#393 - 📑 Journal Club - The Complete Episode from January 17th 2026

Hello friends 👋

Could a simple blood test help identify chronic pulmonary hypertension when echo access is limited? This week on The Incubator Podcast, Ben and Daphna explore this question and others relevant to daily NICU practice. A Toronto study examines NT-proBNP as a practical diagnostic tool in extremely preterm infants.

They also examine a puzzling finding from Italy and Belgium: despite near-universal antibiotic use in neonates with HIE undergoing cooling, actual culture-positive sepsis rates are surprisingly low. What does this mean for our approach to empiric antibiotics?

Ben presents Norwegian data showing that serial physical exams cut antibiotic exposure in half for term and late preterm infants—without compromising safety. Daphna follows with research connecting NICU capacity strain to patient outcomes, underscoring why adequate staffing isn’t just about comfort, but about survival.

The episode concludes with Ben, Daphna, and Eli discussing the recent CDC changes to Hepatitis B birth dose recommendations. With federal guidance now diverging from AAP recommendations, how do we navigate conversations with families? They explore transmission risks parents may overlook and share approaches to shared decision-making when expert opinions conflict.

A full week of neonatal medicine research and real-world clinical challenges, all in one episode

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

Can N-terminal pro-brain natriuretic peptide accurately diagnose chronic pulmonary hypertension among extremely low gestational age neonates: A Retrospective Cohort Study. Garcia-Gozalo M, Jain A, Weisz DE, Jasani B.J Perinatol. 2025 Nov 13. doi: 10.1038/s41372-025-02462-3. Online ahead of print.PMID: 41233504

Antibiotic use in neonates with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia: time to rethink universal empirical treatment. De Rose DU, Piersigilli F, Auriti C, Campi F, Cortazzo V, Samaey A, Carkeek K, Martini L, Maddaloni C, Santisi A, Ronci S, Iacona G, Bersani I, Savarese I, Danhaive O, Cilio MR, Bernaschi P, Dotta A, Ronchetti MP.Eur J Pediatr. 2025 Nov 22;184(12):781. doi: 10.1007/s00431-025-06652-1.PMID: 41275063

Serial physical examination to reduce unnecessary antibiotic exposure in newborn infants: a population-based study. Vatne A, Eriksen BHH, Bergqvist F, Fagerli I, Guthe HJT, Iversen KV, Ud Din FS, van der Weijde J, Kvaløy JT, Rettedal S.Arch Dis Child Fetal Neonatal Ed. 2025 Nov 19:fetalneonatal-2025-329639. doi: 10.1136/archdischild-2025-329639. Online ahead of print.PMID: 41260908

The association of NICU capacity strain with neonatal mortality and morbidity. Salazar EG, Passarella M, Formanowski B, Rogowski J, Edwards EM, Halpern SD, Phibbs C, Lorch SA.J Perinatol. 2025 Dec;45(12):1801-1808. doi: 10.1038/s41372-025-02449-0. Epub 2025 Oct 20.PMID: 41116036 Free PMC article.

American Academy of Pediatrics. (2025, December 15). AAP: CDC decision on universal birth dose of hepatitis B vaccine irresponsible and purposely misleading. AAP News. https://publications.aap.org/aapnews/news/33980/AAP-CDC-decision-on-universal-birth-dose-of?searchresult=1?autologincheck=redirected

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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 👇

[00:01.016] Ben Courchia MD Hello everybody, welcome back to the Incubator podcast. We are back for another episode of Journal Club. We're reviewing one article today. Daphna, good morning, how are you?

[00:10.804] Daphna Yasova Barbeau MD Morning, good morning, doing well. We've had a really nice set of articles at the beginning of the year here to open 2026.

[00:17.878] Ben Courchia MD I was talking to Gabriel about this on the French podcast and we were saying how it looks like a lot of people tried to squeeze in their article before December 31st. There are a lot of good papers that just came in in the nick of time before the new year.

[00:25.450] Daphna Yasova Barbeau MD That's right. For sure. Totally agree. Lucky us.

[00:36.494] Ben Courchia MD Sometimes we feel lucky; sometimes I feel like, dang, lots of work for us.

[00:40.118] Daphna Yasova Barbeau MD We've got a lot to do. Yeah, that's true.

[00:43.374] Ben Courchia MD It's funny because as neonatologists, when we talk to each other, if you talk to someone who is not working with you directly, you ask them, "Is the service busy? How many babies?" and so on. But for us, it's more like, "How many articles have gone?" And it's a busy two weeks now. Lots of stuff came out.

[00:58.723] Daphna Yasova Barbeau MD That's right, that's exactly right. Good for our colleagues for being so prolific.

[01:08.820] Ben Courchia MD Yeah, that's exactly right. Okay. So, the article that we will talk about today is an article that was published in the Journal of Perinatology. It's coming out of Toronto. First author is Macarena Garcia-Gozalo. And it's called, "Can N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) accurately diagnose chronic pulmonary hypertension among extremely low gestational age neonates: a retrospective cohort study." In the introduction, we talk a little bit about the burden of chronic pulmonary hypertension in preterm infants. The incidence of chronic pulmonary hypertension in preemies with BPD specifically has a wide range, about 17 to 37%. It's associated obviously with significant morbidity and increased mortality. Almost half of patients with chronic pulmonary hypertension die within the first two years of diagnosis. It's quite terrifying. The diagnosis of chronic pulmonary hypertension in infants with BPD is frequently delayed because the symptoms are subtle, they overlap with the respiratory symptoms themselves, and so it's a difficult diagnosis. So how do we actually currently diagnose them? Ideally, you would want to diagnose them with cardiac catheterization, which is the gold standard in terms of diagnosis. But as you all know, it's invasive and it's very rarely used in preemies. So the best next alternative is to do a transthoracic echo to diagnose chronic pulmonary hypertension in the NICU based on these non-invasive, validated, and yet somehow reliable measures. But doing an echo has limitations. Some people may not have it available. Sometimes we think if you are like us—having a center where we can get an echo—we tend to think that it's part of the basics of what we can offer our patient. It's not. Some centers don't. There's an additional cost associated with it, and you need personnel who are able to do it. And then obviously, as we often say, the echo is supposed to correlate to catheterization, but it does so to the best of its ability; it's not as good, specifically for pulmonary hypertension. To bridge that gap, there are many biochemical markers that have been investigated as potential screening tools for the diagnosis of chronic pulmonary hypertension. NT-proBNP is one of them. It's a marker of early pulmonary hypertension with a negative correlation, while other studies have investigated it as a surrogate marker of chronic pulmonary hypertension and it is showing some positive correlation. So there's a lot of data out there going for and against. Normative data on NT-proBNP for infants at or below 31 weeks without relevant complications have been published. These data show that ProBNP levels are high and widely distributed during the first week of life and then decrease to a lower and stable level by around one month of age. That being said, there's no well-defined cutoff that exists that can be used reliably to identify preterms with chronic pulmonary hypertension. This is the context in which this study comes about. The AHA guidelines recommend measuring a BNP or an NT-proBNP at the diagnosis of pulmonary hypertension and during follow-up to aid in clinical decisions. The study done in Toronto aimed to assess the sensitivity, specificity, and accuracy of NT-proBNP in screening and diagnosis of chronic pulmonary hypertension in extremely low gestational age neonates. They hypothesized that a serum level of NT-proBNP can identify babies with confirmed chronic hypertension. So how are they going to do that? This is happening at the Hospital for Sick Children in Toronto between 2020 and 2022. All extremely low gestational age neonates—defined as those born before 28 weeks of gestation admitted to the NICU—were identified for this particular database. The clinical charts were reviewed to identify the babies who actually underwent echocardiography screening for chronic pulmonary hypertension and who had a paired serum NT-proBNP. That could have been measured within five days as part of routine clinical practice. I must say that I myself am going through hemodynamics training. SickKids in Toronto is an exceptional center. This is not just any unit; they're not amateurs. They are very, very good. In terms of exclusion, they exclude babies suspected to have sepsis or who were on diuretics at the time of the measurements of the ProBNP. They also excluded infants with major congenital anomalies, structural heart defects, and non-significant PDAs. The idea of excluding the babies who were on diuretics is because it can acutely alter the ProBNP levels and confound the association with the echo. In terms of data collection, they took the EMR and included baseline demographics, gestational age, and so on. They looked at the severity of BPD using the NIH consensus definition at 36 weeks. In terms of echocardiography and the definition of chronic pulmonary hypertension, an echo was performed using their institutional protocol. They had certified individuals review these echoes, and they were blinded. Chronic pulmonary hypertension was defined by the presence of at least one of the following findings: right ventricular systolic pressure greater than 35 mmHg, a flat interventricular septum at the end of systole, or right ventricular dilation. If you are interested in learning more about these echo findings, we're happy to do a series of educational material on hemodynamics. Just let us know. It's something we're considering, but we're not sure if this is going to be pertinent for too many people. But if you are interested in understanding what hemodynamics looks at, that's something we are interested in rolling out. Okay, let's get into some of the results. It's a small study. Among the 63 eligible extremely low birth weight babies that they had, 35 infants had both an echo and a ProBNP measurement. These measurements were obtained at a corrected age of approximately 37 weeks (with a standard deviation of three weeks). Mean postnatal age was about 86 days. The mean gestational age at birth of these infants was 24.9 weeks (with a standard deviation of 1.8 weeks) and the mean birth weight was 680 grams. Regarding the prevalence of chronic pulmonary hypertension: 13 of these 35 infants—which is about 37%—were diagnosed with chronic pulmonary hypertension by echo. There were no significant differences between infants with chronic pulmonary hypertension and those without in terms of their baseline characteristics. Infants with chronic pulmonary hypertension had a higher incidence of needing home oxygen use and a higher rate of mortality. In terms of echo findings: among infants with chronic pulmonary hypertension, all but one was diagnosed based on right ventricular systolic pressure greater than 35 mmHg. I'm going to take two seconds to explain this. Assuming the pulmonary valve is patent and not stenosed, then as the pulmonary valve opens, it is safe to assume that the pressures will equilibrate between the right ventricle and the pulmonary artery. So if you get a right ventricular pressure of 35 mmHg, you can assume that this is going to be what you'll find in your pulmonary artery. You can then look at your systemic pressures and compare. This is usually when your cardiologist tells you that the pulmonary pressures are 1/3 systemic, 2/3 systemic, isosystemic, or suprasystemic. This is where this information comes from. Six infants had a flat interventricular septum at the end of systole, meaning that the septum between the right and the left ventricle was not round, but pushing onto the left ventricle—a sign of increased pressure in the right ventricle. Three infants had significant right ventricular dilation. There were no significant differences between groups in serum creatinine or ventilatory support. Now for the meat of the paper: what about the ProBNP? Plasma NT-proBNP levels were significantly higher in infants with chronic pulmonary hypertension, with a median value of 1,580 ng/L (IQR 1,225 to 2,674). That was compared to values of 893 ng/L in the infants without chronic pulmonary hypertension. So, almost 1,600 versus 900, to give you rounding numbers. The area under the receiver operating characteristic curve (AUC) for diagnosis of chronic pulmonary hypertension using that measurement alone was 68%—so not great—with a confidence interval of 48 to 87. The diagnostic accuracy was slightly improved when combined with gestational age less than 25 weeks, yielding an AUC of about 0.699. The inclusion of bronchopulmonary dysplasia severity did not improve the discrimination. When they looked at cutoffs, they asked: what if we find a cutoff in which we can say with confidence what we're looking at? Lower cutoff values for ProBNP affected diagnostic accuracy. A cutoff value of 1,129 ng/L demonstrated a sensitivity of 85%, meaning you're going to include a lot of people that you think may have the disease, but the specificity was not great at 55%. You really don't know for sure, and it had a positive likelihood ratio of 1.86. Let's say you use a higher cutoff, like 2,674. Then your specificity is 95%. If a baby has an NT-proBNP of 3,000, you can be pretty confident that this is going to be diagnostic. But the sensitivity when you use a higher number is 31%, meaning you may be leaving behind a bunch of babies that still have pulmonary hypertension but didn't meet that high cutoff value. It is the typical sensitivity-specificity issue. And this is where the team in Toronto leaves us. They're saying this is a single-center retrospective cohort study that finds ProBNP levels were significantly higher in extremely low gestational age neonates with chronic pulmonary hypertension. The NT-proBNP demonstrated moderate diagnostic accuracy for detecting chronic pulmonary hypertension when compared with concurrent echocardiography. A cutoff value of about 1,129 demonstrates high sensitivity but low specificity, while a value of 2,674 shows the opposite. The conclusions are that NT-proBNP seems to be a promising tool for early screening, risk stratification, and diagnosis. A stepwise approach using different cutoff values may support personalized clinical decision-making. Obviously, they're recommending more studies. We need more patients to get a better sense. I think this is a very interesting and important study. The diagnosis of pulmonary hypertension is something very much on our mind, but it's not easy to achieve for most centers. If you're at SickKids in Toronto, you have a hemodynamics program; you could get that done at two o'clock in the morning and they'll give you the answer. But if you're a run-of-the-mill center, doing these echoes is not easy. You may not be able to get them on time. There may be a lot of hesitancy from the clinical team about pulling the trigger—maybe the FiO2 is slightly up, and you wonder if it's nothing or something else, but you don't know. Also, there are a lot of cardiologists who don't give you all the information you want from these echoes. So having an additional tool like a ProBNP is an interesting idea, and it's something most centers can do because it's also done in adults.

[16:44.201] Daphna Yasova Barbeau MD Yeah, I totally agree with you. Even if you have great access to Echo, it's different than hemodynamics. We don't always get all the information we need. And this wasn't even talking about pairing a ProBNP and an Echo; it was just using the ProBNP.

[17:05.304] Ben Courchia MD They did pair it, but they only used the pairing to use the Echo as the reference.

[17:10.013] Daphna Yasova Barbeau MD Exactly. As a reference. If you have an Echo plus a ProBNP, then you're pretty sure. ProBNPs are easy; we struggle to get some things in our lab, but even we can get a ProBNP. So, I feel like anybody can get one. This is exciting. We're always looking for biomarkers that will help us make decisions and are easy to get.

[17:39.263] Daphna Yasova Barbeau MD It's really useful, especially because sometimes things are happening quickly, babies are changing, and you need information fast. Thank you for sharing some of your newfound knowledge of hemodynamics as we review this paper.

[17:55.877] Ben Courchia MD Yeah, I'm going to spend two minutes to talk about this. Hemodynamics is something that I'm pursuing training in because when I investigated this, it was made clear to me that without going through proper training, it's not something you can acquire. But I also feel like sometimes the knowledge feels like it's gated by people who know. Before I started training in this, I didn't understand anything they were saying—even saying the pulmonary pressures are two-thirds systemic. I barely understood that. How did they get that? How do we measure that? What is the reflection of that? I didn't know these things. We cannot pretend as The Incubator that we can train people in hemodynamics, but what about making people more literate about the terms and the things that are being done? I think we can do that. If you are interested, we can do it in short, bite-sized segments. If you want to understand how we measure left ventricular output, that's very easy to explain. Can you do an echo and measure it yourself? I'm going to defer to you getting training for that, but we can explain it.

[19:11.624] Daphna Yasova Barbeau MD That's right. Well, I'll say even in our unit where we're not all getting training in hemodynamics—even though you are—we were having different discussions about echoes and clinical findings just because we're able to use a different type of terminology, even if I'm not doing the echoes myself.

[19:31.436] Ben Courchia MD Yeah, I think that being literate means that when your cardiologist calls you and says "no signs of pulmonary hypertension," you could potentially have a more robust conversation and ask, "What did you see there? What about that?" Because until I knew these things, I would say, "All right, no pulmonary hypertension, moving on," because I didn't know what to ask. It's very interesting. In hemodynamics, there are a lot of assumptions that we make that could affect your ability to extract information. This is also where, in this paper, they mentioned that the ultrasonographer who takes the measurement is an important piece of the puzzle. They're absolutely right. When a cardiologist tells you, "I couldn't see very much," that's not something for you to just ignore.

[20:29.006] Ben Courchia MD Correct. All right.

[20:33.969] Ben Courchia MD Okay, Daphna, what are we talking about today?

[20:38.848] Daphna Yasova Barbeau MD Well, I thought that you were going to like this study quite a bit. It's in the European Journal of Pediatrics. It's entitled, "Antibiotic Use in Neonates with Hypoxic Ischemic Encephalopathy Undergoing Therapeutic Hypothermia: Time to Rethink Universal Empirical Treatment." Lead author, Domenico Umberto de Rosé; Senior Author, Maria Paola Ronchetti. And this is coming to us from... they were two different units and I'll get into those details, but Italy and Belgium. So basically they want to help us answer the question: does our baby look like this because they're septic, or do they have HIE because they're septic, or is it possible that these are just independent pathologies? So they wanted to look at the incidence of culture-proven sepsis and current antibiotic use patterns in neonates undergoing therapeutic hypothermia. It's a multi-center retrospective study, including term and near-term neonates with HIE treated with therapeutic hypothermia. And like I said, they had two units and they had universally different antibiotic strategies. The group in Italy was using basically universal empiric antibiotics and the group in Belgium had more selective use of antibiotic therapy. The introduction was actually quite nice. I think people who are new to sepsis and/or HIE should definitely take a look. So many of the pathways overlap in our immune and body response to both of these. And so I think that's why both the clinical features of sepsis and HIE can overlap, and so can the laboratory findings. So sometimes it's hard to say: is it one or the other, or both? That's what they were trying to look at. So I told you there were two centers. The primary objective was to assess the incidence of early-onset sepsis and the antibiotic use in this population. Secondary objectives looked at the incidence of late-onset sepsis before discharge and differences in biomarkers. So they looked at the CRP, procalcitonin, and leukocytes at five different time points: basically across the cooling period—at admission (time 0), 24 hours (time 1), 48 hours (time 2), 72 hours (time 3), 84 hours (time 4), and one week (time 5). So in both centers they give us a little bit of background about what that looked like. Therapeutic hypothermia started for eligible infants within six hours and continued for 72 hours. They said they included "late preterm infants," but these are greater than or equal to 35 weeks gestation. I mentioned that just given our recent discussions about cooling 35-weekers. In the Italy cohort, the universal empiric antibiotics—ampicillin and netilmicin (the US uses gentamicin, but ampicillin and netilmicin) were given to all patients upon admission; that comes from their national recommendations for the management of HIE. In contrast, in the Belgian cohort, antibiotics were used when there were definitive risk factors or symptoms specifically suggestive of infection; they used amoxicillin and amikacin. So it is also interesting for us to learn about what our colleagues across the world are using. The management of HIE included amplitude-integrated EEG (aEEG) monitoring and full EEG monitoring during the cooling and rewarming periods. They defined early-onset sepsis as a bloodstream infection in neonates occurring before 72 hours of life. And they called late-onset sepsis after 72 hours of life and at least 48 hours from NICU admission. So what were the results? This study included a total of 302 newborns. They had 276 term infants and 26 late-term infants who underwent therapeutic hypothermia at the two centers during this time period. Of the 302 infants, 278 in total received antibiotics at birth. That is, if you're paying attention, most of them—still for a median duration of six days, interquartile range of five to seven days. Now, the two different cohorts of newborns—and remember they're different in a number of ways, including their country of origin—showed significant differences in several maternal and clinical factors. Maternal GBS status was unknown for 40% of cases in Italy compared to 6.7% in Belgium. But if you looked at just the group of maternal GBS status for the ones where you did know the results—whether they were GBS positive or GBS negative—there was no significant difference found between the two groups. So it didn't look like the Italy group had a higher proportion of GBS positive moms; just that in Belgium, they were doing more testing of moms. The distribution of intrapartum antibiotic prophylaxis administration differed significantly between the two groups. Additionally, Belgian newborns had lower Apgar scores, but the Italian cohort had more severe Sarnat scores, and they had no mild Sarnat scores. So it looks like they were not routinely cooling mild infants. In the Italian cohort, nine infants faced an early exit from therapeutic hypothermia, and the reasons for this were clinical deterioration due to a number of complications, including pulmonary hypertension for two, multi-organ failure for one, severe hypotension for two, DIC for three, and anuria for one. In the Belgian cohort, no infants underwent early exit from therapeutic hypothermia. Other differences between the two groups during the NICU stay included longer antibiotic therapy and more mechanical ventilation among Italian newborns, while mortality was higher in the Belgian cohort. However, in Belgium, all infants died within the first days of life following redirection of care in agreement with their families because there was evidence of severe brain damage. So what were the results? Admission blood cultures were conducted in 99% of the newborns—in all of the Italian infants and 72 out of 74 of the Belgian infants. Only three blood cultures (1%) were positive, with a median time to positivity of nine hours. The three culprits of these positive blood cultures were E. coli with a time to positivity of six hours; a second culture that grew E. coli and Staphylococcus warneri, a time to positivity of nine hours. It was felt that the Staph warneri was a contaminant, but that baby was still counted for the E. coli. And the third culture was Staph epi and Staph capitis, time to positivity 17 hours, but they were interpreted as contaminants. So considering the identified pathogens, they really only considered these two out of the total 300 cultures—0.66% were considered positive. Among Belgian neonates, eight infants had a clinically suspected early-onset sepsis a few hours after admission, but all the blood cultures performed in these eight infants were negative. A total of 1,680 days of antibiotics were administered, a median of six days. In 30 of 302 patients (10%), there was concern for late-onset sepsis post-therapeutic hypothermia, leading to sepsis workups, including additional blood cultures. Four out of 30 (13%) of this secondary group tested positive with a median time to positivity of 20 hours. And the pathogens identified in this group were Staph capitis, Staph epi, and Staph hominis. And all the patients who had these positive cultures in the late-onset group had received empiric antibiotics upon admission, which is also very interesting. I think sometimes we think, "Oh, let's give them a little antibiotics, maybe they won't have infection." Admission empiric antibiotics would only probably help at the early onset of this late-onset creep. So given the incidence of infected babies in both groups of neonates—again, 0.9% in the Italian cohort

[30:23.835] Ben Courchia MD [Laughter]

[30:42.282] Daphna Yasova Barbeau MD and 0% in the Belgian cohort—the corresponding number needed to treat was 111. So 111 newborns undergoing therapeutic hypothermia would receive antibiotics in order to treat one case of culture-confirmed early-onset sepsis. I told you they were going to look at some of the biomarkers and how they are influenced by therapeutic hypothermia. They looked at CRP, procalcitonin, and leukocytes across these five time points, and they found a significant increase in CRP levels, particularly after 48 hours, followed by a subsequent decline. These pictures are quite useful. Basically, time zero to time one, those first 24 hours, CRPs are low. And I'll tell you from the Florida Neurologic Network Group, those first 24 hours of CRPs are typically quite low in these babies undergoing cooling. They peak at time two and then they come right back down to time three. These graphs are really cool because it looks like they graph the individual babies all across the five time periods. Quite a beautiful graph. Now similarly, procalcitonin levels also significantly increased after the 24-hour mark and then had a slower decline, but decreased significantly over the subsequent time periods and then plateaued back to normal after about time T2 to T3. Now, leukocytes were also very interesting. The leukocyte level showed a significant decrease over time. At time zero, those were really the highest time points for most of the babies. It's an asymptote, but I want people to get the direction here. They started out high, decreasing and really flattening out—plateauing around T3 and normalizing in the 10,000 to 15,000 range.

[32:40.475] Ben Courchia MD Is that what we would define as an asymptote?

[33:06.601] Daphna Yasova Barbeau MD Very cool in the entire cohort. So what's their discussion? Basically, they conclude that the simultaneous occurrence of HIE and early-onset sepsis is presumably rare, albeit still largely unknown. They do remind us that the symptoms—both clinical and laboratory findings—may be overlapping; that their findings are consistent with growing evidence supporting a shift from routine to selective antibiotic initiation in critical care to those babies who have what we know are pretty good risk factors for sepsis. I wonder what you think about this. You're an "antibiotics in HIE" kind of guy.

[34:00.125] Ben Courchia MD I think that it's just very difficult for us to know. It's funny that you pick this paper because tomorrow I have another paper on early-onset sepsis antibiotics. And it's just baffling to me that you take a population—just think about it in those terms: Okay, you take a population, you test them for a disease.

[34:14.229] Daphna Yasova Barbeau MD Mmm.

[34:27.869] Ben Courchia MD Less than a percent of them test positive, and yet, over 90% get treatment.

[34:27.925] Daphna Yasova Barbeau MD Yeah. I know, it's painful. It's nuts.

[34:36.605] Ben Courchia MD This is nuts. But the problem is that we still don't know—I think AI may be able to help us eventually on this particular front. But we really don't have a good discrimination of patients. They arrive and they're so complex. They're so complex in terms of all the things that are going on...

[34:41.972] Daphna Yasova Barbeau MD you don't want to miss. Yes sir.

[35:01.937] Ben Courchia MD To discriminate with a level of certainty whether you are looking at something that is consistent with sepsis versus not is very hard. So on the one hand, I feel like the data is absolutely baffling. But on the other, I completely empathize with the likes of me in the world who like to give a thing. When you have a baby that shows up...

[35:24.937] Daphna Yasova Barbeau MD Well, I think that's what's so hard about our babies. They can't tell us how they feel, right? We just have these vague markers.

[35:29.403] Ben Courchia MD Absolutely. And then the question is, when a baby shows up and has low blood pressure, is on high oxygen, is intubated, you're starting pressors—how confident are you that this is not sepsis? It's an impossible question.

[35:50.963] Daphna Yasova Barbeau MD I will say they didn't tell us so much about all the clinical features of these babies, but we assume that they are—for the most part, they weren't cooling mild babies, so pretty sick-looking infants. They also didn't tell us a lot about sentinel events. I think that's the group that we really have to be concerned about because if you don't have an obvious sentinel event...

[36:03.581] Ben Courchia MD Yeah.

[36:19.733] Daphna Yasova Barbeau MD And that's only about 50% of cases. Then you have to say, "What else is going on here?" But maybe in the babies where they have a straightforward sentinel event, we can feel a little bit more comfortable about evaluating them with their sepsis risk factors.

[36:25.789] Ben Courchia MD Sure.

[36:37.893] Ben Courchia MD I'm going to add one more thing. The graph that you mentioned—I didn't find it particularly helpful. No, I thought there was a lot of lines. Then to be honest with you, if you look at the CRP...

[36:42.772] Daphna Yasova Barbeau MD You didn't?

[36:47.615] Daphna Yasova Barbeau MD But all the lines say the same thing.

[36:50.493] Ben Courchia MD But in—for example, CRP—when have you seen a CRP of 36? When the CRPs are within the range... but I think at least I didn't particularly like the one on leukocytes. It's my personal opinion.

[37:07.913] Daphna Yasova Barbeau MD Well, I think what is important about the one on leukocytes—we reviewed this in the ID section of the Board Review podcast. This is basically what leukocytes do. So what I took away is this is not so different from what we see in leukocytes postnatally. So, okay, it's not that helpful to follow leukocytes potentially, but that's helpful to know. And I think if you have a CRP that's very elevated or procalcitonin—maybe procalcitonin is better than the CRP outside of this timeframe—then maybe you should think about sepsis because it's unlikely to be related to the therapeutic hypothermia or the HIE.

[37:51.887] Ben Courchia MD Yeah. Absolutely.

[37:59.542] Ben Courchia MD I have a very interesting paper kind of following in your footsteps from yesterday. It's a paper I found in the Archives of Disease in Childhood - Fetal and Neonatal Edition. It's coming out of Norway. The first author is Anlaug Vatne. It's called "Serial Physical Examination to Reduce Unnecessary Antibiotic Exposure in Newborn Infants: A Population Study." The introduction talks a little bit about what we said yesterday. So the initial clinical signs of neonatal early-onset sepsis (defined as sepsis within the first three days of life) are often subtle. If they're not subtle, you don't need our help. You don't need us for that. And they can mimic other neonatal conditions, such as delayed or prolonged cardiopulmonary transition. We don't really have good lab tests that can help us with high sensitivity, high specificity. Again, we were talking about CRP yesterday, and we don't really have the tests that we need. These diagnostic challenges are addressed in the 2018 American Academy of Pediatrics Guidelines and in the Swiss Network's recommendation, with the latter suggesting the use of serial physical examination for enhanced clinical observation or continuous monitoring every hour in the NICU to identify infants with suspected early-onset sepsis. Other approaches include risk stratification using sepsis risk calculators or algorithms based on the presence or absence of maternal risk factors. The clinical implementation of these different approaches has resulted in contemporary antibiotic exposure in term infants (defined as those born at a gestational age of 37 weeks or greater) and late preterm infants (34 weeks to 36 and 6/7) in high-income countries ranging between 1.2% to 12%. So just for comparison, yesterday we were talking about babies with HIE who give us a lot more anxiety. We were talking about numbers like 92% yesterday. But for your run-of-the-mill admission with a little bit of TTN and some of these things, we're talking about 1.2% to 12%. And they're making the point that we made yesterday, which is where I got this sort of epiphany. The exposure is disproportionately high compared to the incidence. Culture-positive early-onset sepsis ranges from 0.3 to 0.73 cases per 1,000 liveborn term and late preterm infants. So this study comes in this particular context. Building on previous findings, serial physical examination was previously tested and shown to be safe, including in late preterm infants, supporting the inclusion of infants born at about 34 weeks or greater. And within the framework of a quality improvement project, the aim of the study was to evaluate whether serial physical exams could reduce antibiotic exposures for these infants. So did they do it? Did they jeopardize the lives of babies? Study setting: This is conducted in six hospitals across all four Norwegian health trusts. And that covers about 25% of the birth cohort in Norway. This was a multicenter population-based interventional study evaluating the effect of this new approach, serial physical examination in the NICU for all inborn infants with a gestational age of 34 weeks or greater who were suspected to be at risk of early-onset sepsis. All live-born infants were included, including all infants who received antibiotics for suspected early-onset sepsis in their respective geographical areas. Infants at risk of early-onset sepsis were defined as infants who had mild or transient clinical signs of possible sepsis, infants born to mothers who had clinical chorioamnionitis, or infants with a sibling who had GBS sepsis. Infants who received antibiotics prophylactically as part of the national protocol for therapeutic hypothermia were excluded, kind of like the patients we were talking about yesterday, as well as infants with congenital heart disease or neurological malformations in need of surgery. So what does that mean that they did this serial physical exam? Infants appearing well at birth remained with their mothers in the nursery. Infants with clinical signs were promptly admitted to the NICU. These infants were exposed to chorioamnionitis or had siblings with a history of GBS sepsis and were admitted within the first two hours of life. All infants in the nursery were monitored according to standard practice, screening vital signs, oxygen saturation at two to four hours of age. Further assessments were performed in infants at risk of infection, infants with an initial screening, or who developed clinical signs of sepsis or infection during their stay. Infants identified as being at risk were admitted to the NICU for structured serial physical exams and vital signs hourly for the first 48 hours. Full sets of vitals were obtained every hour except blood pressure, which was obtained only when cap refill time exceeded three seconds. Continuous pulse ox was used. Skin-to-skin was encouraged, and parents were welcomed to accompany their newborn in the NICU. Antibiotics were administered without delay if clinical signs indicated severe sepsis or shock, if the clinical condition deteriorated despite corrective action, or if vital signs did not improve over time. The decision to initiate antibiotics was made by the team in agreement with the consultant neonatologist or pediatric consultant. So the baseline period extended from 2018 to 2019, post-implementation 2020 to 2021. And IV antibiotics was basically IV antibiotics for early-onset sepsis. Culture-negative sepsis was defined using the International Classification of Diseases 10 (ICD-10) and the Norwegian Pediatric Association looking at clinical signs of infection, C-reactive protein levels, duration of antibiotics, exclusion of other stuff, et cetera. OK, so did this pan out? A total of 54,713 live-born infants with a gestational age of 34 weeks or greater were included. Of these, 27,385 infants were born during the baseline period and 27,328 during the post-implementation period. Looking at antibiotic exposure: after the implementation of serial physical exams, the percentage of infants receiving antibiotics was reduced by 50%. Antibiotic exposure decreased from 1.8% (with a 95% confidence interval going from 1.6 to 2) to 0.9%. When comparing baseline with the post-implementation period, antibiotic exposure decreased from 1.7% to 0.9%. The number of infants receiving prophylactic antibiotics remained unchanged, with 22 infants in 2018, 24 in 2019, 26 in 2020, and 25 in 2021, with a p-value of 0.9. The percentage of infants receiving antibiotics for any reason, including prophylactic and empirical, was 1.9%, 1.8%, et cetera. So the point they're trying to make here is that it's not like their entire system shifted. The kids who were supposed to receive prophylactic antibiotics, kind of like the babies with HIE, they continue to get it. There was not a big shift in their approach. This basically hints at the fact that the reduction by 50% in early-onset antibiotic exposure was most likely due to their intervention. And then the follow-up question is: did they have more early-onset sepsis? The incidence of culture-positive early-onset sepsis was 0.4 per 1,000 live-born infants. And there was a decrease in culture-negative early-onset sepsis observed—I don't have the exact data, but it was statistically significant. Neonatal intensive care unit admission rates and time to antibiotic administration remained unchanged. There were no infection-related deaths, and no readmissions for infection within 14 days. The conclusions are that the implementation of serial physical examination for suspected early-onset sepsis in six Norwegian NICUs, including more than 50,000 infants born after 34 weeks, reduced antibiotic exposure in the first three days of life by 50 percent. Serial physical examination represents a safe and effective strategy to reduce unnecessary antibiotic exposure in term and late preterm infants at risk of early-onset sepsis. They say more studies are needed. I don't know. This is pretty convincing. Maybe the answer to this solution has always been this: just better eyes on our patients. Yeah, right? How fascinating is that?

[48:16.060] Daphna Yasova Barbeau MD Spend more time at the bedside. I love that. I mean, isn't that just the crux of medical care as we were taught? To observe and monitor and watch our patients?

[48:25.078] Ben Courchia MD It's the essence.

[48:29.686] Ben Courchia MD You now have joined the faculty teaching principles of medicine at the medical school where we teach medical students a lot of things related to physical examination. And it is, like you said, the core of our practice is assessing a patient at the bedside and making a decision.

[48:47.479] Daphna Yasova Barbeau MD That's right. Yeah, I actually love that. But it's a reminder that how many of our administrative tasks, our EMR tasks, all this stuff is taking us away from making these decisions. And into the credit of all of our colleagues, I think if you don't have a lot of time to assess the baby, then you feel like, "Well, better put them on antibiotics, I won't be able to assess them." You know, I think about other units; we are always in-house. So we have that luxury of being able to reassess and assess with a trained eye multiple times a patient. It's interesting taking us back to our principles, but easier said than done in today's modern medicine.

[49:36.470] Ben Courchia MD But you know, I'm sorry, I'm going to push back on that. When you were a resident and you were on the floors, we had this. Like there were patients that were there for serial exams. And I would remember I would go every couple of hours and do an assessment.

[49:48.032] Daphna Yasova Barbeau MD For sure. Yeah, like the kids with asthma, you were doing every hour sometimes.

[49:54.612] Ben Courchia MD Right, we would do these respiratory checks and then you would do... like patients with abdominal pain, and you would say, "Let's just reassess." It's how we were trained, and somehow we get to the NICU and this gets lost when it shouldn't. And again, I think it has to do with our load, and then I'm gonna point you to the section on neonatal and perinatal medicine to look at the neonatal staffing toolkit because...

[50:13.652] Daphna Yasova Barbeau MD Whether the babies are even more critical. And that will segue nicely into my article tomorrow.

[50:27.124] Ben Courchia MD Your next paper tomorrow? Awesome. Okay, so then we'll do that. But yeah, I mean, it's not an excuse to say, "We're stretched so thin." It's like, well, then maybe that's a problem. Because every time I have parents who ask about antibiotics—not push back, they're like, "Okay, what are the risks of giving this antibiotic?" I go... like, it's never fun to explain ototoxicity and nephrotoxicity, and then tell them, "But it's okay."

[50:51.520] Daphna Yasova Barbeau MD Yeah, it's real hard to convince them after that. And they say, "How sure are you that my baby has an infection?"

[51:01.766] Ben Courchia MD 0.3%. I was like, "Oh my god." Yeah, I think these discussions are always helpful for us as physicians because they put us back in front of the reality of the data. And it's hard. If there's an alternative—can you imagine if you had to get a consent and you said, "Have this medication that can potentially impair hearing, can have kidney damage, or if I check on your baby every couple of hours and everything is okay, then we can avoid it altogether." It's not going to be a tough decision for anyone.

[51:32.214] Daphna Yasova Barbeau MD Sure, for sure. What I also am taking away is when some of our team members say, "Dr. Barbeau, why have you pulled that chair up by the baby's bedside? We don't want you right here all the time." I can say, "Well, in this paper, they said that I could do this, sit by the bedside and watch the baby." Is that not the right takeaway?

[51:50.268] Ben Courchia MD I don't know. I don't know if pulling the paper is going to do much good for you. It is the right takeaway. I have to mention for the audience that the staff members in our NICU are a little bit concerned when you pull the chairs because ideas come to you. And then you sit there and you're like, "What if we got this test?" But I think that was really... That was really something, like I think people have learned to appreciate how dedicated you are. So I think this is no longer something that I hear.

[52:25.654] Daphna Yasova Barbeau MD Or at least to pay attention to the babies of which I'm sitting at their bedside.

[52:29.630] Ben Courchia MD Correct. Correct.

[52:31.945] Daphna Yasova Barbeau MD Okay, well, I have another paper as we're finishing out this week. It's in the journal Journal of Perinatology. It relates to our discussion yesterday about spending more time at bedside and can we prevent unnecessary antibiotics that way? So definitely check it out if you haven't. It's entitled, "The Association of NICU Capacity Strain with Neonatal Mortality and Morbidity." Lead author, Elizabeth Salazar. Senior author, Scott Lorch, who obviously is an expert in this area. So they wanted to look at this association of "admission NICU capacity strain" with neonatal mortality and morbidity. I didn't know much about NICU capacity strain, so they tell us a little bit about it. I'll give some background here. ICU capacity strain is the ICU's time-varying stressors. So demands from patient census and acuity as well as current resource availability. It is taking into account a lot of factors about our accessibility to patients. Capacity strain is influenced by physical and human resources as well as patient volumes, the patient acuity, and the specialized needs of the patients. Now, this has been well described in the adult literature. Increased ICU capacity strain on an adult patient's day of admission is associated with decreased in-hospital survival and safety practices. Despite the strong evidence in the adult ICU, they state that the role of NICU capacity strain as a driver of hospital variation has been understudied. So that's what they're trying to do. They wanted to examine the association of NICU capacity strain on the day of admission within hospital term and preterm mortality and complications. They looked at both groups of babies. They chose to focus on capacity strain at admission given the prior research about that. And they are using a novel measure of NICU capacity strain that incorporates the census of high-risk infants by measuring the standardized daily sum of infants less than 44 weeks gestational age with a congenital anomaly plus all infants born less than 34 weeks gestational age. And it also looks at the role of admissions. I'll tell you a little bit more about that in just a second. Their hypothesis was that increased NICU capacity strain would be associated with worse neonatal outcomes when controlling for patient-level and hospital-level factors. This is a retrospective cohort study. It looked at records from 2008 to 2021 in the South Carolina Vital Statistics and Linked Hospital Records for infants born between 22 and 44 weeks gestational age. They tell us how they were able to identify which infants were cared for in the NICU. They looked at hospitals with neonatal care level II or greater and with greater than or equal to five births of infants less than 34 weeks gestational age per year. They wanted to make sure that these units had potentially been caring for small babies. Infants were excluded if they had a missing birth certificate, if the birthing parent or the infant hospital data was missing, or a birth weight greater than five standard deviations from the mean for gestational age. If any of these things looked abnormal, those babies were excluded. The study cohort was 11% of the entire birth cohort, and they highlight that this is consistent with other estimations of NICU admissions being about 12%. The study variables: Admission NICU capacity strain was defined using a standardized measure of the daily census of higher-risk infants. So this was defined as infants less than or equal to 44 weeks gestational age with a congenital anomaly plus all infants born less than 34 weeks gestational age. So that was kind of the high-risk infant group, which is interesting because it still misses some babies who are potentially term and high risk. To define NICU capacity strain, again, they told us about which babies were considered high risk and potentially requiring more resource-intensive care as a proxy for unit-level acuity. And then they did standardization performed by subtracting the average annual hospital census of this higher-risk population from the daily census of this high-risk population, and then dividing by the average daily hospital census of high-risk population for that given year. So they basically created this metric standardizing a unit's annual average daily census of high-risk infants so that it incorporates how used to this type of care a given hospital is. So that is separate from NICU capacity strain looking at individual hospital factors. They wanted to highlight they chose this definition of NICU capacity strain that is intentionally different. It didn't incorporate care resources such as nursing staffing ratios, since a lot of times that data is not available. We know that sometimes staffing ratios aren't always followed to the letter of the law. And that other annual values vary by other hospital factors, things like financial health and stability that can change over time for any given hospital and can confound relationships observed in the study. They also examined the total number of NICU admissions on a given day as an alternate definition of NICU capacity strain as part of their sensitivity analysis. This has also been well studied in the adult population. The primary outcome was a composite of mortality and complications for all term and preterm infants. For preterm infants, complications included severe—so grade 3 or 4—IVH, NEC, surgical retinopathy of prematurity, chronic lung disease, or infection, and these were pulled from ICD codes. For term infants, complications included moderate and severe unexpected newborn complications as previously defined in other papers looking at some of the same data. They had a whole slew of covariates at the patient level, looking at gestational age, weight, multiple gestation. They had a number of covariates looking at the birthing parent race, ethnicity, insurance, education, BMI, and examined a number of hospital characteristics: hospital ownership, rurality, number of NICU beds, NICU level of care, and annual birth volumes. So there is a lot of data in this paper. The results: The study cohort included 64,647 infants from 30 hospitals. This is 273 hospital-years. 46% of the cohort, about 29,000 infants, were term and 35,000 or 54% of infants were in the preterm category. In the cohort, 24% of infants experienced zero capacity strain. 23%—again this was on their day of admission—experienced low capacity strain. 37% experienced typical capacity strain, and 10,000 infants, or 16%, experienced high capacity strain at admission. Infants exposed to typical capacity strain were more frequently preterm, multiple gestation, had a major congenital anomaly, and were born to Black birthing parents with government insurance, diabetes, hypertension, and obesity, and delivered via C-section. Interesting. Infants born during a period of high capacity strain were also more likely to be born at lower level NICUs with lower annual birth volume. So then we get into the nitty-gritty here. Hospitals with an average daily hospital census of higher risk infants less than one had larger values of NICU capacity strain as the NICU capacity strain measure was created again by dividing by a number less than one. They talk about Figure 2 here, and Figure 2 basically looks at variation across the hospital. And you can see that there's a lot of variation across the different hospitals in their degree of NICU strain. They had an unadjusted bivariate analysis. Infants born during times of typical capacity strains more frequently experienced composite term and preterm adverse outcomes: 29% in the typical capacity strain versus 21% in high capacity strain and 26% in low capacity strain respectively. Again, an unadjusted analysis, there was actually a decreased incidence rate ratio of the primary outcome in infants exposed to the highest capacity strain deciles and the lowest capacity strain deciles compared to the second capacity strain decile. However, in models where they were able to adjust for patient covariates with a fixed effect for hospital, birth during periods of high NICU capacity strain in a given hospital was associated with an increased risk of mortality and complication compared to birth during the second capacity strain decile. So they recognize that this suggests that within a given hospital, birth during periods of increased NICU capacity strain was associated with increased mortality and complication when controlling for these additional patient covariates. And when adjusting for patient covariates with a fixed effect for hospital and neonatal level of care, birth during the highest deciles of capacity strain remained associated with increased mortality and complication. In models examining the secondary outcomes unadjusted for covariates, the highest capacity strain deciles associated with a lower risk of term adverse outcomes. But after adjustment, none of the deciles of NICU capacity strain were associated with adverse outcomes. Now for preterm infants, the eighth and ninth deciles, so the highest capacity strain, were associated with decreased risk of adverse preterm outcomes before adjustment. However, after adjustment for patient covariates with a fixed effect for hospital and neonatal levels of care, these deciles were associated with a significantly increased risk. They also performed a separate sensitivity analysis which excluded all the Level II NICUs and this showed a persistent association of the highest decile NICU capacity strain with adverse composite outcomes in these models adjusting for patient and hospital-level factors. They looked at other alternate definitions of NICU capacity strain. They looked at number of daily admissions. Higher deciles of NICU capacity strain were significantly associated with composite term or preterm outcomes in unadjusted models, but these effects were no longer seen when adjusting for patient factors with this fixed effect for hospital or for hospital and level of care. So what does this all mean? They highlight that the study is the first to report the association with NICU capacity strain at admission with neonatal mortality and complications. They state that their findings are similar to the original adult ICU study and that using their novel standardized census measures, they were associated with less mortality and complications in the unadjusted analyses. But when this association was looked at adjusted for patient acuity and hospital-level factors, that increased ICU strain was associated with higher mortality and complications. They say without adjusting for these hospital and patient trends, high capacity strain appears to be associated with improved outcomes. You know, we're all saying the levels with the most volume have the best outcomes. But by controlling for hospital effects, doing this fixed effect model, looking at the level of NICU care and the individual patient acuity, this highlights the true impact of increased ICU capacity strain within a given unit, and again, is associated with increased adverse outcomes. This is especially true, they highlighted, with the adverse preterm outcomes which was not seen specifically for term infants. But like we said, this may have missed some of the term infants that would have increased the level of acuity. So they talk about their limitations. Obviously, this is a novel model. They are not able to adjust for all of the covariates, which may impact levels of strain, and they weren't able to look at capacity strain across an admission. So they were just looking at what did the capacity strain look like on the NICU admission day. In conclusion, they say exposure to high NICU capacity strain at admission was associated with increased risk of neonatal mortality and complication when we were able to adjust for the infant, the birthing parent, and hospital characteristics, including level of care. And I think this speaks exactly to what you said, Ben, yesterday, that the system is going to put a lot of strains on us, but we still have to make it to the bedside in one way or another. It's the right thing to do for patients.

[1:11:10.270] Ben Courchia MD Yeah, right. I mean, sometimes there's like this lore of neonatology of just bragging about how busy we are. "I got slammed with admissions," but it may not be such a glamorous thing to be proud about. I think that it seems to be that it's great that a center gets this reputation, gets lots of patients, gets expertise, but this must be then matched by appropriate staffing and reducing the strain on the staff. So yeah, I feel like sometimes it's a point of pride to make it sound like we're in the trenches, but it shouldn't be because it's quite concerning, right? Mortality is the direct resultant of that. So I feel like for those of us who sometimes used to rotate—maybe you spend some time at the big Level III, Level IV, then you go rotate at the Level II. And then sometimes you wonder like, "Why am I having such a good outcome on this baby here in the Level II?" And the question often is, is it because the strain is different and the staff is more available and the team has a lot more time and more time is spent at the bedside? So I think it's not really negligible. And the question is, how do we convince the C-suites and hospital administration that this is worth investment in? I think that transparency will be the answer. I was very impressed when we visited not too long ago the cardiac department at Nicholas Children's Hospital, that they're very transparent about their outcomes. They will publish every surgery, what outcome they had. And I feel like if maybe we did that in neonatology, then we would be very much geared towards how do we get the best outcome? And then we would get to the crux of these issues, staffing, resources, et cetera. So it's very interesting.

[1:13:12.975] Daphna Yasova Barbeau MD Yeah, giving us some things to think about. I think this is especially important. It dovetails with the work being done by the Women in Neo Group, by Dr. Satyan, about just the future of neonatology. We're being asked to see way more patients with a much smaller workforce. I mean, this will be the result. Worse outcomes, unfortunately.

[1:13:33.770] Ben Courchia MD Correct. Correct.

[1:13:37.006] Eli We're coming back to you with our next article that we're going to talk about this month, which is an issue that we have covered, and we will keep covering. And that is the issue of vaccines.

[1:14:04.125] Daphna Yasova Barbeau MD It's not because we want to keep covering it, it just keeps coming up.

[1:14:06.852] Eli It's not because we want—it's not because we love it. Just, you know, something... there's just been a little chirping about this topic. Anyway, what we're covering this time is what everybody has already heard about. Certainly, it's the CDC decision on the universal birth doses of the Hep B vaccines. Certainly, the American Academy of Pediatrics, Dr. Susan Cressley, the outgoing president, has been very vocal about this. We applaud her courage and advocacy in talking about the impact of the vaccines. But just to lay out the actual changes, so that people know what is actually changing as opposed to all the rhetoric around the changes: the actual change in the CDC schedule. Again, you have to remember in today's age, there are now multiple different schedules floating around. The AAP has its own schedule, but in the CDC schedule, it says now that infants whose mothers test negative for Hep B would not be explicitly recommended for vaccination, but could get vaccinated if their parents choose to do so after shared clinical decision-making. It also recommends that the initial dose be administered no earlier than two months of age. Right? So if the birthing person tests positive for Hep B in prenatal testing, the recommendation would be universal vaccination of the infant at two months. If the birthing person does not test positive for Hep B, or as we will get into, has not been tested for Hep B, then there is no recommendation for or against by the CDC. And if they chose to vaccinate, the CDC recommendation would be to do so again at 60 days or later of post-menstrual age. So, guys, how do you interpret these changes? What are you hearing from your patients and from the community about how families are reckoning with this and how doctors and the neonatologists are responding to it?

[1:15:17.485] Daphna Yasova Barbeau MD I mean, I'd say in our community, we had a pretty high rate of Hep B birth vaccine refusal to begin with. We have to sign all those forms as they come in. And the numbers... I hear Ben chuckling because I have a vendetta against these forms. But that's a separate story for a separate day. So, we were seeing it quite a bit already in the state of Florida in the last 18 months to two years, but it's definitely getting worse. I think there are really two issues here. One is: what is the right recommendation? And I got to say, I really had to go back and do some educating myself about why the birth dose was recommended, and what happened when the birth dose was recommended. Hep B was really, really common. Lots of babies were getting Hepatitis B and the moms were not always testing positive. So that's why we initiated a birth dose of Hep B—so that we could cover moms that maybe hadn't seroconverted, or babies that were picking it up after mom's testing. They were getting it at daycare. They have multiple caregivers. They have family members that don't know that they're infected. Across the country, Hep B vaccination statuses are waning and Hep B infections are increasing for adults. So it seems like a ridiculous time to be doing something like this. And it's like so many other vaccine stories: we started doing something and the rates of those illnesses just plummeted, which is a huge success of the public health system. Unfortunately, I think that the pendulum will just have to swing. People will just have to see what happens, but at the risk of some of those babies, unfortunately. And for us, I do think it puts physicians in an interesting predicament when our professional societies are recommending one thing, the government's recommending another thing, and you feel like, "What am I supposed to tell patients?" I think what I have adopted is telling patients the data that I have. They want shared decision-making, so I'm continuing to do shared decision-making with families based on the data.

[1:17:00.712] Ben Courchia MD Based on the data. It's very interesting. I have a funny story because when I was a resident, I was practicing close to where Dr. Schuchat, which we've mentioned on last week's episode, was practicing. And one of his big areas of work was vaccines. And I always thought it was kind of weird. I was like, "Vaccines? It's a done deal. Like, what are we studying vaccines for?" And look at us now. I always chuckle when we talk about the importance of discussions on vaccines, because there was a time when I thought... This is very much accepted, that there's no conversation to be had about this, but here we are. And I agree with everything you guys have said. I do think that it is very important for physicians and clinicians to understand: what was, like you said Daphna, the reason for us giving the birth dose of the Hepatitis B vaccine? I think that parents have this very individualistic perspective of saying, "Well, I tested negative, so my baby can't get it, right?" And while that is obviously an important piece of the equation—because if the parent was positive, then it's a whole different situation—it is important for parents to know that babies can contract Hepatitis B very readily. And when they do, their likelihood of progressing from Hepatitis B infection to cirrhosis of the liver and potentially needing a transplant is quite high. If you look at the statistics on the rates of babies who develop chronic liver disease from Hepatitis B, it is above 80%. And so the question that I pose to patients in general is, "How do you know the people that your child is going to come in contact with? Do you know if a person who's going to give your child a kiss is Hepatitis B negative? And how confident are you about all that?" How much are you willing to risk the health of your child on this particular situation, knowing that there is a vaccine that you could give right now that's been tested and that's quite safe? So I really want to make sure that I share this perspective regarding my counseling, because I think the discussion on vaccines has centered around a sentiment that prompts us to think as if we're not living in a society. It's like, yeah, if you are Hepatitis B negative and you live in a tree house in the middle of the jungle by yourself... maybe a baby is not going to catch it. Right. Maybe. But we don't. We live with our neighbors. We live with our peers. We live in a community and things are around. And by the way, as physicians, we know that private information about people's health condition is very much suffocated in community. You don't know what germs your neighbor has because of HIPAA and because of all that—and that's great—but that means that you have to protect yourself. And the same way that you get car insurance, even if you're a very safe driver, is because somebody may run into you. And I think that it's the same idea.

[1:19:03.850] Daphna Yasova Barbeau MD Yeah, I think just what you said specifically there, I think that's what's been lost in the discussion. People think that the only way that babies are getting it is from their moms who tested negative. So that is a huge problem in the education. So that has worked really well saying, "How do you know how babies get it?" And they don't know how babies get it. When I say, "Will your baby go to daycare? Will your baby be out of your home? Do you know the health status of all of your family members?" And people say, "Actually, I don't." So I mean, I think that is a very important way to partner with families. Like, it's so confusing. There's so much information out there. It's hard to weed through it, but these are things that we know for sure.

[1:19:53.830] Ben Courchia MD And remind people of two things, I think: that while the CDC, like you guys said, has made recommendations based on the ACIP vote, it is important to remember the stance of the American Academy of Pediatrics, which represents pediatricians around the country. And I don't know if the American Academy of Pediatrics has run a poll on this, but I suspect it's going to be almost unanimous in terms of supporting the recommendations of the AAP to continue with vaccination at birth. And sometimes we have to remind parents: is the information you're getting about this issue from people who really have your interest in mind? Because that's also sometimes important to reflect on. Is the person on TikTok really going to stand by you when things don't pan out the way they should? Or should you rely on people around you in your community who do want your baby to be safe, who do want you and your family to have a happy life, instead of an Instagram post that's just there to rack up some likes? I think that that is also something that needs to be reframed. We are living in a society, we're living in a community, and the people that are posting on Instagram may not be living in our community. And it's important maybe sometimes to reframe and remember that we are looking out for each other in our own milieu, in our own locale. And maybe that will give more credence to some of the things we have to say.

[1:21:20.236] Daphna Yasova Barbeau MD Yeah, I mean, I think it's hard because it's not just TikTokers, right? It's the US government. So I think it is hard for families. And I've really... I don't know if this is the right thing to do. I've really taken the approach with families saying like, "It must be impossible to try to weed through this and try to make a decision." I really am feeling for families. And again, I return a lot to... everything in life, especially medicine, is about risk-benefit ratio. And for this scenario, the Hep B vaccine is like one of the best-studied medications ever, ever, ever. The childhood vaccine series has had so much scrutiny. And do the risks outweigh the benefits? That's right.

[1:22:08.600] Eli Yeah, I agree with so much of what you both said. I think I appreciate you bringing up this question of "when the TikTokers are the federal government," because I think that's really important because that is literally true. Like federal government policies are being announced first on social media websites, whether that's Truth Social or X (formerly known as Twitter), or Instagram or TikTok. You're right, that's exactly what's happening. The challenge that I've heard both in my time on the unit as well as in reporting is that sort of at base value, a lot of people assume the federal government—regardless of your opinions of the federal government—have your best interest at heart. Now you may disagree with their approaches to others, but the science shows like when you ask people about whether the federal government is doing good things for you, generally people seem to think—if you're in one of the majority groups that's not facing ICE raids and other things that we talk about and have covered over and over—that people think the federal government is generally doing good things for them. That may not be true of a given administration, but over the long run, people tend to believe that the government has their back, even if there are ways that it can do that better. And so I think the challenge we're facing in this day and age is while I, on one hand, feel that it is a courageous and laudatory step for the AAP to come out with their own vaccine schedule, I worry a little bit about splitting the public against the government, and in particular splitting the government against the CDC, who three years from now, God willing, there's an opportunity to start doing the long process of rebuilding the credibility of the CDC and reclaiming the public health functions of the CDC. And if in the short run, we split the public against the CDC or tell them that the CDC is not the authority on this thing, what does that mean for the long run? The next time we come out with an RSV vaccine and we say, "Hey, you should do the RSV vaccine." Or if the noro vaccine gets approved for everybody, what are we going to do then? And so I think I have tried to focus, as Daphna and Ben you both have said very elegantly, on what we know about the data. And I think the mode of transmission is a conversation that I've seen lots of epiphany light bulbs going off in patients when you say, "Hey, this isn't... vertical transmission is one route, but there are so many settings in which a child may live." Maybe not in the first two months, but to the extent we're delaying the entire vaccination series, who knows when that first vaccine happens? Who knows when they're fully covered and have completed the series? Certainly within the first year of life, there are so many opportunities to scratch your knee in the sandbox or get coughed on or spit on or sneezed on or whatever by any number of people. And so I think the mode of transmission conversation is so important. I think also the rate of diagnosis conversation is really important. So CDC data—I believe this is an MMWR study from 2023—says that of an estimated 1.9 million Americans who have chronic Hepatitis B, only about 900,000 of them are in fact diagnosed. So about half. And the same story is true when you look at the approximately 20,000 babies who this CDC study looked at who acquired Hepatitis B through vertical transmission—that 53% of the birthing people were diagnosed with Hep B at the time that their infant acquired it. So I think the conversation around this recommendation is conditional on a diagnostic state of reality that is inconsistent with where we are in the country. Meaning most people—half of people with Hep B—do not know they have Hep B, whether those are birthing people or whether they're not. That is really important to describe. Then you might say, "Well, why doesn't the federal government make sure that everybody just gets prenatally screened for Hep B?" And I think that would be a valid argument. And I could appreciate this policy if the government said, "Hey, we're going to defer universality if you're Hep B negative, at the same time that we're going to pour resources into making sure that people get additional prenatal care." Of course, anyone who's been following the war on Planned Parenthood and other maternal care and sort of antenatal care and Medicaid and all of these changes knows that the federal government is, if anything, pulling resources away from prenatal care. So my concern is the state of reality is both that fewer people, not more people, are diagnosed with Hep B prenatally, and then either because you don't know your status or because you've been diagnosed negative, you defer this vaccination series. And then all the routes of transmission can happen to the infant. That's the conversation that I am trying to have with people, encouraging them. If they think, as many people—you know, I had an experience recently with a very dear friend, as things happen to happen over the holidays every year—very dear friend, radically different opinions on a number of issues, including this friend feels that the principle of autonomy is a deeply important one and a sacred one that we should apply in all realms of life, including around vaccination. And I can get behind that under the context that the conditions for making good decisions are there. And I just am not confident that people actually have the information they need to make these decisions. So when we talk about shared decision-making, which I think we all think we've been doing forever, I think part of shared decision-making is making sure individuals have enough information to make good decisions. And I think that in ways that are frankly very subtle, the federal government has actually been removing people's ability to get good information in every outlet of life, whether that means getting information on themselves through healthcare services, or getting information on the population prevalence of Hep B, which we don't know anymore because we're not publishing the MMWR with any frequency. So I think this is a much bigger conversation. I try to convey some of that nuance in conversation with the families and to say, "At the end of the day, this is your decision. We're here to support you." Because for sure, if a family defers vaccination and their child is diagnosed at four months of life or whatever with Hep B, we need them to trust us. So even in the case where they don't get the vaccination upfront, we still need people to think we have their best interests at heart. And I think that also needs to be conveyed in our conversations: that while we have a recommendation, you are entitled and empowered to disagree with our condition and hopefully you still trust us. So if the worst happens, you can still get the care you need for your child to survive and thrive.

[1:29:29.474] Daphna Yasova Barbeau MD Yeah, and that we're still gonna be here to help your baby if they need it, you know?

[1:29:33.094] Ben Courchia MD Yeah. And I don't know if the splitting from the CDC is something that's inevitable. Unfortunately, I think that when an organization like the CDC is able to make changes so quickly and there's no guardrails to prevent these things from happening, it's a poor prognostic factor for that institution. And maybe we will go back to a more traditional form of medicine where people will trust their local physician over big bodies. And that might be better, that might be worse. Sadly, we'll have to find out.

[1:30:12.068] Daphna Yasova Barbeau MD Another big issue.