Hypoxic Ischemic Encephalopathy

Happy April! 🌸

Spring is here, and here in LA, the weather has been absolutely gorgeous lately! Flowers blooming, longer days, and that energy that makes everything feel a little more possible.

April is also HIE Awareness Month, and it felt like the perfect time to dig into a topic that so many of us encounter at the bedside. This month also marks the very first HIE Hold-a-thon, which got me thinking: does your NICU offer holding during therapeutic hypothermia? If not make sure you keep reading and check out the resources from Hope for HIE and Newborn Brain Society on holding during cooling.

Speaking of showing up fully for your babies and families, that starts with you feeling confident and prepared. My Neonatal Certification Course was built for NICU nurses who are ready to deepen their knowledge and tackle the RNC-NIC or CCRN-N exam. Because when you thrive, your whole unit does too. 💛

Join me here! It's your season to bloom 🌸

🧠 What is HIE?

April is HIE Awareness Month, and this week we are talking all about one of the most critical and complex conditions we encounter in the NICU: Hypoxic Ischemic Encephalopathy (HIE).

HIE is a type of brain injury caused by a lack of oxygen (hypoxia) and reduced blood flow (ischemia) to a baby's brain. While it most commonly occurs during the perinatal period, HIE can happen at any point in life. Understanding the pathophysiology, treatment strategies, and evolving nature of this condition is essential to providing high-quality, neuroprotective care.

⚠️ Why Does HIE Happen?

While we often associate HIE with complications during delivery, it can occur at any point in life. Current research suggests that a significant portion of cases have no identifiable intrapartum cause and may be related to antepartum factors. Known risk factors include:

• Maternal conditions: preeclampsia, HELLP syndrome, maternal diabetes, thyroid disorders

• Acute events: uterine rupture, cord prolapse, placental abruption, maternal cardiac arrest

• Delivery complications: shoulder dystocia, prolonged fetal heart rate decelerations, difficult instrumental delivery

Ultimately, HIE results from impaired fetal gas exchange, hypoxemia, and cerebral ischemia, leading to disruption of cerebral energy metabolism.

🔄 The Evolving Injury: Phases of HIE

HIE is not a one-time event—it unfolds in phases:

1. Primary Energy Failure: The initial asphyxia event reduces oxygen and glucose to the brain. Cells switch to anaerobic metabolism, leading to:

• ATP depletion

• Intracellular flooding of sodium, water, & calcium

• Cellular swelling and necrotic cell death

• Release of excitatory amino acids (especially glutamate) and inflammatory markers

2. Latent Phase (0–6 hours post-resuscitation): This brief window shows partial clinical improvement, but the injury is still progressing on a cellular level. This is the crucial window for initiating therapeutic hypothermia.

3. Secondary Energy Failure (6–72 hours): The most damaging phase, with increased excitotoxicity, oxidative stress, mitochondrial failure, and delayed neuronal death via apoptosis.

4. Tertiary Phase (days to years later): Characterized by persistent inflammation, altered epigenetics, impaired oligodendrocyte maturation, and abnormal neuronal circuit development influencing long-term outcomes.

🧊 Therapeutic Hypothermia: The Gold Standard

Initiating cooling within 6 hours after birth is key. Therapeutic hypothermia slows metabolism, reduces glutamate release, and decreases free radical production. Multiple randomized controlled trials have shown that:

• Moderate hypothermia (33-34°C) for 72 hours

• Started within 6 hours of birth

• Reduces mortality and major neurodevelopmental disability in eligible infants by approximately 25%

Who qualifies?

• ≥36 weeks gestation and birth weight ≥1800g

  • Some NICUs cool >35 weeks

• Evidence of perinatal depression with either:

  • Cord or postnatal blood gas (within 60 min) with pH <7.0 or base deficit ≥ -16

  • OR pH 7.01–7.15 with base deficit -10 to -15.9 AND history of acute perinatal event plus either need for ventilation at 10 minutes or Apgar ≤5 at 10 minutes

• Evidence of moderate to severe encephalopathy via neurologic exam (modified Sarnat Exam)

🧪 Diagnosing HIE: Tools We Use

A combination of clinical assessment and diagnostics helps us stage and manage HIE:

• Apgar scores (especially at 5, 10, and 15 minutes)

• Neurologic exam & modified Sarnat staging (assessing level of consciousness, tone, reflexes, autonomic function)

• Blood gases (cord and postnatal)

• EEG/aEEG monitoring (to detect subclinical seizures and assess background patterns)

• MRI findings (ideally performed 5-7 days after birth to assess pattern and extent of injury)

🩺 Clinical Considerations at the Bedside

These babies require vigilant, skilled nursing care:

🧠 Seizures

• HIE is the #1 cause of neonatal seizures, occurring in 30-60% of moderate to severe cases

• Continuous EEG/aEEG monitoring is essential as 50-65% of seizures may be clinically silent

• First-line treatment typically includes phenobarbital

  • Levetiracetam (Keppra) is a promising alternative for neonatal seizures. However, its efficacy can vary, and further research is needed to optimize dosing and fully understand its role in neonatal seizure management.

🫁 Respiratory Support

• Risk for PPHN, MAS, and respiratory failure

• Avoid both hypercarbia (worsens acidosis) and hypocarbia (decreases cerebral blood flow)

• Maintain normal oxygenation (SpO2 92-98%) to avoid secondary injury from hypoxemia or hyperoxemia

❤️ Cardiovascular Management

• Risk of myocardial dysfunction and hypotension (present in up to 62% of HIE infants)

• Individualize use of inotropes and vasoactive drugs to maintain blood pressure

• Consider echocardiography to guide cardiovascular support

🩸 Metabolic & Hematologic Issues

• Avoid rapid sodium bicarbonate boluses (this is linked to worse outcomes and intracranial hemorrhage)

• Monitor and treat hypoglycemia aggressively (maintain euglycemia)

• Anticipate thrombocytopenia and coagulopathy

👶 Multisystem Impacts

• Renal: Acute kidney injury in 30-70% of cases, fluid overload (SIADH), and acute tubular necrosis

• Hepatic: Poor glucose regulation, elevated transaminases, coagulopathy

• GI: Paralytic ileus, NEC risk from mesenteric hypoperfusion

I'll never forget one speaker talking about HIE at a conference clearly stating, HIE isn't just brain injury...it's "hypoxic ischemic everything!" Every organ system is affected!

🧬 Cooling in Late Preterms: What the Evidence (and the Debate) Is Telling Us

A 2025 RCT published inJAMA Pediatricshas raised serious questions about cooling late preterm infants. The study enrolled 168 infants born at 33–35 weeks gestation with moderate or severe HIE, randomized to therapeutic hypothermia versus normothermia within 6 hours of birth. The primary outcome (death or moderate/severe disability at 18–22 months corrected age) occurred in 35% of cooled infants compared to 29% in the normothermia group. Bayesian analysis showed a 74% probability of increased death or disability and an 87% probability of increased death with hypothermia.

One particularly notable safety signal: 32 infants randomized to hypothermia overshot to temperatures below 32°C, which may have contributed to worse outcomes. Late preterm infants have a higher surface-area-to-weight ratio and a more immature epidermal barrier than term infants, making temperature regulation during cooling more challenging.

Other neonatal experts have raised data and analysis concerns about the trial, noting limitations including baseline imbalances, limited stratification by gestational age and encephalopathy severity, and the absence of neuroimaging or EEG data. A recent international survey of 88 centers found heterogeneous practices, with many continuing therapeutic hypothermia at 34–35 weeks despite the trial's findings, and real-world data from 22 centers showed lower mortality than what was reported in the RCT.

The emerging clinical consensus seems to be stratified by gestational age: cooling may remain appropriate for select 35-week infants, while routine use at 34 weeks and below should be limited to research settings pending further data. Some experts are also calling for an informed consent process when considering therapeutic hypothermia for infants born under 36 weeks, creating an opportunity for shared decision-making with families.

🧠 Why this matters for NICU nurses: This is exactly the kind of evolving evidence that makes our role so important. The data doesn't give us a clean answer yet and that means advocating for individualized care, asking questions when protocols are applied broadly, and staying current. Cooling remains the gold standard for term infants with moderate-to-severe HIE. For late preterms, the conversation is very much still happening.

Holding During Cooling: What the Evidence Says 🐻‍❄️

For years, many NICUs operated under the assumption that babies receiving therapeutic hypothermia shouldn't be held; that the risks of temperature disruption or clinical instability were too great. But the evidence is shifting that narrative in a meaningful way.

Research has shown that parental holding during therapeutic hypothermia is safe for the newborn, beneficial for parents, and infant temperatures and vital signs remain stable during holding sessions. Parents report high satisfaction, and nurses express strong support as well. Importantly, holding does not appear to compromise the effectiveness of cooling therapy.

This has caught the attention of major organizations. The 2026 AAP Clinical Report on Therapeutic Hypothermia now includes evidence that holding and feeding during cooling is safe for many babies with HIE, and can reduce parental stress, anxiety, and the impacts of trauma.

I can speak to this personally. My NICU started offering holding during cooling around 2022, and since implementing our own guideline, we haven't had any complications. More than the data, though, what stays with me is what families have shared: how meaningful it was to simply hold their baby during one of the hardest experiences of their lives. Parents often describe those first days as deeply isolating, wanting to comfort and bond but feeling unsure or unable to. Safe holding can help families feel like parents (not just visitors) during an overwhelming and traumatic time. That resonates deeply with what I've witnessed firsthand.

This is the heart of the HIE Hold-a-thon, a first-of-its-kind initiative this April from the Newborn Brain Society and Hope for HIE. Rather than prescribing protocols, it encourages hospitals to develop their own multidisciplinary, evidence-based holding guidelines. Each institution maintains full clinical autonomy while joining a global movement to advance family-centered care.

So I'll ask again: does your NICU offer holding during therapeutic hypothermia?If not, what would it take to get there?

Want more info on HIE?

2026 HIE Hold-a-thon Resources

Support Hope for HIE

Cooling Courses from Synapse Care, get 10% off with my code Amanda10

What questions do you have about HIE or therapeutic hypothermia. Email me back and let me know what you'd like me to cover or if you have any questions.

Wishing you the best

Amanda

References

Faix RG, Laptook AR, Shankaran S, et al. Whole-Body Hypothermia for Neonatal Encephalopathy in Preterm Infants 33 to 35 Weeks' Gestation: A Randomized Clinical Trial.JAMA Pediatr. 2025;179(4):396-406. doi:10.1001/jamapediatrics.2024.6613

Volpe, J. (2025). Volpe's Neurology of the Newborn, Seventh Edition. Elsevier

Verklan, M. T., &Walden, M. (2015). Core curriculum for neonatal intensive care nursing (Fifth ed.). St. Louis, Missouri: Elsevier Saunders

Gardner, S. L., Carter, B. S., Hines, M. E., & Hernandez, J. A. (2016). Merenstein & Gardner's Handbook of Neonatal Intensive Care (Eighth ed.). St. Louis, Missouri: Elsevier.

Gomella T, & Eyal F.G., & Bany-Mohammed F(Eds.), (2020). Gomella's Neonatology: Management, Procedures, On-Call Problems, Diseases, and Drugs, 8e. McGraw Hill.

Hope for HIE (2023) What is HIE: HIE Overview. Retrieved fromhttps://www.hopeforhie.org/whatishie/

Douglas-Escobar, Martha & Weiss, Michael. (2015). Hypoxic-Ischemic Encephalopathy: A Review for the Clinician. JAMA pediatrics. 169. 10.1001/jamapediatrics.2014.3269.

Power, B., McGinley, J., Sweetman, D.U., & Murphy, J.F. (2019). The Modified Sarnat Score in the Assessment of Neonatal Encephalopathy: A Quality Improvement Initiative. Irish medical journal, 112 7, 976 .

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