#434 - [Journal Club] - 📌 Could Intranasal Breast Milk Be the Next Adjunct Therapy for HIE?

In this Journal Club episode, Daphna presents the F-NeoBright trial — a pilot feasibility and safety study out of Hungary exploring intranasal fresh breast milk administration in neonates with moderate to severe HIE undergoing therapeutic hypothermia. With so few adjunct therapies available beyond cooling, the idea of harnessing breast milk's rich bioactive components — including neurotrophic growth factors, cytokines, and multipotent stem cells — to support the developing brain is both compelling and refreshingly low-risk. Daphna walks us through the protocol, the feasibility outcomes, and why 100% of approached families consented, including those who had never planned to breastfeed. Sometimes the simplest intervention really is the right one!

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F-NEO-BRIGHT: feasibility and safety of intranasal fresh breast milk in neonatal encephalopathy. Tarjanyi E, Jermendy A, Szabo M, Brandt FA, Szasz B, Nyilas N, Meder U.Pediatr Res. 2026 Mar 3. doi: 10.1038/s41390-026-04847-2. Online ahead of print.PMID: 41776367

Transcript

Ben Courchia (00:00.823) Hello everybody, welcome back to another episode of Journal Club. Daphna, good morning. How are you?

Daphna Yasova Barbeau (00:05.336) Good morning. I'm good. I'm very excited about the paper I'm going to present today. I've been waiting for this one.

Ben Courchia (00:11.403) You are getting your dream lineup of neonatal neurology topics this week.

Daphna Yasova Barbeau (00:22.798) Yes, I'm lucking out. That's right.

Ben Courchia (00:26.711) For the foreseeable future. But these are important studies, and I think people need to understand that we do have an editorial process in place — it's not just articles we pick randomly, but ones that are going to impact our field. So today you're talking about the F-NeoBright trial, which — not the best acronym. It's a bit of a stretch.

Daphna Yasova Barbeau (00:48.258) Yeah, it's a stretch. It's a stretch.

Ben Courchia (00:55.319) I'm happy you said that. I'm going to present another article later this week with a similarly stretched acronym, so I'm not just being critical.

Daphna Yasova Barbeau (01:01.678) Props to people for trying though. When we talk about the article, having common shared language helps.

Ben Courchia (01:11.947) F-NeoBright: Feasibility of Neonatal Intranasal Breast Milk Impact on Brain Growth in HIE Therapy.

Daphna Yasova Barbeau (01:19.022) So this is published in the Society for Pediatric Research and comes to us out of Hungary. F-NeoBright is a feasibility and safety study of intranasal fresh breast milk in neonatal encephalopathy — a pilot study looking specifically at safety and feasibility in this group of babies.

In the introduction, they note — as we just discussed this week — that we still don't have many adjunct therapies to therapeutic hypothermia in HIE. We know that breast milk is rich in bioactive components, including neurotrophic growth factors, cytokines, immunoglobulins, hormones, and multipotent stem cells. Exclusive breastfeeding in early development has been shown to positively impact cognitive outcomes. Animal studies have also shown that neurotrophic substances found in breast milk, when administered intranasally, can enter the central nervous system and reduce the extent of neurologic damage. We've also recently seen the impact of intranasal breast milk on post-hemorrhagic hydrocephalus — reducing the degree of ventricular dilation in babies who had IVH.

So they wanted to look at this in babies with HIE. It's a single-center feasibility study in one NICU in Hungary — and notably, this unit treats outborn patients only, which is interesting because outborn babies are often excluded from HIE studies.

They enrolled 10 consecutive neonates born between December 2024 and February 2025, diagnosed with moderate to severe HIE. And yes — I know it's only 10 babies. I noticed. But this is a feasibility and safety study.

Ben Courchia (03:30.945) But it is a feasibility and safety study.

Daphna Yasova Barbeau (03:43.79) Exactly. I'm excited about the paper. So the exclusion criteria mirrored the standard criteria for ruling babies out of therapeutic hypothermia: congenital malformations, concurrent cerebral lesions, need for ECMO, and contraindications to fresh breast milk provision.

The intervention used mother's own fresh breast milk expressed within four hours, transported at room temperature in a standard 1 mL plastic syringe. They administered 0.4 mL of freshly expressed milk twice a day in each nostril over one minute, with each nostril treated 15 minutes apart.

What was really interesting about the protocol: the first doses were performed by nursing staff or the attending physician, with parents observing. Parents then received training and continued the administration themselves throughout the hospital stay and at home. The plan was for babies to receive intranasal breast milk up to day 28. Intervention was initiated as soon as possible but always within 48 hours of age. Parents were contacted at least twice a week for ongoing support and confirmation of home doses.

The maximum number of doses — twice daily over 28 days — was 56. Given anticipated challenges with breast milk transport, a pragmatically achievable target was set at 50 doses per patient. For those in stem cell research: 50 doses were estimated to deliver 1.4 × 10⁶ stem cells per kilogram, which was considered a sufficient dose.

Daphna Yasova Barbeau (06:29.198) 11 babies were assessed for moderate to severe HIE. 10 were enrolled. The one who was not enrolled required therapy for severe meconium aspiration syndrome with PPHN. Based on exam, aEEG, and MRI, two patients were classified as severe and eight as moderate HIE.

Of the two with severe HIE: one died at day seven due to multi-organ failure, felt to be unrelated to the study protocol; the other had a severe respiratory condition requiring prolonged intensive care. At enrollment, all patients were already intubated and ventilated. Prior to initiation of fresh breast milk therapy, four patients required non-invasive support following extubation, and six neonates received vasopressors and/or inotropes for circulatory support.

aEEG activity normalized in six neonates at a median age of 35 hours. Onset of sleep-wake cycling was observed in eight neonates at a median age of 25 hours. Seizures were observed in two neonates before intranasal therapy was initiated — both received a single loading dose of phenobarbital and required no further anti-seizure medication. MRI was performed in all infants at a median age of 4.3 days with a median WIKI score of 2.0, indicating some neurologic damage.

Looking at feasibility: the first dose was administered at a median age of 24.7 hours — range 14.8 to 40 hours — within the 48-hour target in all patients. The median treatment duration in surviving infants was 28 days, which was the goal. The median total doses administered in surviving infants was 51 — just above the target of 50. The primary reason for dose omission during the hospital stay was unavailability of fresh breast milk, as some outborn patients had it transported from significant distances.

In terms of safety: no respiratory, cardiovascular, or neurologic adverse events were recorded in association with the administration during the hospital stay. Parents were trained to safely administer the milk during the NICU admission and continue at home. Without home cardiorespiratory monitoring, parents were asked to report complications such as choking, aspiration, nasal bleeding, or any symptoms requiring an emergency department visit.

Daphna Yasova Barbeau (08:44.098) Regarding enteral feeding: it was initiated as early as possible using mother's own breast milk at a median time of 27 hours. Median time to full enteral feeds was day eight.

The take-home from their discussion: intranasal breast milk administration twice daily in infants with HIE appears to be feasible and safe both in the hospital and at home. Notably, all parents approached for participation consented — including those who had not planned to breastfeed or had been unsuccessful with breastfeeding previously. That is not a small thing. They also observed high adherence to the protocol among all surviving infants for more than three weeks. Seven out of nine surviving infants completed the full 28-day treatment course — one while still in the NICU, the remaining six at home.

Through a multidisciplinary approach, it was feasible to initiate treatment in 100% of patients within the target of 48 hours of age, and 50% of infants had their first treatment within 24 hours of life. The long-term effects of intranasal EBM are still to be studied, but this is the critical first step.

Ben Courchia (10:11.699) You're clearly a strong advocate for this intervention. Why is that?

Daphna Yasova Barbeau (10:20.846) I think what we've learned — on the podcast and through our work with the Delphi Conference — is that sometimes the simplest, most obvious intervention is the right one. We still have to study it, and we still need to confirm babies can tolerate it. But as the data comes in, and given the lack of other well-supported adjunct therapies, giving these developing brains stem cells just makes a lot of sense.

Ben Courchia (10:56.171) It checks a lot of boxes already. It's physiologically sound, it doesn't appear to be a high-risk intervention — so we have to study it rigorously, but why not? Very helpful. Thank you, Daphna. See you tomorrow.

Daphna Yasova Barbeau (11:11.661) Very hopeful. Sounds good.