alternate between the nasal mask and the nasal prongs.
But notably, 130 respondents actually preferred a different interface that was typically used in their units. So I'm just going to pull up the rest of my notes here. So yeah, so I thought that was interesting that there's not a great level of satisfaction with these interfaces strategy.
Ben Courchia, MD (43:09.23)
Altogether, when it comes to the perceived difficulty of non-invasive respiratory support, 62 % of physicians, 45 % of nurses, and 45 % of RTs found that the provision of non-respiratory support was challenging.
So in terms of perspectives on monitoring and managing events, so across all provider groups, there were strong agreements that suboptimal positioning, airway obstruction, and poor interface fit contribute to respiratory events. But again, there were some interesting differences that came up. Nurses and RITs were more likely than physicians to view gastroesophageal reflux and anemia as important contributors to the respiratory instability. Documentation was another pain point. Around 20 % felt that the apnea documentation by nurses were not often reliable.
with similar concerns for desaturation and bradycardia entries. However, there was a near consensus on what constitutes a reportable event. 88 % agreed that events requiring intervention and 69 % agreeing that those lasting more than 20 seconds should be clearly documented. So perspective on failures and solutions, when asked about re-intubation, 57 % perceived that their unit was highly tolerant to respiratory events before acting. And somehow...
This brought me back to a lot of awkward interactions sometimes. 39 % noted that tolerance threshold vary widely depending on the physician on call. So again, something we've all encountered. Interestingly, 44 % of physicians believed that reintubation, I'm sorry, 44 % of physicians believed reintubation could often or always be prevented. But nurses, 29%, and RITs, 28%, shared that optimism.
Not as much of a... That's pretty bad. Yeah. As for preventive strategies, there was strong support for protocolizing practices related to noninvasive respiratory support, increasing nurses to patient ratio and RT to patient ratios, establishing clear criteria for reintubation supported by 88 % of all respondents. Talking about the value of having in-house neonatologists,
Daphna Yasova Barbeau, MD (45:00.942)
44 % always.
Ben Courchia, MD (45:27.182)
33 % of the doctors felt like this was helpful, but 57 % of the nurses thought this was helpful. clearly, clearly some bias happening there from the doctors. On the topic of training, 17 % rated their non-invasive respiratory support education as neutral or insufficient, and hands-on workshop were supported by 84 % of physicians, 76 % of nurses, and 63 % of...
Daphna Yasova Barbeau, MD (45:37.614)
I'm so sorry.
Ben Courchia, MD (45:57.102)
So this study just underscores how complex, I guess, this practice really is, even though we use it fairly commonly, and how collaborative really it needs to be. It's not just about the technology or the interface. It's about how we apply it. It's about who's at the bedside. It's about what kind of training we get, what kind of protocols we have in place. And so the authors really emphasize that we need better scientific evidence on the application, maintenance, and monitoring. We need interprofessional collaboration to understand behavioral and organizational influences and standardized guideline and harmonized training to reduce variability.
So it's a team-based approach, and this was definitely a good read.
Daphna Yasova Barbeau, MD (46:30.636)
Yeah, for sure. It's nice to see that, especially when lots of our different staff types and members are included in the evaluation. I had a really quick one, which will hopefully allow you to do your last one. This is in Jam of Pediatrics about prenatal cannabis use and neonatal outcomes. Lead author, Jamie Lowe, senior author, Devin Cansegaro.
Basically, they wanted to see if cannabis use in pregnancy associated with neonatal outcomes. This was like a meta-analysis, and we don't like to do a lot of review papers like this, but even in their background, they basically said it's not ethical to conduct randomized clinical trials of prenatal cannabis use, given our concerns about its safety. So observational studies are basically the best thing.
that we have. GMAPediatrics. Basically, where did they get? They used 51 studies in 69 publications. This was 21 million, 146,938 infants. No.
Ben Courchia, MD (47:30.926)
Where was that published you said? Sorry. Thank you. Yeah.
Daphna Yasova Barbeau, MD (48:00.11)
So they had done this meta-analysis once, and then they're doing it a second time using eight more studies since the original publication date, adding a million new participants. The other thing that was different about this study was they wanted to also look at, was there a dose response?
So some of the studies provided information about dose response and basically they extracted the heaviest users from those studies. for instance, they say if a study reported outcomes for cannabis monthly or less weekly or daily, then that daily use group was included in the heavy use group. Okay. So,
Ben Courchia, MD (48:52.749)
Mm-hmm.
Daphna Yasova Barbeau, MD (48:56.174)
They found 24 studies analyzing this association between prenatal cannabis use and low birth weight infants. And in their meta analysis, they found an increase odds of low birth weight infants in those with prenatal cannabis use and odds ratio of 1.75. And in their dose response, they found that in those with heavy cannabis use, the odds of low birth weight increased to an odds ratio of 2.3.
six. Certainty of evidence is moderate. So then they looked at prenatal cannabis use and preterm birth. Odds of preterm birth were increased for those using cannabis in pregnancy and odds ratio of 1.52. And for those with heavy use, higher odds, a combined odds ratio of 1.95. Certainty of evidence is moderate. Then they wanted to look at perinatal mortality.
So they found an increased odds of perinatal mortality with cannabis use and odds ratio of 1.29. And there were three studies that had this specification about heavy use, but they actually found that the ads were no longer statistically significant in this three studies that included heavy use. They found 21 studies that looked at cannabis use and small for gestational age.
and the odds of SGA increased with prenatal cannabis exposure and odds ratio of 1.57. And for those with heavy use, an odds ratio of 1.63, certainty of evidence moderate. So I was hoping there would actually be more perinatal outcomes, but these are the biggies. I think that we are seeing more more marijuana use. So I always like to take a look at the marijuana papers when they come in.
Ben Courchia, MD (50:52.238)
For sure. think that, yeah, I I haven't gotten off my initial of stance on this. It's not because legalization doesn't mean beneficial. I mean, I think that because you have more access to something, it doesn't mean that it's good for you. we kind of know the effects of marijuana, unfortunately, and the legalization doesn't change that. Just have to be careful.
Daphna Yasova Barbeau, MD (51:18.616)
Yeah, agreed. Agreed. Yeah. I mean, it's like so many other things. Alcohol, cigarettes. Yeah.
Ben Courchia, MD (51:23.246)
Yeah. Alcohol, cigarettes. Absolutely. Exactly. Yeah. Or even illegal drugs. yeah, the political context doesn't change the substance itself. The substance is what it is. I just, don't, I mean, we're close to the end. I'm not going to extend this journal club too much, but there was an article that came out in the archives of this in childhood that caught my eye and it was less impactful than I thought.
I mean, now you'll see why. It's called near infrared spectroscopy during respiratory support at birth, a systematic review. And this is first author is Vicks Monelli and it's coming from the Ilcor from the International Liaison Committee on Resuscitation Neonatal Life Support Task Force. So obviously a big group publishing on a potentially maybe an innovative approach to management in the delivery room. And obviously they're talking about perinatal transition and compromised cerebral oxygenation that may lead to morbidity, mortality.
And the question really is, should we start using NIRS in the delivery room to sort of guide respiratory management? Now, there are some issues, obviously, with the potential randomization. So this is just a systematic review and mid-analysis based on Ovid Medline, Embase, and Cochrane Central. So they looked at newborn infants of all gestation. They were looking at studies that looked at any newborn receiving CPAP.
or NIMV during resuscitation. They looked at the intervention from studies that would look at CRS02, like cerebral original saturation, with a dedicated treatment guideline. And they were looking at outcomes that involved survival without neurodemental impairment, survival alone, severe IVH, PVL, et cetera. Now, they reviewed close to 600 articles, and they only found three articles reporting the outcomes from two randomized trials.
And what they're saying is that no data was found for survival without neurodevelopmental impairment. And so they could not exclude benefit or harm from delivery room monitoring of cerebral regional saturation for survival, for severe IVH, for PVL and cerebral regional saturation below the 10th percentile. so this paper basically just highlights that the limited evidence can't really exclude either benefit nor harm.
Ben Courchia, MD (53:48.31)
So if you want to read the paper, you're more than welcome to. I thought, is this the paper that's going to lead to a revision of our approach to resuscitation? But the data is just not there yet, so not much to add.
Ben Courchia, MD (54:06.316)
You're muted, no thoughts. By the way, since it's the end of the episode, we've had a very long day.
Daphna Yasova Barbeau, MD (54:07.374)
I'm here, I'm here, too, too bad, too bad.
Daphna Yasova Barbeau, MD (54:13.998)
The longest day we've had in a very long time. But should I do one more? Should I my last paper? Okay.
Ben Courchia, MD (54:17.698)
Alright, it was, yeah, that was...
Please, yeah, don't let me obstruct.
Daphna Yasova Barbeau, MD (54:26.37)
And then we can be done. we're still not done with our long day after this. No. Okay. I'm going to try to review this quickly. You know, I'm not very good about that, but this is in Journal of Perinatology. This is coming to us from our colleagues in Japan and it's entitled Neurodevelopmental Outcomes at Age Three Years of Preterm Infants Born at 22 to 31 Weeks Gestation. I'm not taking the smallest, but I didn't want it to...
Ben Courchia, MD (54:30.06)
No, we're not.
Ben Courchia, MD (54:50.286)
You're not taking the smallest of papers.
Daphna Yasova Barbeau, MD (54:54.766)
linger. I think people are always wondering and the paper came out and I just wanted to make sure we do it. So they were looking at infants born before 32 weeks and they were actually looking at this group from 2012 to 2014. So this is almost a decade ago, okay, from their improvement of NICU practices and team approach cluster trial. This was the intact trial and they were looking for survival without moderate or severe neurodevelopmental impairment. So basically,
they, the intact trial was like this quality improvement program in, in Japan that didn't have the effect that they had hoped it would in changing outcomes for babies who were enrolled in this, kind of package of interventions, but they did, are just now reporting on the neurodevelopmental,
follow up. So they had 40 NICUs that were allocated to the intervention. Initially were 19 NICUs and 21 control NICUs. They had, then this is for the initial study, the intact trial.
I'm actually going to skip telling you any more about this, the original trial. I'm going to just tell you about the current trial. Wait, we're running short of time and you want to know about the long-term outcomes. Okay? So this was a secondary analysis. They combined then both the intervention and control groups to get this cohort. So outcomes, they wanted to look at infant survival at age three.
Ben Courchia, MD (56:18.752)
Okay.
Daphna Yasova Barbeau, MD (56:42.294)
And this is how they defined disability. So moderate neurodevelopmental impairment was defined as neurologic disability with one or more of following conditions, cerebral palsy with a GMFCS level of two. They use the Coyote scale of psychological development test. So less than 70. Visual impairment requiring correction, but not been fully corrected.
some other things about vision here. And I wanted to tell you, so this developmental quotient less than 70 is basically equivalent to a Bailey three score less than 85. So pretty similar.
Ben Courchia, MD (57:26.414)
Yeah, it feels more like a Bailey 2 almost where they get this one single score. On the Bailey 3, you would have subcategories, you could break that down. It feels almost like this MDI that you used to have on the Bailey 2.
Daphna Yasova Barbeau, MD (57:33.079)
Yeah.
Daphna Yasova Barbeau, MD (57:36.44)
Yeah, with the composite.
Daphna Yasova Barbeau, MD (57:43.662)
Um, perfect. And then severe NDI included cerebral palsy with a GMFCS level three to four. And this, uh, coyote score less than a 55 blindness or ability to perceive light only impaired hearing. That's not correctable. And then any individual residing in a facility for children with severe physical disabilities was considered to have severe neurodevelopmental.
So then they have these beautiful tables, I mean by week of gestational age, which we will get to in just a second. They had 2,722 evaluated at NICU discharge. And then they had a total, let's just say 2,360 infants.
which were 90 % of the survivors that were able to attend the fall visit and were included in the analysis of the outcomes. So for the group, I wanted to tell you there are 43 22-weekers, there are 152 23-weekers, there are 197 24-weekers, 220 25-weekers, 280 26-weekers, 350 27-weekers, 370 28-weekers, 429-weekers.
almost 430 leakers and 284 31 leakers. So we can talk a little bit about the clinical characteristics and morbidities. A higher percentage of SGA infants, so a birth weight below the 10th percentile was observed with increasing gestational age. Interestingly, antenatal steroids were observed for 44 % at 22 weeks and greater than 60 % at the other weeks.
Ben Courchia, MD (59:09.87)
Mm-hmm.
Daphna Yasova Barbeau, MD (59:37.198)
So most of their 22-weekers still didn't get antenatal co-degluteroids. A higher incidence of chronic lung disease requiring continued oxygen use and respiratory support at 36 weeks. IVH, sepsis and neck was noted with decreasing gestational age. The incidence of PVL was the highest at 24 weeks gestation, only 5%, followed by 4 % at 23 weeks and 3.5 % at 28 weeks. The overall NICU mortality rate was 3.5%.
5 % for all infants. The mortality rate decreased with increasing gestational age, ranging from 28 % at 22 weeks to . . . Yeah, yeah, 28 % at 22 weeks, .4 % for those at the 31 week gestation mark. So that was
Ben Courchia, MD (01:00:15.884)
Let that sink in for a little second,
Daphna Yasova Barbeau, MD (01:00:29.806)
death, then they did neurodevelopmental outcomes at age three, and then they do the composite outcome, which was basically they wanted to see survival without moderate or severe neurodevelopmental impairment. So for the neurodevelopmental outcomes, like I said, there's a lot of information here.
But a higher percentage of SGA children was observed with increasing gestational age, which was interesting, 0 % in the 22-weekers and 56 % at 31-weeks gestation. Infants with cerebral palsy of GMFCS level 2 to 4 was 4.7 % and was highest in the infants born at 23-weeks gestation, 10 % of infants in the 23 weeks.
All infants born at 22 weeks gestation with cerebral palsy, this was 10 % of infants had higher levels of cerebral palsy. So GMFCS greater than or equal to level three. The percentage of children with cognitive delay decreased over gestational age. So 54.8 % for those born at 22 weeks to 10.8 for those born at 30 weeks.
Ben Courchia, MD (01:01:31.703)
Mm-hmm.
Daphna Yasova Barbeau, MD (01:01:48.398)
Additionally, the proportion of children with severe cognitive delay correlated again with gestational age. But the proportion of children with this borderline cognitive level was similar in children born at 22 to 27 weeks gestation. 12.9 % of children born at 22 weeks and 24 % of those at 23 weeks
had what was considered quote, normal cognitive development. Two infants born at 25 and 29 weeks had blindness or light perception only. The percentage of visual impairment requiring slight correction but not fully corrected was 2%. Two infants born at 26 and 27 weeks had severe hearing impairment that was not correctable.
And then among the infants with the full evaluation, 13 % had moderate neurodevelopmental impairment and 7.8 % had severe neurodevelopmental impairment. The survival without moderate or severe neurodevelopmental impairment for the whole group was 79%. But this was higher, obviously, in the higher gestational ages. So survival...
Sorry, survival without moderate to severe neurodevelopmental impairment was 45 % at 22 weeks, 57 % at 23 weeks, and 88 % at 31 weeks.
Ben Courchia, MD (01:03:26.946)
Yeah, but those numbers at 22 weeks were quite low in terms of the census that they had.
Daphna Yasova Barbeau, MD (01:03:31.918)
Yeah. So basically they had 31, I told you they had 31 surviving infants at 22 weeks. The babies with no cerebral palsy was 87%. But all the babies who had cerebral palsy, this 10%, almost all of them had severe cerebral palsy. 3 % had mild, 10 % had severe, and 87 % had no cerebral palsy.
Of the 22-weekers, 12.9 % had no cognitive delay. This 32 % in this kind of borderline cognitive delay. So they didn't classify as moderate to severe neurodevelopmental disability. That's where the big number comes from. 12.9 plus 32.3 is about 45%. 32.3 were delayed and 22.6 severely delayed.
Ben Courchia, MD (01:04:29.133)
Mm-hmm.
Daphna Yasova Barbeau, MD (01:04:30.36)
So that's where the numbers really come from for the kind of composite outcomes. But I thought it was interesting. They have these nice graphs that look at, know, by gestational and eight week of life, looking at survival, moderate and severe neurodevelopmental impairment. So that's where they are. And again, these were from a cohort.
almost a decade ago. So they've been doing the 22 week thing longer than most centers in the States. So I'd love to see an updated cohort. But I these outcomes are consistent with our say United States cohort, potentially better than our United States.
Ben Courchia, MD (01:05:05.55)
for some time. Yeah.
Ben Courchia, MD (01:05:23.468)
Yeah, it's an interesting story because we've always been very interested by what the Japanese have been doing because we know they have good outcomes. And so we've been following that closely. So for the first edition of Delphi, we wanted to take that opportunity to bring someone from Japan to talk to us. we were able to. Dr. Namba from Japan came and gave a presentation on what is the approach to
Daphna Yasova Barbeau, MD (01:05:42.562)
Mm-hmm.
Daphna Yasova Barbeau, MD (01:05:50.19)
It was great.
Ben Courchia, MD (01:05:51.79)
babies on the edges of viability. It cost us a fortune, as you can imagine. We were a small conference and it's so funny because, but that was important. And the video is now on YouTube and it's been quite popular, I guess, not popular, popular is the wrong word, but people have watched it. It's important to share that. And so what's great about it is that we've been able to engage with this community and talk to them about their protocols and their guidelines and so on.
Daphna Yasova Barbeau, MD (01:05:56.343)
The whole budget.
Daphna Yasova Barbeau, MD (01:06:08.27)
We'll see you tomorrow.
Ben Courchia, MD (01:06:21.217)
So.
Daphna Yasova Barbeau, MD (01:06:21.846)
And he does provide from their institution their outcome data during that talk. So definitely for people to take a look.
Ben Courchia, MD (01:06:30.166)
Yeah. And one of the things that he's mentioned is that he has said that their outcomes are phenomenal for survival, right? He was saying like, and they have a very interesting approach. So they mentioned how survival they do phenomenal, but in his presentation, they were saying the next frontier for us is going to be survival plus neuro free, free of neurodevelopmental impairment. So it's not surprising to see those numbers and it's important, I guess, for people to understand that they are.
a little bit ahead of us in the sense that
they're doing very, very well when it comes to survival. And now they're going to start tackling, modifying their protocols so that they can optimize for another metal outcome. So it's very interesting. But we do have to take everything with a grain of salt just because, again, I don't know the Kyoto developmental scale. I don't know if that translates one-to-one with a Bailey, but...
But again, some other things are a bit more objective, like the CP diagnosis. That is fairly similar in terms of how we diagnose that. there's still some differences, but yeah, the Japanese, think it's kind of nice when you're able to sort of blaze your, put a trail of like, and in a style, I know that we have the Scandinavian approach, we have the Japanese approach. And so I'm always interested in seeing what are the tenets of these different methods.
Daphna Yasova Barbeau, MD (01:08:03.054)
All right, buddy. No. I'm done.
Ben Courchia, MD (01:08:03.98)
All right, do you have one more? You're done. Okay, well, thank you very much. This was a great journal club and we will see you all next time. Bye.
Daphna Yasova Barbeau, MD (01:08:13.912)
Bye Betty.
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