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Background <p>Neonatal encephalopathy remains the leading cause of acquired brain injury in term infants. While therapeutic hypothermia (TH) has significantly improved outcomes in moderate to severe cases, many infants continue to experience long-term morbidity. Early, non-invasive biomarkers are needed to better identify infants at risk. This study assessed changes in high-frequency heart rate variability (HF-HRV), reflecting parasympathetic tone, during TH and rewarming.</p> Methods <p>This prospective, observational study analyzed electrocardiograms from infants during TH and rewarming. Brain injury was determined post-TH using an MRI-based standardized scoring system. Differences in trajectories of HRV and heart rate during TH and rewarming, by post-TH brain-injury status, were analyzed using linear mixed models.</p> Results <p>Among thirty-nine infants, five (13%) were identified as having brain injury. HF-HRV increased over time during TH in both groups (<i>p</i> &lt; 0.0001). However, the brain injury group exhibited consistently lower HF-HRV (<i>p</i> = 0.011) and higher heart rates (<i>p</i> = 0.008) compared to those without brain injury, indicating diminished parasympathetic tone.</p> Conclusion <p>Despite similar trends, the blunted HF-HRV response observed in the brain injury group highlights its potential utility as a non-invasive biomarker for identifying and monitoring infants at higher risk for adverse outcomes.</p> Impact <p><UnorderedList Mark="Bullet"> <ItemContent> <p>Infants undergoing therapeutic hypothermia (TH) for neonatal encephalopathy demonstrated a progressive increase in high-frequency heart rate variability (HF-HRV) throughout TH.</p> </ItemContent> <ItemContent> <p>Compared to infants without brain injury, those with signs of brain injury on post-TH MRI had lower HF-HRV and higher heart rates during both cooling and rewarming phases.</p> </ItemContent> <ItemContent> <p>Our results suggest a gradual increase in parasympathetic tone during TH, as indicated by increasing HF-HRV in both groups, although it remained lower in the brain injury group.</p> </ItemContent> <ItemContent> <p>This is one of the few studies reporting a comparative analysis of HRV changes during TH in infants with potential brain injury.</p> </ItemContent> </UnorderedList></p>

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Assessment of parasympathetic tone during therapeutic hypothermia in infants with brain injury following neonatal encephalopathy

  • 期刊论文

  • 发表日期：

    2026年5月21日

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  • John Sunwoo,
  • Sara Cherkerzian,
  • Seh Hyun Kim,
  • Katie Hannon,
  • Aisling Garvey,
  • Eniko Szakmar,
  • Chelsea Munster,
  • Hoda El-Shibiny,
  • Helen Christou,
  • Terrie E. Inder,
  • Maria Angela Franceschini,
  • Mohamed El-Dib

摘要

Background

Neonatal encephalopathy remains the leading cause of acquired brain injury in term infants. While therapeutic hypothermia (TH) has significantly improved outcomes in moderate to severe cases, many infants continue to experience long-term morbidity. Early, non-invasive biomarkers are needed to better identify infants at risk. This study assessed changes in high-frequency heart rate variability (HF-HRV), reflecting parasympathetic tone, during TH and rewarming.

Methods

This prospective, observational study analyzed electrocardiograms from infants during TH and rewarming. Brain injury was determined post-TH using an MRI-based standardized scoring system. Differences in trajectories of HRV and heart rate during TH and rewarming, by post-TH brain-injury status, were analyzed using linear mixed models.

Results

Among thirty-nine infants, five (13%) were identified as having brain injury. HF-HRV increased over time during TH in both groups (p < 0.0001). However, the brain injury group exhibited consistently lower HF-HRV (p = 0.011) and higher heart rates (p = 0.008) compared to those without brain injury, indicating diminished parasympathetic tone.

Conclusion

Despite similar trends, the blunted HF-HRV response observed in the brain injury group highlights its potential utility as a non-invasive biomarker for identifying and monitoring infants at higher risk for adverse outcomes.

Impact

Infants undergoing therapeutic hypothermia (TH) for neonatal encephalopathy demonstrated a progressive increase in high-frequency heart rate variability (HF-HRV) throughout TH.

Compared to infants without brain injury, those with signs of brain injury on post-TH MRI had lower HF-HRV and higher heart rates during both cooling and rewarming phases.

Our results suggest a gradual increase in parasympathetic tone during TH, as indicated by increasing HF-HRV in both groups, although it remained lower in the brain injury group.

This is one of the few studies reporting a comparative analysis of HRV changes during TH in infants with potential brain injury.