Common Causes of Hypoxic Ischemic Encephalopathy
Hypoxic ischemic encephalopathy results from impaired cerebral blood flow and oxygen delivery to the brain, with distinct etiologies varying by age group—in neonates, the primary causes are perinatal asphyxia from placental abruption, umbilical cord prolapse, and uterine rupture, while in adults, cardiac arrest is the predominant cause.
Neonatal HIE Causes
Perinatal Asphyxia Events
The most frequent obstetrical causes of neonatal HIE include 1:
- Placental abruption (detachment of the placenta)
- Umbilical cord prolapse
- Uterine rupture
These events lead to fetal asphyxia at birth, resulting in a clearly recognizable clinical syndrome in term newborns 1. The underlying mechanism involves impaired cerebral blood flow and oxygen delivery, causing primary and secondary energy failure in the brain 2.
Associated Neonatal Conditions
Neonatal encephalopathy frequently occurs alongside 3:
- Prematurity or low birthweight (34.3% hypoxemia prevalence)
- Neonatal sepsis (21.0-44.1% hypoxemia prevalence)
- Pneumonia (37.3% hypoxemia prevalence)
Important Diagnostic Exclusions
Before diagnosing birth asphyxia as the cause of HIE, you must exclude other conditions that can present with low Apgar scores 4:
- Congenital heart disease
- Inborn errors of metabolism
- Prematurity complications
- Maternal medication effects
Adult HIE Causes
Cardiac Arrest
Cardiac arrest is the most common cause of hypoxic-ischemic encephalopathy in adults, leading to long-term neurological dysfunction 5. With improved prehospital emergency systems, more patients survive cardiac arrest but face increased risk of neurological sequelae 5.
Respiratory Conditions Leading to Hypoxemia
In adults presenting to healthcare facilities, hypoxemia (which can progress to HIE if severe) occurs with 3:
- COVID-19 (44.2% hypoxemia prevalence)
- Sepsis (25.3% hypoxemia prevalence)
- Pneumonia (20.4% hypoxemia prevalence)
- HIV complications (16.6% hypoxemia prevalence)
Pathophysiologic Mechanism
The underlying pathology involves 2:
- Impaired cerebral blood flow
- Reduced oxygen delivery to brain tissue
- Primary energy failure (immediate)
- Secondary energy failure (delayed, hours to days)
This secondary energy failure phase represents a critical therapeutic window, as the majority of pathologic events result from this delayed process rather than the initial insult 2.
Clinical Recognition Criteria
Neonatal Presentation
Diagnostic criteria include 1:
- Partial or total inability to cry and breathe at birth despite stimulation
- Requirement for assisted ventilation in delivery room
- Apgar score < 5 at 5 and 10 minutes
- Acidemia (pH ≤ 7.0 and/or base deficit ≥ 12 mmol/L)
- Alterations in consciousness and reflexes (Moro, grasping, suction)
- Abnormal muscle tone and stretching
Organ System Involvement
HIE diagnosis requires hypoxic-ischemic organ injury with at least one organ dysfunction 4, affecting:
- Brain (primary concern)
- Kidneys
- Heart
- Liver
- Intestines
Epidemiology and Risk Context
The incidence varies dramatically by resource setting 1:
- Developed countries: 1-8 per 1,000 live births
- Developing countries: 25 per 1,000 live births
- Overall pooled estimate: 1.5 per 1,000 (95% CI 1.3-1.7)
Among hospitalized neonates with encephalopathy, 32.8% have hypoxemia 3, representing one of the three commonest causes of neonatal illness and death alongside prematurity and sepsis 3.
Critical Clinical Pitfall
Do not assume all neonatal encephalopathy is hypoxic-ischemic in origin. Other potential causes include infection, intracranial hemorrhage, stroke, brain malformations, metabolic disorders, and genetic causes 6. The appropriate management depends on identifying the specific cause and stage of injury evolution 6.