Perinatal asphyxia and hypoxic-ischemic encephalopathy

Last updated: January 19, 2021

Summarytoggle arrow icon

Perinatal asphyxia, a common cause of death in neonates, is caused by compromised placental or pulmonary gas exchange and can occur during the antepartum, intrapartum, or perinatal period. Persisting impairment of blood gas exchange results in oxygen deficiency, hypercapnia, and blood acidosis with potential subsequent compromise of cell function in various tissues (e.g., heart, muscle, brain). The brain is the most vulnerable organ in the context of perinatal asphyxia and the development of hypoxic-ischemic encephalopathy is a potential consequence. After rapid evaluation, eligible patients require therapeutic hypothermia over a period of 72 hours to minimize brain damage. Depressed myocardial function can exacerbate ischemia and cause subsequent short-term complications with end-organ damage in other tissues (e.g., kidneys, lung, liver, gastrointestinal tract, bone marrow). Long-term complications of perinatal asphyxia include irreversible neurological damage, cerebral palsy, and periventricular leukomalacia.

Definitiontoggle arrow icon

Epidemiologytoggle arrow icon

Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon

Pathophysiologytoggle arrow icon

Clinical featurestoggle arrow icon

Signs and symptoms of asphyxia

Clinical features of hypoxic-ischemic encephalopathy [6]

Clinical stages of neonatal encephalopathy [6]
Mild Moderate Severe
Mental status
  • Hyperalert

Muscle tone

  • Normal or slightly increased


  • Normal
  • Irregular breathing



  • None
  • May occur within 24 hours after birth
  • Usually generalized
  • Increase after 24–48 hours of birth

Additional features

  • Temporary behavioral abnormalities: poor feeding, irritability, or excessive crying/sleepiness
  • Self-limited (typically lasts < 24 h)
  • Recovery after 1–2 weeks is possible
  • Ocular motor disturbances (e.g., nystagmus, bobbing)
  • Pupillary abnormalities: dilation, fixation, or unresponsiveness to light
  • Symptoms may improve after ∼ 5 days of life
  • Continued support necessary if neonate survives

Diagnosticstoggle arrow icon

Neonatal assessment [7]

Further diagnostic measures

Treatmenttoggle arrow icon

While maintaining adequate organ perfusion is important in children with HIE, volume overload should be avoided due to the possible subsequent development/worsening of brain edema.

Complicationstoggle arrow icon

CNS complications

Other organ complications

We list the most important complications. The selection is not exhaustive.

Prognosistoggle arrow icon

  • Mild encephalopathy: usually normal development
  • Moderate to severe encephalopathy
    • Long-term neurologic manifestations
    • Severe abnormalities seen in MRI and EEG are associated with a poor outcome

Referencestoggle arrow icon

  1. Preventing those so-called stillbirths. Updated: April 1, 2008. Accessed: November 3, 2020.
  2. Kurinczuk JJ, White-Koning M, Badawi N. Epidemiology of neonatal encephalopathy and hypoxic–ischaemic encephalopathy. Early Hum Dev. 2010; 86 (6): p.329-338.doi: 10.1016/j.earlhumdev.2010.05.010 . | Open in Read by QxMD
  3. Popescu MR, Panaitescu AM, Pavel B, Zagrean L, Peltecu G, Zagrean A-M. Getting an Early Start in Understanding Perinatal Asphyxia Impact on the Cardiovascular System. Front Pediatr. 2020; 8.doi: 10.3389/fped.2020.00068 . | Open in Read by QxMD
  4. LaRosa DA, Ellery SJ, Walker DW, Dickinson H. Understanding the Full Spectrum of Organ Injury Following Intrapartum Asphyxia. Front Pediatr. 2017; 5.doi: 10.3389/fped.2017.00016 . | Open in Read by QxMD
  5. Nair J, Kumar VHS. Current and Emerging Therapies in the Management of Hypoxic Ischemic Encephalopathy in Neonates.. Children (Basel). 2018; 5 (7).doi: 10.3390/children5070099 . | Open in Read by QxMD
  6. Allen KA, Brandon DH. Hypoxic Ischemic Encephalopathy: Pathophysiology and Experimental Treatments. Newborn Infant Nurs Rev. 2011; 11 (3): p.125-133.doi: 10.1053/j.nainr.2011.07.004 . | Open in Read by QxMD
  7. Task Force on Neonatal Encephalopathy. Neonatal Encephalopathy and Neurologic Outcome, Second Edition. Pediatrics. 2014; 133 (5): p.e1482-e1488.doi: 10.1542/peds.2014-0724 . | Open in Read by QxMD
  8. Aly H, Hassanein S, Nada A, Mohamed MH, Atef SH, Atiea W. Vascular endothelial growth factor in neonates with perinatal asphyxia. Brain and Development. 2009; 31 (8): p.600-604.doi: 10.1016/j.braindev.2008.09.004 . | Open in Read by QxMD
  9. American Academy of Pediatrics. Hypothermia and Neonatal Encephalopathy. Pediatrics. 2014; 133 (6): p.1146-1150.doi: 10.1542/peds.2014-0899 . | Open in Read by QxMD
  10. Razak A, Hussain A. Erythropoietin in perinatal hypoxic-ischemic encephalopathy: a systematic review and meta-analysis. J Perinat Med. 2019; 47 (4): p.478-489.doi: 10.1515/jpm-2018-0360 . | Open in Read by QxMD
  11. Frymoyer A, Van Meurs KP, Drover DR, Klawitter J, Christians U, Chock VY. Theophylline dosing and pharmacokinetics for renal protection in neonates with hypoxic–ischemic encephalopathy undergoing therapeutic hypothermia. Pediatr Res. 2020.doi: 10.1038/s41390-020-01140-8 . | Open in Read by QxMD
  12. Pediatric Clerkship - Perinatal Asphyxia. Updated: January 1, 2013. Accessed: January 20, 2019.

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