Hypoxic-ischemic encephalopathy: new insights and evolving therapies [Session]

What an incredible morning session here at CEPAS! We just wrapped up a packed HIE-block covering everything from late-preterm cooling debates to trial integrity and family-centered neurocritical care.

For those following our live reporting, here is a quick breakdown of the core messages from each talk:

• Therapeutic Hypothermia in Late Preterm Infants (Floris Groenendaal)

  • Recent data highlights that there are higher risks and complications associated with cooling late preterm infants, calling into question the overall positive effect of the intervention in this population.

  • Major cooling trials have historically underrepresented these infants, making it difficult to establish strong, uniform guidelines.

  • Despite the risks, cooling at 35 weeks can still be considered depending on individual underlying clinical factors and severity, whereas cooling at 34 weeks presents a distinctly riskier profile.

• Cerebral Proton MRS and School-Age Neurodevelopment (Lorea Vicente Elcano)

  • Early neonatal proton magnetic resonance spectroscopy (performed on days 4–6) provides strong long-term prognostic value in infants with HIE treated with hypothermia.

  • The lactate to N-acetyl aspartate (NAA) ratio emerges as the most robust biomarker, maintaining high predictive accuracy for adverse outcomes at school age (5–8 years).

  • This predictive power is particularly strong for cognitive outcomes compared to motor domains.

• Beyond Cooling: Latest HIE Trials and Precision Phenotyping (Lina Chalak)

  • Second-generation trials attempting deeper/longer cooling or adjunctive erythropoietin did not show improved survival and pointed toward potential harm.

  • The newly completed enrollment of the Cool Prime trial highlights that "mild" HIE carries significant risk, with many infants eventually meeting thresholds for early intervention.

  • Future Advancements: The next frontier relies on continuous, precision physiological tracking rather than a single-point clinical exam (like an early SARNAT score). By utilizing real-time EEG (to monitor neuronal activity), broadband NIRS (to measure mitochondrial function and cerebral oxygenation), and advanced MRI, clinicians can track the dynamic trajectory of reperfusion injury. This functional phenotyping allows us to identify infants who initially present as "mild" but progressively worsen between 6 and 24 hours, paving the way for delayed or highly tailored neuroprotective strategies.

• Cortical Activity Mechanisms and HIE Severity (Timo Syvälahti)

  • A multicenter validation study utilizing the ALBINO trial cohort demonstrated that automated computational EEG metrics correlate strongly with clinical HIE severity (Thompson scores).

  • Lower local cortical amplitudes and higher large-scale network connectivity map consistently across the entire clinical severity spectrum, including mild HIE cases.

  • These automated metrics hold strong potential as objective endpoints for future clinical trials.

• Cuddling During Therapeutic Hypothermia / Cool Cuddle (Ela Chakkarapani)

  • Structured parental cuddling (up to two hours) during active therapeutic hypothermia is safe and does not clinically compromise core/surface temperature regulation or intensive care stability.

  • Infants experienced improved comfort during cuddles, reflected by increased sleep-wake cycling on amplitude-integrated EEG and lower pain scores.

  • Implementing Cool Cuddle fosters a sense of normality for families and significantly reduces risks of poor parent-infant bonding.

  • Resource: You can watch a great animated explainer on the Cool Cuddle process here: https://youtu.be/dC7SriN99SA?si=P5PKrzUfc8ymUHef

• Trustworthiness of Trial Evidence in HIE Cooling (Anna Lene Seidler)

  • A systematic integrity assessment of 34 randomized trials on therapeutic hypothermia revealed major concerns or potential red flags in 41% of studies.

  • When excluding these compromised trials, overall effect estimates shift, though the core neuroprotective benefits of cooling in high-income settings remain supported.

  • The findings underscore the critical need for rigorous trial integrity screening and individual participant data (IPD) meta-analyses in neonatal research.

We would love to hear how these findings resonate with your clinical practice back home. Jump into the discussion below:

1. Late Preterm Cooling: Given the conflicting data and nuances between 35 and 36 weeks, how is your unit currently approaching cooling eligibility for late preterm infants (35 weeks)?

2. Future HIE Protocols: Between advanced prognostication (like MRS) and the search for adjunct therapies, what do you think will be the next major protocol shift in HIE management?

3. Family-Centered Neurocritical Care: What practical or cultural hurdles has your team faced when considering family integration strategies like "Cool Cuddle" during active hypothermia, and how have you navigated them? Is it being used or considered at your unit?

   Disclosure: This is an AI-assisted summary of the session, generated from a recording made by our team in attendance. We believe it is as accurate as our own notes would be, but please refer to the speakers’ original work before applying anything in clinical practice.