Neonatal Hypoxic-Ischemic Encephalopathy Pathophysiology

Neonatal hypoxic-ischemic encephalopathy (HIE) is a serious brain injury resulting from the severe reduction of cerebral blood flow and oxygen around the time of birth. Affected neonates can display altered levels of consciousness, decreased or absent reflexes and muscle tone, seizures and signs of organ failure (Source). Accounting for 1 million deaths a year which is 24% of all neonatal deaths worldwide, neonatal HIE is a primary global medical concern (Source).

According to the Levels & Trends in Child Mortality Report 2017 from UN Inter-agency Group for Child Mortality Estimation, infectious diseases and neonatal complications are still the leading causes of death among children under age 5, while the majority of cases have been registered in the developing countries.


Did you know?

Brain injury in HIE evolves over hours, days and even months. It follows a temporal sequence of brain injury. The window time for treatment like therapeutic hypothermia may be initiated during:

  • Primary Energy Failure - 0-6 hours after the hypoxic-ischemic injury.
  • Latent phase - 30-60 minutes after the primary energy failure.
  • Secondary energy failure - 7 to 72 hours after the hypoxic-ischemic insult.
  • Tertiary energy failure - 72 hours from onset of the HI injury and may last for days to months.

Learn more about Neonatal Hypoxic Ischemic Encephalopathy: Pathophysiological Features

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About the author

Ma. Esterlita Villanueva Uy, M.D.

Associate Clinical Professor, University of the Philippines College of Medicine, Manila, Philippines

Assistant Research Professor, Institute of Child Health and Human Development, Manila, Philippines


1. Lawn JE, Kerber K, Enweronu-Laryea C, Cousens S. 3.6 million neonatal deaths--what is progressing and what is not? SeminPerinatol. 2010 Dec;34(6):371–86.

2. Kurinczuk JJ, White-Koning M, Badawi N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev. 2010 Jun;86(6):329–38.

3. National Perinatal Neonatal Database. Available from URL: Accessed Apr 11, 2016.

4. Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev. 2013;1:CD003311.

5. Levels & trends in child mortality - Report 2017. Estimates developed by the UN inter-agency for Child Mortality Estimation.

6. Perinatal asphyxia in the term newborn Roberto Antonucci1, Annalisa Porcella1, Maria Dolores Pilloni 21 Division of Neonatology and Pediatrics, “Nostra Signora di Bonaria” Hospital, San Gavino Monreale, Italy 2 Family Planning Clinic, San Gavino Monreale, ASL 6 Sanluri (VS), Italy.

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Therapeutic hypothermia - mechanism of action


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