#445 - 📑 Journal Club - The Complete Episode from May 30th 2026

Hello friends 👋

Opioid withdrawal dosing, intranasal breast milk, human milk fortification in Japan, neonatal dysphagia, and vaccine policy. A full week on the Incubator Journal Club.

Ben opens with the Optimized NOW trial in JAMA: symptom-based dosing reduced time to medical readiness for discharge by nearly two and a half days in NOWS infants managed with Eat Sleep Console, and allowed 65% of pharmacologically treated infants to avoid scheduled opioids entirely.

Daphna reviews a small RCT out of Turkey showing improved cerebral oxygenation and favorable vital sign trends after intranasal breast milk administration in preterm infants, adding to the growing tolerability data for this intervention.

Ben then covers the JASMINE trial, a Phase 3 RCT in Japan showing significantly better weight gain velocity with an exclusive human milk diet in very low birth weight infants.

Daphna closes with a retrospective cohort study on FEES-confirmed dysphagia in preterm infants. Of those who met criteria for evaluation, every single one had laryngeal penetration and 57% were aspirating.

Ben and Eli close the week on the quiet dismantling of vaccine infrastructure in the US and what it means for the populations in your NICU.

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

Symptom-Based Dosing for Neonatal Opioid Withdrawal: The OPTimize NOW Randomized Clinical Trial. Devlin LA et al HEAL Evaluation of Limited Pharmacotherapies for Neonatal Opioid Withdrawal Syndrome (HELP for NOWS) Consortium.JAMA. 2026 Apr 25:e265782. doi: 10.1001/jama.2026.5782. Online ahead of print. PMID: 42033722

Effect of intranasal breast milk administration on cerebral oxygenation, vital signs, and transition time to full oral feeding in preterm infants: a randomized controlled study. Yücel A, Küçükoğlu S, Konak M.Eur J Pediatr. 2026 Apr 16;185(5):272. doi: 10.1007/s00431-026-06922-6.PMID: 41986747

Growth and safety evaluation in very low birth weight infants receiving an exclusive human milk diet: a phase III randomized control trial in Japan. Mizuno K, Miyazawa T, Kondo U, Nishikubo T, Yamamoto Y, Nakano Y, Hiroma T, Ikeda K, Murase M, Jimi H, Hokuto I, Miyata M.J Perinatol. 2026 Apr 27. doi: 10.1038/s41372-026-02695-w. Online ahead of print.PMID: 42045666

Incidence and factors associated with dysphagia in infants born very preterm or very low birth weight. Reynolds J, Suterwala M, Desai S, Chiruvolu A.J Perinatol. 2026 Apr 29. doi: 10.1038/s41372-026-02701-1. Online ahead of print.PMID: 42056238

Neo News

• https://thehill.com/policy/healthcare/5689850-kennedy-dismisses-vaccine-advisors/

• https://www.washingtonpost.com/opinions/2026/01/15/rfk-jr-vaccines-autism-vicp/

• https://www.nytimes.com/2026/02/18/health/fda-moderna-flu-vaccine-mrna.html

• https://www.nytimes.com/2026/02/16/health/rfk-vaccine-manufacturers.html

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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 👇

Ben Courchia (00:00.936) Hello everybody, welcome back to The Incubator Podcast. We're back today for Journal Club. What's up?

Daphna Yasova Barbeau (00:10.722) So intense this intro this morning.

Ben Courchia (00:13.832) It's the mood of the day. We're trying to catch up. This is the first Journal Club since we came back from PAS. It's been a rough ride. People have encouraged us to share some of our mental state, so...

Daphna Yasova Barbeau (00:29.602) We had to catch up a little bit. Yeah.

Ben Courchia (00:42.906) It's very difficult when you come back from a conference. There's that ambiguity — the schedule allowed you to go, but you come back tired, you have shifts waiting for you, and you're not allowed to complain. Nobody wants to be that person who comes back from the conference exhausted.

Daphna Yasova Barbeau (01:06.966) Yeah, the people who didn't get to go have been working.

Ben Courchia (01:09.702) They don't want to hear that you're tired from your escapade to Massachusetts. You just have to take it on the chin and be miserable alone. But we both got to go — we got to commiserate during sign out.

Daphna Yasova Barbeau (01:22.892) Travel is harder than it used to be. Are we showing our age? We're almost in mid-career now. PAS is just a whirlwind. A big thank you to everybody who came to chat with us — even if not to be on the podcast — just to come and tell us about your experience, give us some ideas, chat with other listeners, get some swag. That was so much fun, but it was three full days of being on. So we're back.

Ben Courchia (02:08.828) We're back, and we're going to try to continue to partner with PAS in some way. We're having ongoing conversations, and there's no hesitation from anybody — but it is a first for everyone. PAS has never partnered with a podcast before, so we're just trying to make sure we do this carefully and correctly.

Daphna Yasova Barbeau (02:45.070) I was just going to say — we've always learned from the community. If you've been listening to the PAS coverage or any of our conference coverage and you like it, think it could be different, or have an idea, please share with us about that experience on the receiving end.

Ben Courchia (02:58.534) Yeah, absolutely. And I think that's a good segue, because the paper I'm reviewing today is a big study published in JAMA.

Daphna Yasova Barbeau (03:16.620) Did you want to do some announcements first, or did you just want to get going?

Ben Courchia (03:20.902) We'll do them tomorrow. Three minutes in — that's enough banter for today. Tomorrow there will be some big announcements. Stay tuned. We'll trickle them throughout the week. Back to my paper.

Daphna Yasova Barbeau (03:40.376) Please go ahead.

Ben Courchia (03:42.248) Published in JAMA — symptom-based dosing for neonatal opioid withdrawal syndrome (NOWS), the Optimized NOW randomized clinical trial. Going forward, we're also going to start linking to the clinical trial sessions from PAS that are available online as on-demand oral abstracts. The authors recorded a presentation of their slides — you won't be watching the live talk, but it's the same content, almost like a mock lecture. Very helpful. We'll link to that so you can go check it out.

Daphna Yasova Barbeau (05:14.070) I also want to highlight the lead author, Dr. Lori Devlin. We were able to sit down with her at the PAS Incubator booth — that's episode 439, "Can We Give Fewer Opioids to Babies with Withdrawal Syndrome?" — so listeners can follow up after hearing Ben review the paper.

Ben Courchia (05:30.534) Great. So the background — a brief overview of the situation with NOWS in the US. One infant is diagnosed with NOWS approximately every 27 minutes. And the rates are going up, not down.

When managing this condition, the Finnegan-based approach focuses on detailed scoring of the signs of withdrawal. The other approach — also evidence-based — is Eat Sleep Console (ESC), which emphasizes the functional well-being of the infant: specifically eating, sleeping, and the ability to be consoled. Both care models are still present in practice, though ESC is becoming more and more the norm based on data showing reductions in hospital stay and opioid exposure.

Non-pharmacologic care is always the initial line of treatment we want to favor for babies with NOWS. However, when babies do not adequately respond to non-pharmacologic intervention, that's when medications are needed.

The two most frequently used pharmacologic approaches are: (1) the traditional scheduled opioid taper approach, where you start medication, check scores, and taper as scores improve; and (2) a newer symptom-based dosing approach, which is really what this paper is about.

With symptom-based dosing, pharmacologic treatment is provided as a single opioid dose when a specified withdrawal threshold is met. Monitoring continues, and additional doses are given only if withdrawal severity remains above or escalates back to that threshold. The authors note that with consistent application, symptom-based dosing may decrease postnatal opioid exposure and shorten the duration of hospitalization for infants whose withdrawal is adequately controlled with intermittent dosing.

To date, there had been very limited data supporting one approach over the other — mostly retrospective data and quality improvement initiatives from single centers or small regional collaboratives. Promising, but not rigorously generalizable. That led to this trial, conducted under the National Institutes of Health's Helping to End Addiction Long-term (HEAL) initiative — specifically, the Evaluation of Limited Pharmacotherapies for Neonatal Opioid Withdrawal Syndrome, known as the HELP for NOWS consortium.

The objective: to evaluate the safety, efficacy, and generalizability of symptom-based dosing compared with a traditional scheduled opioid taper for infants with NOWS at risk for pharmacologic treatment.

Ben Courchia (10:33.660) The study design is extremely rigorous. It's a multicenter, stratified, cluster randomized clinical trial — with one cluster, the Finnegan cohort, subordinate to the other, the ESC cohort. The trial was conducted at 23 US sites between March 2024 and April 2025.

To reflect current clinical practice while acknowledging the growing use of ESC, the investigators included hospitals using either ESC or Finnegan-based care, but powered the primary analysis on the ESC cohort. The goal was to test traditional scheduled taper versus symptom-based dosing specifically within that ESC context.

Enrolled infants were at least 36 weeks gestational age at birth, had documented opioid exposure during the middle or final trimester of pregnancy, and were assessed as at risk for pharmacologic treatment — meaning at least one Finnegan score ≥ 8, or at least one "yes" for difficulty with eating, sleeping, or consoling on an ESC assessment.

Infants were randomized 1:1 to one of two sequences. Sequence 1: symptom-based approach for five months, then scheduled taper for five months. Sequence 2: scheduled taper for five months, then symptom-based approach for five months. Sites cycled through both approaches. I'd encourage listeners to look at Figure 1 for the full treatment algorithms.

During the scheduled taper approach, pharmacologic management followed the site's routine algorithm without modification — including the threshold for initiation and the weaning strategy. During symptom-based dosing, the same site-specific treatment thresholds were used, but rather than initiating scheduled dosing when the threshold was met, infants received a single opioid dose equivalent to what would have been the first dose of a taper. Withdrawal severity was then monitored, and additional doses were only given if signs of withdrawal again met the threshold.

Each time the threshold was met, another as-needed dose could be given — as long as the infant had not already received three doses in the preceding 24 hours or two consecutive short-interval doses. Short-interval doses were defined as morphine every 2 hours, buprenorphine every 3 hours, or methadone every 4 hours. If either of those thresholds was crossed, the site's scheduled opioid taper was then initiated. Throughout the trial, sites used their consistent assessment method — ESC or Finnegan — and their preferred primary opioid: morphine, buprenorphine, or methadone.

Ben Courchia (14:19.144) The primary outcome was time from birth until medical readiness for discharge in the ESC cohort. Infants were considered medically ready at the time of discharge by the medical team, or when they met the study criteria — whichever came first. The criteria for medical readiness were being at least 96 hours of age and at least 48 hours from the final dose of opioid.

Secondary outcomes included receipt of pharmacologic treatment, length of hospital stay, time to medical readiness among infants who received pharmacologic treatment, number of opioid doses, days of primary opioid administration, length of opioid treatment, and receipt of secondary medications. An important secondary outcome specific to the symptom-based group was the proportion of infants who ultimately required transition to scheduled opioid dosing for persistently elevated signs of withdrawal.

Now the results. The ESC cohort included 189 infants in the symptom-based dosing group and 194 in the scheduled taper group. Maternal and infant characteristics were similar between groups.

For the primary outcome, mean time to medical readiness for discharge was significantly shorter with symptom-based dosing: 9.2 days versus 11.6 days with scheduled taper — adjusted means ratio 0.79, p = 0.02. That's a reduction of nearly two and a half days.

For secondary outcomes: the likelihood of receiving pharmacologic treatment was 0.40 in the symptom-based group versus 0.41 in the scheduled taper group — not statistically significant. Length of hospital stay was 10.9 days versus 12.1 days, a similar trend. Among infants who did receive pharmacologic treatment, mean time to medical readiness was also shorter with symptom-based dosing: 13.1 days versus 17.56 days, adjusted means ratio 0.75.

Thirty-five percent of pharmacologically treated infants in the symptom-based group required transition to scheduled dosing for persistently elevated signs of withdrawal — a number needed to treat of 1.5 to prevent one infant from receiving scheduled opioids. There were no significant differences between groups in mean opioid doses, opioid treatment days, length of treatment, or receipt of secondary medications.

Ben Courchia (18:55.826) The conclusion: in this randomized clinical trial, symptom-based dosing decreased time to medical readiness for discharge and resulted in avoidance of scheduled opioid dosing for 65% of infants cared for with Eat Sleep Console with NOWS. For infants in the ESC setting, symptom-based dosing should be considered an effective, evidence-based approach for pharmacologic treatment.

I love when trials are well-designed, because the conclusion doesn't say "we need more data." It says: this is what we should be doing. For me, it's a no-brainer. Reducing opioid exposure makes sense. The approach pairs a single dose with rigorous, ongoing assessment and the opportunity to intervene based on symptoms. And the reduction in length of stay — nearly two and a half days — is enormous. People might say it's just a couple of days, but if someone told you your child was going to be in the hospital two and a half days longer, nobody would say that's not a big deal.

Daphna Yasova Barbeau (20:00.279) In some hospitals, that's on the pediatric ward. In many hospitals, that's two and a half more days in the ICU. We've all had that experience — a baby who needed some treatment, did great, and you're just weaning, weaning, weaning. Obviously some kids don't fit that paradigm, and the study addressed that. But I think this is a new way to look at a group of babies who already needed medication beyond Eat Sleep Console — and that shift in itself was already a change from how we managed things in training. Exciting nonetheless.

Ben Courchia (20:44.368) Agreed. This is why I wanted to start here today — it's a very important study. To me, this is the type of study we'll see in the next edition of 50 Studies Every Neonatologist Should Know. These are the studies that define practice. I'm very curious to see the long-term outcomes. We know that in utero opioid exposure has negative effects on neurodevelopment, and we know that postnatal opioid exposure does as well. What we don't know is how much of the neurodevelopmental impairment we see after in utero exposure is driven by the prenatal phase versus our own treatment after birth. If we can reduce the postnatal opioid load, what improvement might we see down the road? I'm sure they'll come out with long-term data.

Daphna Yasova Barbeau (21:59.757) It's also compounded because — for systems that have adopted ESC — Eat Sleep Console doesn't stop when we start pharmacologic treatment. Before, we'd keep babies in a closed dark room. But now it's eat, sleep, and console: pick up this baby, spend time with this baby, hold this baby. I really hope we'll find that long-term outcomes are improving significantly for these kids.

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Ben Courchia (01:09.967) we mentioned yesterday that we had some announcements to make. For today, what we can share is that we sort of overlooked our podcast anniversary. May 4th was the date.

Daphna Yasova Barbeau (01:34.997) I know. It came and went.

Ben Courchia (01:37.423) May 4th, 2021 was the first episode we released, and it's now been five years. Congrats to us.

Daphna Yasova Barbeau (01:43.852) Wow. We said it was five years and I didn't actually believe it. It has literally flown.

Ben Courchia (01:53.233) Not that we need people singing Happy Birthday in their cars right now, but we do take this opportunity every year to check in with our listeners. We're going to have a survey on our website for people to fill out — it's very quick, maybe two minutes. We just want to hear how people feel about the changes we make to the podcast. Every year there are changes, subtle but real, driven by the feedback we receive from the community. And sometimes, despite our best intentions, we implement changes that don't land well. That's exactly what warrants this continuous cycle of feedback. We really appreciate people taking a few minutes in May to fill it out.

To show our appreciation, we always have a cool set of giveaways. My goal is for every person who fills out the survey to get a prize — that's a lot of people, so it's hard to pull off, but we're going to try to send out around 20 prizes. We'll have Incubator swag, some books, signed copies of 50 Studies Every Neonatologist Should Know — great especially for trainees. And for the top prizes this year: a pair of AirPods Pro, an iPad, and an Apple Watch. Three fancy prizes, plus a lot more.

So we invite you to fill out the survey — it helps us tremendously, and Daphna and I sit down and go through every single response.

Daphna Yasova Barbeau (04:39.030) People should know it's anonymous, so we'll never know who said what. Constructive feedback is absolutely welcome. And if things are working for you, that's fine too. We also get feedback on length, type of programming, topic ideas — things we haven't done yet.

Ben Courchia (05:05.361) Topics are huge — people will say, "I want you to bring someone on for this topic." And demographics are very important to us. We're a quickly growing specialty, and we've been doing this for five years now. Many people who were listening as fellows are now attendings, so it's important for us to know what kind of audience we're catering to — though trainees and early-career folks are still very much our people.

Daphna Yasova Barbeau (05:29.152) Generationally, things are changing with podcast listeners, so we'll see.

Ben Courchia (05:35.404) That was the announcement for today. There'll be more this week — but check out the survey. Links will be on social media and on our website at the-incubator.org.

Daphna Yasova Barbeau (05:49.016) What if they're not on social media?

Ben Courchia (05:54.693) It'll be on our website too. The-incubator.org is the only place we're visible online. We will not be sending out cards.

Daphna Yasova Barbeau (06:08.416) Fair enough. Okay — I have a paper that you actually selected for me, because you knew I was going to want to review it.

Ben Courchia (06:32.304) Every article I saved in the drive, I kept thinking, Daphna's going to take this one. By the end I figured at least she can't take all of them. But there's definitely a good bunch that you would read whether or not they make it on the air.

Daphna Yasova Barbeau (06:52.814) For sure. Well, this one comes from the European Journal of Pediatrics — and I like to highlight journals people may not always have access to or be following. It comes out of Turkey and it's entitled: "Effect of Intranasal Breast Milk Administration on Cerebral Oxygenation, Vital Signs, and Transition Time to Full Oral Feeding in Preterm Infants: A Randomized Controlled Study." Lead author Adelette Ussel, senior author Murat Konak.

It's no secret to podcast listeners that I'm really excited about the future of intranasal breast milk (EBM) administration. This study was looking at the physiologic effects of that intervention specifically.

They have a nice introduction for anyone unfamiliar with the concept. A number of studies in animal models and in adults have demonstrated that the intranasal route of administration serves as an alternative pathway for stem cells, growth factors, and other pharmacological agents. It's believed that the intranasal route — through its rich vascular density — provides a biological pathway that can deliver therapeutic agents directly to the central nervous system via the olfactory epithelium and the trigeminal nerve.

Ben Courchia (08:28.401) Can I ask a quick question? On our website we have all episodes categorized by topic — cardiovascular, bilirubin, and so on. When you talk about intranasal breast milk, is that a nutritional intervention, a neurological one, or neurodevelopment?

Daphna Yasova Barbeau (08:51.318) I don't consider it nutritional, though stimulating the olfactory system does have known effects on digestion — but that's a different topic. Most existing studies are primarily focused on brain injury, intraventricular hemorrhage (IVH), and neurodevelopmental outcomes. So I think this still falls under the developmental category.

Ben Courchia (09:20.293) That makes sense — for people who don't know, they might assume it's just a new route for administering EBM. But the point is really to impact neurodevelopment. Got it, go ahead.

Daphna Yasova Barbeau (09:34.307) Exactly. The hope is that breast milk — containing stem cells and other bioactive components — is transported into brain tissue via the permeability of the nasal epithelium. There have been a number of pilot studies asking whether babies can even tolerate the procedure, and I think this study adds to that reassurance.

The aim was to look at several physiologic parameters: cerebral oxygenation, vital signs, and time to transition to full oral feeding. They also looked at daily vomiting frequency, stool frequency, and length of hospital stay.

This was an assessor-blinded randomized controlled trial conducted between June 2024 and October 2025 in the NICU of a university hospital in Turkey, involving preterm infants. The sample was 40 preterm infants — 20 intervention and 20 control.

Included infants were between 28 and 37 weeks gestational age, birth weight greater than 1,000 grams, being fed enterally, had an Apgar score greater than 8, and had available breast milk. Infants were withdrawn from the study if breast milk became unavailable, if their clinical condition deteriorated, if they required new respiratory support, received a new diagnosis of infection, or if parents requested withdrawal.

Outcome measures — cerebral oxygenation and vital signs — were recorded at four time points during each of three daily intervention periods: T0 (baseline, before intervention), T1 (5 minutes), T2 (15 minutes), and T3 (30 minutes after intranasal EBM administration). The same time points were used in the control group.

Daphna Yasova Barbeau (11:46.799) The intervention protocol was adapted from prior intranasal EBM studies. The intervention group received 0.2 mL of fresh breast milk via the intranasal route three times daily for three consecutive days — 0.1 mL per nostril per administration. The control group received otherwise identical standard protocolized care, without the EBM.

Baseline characteristics were similar between groups, suggesting good homogeneity.

For cerebral oxygenation: there were no statistically significant differences between groups at baseline (T0). But at T1, T2, and T3, cerebral oxygenation levels in the intervention group were significantly higher than in the control group. There was also a significant group-by-time interaction, with values in the intervention group showing a greater change over time. They have some nice graphs illustrating this clearly.

For oxygen saturation (SpO2): no differences at baseline, but a significant group-by-time interaction showed greater changes in mean SpO2 in the intervention group. Looking at the tables, you can see that babies in the intervention group trended upward in oxygenation over time, while the control group remained stable or even showed a slight decrease.

For heart rate: no significant differences at T0, but the group-by-time interaction was significant. In the intervention group, mean heart rate decreased slightly over time — from roughly 153 to around 151 — whereas the control group showed an increase in heart rate over time.

For respiratory rate: no significant difference at T0 or T2, but at T2 and T3, measurements were statistically lower in the intervention group than in the control group. The group-by-time interaction for respiratory rate was also significant, with more variation seen in the intervention group.

Mean time to full oral feeding and length of hospital stay were similar between groups — not statistically significant. There were also no significant differences in vomiting or stooling frequency.

Daphna Yasova Barbeau (15:58.179) The study concludes that intranasal breast milk administration may be a potential intervention to increase cerebral oxygenation in preterm infants. The vital sign data also supports tolerability — no major desaturation or bradycardia events, and potentially some short-term physiologic benefit.

Obviously it's a small study and the timeframes are short. But for those who were genuinely concerned that babies wouldn't tolerate this — that they'd Brady or desat with intranasal administration — this is a reassuring data point. The cerebral oxygenation findings are interesting, though we're still learning a lot in that space.

What excites me overall is the growing body of literature on intranasal EBM — a potentially easy, quick, and inexpensive intervention. I say that with some caution, because fresh breast milk at the bedside is still a challenge in many units. But thoughts?

Ben Courchia (17:48.975) I do believe the intervention has merit. But I'm wondering — physiologically it makes sense, and we do use it in our unit — but what are we actually expecting in terms of measurable outcomes? I feel like sometimes we're trying to study this and hoping to show that 22-weekers survive on room air. It's a valuable intervention, but I'm not sure we're equipped today to measure its true impact. This study does a nice job targeting something that could realistically be affected — vital signs, cerebral oxygenation. But at some point, the question becomes: how much more do we need to study this before we just do it?

Daphna Yasova Barbeau (18:42.851) Well, I think that's exactly the point. People still say, "I can't try this — this baby isn't stable enough, they won't tolerate it." I hope this data gives those clinicians permission to at least trial the intervention. Did I think it was going to change time to full feeds? No. Did I think it was going to change feeding parameters the way oral colostrum does? No. But establishing these safety parameters matters. And if babies are showing improved stability after each of these touch-time interventions — if we're reducing those post-care destabilization events — that matters. All care is brain care, and we know those daily decompensations are not good for babies.

Ben Courchia (19:59.229) It's a genuine curiosity question for me. It's like music therapy in the NICU — stop measuring Bayley scores at two years old. You may not detect the signal with that instrument. That doesn't mean the intervention has no benefit. It's just that at some point, you have to acknowledge the limits of your measurement tools. Very interesting nonetheless.

Daphna Yasova Barbeau (20:25.305) Thanks for finding it for me.

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Ben Courchia (00:26.959) I'm going to review a paper recently published entitled "Growth and Safety Evaluation in Very Low Birth Weight Infants Receiving an Exclusive Human Milk Diet: A Phase Three Randomized Controlled Trial in Japan."

First author is Professor Katsumi Mizuno from Japan. In the first part of today's Journal Club, I will review the paper and get into the data. After that, we will have a unique opportunity to speak with Professor Mizuno directly from Japan. He will be joined by Dr. Melinda Elliott, who is the CMO of Prolacta Bioscience. It will be very interesting to dive deeper into the motivations behind the trial and what some of the ramifications of this study are for the use of human milk fortifiers in Japan.

Without further ado, let me start with the introduction, which I think is quite interesting. It gives us a fascinating glimpse into the world of neonatology in Japan.

Japan is one of the world leaders in survival rates of extremely preterm infants, with survival rates close to 80 to 90% for babies born between 22 and 24 weeks of gestation. As of 2022, they have incredibly low rates of necrotizing enterocolitis (NEC), reported as low as 2% in the introduction of this paper. That alone is what piqued my interest. I am always eager to learn how things are done in Japan given these remarkable outcomes.

The authors highlight the gap this study is here to address. Despite these exceptional outcomes, there is not yet wide availability of human donor milk in Japan, and there is reportedly great hesitancy to feed and fortify infants with cow milk-based products early, often leading to poor growth outcomes. This gap is being addressed through efforts to expand access to donor breast milk. The Japan Human Milk Bank Association was established in 2017 to facilitate donor milk availability, followed by the Nippon Foundation Human Milk Bank, which opened in 2022. As of 2024, 114 NICUs in Japan are able to use donor breast milk, representing approximately 60% of NICUs in the country. In NICUs where donor milk is not yet available, a shortfall of mother's own milk is filled with whatever is available, whether that is preterm formula or milk supplied by another nursing mother in that NICU. This is something we read about in the early days of neonatology and tend to forget is still a reality in some parts of the world.

The paper also references recommendations from both the American Academy of Pediatrics (AAP) and the Japan Pediatric Society (JPS) advocating for fortification of mother's own milk or pasteurized donor milk with protein, calories, minerals, and vitamins for very low birth weight (VLBW) infants to ensure optimal nutritional intake. At present, only cow milk-based fortifiers are available for human milk fortification in Japan. Professor Mizuno will tell us more about how that transition actually came about later in the episode.

At the time of the study, two fortifiers were available as powdered multi-nutrient fortifiers that do not contain iron or vitamins. In consideration of these limitations, something very notable is happening in NICUs in Japan: physicians tend to avoid cow milk-based fortifier in VLBW infants, instead opting to give unfortified mother's own milk or donor breast milk when available. Similarly, when mother's milk is unavailable, many physicians in Japan will opt to wait for donor breast milk rather than use cow milk-based infant formula, which has led to a prevalence of fasting practices among lower birth weight infants. Published data shows that among Japanese physicians, 15% applied fasting to infants with a birth weight less than 750 grams, and sometimes 20% of providers will apply fasting to babies born before 500 grams.

An exclusive human milk diet (EHMD) is defined as human milk with the addition of a human milk-based fortifier and no added cow milk-based substances. The use of a human milk-based fortifier, rather than a cow milk-based fortifier, has been associated with several advantages in peer-reviewed literature, including earlier establishment of enteral nutrition, reduced duration of parenteral nutrition, and shorter hospitalization. Additionally, compared to a cow milk-based diet, human milk-based fortification has been reported to reduce mortality and common complications of extremely preterm infants including NEC, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and late-onset sepsis. Late-onset sepsis is particularly significant in this context, as it is the leading acquired cause of neonatal death in Japan.

The objective of the JASMINE trial, the paper we are reviewing today, is to assess the safety and growth efficacy of an exclusive human milk diet compared to the current standard diet in very low birth weight infants in Japan.

The study is designed quite rigorously. It is a multicenter, randomized, open-label, phase three trial conducted at 11 centers in Japan between October 2021 and March 2023. Participants were randomized to receive either an exclusive human milk diet or a standard diet, defined as mother's own milk or donor breast milk fortified with cow milk-based fortifier, or cow milk-based preterm formula. This feeding assignment extended from the first feeding after birth through to a corrected gestational age of 34 weeks.

The authors are upfront about the inclusion of cow milk-based formula in the control group, acknowledging it could be considered a limitation. However, formula use remains standard practice in Japan in the setting of mother's own milk shortage. Donor milk is not yet considered standard of care there and is still regarded as investigational, which is quite striking. That said, all 11 centers participating in the study did have access to donor breast milk.

Enrolled infants were very low birth weight, meaning less than 1,500 grams at birth, born before 31 weeks of gestation, within the first 10 days of life, and were either receiving an exclusive human milk diet or were NPO prior to enrollment. Parental consent was obtained before the infant reached a designated intake threshold. Standard exclusion criteria applied, including known lethal chromosomal anomalies, gastrointestinal malformations, and significant congenital anomalies.

Regarding the feeding protocol: VLBW infants were randomized into two groups. The exclusive human milk diet group received mother's own milk and/or donor breast milk with human milk-based fortifier. The standard diet group received mother's own milk and/or donor breast milk with cow milk-based fortifier, or cow milk-based preterm formula. Donor milk in the standard diet group was typically administered up to a feed volume of approximately 100 mL per kg per day before transitioning to formula.

Starting enteral feed volumes for both groups were trophic, at 10 to 20 mL per kg per day divided every two to three hours. Total parenteral nutrition (TPN) was initiated within a few hours after birth and discontinued once enteral intake reached 120 mL per kg per day, provided glucose levels were stable. Feed volumes were increased by 10 to 30 mL per kg per day until reaching the target total feed volume of 160 mL per kg per day. Fortification with human milk-based fortifier began at a feed volume of 50 mL per kg per day, with further dosing adjustments based on individual infant characteristics.

The study endpoint was reached when the infant transitioned at 34 weeks and one day corrected gestational age, at which point they were gradually transitioned off the exclusive human milk diet over a minimum of three days, with adjustments allowed based on clinical judgment. In the standard diet group, fortification with cow milk-based fortifier started at half the standard recommended dose once feedings reached 50 to 100 mL per kg per day. The dose was increased to the full standard dose after a few days, provided there was no abdominal distension or feeding residuals. For VLBW infants weighing less than 1,000 grams, physicians were encouraged to initiate fortifier earlier, at 50 mL per kg per day.

Now let me walk through the outcomes. The primary efficacy outcome was growth, specifically non-inferiority of weight gain velocity calculated using the Patel exponential method. Secondary outcomes included weight z-score change, length and head circumference velocity and z-score changes, days from birth to full feeds, number of days on antibiotics after 72 hours of life, chemistry parameters, and comorbidities associated with prematurity. Treatment-emergent adverse events (TEAEs) were defined as adverse events that began or worsened after the start of the trial. A morbidity and mortality index was also constructed to evaluate between-group differences using incidence rates of common comorbidities including late-onset sepsis, NEC, BPD, severe ROP, and mortality.

On to the results. 147 infants were randomized: 77 in the exclusive human milk diet group and 70 in the standard diet group for the intention-to-treat analysis. There were slight discrepancies in the baseline characteristics between groups. Most notably, the gestational age of infants in the exclusive human milk diet group was slightly lower than that of the standard diet group. That difference was not statistically significant, but when diving into the data, the number of 22 to 23-week infants was larger in the exclusive human milk diet group. Mean birth weight was also numerically lower in that group: 908.1 grams versus 947.6 grams. Again, not statistically significant, but worth noting.

For the primary outcome: the mean weight gain velocity in the exclusive human milk diet group was 13.44 grams per kg per day in the intention-to-treat analysis, and 14.3 grams per kg per day in the per-protocol set. In the standard diet group, mean weight gain velocity was 11.96 grams per kg per day in both the intention-to-treat analysis and the per-protocol set. Non-inferiority was demonstrated, and on the subsequent superiority analysis, the exclusive human milk diet group was statistically significantly superior in terms of weight gain velocity. The difference of 13.44 versus 11.96 grams per kg per day reached statistical significance with a p-value of 0.006, in both the intention-to-treat population and the per-protocol set.

Looking at mean weight gain from the day of birth weight regain through 34 weeks, the difference was also statistically significant: 17.3 grams per kg per day in the human milk diet group versus 15.48 in the standard diet group, p-value less than 0.01.

For secondary outcomes: mean changes in weight z-scores from the Fenton curves from birth to the end of the feeding period were significantly improved in the exclusive human milk diet group compared to the standard diet group. The same trend was observed in mean length gain velocity and length gain z-score change, both before and after adjusting for gestational age.

Overall, 34 infants in the exclusive human milk diet group and 33 infants in the standard diet group achieved full feed volume as defined by the study, which was 160 mL per kg per day. The exclusive human milk diet group reached full feeds significantly faster, with a mean of 20 days compared to 26 days in the standard diet group. A note on why only about half of each cohort met this specific threshold: per their protocol, some infants required fluid restriction and were maintained between 130 and 160 mL per kg per day. For the purposes of the study, full feeds were only counted if the infant was unrestricted and reached exactly 160 mL per kg per day. That nuance is addressed in the supplementary material for those who want to explore it further.

For clinical and safety outcomes: a significantly lower number of antibiotic days was observed in the exclusive human milk diet group, with a mean of 17.1 days versus 17.6 days after 72 hours of life. A small but statistically significant difference of approximately half a day. There were no significant differences between groups in feeding intolerance events.

There was a numerically higher proportion of infants in the human milk diet group who experienced TEAEs compared to the standard diet group, though this difference did not reach statistical significance. There was only one case of NEC in the entire trial, and that infant was in the exclusive human milk diet group. Given the very small numbers, the study was not powered for this outcome and no meaningful conclusion can be drawn from it.

TEAEs resulting in death were experienced by 3.9% of the exclusive human milk diet cohort, all at gestational ages of 22 to 23 weeks and 24 to 25 weeks, from sepsis and septic shock. In the standard diet group, TEAEs resulting in death were experienced by 2.9% of the cohort, at gestational ages of 22 to 23 weeks and 26 to 27 weeks, from persistent pulmonary hypertension of the newborn (PPHN) and Pseudomonas aeruginosa meningitis. None of these events were considered treatment-related, and again, the more immature profile of the exclusive human milk group is likely a contributing factor here.

In the safety analysis, 78% of the exclusive human milk diet group experienced at least one event component associated with the morbidity and mortality index, compared with 68.6% in the standard diet group. No significant differences were seen in BPD or ROP. Morbidity and mortality rates decreased consistently with increasing gestational age in the exclusive human milk diet group, a trend that was not as clearly paralleled in the standard diet group. The proportion of infants at 22 to 24 weeks was again notably higher in the exclusive human milk diet group, representing 13% of that cohort compared to only 7% of the control arm. Finally, there were no significant differences between diet groups in electrolytes, mineral concentrations, or nutritional lab parameters.

In terms of conclusions, the authors state that this study confirms the safety and efficacy of a human milk-based fortifier and an exclusive human milk diet, suggesting it is a viable nutritional management strategy for Japanese VLBW infants that facilitates better growth outcomes without heightened safety risk.

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Daphna Yasova Barbeau (00:15.310)I just wanted to mention the Gravens Conference. We've talked about it before, and they wanted to highlight that they are moving both the date and location this year. It's June 16th to 18th, with a pre-conference day on June 15th entitled Reimagining the NICU 3.0. It's located at the University of Notre Dame. The conference title this year is Sensitive Issues in Sensational Times. That should get people excited.

I've shared before that I love the Gravens Conference. It's a truly multidisciplinary conference covering trauma-informed care, family-centered care, and developmental care. There is so much to learn beyond your specific area of expertise in neonatology. Whether you focus on hemodynamics, bronchopulmonary dysplasia (BPD), the patent ductus arteriosus (PDA), nephrology, or anything else, the conversations about how we interact with families, with each other, and with babies will optimize everyone's work.

There is a discount code for Incubator listeners. You can register either in-person or virtually this year. The discount code is SPECIAL10 to receive a 10% discount.

Ben Courchia (02:08.762) Thank you to the Gravens organizing committee for making that happen for our listeners. Budgeting for conferences is not easy, so any discount is always welcome.

Daphna Yasova Barbeau (02:25.454) And credit to them this year. They offered scholarships for trainees, for nurses, and for therapists. And they are really on the forefront of providing paid conference registration, transportation, and lodging for parents to attend. Really impressive.

Moving along, I have an article from the Journal of Perinatology entitled "Incidence and Factors Associated with Dysphagia in Infants Born Very Preterm or Very Low Birth Weight." This comes out of Texas, lead author Jenny Reynolds and senior author Arpita Chiruvolo.

We did a trivia night with Dr. Brown's and had a full segment on feeding in the NICU. It was striking how little people understood about feeding, even though we are all prescribing it and discussing it on rounds every day. So I think it's important to highlight the prevalence of neonatal dysphagia. Difficulty with feeding and swallowing has been reported to range from 23% in preterm infants, 28% in extremely low birth weight infants, and 27 to 46% in extremely preterm infants. These feeding difficulties can lead to long-term adverse outcomes and further complicate already medically complex babies, impacting both health and development. Feeding is not just nutrition and not just developmental care. It is really both.

How do we assess feeding in the NICU? It typically begins with a clinical feeding evaluation including medical history, oral motor examination, and feeding and swallowing skill assessment. This is typically done by bedside nurses and speech-language professionals. However, clinical feeding evaluation may not fully predict aspiration. Two additional instrumental assessment tools exist: the video fluoroscopic swallow study (VFSS) and the flexible endoscopic evaluation of swallowing (FEES). These are the two most common instrumental tools used in infants.

The VFSS provides real-time imaging of the oral, pharyngeal, and upper esophageal phases of swallowing as the infant consumes barium liquids in a sidelying position on an inclined wedge or upright in a chair, directly evaluating disruptions in swallowing physiology. The FEES is also available for evaluating pharyngeal swallowing in both breastfed and bottle-fed infants. Advantages of FEES in the preterm population include no radiation exposure, the ability to be done at bedside, the use of breast milk or formula rather than barium, direct visualization of anatomy, and a longer assessment window that allows for evaluation of fatigue. Sometimes babies do well for the first few minutes and then begin to make errors as they tire. FEES also allows you to see the response to treatment strategies in real time, such as whether thickening feeds or changing the bottle makes a difference.

Daphna Yasova Barbeau (06:30.434) The purpose of this retrospective cohort study was to look at the incidence of dysphagia confirmed by FEES in the NICU, not just by clinical description. They also wanted to examine maternal characteristics and infant morbidities associated with dysphagia, and look at the frequency of therapeutic interventions at discharge in very preterm infants (less than 32 weeks) or very low birth weight infants (less than 1,500 grams).

It was a retrospective cohort study of infants born very preterm or very low birth weight between 2019 and 2021, conducted at an urban level four maternity hospital. Their NICU cares for approximately 125 very preterm or very low birth weight infants per year. All infants received a clinical bedside evaluation and follow-up interventions from either a speech-language pathologist (SLP) or an occupational therapist (OT). In many units, one type of therapist provides many types of intervention, and it is worth noting that here.

The neonatal therapist completes the clinical bedside evaluation during bottle and/or breastfeeding based on the mother's feeding goal, once the infant begins oral feeds. Oral feeding is reassessed at least weekly based on individual needs. Per their protocol, if an infant continues to exhibit feeding difficulties or poor feeding progression around 38 weeks post-menstrual age (PMA), the team proceeds with a FEES to obtain more detailed information about dysphagia. Criteria for performing FEES included being 38 weeks PMA or above, consistent signs of feeding difficulty despite compensatory strategies such as positioning, pacing, or an extra slow-flow nipple, regression or plateau in oral feeding progress, baseline physiologic stability, and respiratory support of no more than 2 liters per minute of nasal cannula. In their unit, the FEES is performed by an SLP as the endoscopist and a second neonatal therapist as the feeder during the exam.

Ben Courchia (09:06.222) And FEES stands for flexible endoscopic evaluation of swallowing.

Daphna Yasova Barbeau (09:09.858) That's right. That's why you need multiple hands for this evaluation. Upon completion, an ENT reviews the FEES video to assess upper airway anatomy and physiology and make further recommendations if needed.

Diagnosis of dysphagia on FEES was made if the infant had either laryngeal penetration with or without aspiration on thin liquids. To clarify: laryngeal penetration is defined as passage of material into the laryngeal vestibule that does not pass below the vocal cords, whereas aspiration is defined as entry into the trachea below the level of the vocal cords.

On to the results. During the two-year study period, 190 very preterm or very low birth weight infants were admitted to the NICU. After excluding 32 infants, 158 were included in the study. All 158 received the bedside clinical exam by the certified neonatal therapist per protocol. Of those 158, 40 infants (25%) met the criteria for FEES evaluation at around 38 weeks PMA, with documented consistent signs of feeding difficulty with regression or plateau despite feeding strategies.

All 40 infants with a FEES-confirmed diagnosis of dysphagia were compared to 118 infants with no dysphagia as the control group. There were no significant differences in maternal characteristics between the two groups. Median gestational age and birth weight were significantly lower in infants who developed dysphagia. Looking at Table 2, the gestational age range in infants with dysphagia was 25.8 to 29.3 weeks (mean approximately 28 weeks), versus 28.4 to 31 weeks (mean approximately 30 weeks) in infants without dysphagia.

Logistic regression adjusting for birth weight and gestational age showed that infants with dysphagia had an increased incidence of other morbidities, including BPD and intracranial hemorrhage. Multiple regression analysis adjusting for both birth weight and gestational age showed that dysphagia was significantly associated with higher central line days and longer hospital length of stay.

The median PMA at the time of FEES was 38.4 weeks. Laryngeal penetration was detected in all 40 infants who underwent FEES. Among those, tracheal aspiration was detected in 23 infants (57%). Three infants (approximately 7.5%) were discharged home with a G-tube, and 38 infants (95%) required thickened feeds upon discharge.

Daphna Yasova Barbeau (13:40.722) I think this data is alarming. At 38 weeks, babies who were showing clinical signs of feeding difficulty were found to have laryngeal penetration on FEES. Nearly 60% were aspirating. That is potentially very clinically significant.

One thing I was actually pleased to see is that approximately 7% were discharged with G-tubes, which means the team was able to intervene in the vast majority of babies and get them to where they needed to go without a G-tube. That is exciting. But 95% required thickened feeds at discharge, which is worth noting given that thickened feeds have fallen in and out of favor.

I wonder how many babies would benefit from these kinds of assessments but are simply not getting a FEES to characterize their dysphagia. I also think it would help families. We often say "your baby just isn't there yet" or "they haven't figured it out yet." But what specific skill is your baby actually struggling with? What are the risks? And for the bedside nurses, parents, or whoever is feeding, this reframes the conversation. It is not about just making the baby do it. This baby has a medically documented incoordination. I think having more information would be valuable for everyone on the team, and raises the question of whether we are continuing to push babies who may actually be aspirating.

Ben Courchia (14:24.272) It is a very interesting study. It is rare that we review a retrospective study, but this raises a real conundrum in the NICU. Setting aside the potential for residual confounding, what strikes me is that we almost never document dysphagia. I am becoming a bit of a note police in our unit about this. There are babies who clearly have dysphagia, and I wonder if we actually named it and called it what it is, whether that would prompt us to pursue a modified barium swallow study or FEES earlier. In this paper, FEES was done at around 38 weeks PMA, but I feel like in our practice we tend to get there much later. And I wonder whether that happens because we wait until we are frustrated with lack of progress rather than acting on an earlier naming of the problem. Would we order it sooner if the word dysphagia appeared in every daily note?

Daphna Yasova Barbeau (15:43.055) Exactly. Part of it is also whether we are treating dysphagia as expected or normal for this type of baby given their degree of immaturity. And there is some degree of that. Some babies just figure it out. Others do not. But labeling it and saying it is not that your baby is lazy or not getting it right, they have a medical incoordination, I think that helps everyone on the team. It changes the conversation from "just keep trying" to asking: do we keep pushing a baby who may be aspirating with every trial, or do we find out early what the risk actually is and intervene appropriately? There are always those babies who have a real setback when oral feeding is advanced too aggressively. This will definitely make me rethink those babies who are near term corrected and still struggling.

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Eli (00:01.857) I'm speaking very fast because we're at the tail end of our recording session here. Ben just told me he has a meeting he's going to run to. So we're going to talk at 1.3 speed and then you guys are going to zoom it up even further. You are going to get delirium and maybe you will get vertigo from listening to this podcast. Let's dive into it. This week's episode, we are going to talk about something we have never talked about on Neo News before: vaccines. Just kidding. We talk about vaccines all the time, but it's a moving target. There is ever more news on vaccines. We're going to cover two recent developments here that we think you guys need to be aware of. The first is...

Ben Courchia MD (00:42.19) Ha.

Eli (00:57.243) ...we're a little bit delayed on this. This is admittedly something that has gotten pushed a little bit on our podcast recording schedule, but I think it is still relevant to talk about and something that we will continue to see the consequences play out. And that is the upheaval of the Vaccine Injury Compensation Program. When you think about the way the government is structured, obviously there are the government appointees and then lots of government staff. There are also lots of advisory committees and commissions, and other structures on which we depend to bring in experts who are not formally government employees, but to advise the government in all the things the government does. One of those advisory commissions is the Advisory Commission on Childhood Vaccines. This commission reviews issues related to the Vaccine Injury Compensation Program, the VICP, and makes recommendations to the Department of Health and Human Services Secretary around thinking through that program. The Vaccine Injury Compensation Program has long been targeted by Secretary Robert F. Kennedy Jr. He says that this is something we need to expand, which is interesting because this government has been so focused on cost-cutting. What pundits say is behind the effort to expand this program—which is very complicated and basically gets money from vaccine makers to compensate patients if and when certain very rare consequences happen inevitably from vaccines that we know statistically will happen in very low numbers—is that Kennedy says we need to include a lot more kinds of vaccine injuries and reimburse a lot more people. What pundits say is that this basically will bankrupt the drug companies and dissuade them from looking into vaccine prevention because it would become so expensive and there will be so many claims of injuries that it is a quiet and oblique way of targeting vaccines by pushing drug makers out of the industry.

Eli (03:15.787) What this article in The Washington Post says, which was also covered by The Hill, is that Kennedy understands he can take vaccines away from Americans if he makes vaccines unprofitable. If the Vaccine Injury Compensation Program is overwhelmed by too many claims and goes bankrupt, manufacturers become financially liable. Facing new risks of lengthy and expensive litigation, they will stop selling vaccines in the United States. Ben, what did you think of this series of actions around the advisory committee and the bigger political agenda here?

Ben Courchia MD (04:07.758) I think this is the cleverest way of solving the vaccine problem as they have identified it by just making it not profitable. In the NICU, we know very well that once you make something not profitable, it just stops being made. What is currently going on with the new Moderna mRNA flu vaccine that was submitted for review and was denied review is just an example of that. Trying to undermine this vaccine industry from its foundation so that the problem is no longer whether people decide to get vaccinated, but just the fact that maybe vaccines are not going to be rolled out anymore. There is truly a dedication by the administration to really undermine the safety and efficacy of vaccines. They're trying to say everything at once, but it's clear in the way the administration goes about its business that they are strong proponents of the fact that vaccines are harmful and should not be readily accessible by everybody. This has to be made clear. This particular iteration is really something to be careful about. The article is very good in quoting Secretary Kennedy saying they would not be taking vaccines away from anybody. But you don't have to take vaccines away from anybody if they're just not there to take. There is a desire to look into these conspiracy theories of associations between vaccines and specific diseases in order to really undermine public trust in a preventive healthcare measure that has been proven and has saved millions and millions of lives.

Ben Courchia MD (06:30.016) The article mentions how the Centers for Disease Control and Prevention, the CDC, has made changes to the website to change the claim from 'vaccines do not cause autism' to something saying that this claim is not evidence-based because studies have not really ruled out the possibility. I think that this is just so damaging. We just have to be prepared. If you are listening to this, I'm assuming we've all started seeing this. Working in Florida, a lot of people do not even take the hepatitis B vaccine at birth anymore. I would not be surprised if we see a complete unwinding of vaccination in the pediatric population because of the risks. It is truly terrifying. This particular iteration of really just not making this a financially viable option is going to undermine immunization for millions in the US and abroad as well.

Eli (07:37.343) I think you said it in terms of two things. First, this being a brilliant political strategy. You can say a lot of things about this administration, but they are genuinely creative in the ways they are pursuing their political agenda.

Ben Courchia MD (07:57.326) I believe that this is probably the most damaging critique of the administration, to say they're a bunch of idiots. They're not. The way in which this is unfolding is quite clever. We tend to dismiss somebody if we say this person is not smart enough. Somebody who is not smart enough to swing a bat at you, you're not too worried that the bat is going to hit you in the head. This is not the case here. The way they're undermining just very meticulously this whole establishment that has been there for decades is quite alarming.

Eli (08:33.623) If you ever wondered how politically savvy they are, take a gander and read a nice little document called Project 2025. It's a nice little piece of literature you can read that really lays out how creative and thoughtful this administration is in terms of pursuing their agenda, like it or not. They are effective. There is something incredibly devious about testifying before Congress at your appointment hearing and saying you're not going to take away any vaccines from anybody, including saying that to a GI doctor who is a critical swing vote. And then what you do is you don't take vaccines away from people. You just make sure that vaccines don't exist on the market. I just got back from Nepal. In Nepal, there are lots of electric cars because the government subsidizes them, which is a beautiful thing. In particular, there are a lot of electric cars that come from China and India, which are fabulous, incredible, amazing cars. The car that we drove in all across the country, including many hours on unpaved roads—Ben, I've never been so grateful for paved roads. Anyway, we spent many hours driving on unpaved roads.

Ben Courchia MD (10:01.314) Ha ha ha.

Eli (10:05.309) ...in what's called a BYD, Build Your Dreams, which is a Chinese electric car company. This car toughed its way out through hundreds of miles of unpaved roads. I'm like, why do we not have this car in the US? It's cheap. It's amazingly effective. It's a pretty beautiful thing. It's got lots of lights. It's got its own little Siri thing that interrupts your conversation half the time because it thinks it's talking to you.

Ben Courchia MD (10:29.582) Alright.

Eli (10:32.246) The reason that this car doesn't exist in the US is because we have tariffed the living heck out of foreign vehicles. I think we've banned specifically electric cars from China, as opposed to electric cars from other places. In that situation, nobody has taken BYDs away from American customers. BYDs just don't exist on the market because we've erected such incredible obstructions to trying to get them over that it is just not worth it or not possible for China to send these vehicles. That is the same approach that we are now taking with vaccines in terms of making them economically unsustainable. The other way in which this administration is targeting the economics of vaccines is through the measures that it is taking through the regulatory agencies, namely the Food and Drug Administration, around how they are approaching vaccine approvals. More recently, in the beginning of February, top Food and Drug Administration officials were all set to review Moderna's new flu vaccine. Top FDA official Vinay Prasad, who is a physician himself and a very controversial physician, overruled the agency's lifelong staffers and refused to accept the application outright for this new vaccine. There was a lot of back and forth about this. The FDA has since this past week said they are going to review this product. But suffice it to say, when you read about how industry is responding to the FDA arbitrarily deciding they're not even going to review new vaccines—to say nothing of whether or not they approve it in the end, but they're going to say, 'We're not even going to accept applications for review'—you're basically making the business model of vaccines completely financially unfeasible. You will never be able to sell the thing, or the trials that you'll have to do to get it through the FDA are so complex that you're going to spend gazillions of dollars that you can't justify from an economic perspective producing vaccines.

Eli (12:54.615) So this is another thing to watch because again, it is the slow, quiet way to make sure that people don't get vaccines.

Ben Courchia MD (12:57.856) These companies are not ideologically driven. If the business end is not there for them, it's an automatic halt and stop. They're not going to continue creating something for global health and humanism. That's not how they function and how they pay their employees. So it will come to a crashing halt.

Eli (13:24.171) That's it. Homo economicus, Econ 101. They're just going to move on to other things. Maybe they'll just sell peptides. Peptides are doing great. People love peptides.

Ben Courchia MD (13:26.178) Mm-hmm. Yeah, that's exactly right.

Ben Courchia MD (13:33.518) Specifically when we're talking about pediatrics, remember that we have one of the smallest patient populations compared to adults. It's always pediatric drugs that get cut. We need special kinds of funding to find medications for children and neonates. The Moderna vaccine we're talking about is for adults 55, 65 plus. This is unprecedented.

Eli (14:07.427) You say, 'Well, we can't get a flu vaccine. That stinks. The flu is terrible this year, we can't get a flu vaccine.' But this is a much bigger story. Moderna is not going to go out of business, but The New York Times has looked at lots of...

Ben Courchia MD (14:19.053) Yeah.

Eli (14:25.569) ...companies that are going out of business that produce vaccines, lots of companies that have laid off employees, they've stopped trials on vaccines. Moderna specifically has stopped trials around a number of vaccines. They've halted vaccines for Epstein-Barr virus, which of course is something that many people have and have consequences of. We think about it all the time in the NICU in terms of having consequences for neonates. They've stopped...

Ben Courchia MD (14:37.271) Mm-hmm.

Eli (14:52.011) ...vaccines for other sorts of conditions, herpes, chickenpox, shingles, more things that we think about in our patient population. This isn't just about the flu vaccine. This is about the economic consequences of the precedent of saying randomly, 'Actually, we're just not even going to review this thing.' To say nothing of the smaller companies that are shutting down, to say nothing of entire lines of technology. Moderna is known because they invested in mRNA vaccines, which was a technology that was theoretical really until the COVID pandemic. And then obviously showed immense success in terms of mRNA vaccines that rolled out during the COVID pandemic. So not only are you going to shut down specific vaccines, not only are you going to shut down companies, but entire realms of scientific enterprise in terms of mRNA technology now are also being targeted on the chopping block. In fact, the federal administration has said they're not even going to fund mRNA technology, which is not just a vaccine question. mRNA could potentially have lots of other uses, and yet we're just not even going to fund it.

Ben Courchia MD (15:55.97) Just so that we leave people with more content to read, you shared with us a Rolling Stone article about these emails that were sent back and forth between HHS and this group out of Denmark who is trying to do a study on the hepatitis B vaccine. It's quite appalling. It gives you a glimpse into how deliberate they are in picking their moves in order to sustain a very deliberate agenda. It's in Rolling Stone. The article is called 'HHS Gives $1.6 Million Grant to a Controversial Vaccine Study. These Emails Show How That Happened.' Fascinating read, highly recommended.

Eli (16:38.871) Highly recommend, obviously. I have a personal dog in this fight. I'm a contributor at Rolling Stone. Obviously, I think very highly of our coverage. I should say the author of this is Katherine Eban, who is one of my very dear mentors, very close friends, someone I've admired for years and years now, and is my partner in crime over at Rolling Stone. My editor edited this thing, which is why she's not editing my stories. So she's editing Katherine's stories, which I have feelings about anyway. We will cover this one in a subsequent...

Ben Courchia MD (16:49.262) We'll cover this one. Yeah, because it does provide substance to the argument that things are being done deliberately and that there is a plan. There's a plan for how this unfolds. It is not just like a bull in a china shop really trying to fix a problem but breaking a few items along the way. It's deliberate. So take a look at that.

Eli (17:08.825) But worth reading in the meantime.