Hypoxic-Ischemic Encephalopathy (HIE)

Woman sitting in the NICU holding baby


  • Hypoxic (hi – poks- ick)= not enough oxygen
  • Ischemic (Iss- key- mick ) = not enough blood flow
  • Encephalopathy (En- cef-a- lop -athee) = brain injury/dysfunction
  • Hypothermia (Hi- po- therm- ia)= cooling
  • Preeclampsia = Condition in pregnancy characterized by high blood pressure.
  • Cerebral palsy = Condition marked by impaired muscle coordination and/or other disabilities.
  • Tomography = Technique used to display a representation of a cross section through the human body by using X-rays or ultrasound.

What is Hypoxic-Ischemic Encephalopathy?

  • Hypoxia refers to a reduction in the supply of oxygen to organs including the brain.
  • Ischemia refers to an inadequate supply of blood to the organs.
  • Encephalopathy is a term used to describe any form of generalized brain dysfunction.
  • Hypoxic-Ischemic Encephalopathy (or HIE) is a non-specific term for brain dysfunction caused by a lack of blood flow and oxygen to the brain.
  • Sometimes, HIE is also referred to as birth asphyxia, but this term only pertains to a very strict criteria of infants with brain injury.

How and when does HIE occur?

There are many problems during pregnancy, labor, delivery, and after delivery that can cause HIE. However, in many cases the cause of HIE is not known.

Possible problems during pregnancy:

Preeclampsia, maternal diabetes with vascular disease, congenital infections of the fetus, drug and alcohol abuse, severe fetal anemia, cardiac disease, lung malformations, problems with blood flow to the placenta.

Problems during labor and delivery:

Umbilical cord accidents, rupture of the placenta or uterus, excessive bleeding from the placenta, abnormal fetal position, prolonged late stages of labor, very low blood pressure in the mother (caused by drugs, bleeding, anesthesia.)

Problems after delivery:

Severe prematurity, severe lung or heart disease, serious infections (especially meningitis or sepsis), trauma to the brain or skull, congenital malformations of the brain, very low blood pressure in the baby.

How common is HIE?

Regarding full-term infants, HIE occurs in approximately 3-20 per 1000 live births. In the preterm infant, HIE occurs in up to 60% of live births.

What are possible long-term problems for babies with HIE?

The disabilities infants with HIE display as they grow vary with the severity of HIE. While infants with mild HIE exhibit little to no long-term disabilities, infant who have suffered moderate to severe HIE may die in the newborn period or have medical conditions including Cerebral Palsy, Mental Retardation, feeding difficulties, learning disabilities, visual or hearing impairment and seizures.

How is HIE diagnosed?

The diagnosis of HIE is made after the infant is delivered and monitored for several days. Clinical, laboratory and radiological tools aid in the diagnosis of HIE. Occasionally there are clues that the infant was in distress prior to birth.

Some of the markers that assist in making the diagnosis of HIE include:

Before Birth:

  1. Measurements of fetal movement and/or heart rate variability before birth.
  2. The presence of meconium (the baby’s first stool) in the amniotic fluid. This is a poor predictor of increased risk for HIE, but may indicate the fetus was in distress prior to birth.

Clinical Evaluation:

  1. APGAR Score (scores given to infants after birth as a measure of the infant’s well-being)
  2. APGAR scores remaining low for more than 10 minutes may correlate with HIE severity.
  3. An abnormal neurologic exam is essential for making the diagnosis of HIE. Some of the abnormal findings on physical exam are:
    1. Changes in mental status (decreased alertness)
    2. Increased or decreased muscle tone
    3. Seizures
    4. Abnormal pupils
    5. Changes in reflexes
    6. Changes in breathing and heart rate
  4. The exam is repeated 2-3 times a day for the first several days of life to help the doctor determine if the infant is improving or worsening.
  5. EEG: electrodes are placed on the infant’s scalp to evaluate the brain’s electrical activity. EEG finding can help identify seizure activity and also may correlate to the infant’s outcome. EEG data is read by a pediatric neurologist.

Laboratory Evaluation:

Blood tests can evaluate for evidence of other injured organs caused by HIE. This is because a decrease in blood flow and oxygen can affect all organs and not just the brain. The kidneys, liver, heart, and lungs are the most common organs affected by HIE. Umbilical cord blood samples may show an increase acid build-up. This can be a sign that the infant was in distress prior to birth.

Radiological Evaluation:

Brain imaging, using Ultrasound, CT scans (computed tomography) and MRI (magnetic resonance imaging) may be used to evaluate for an underlying brain malformation and to look for evidence of brain injury. Currently, MRI is the most sensitive way to look for brain injury, but the infant may be too sick to transport for MRI or he/she may not tolerate the long scanning time (approximately 45 minutes).

Are there different stages or degrees of HIE?

HIE can be classified as mild, moderate or severe based on the infant’s neurological exam. This classification system is titled the Sarnat Classification and can be helpful in predicting long-term neurological risk.

How is HIE treated?

Unfortunately, there is no definitive treatment for infants with HIE. Most therapies are directed at supporting the infant’s affected organs including:

  1. Supporting the heart and blood pressure
  2. Sustaining kidney and liver function
  3. Mechanical ventilation may be required if the infant can not breath completely on their own
  4. If the baby has seizure, they must be controlled with medications

Currently, the only brain-specific therapy that has been proven to reduce the risk of long-term neurodevelopmental handicaps is brain or whole body hypothermia (cooling the infant’s body temperature to approximately 33.5 degrees Celsius or 92 degrees Fahrenheit) for 3 days. See section below on Hypothermia.

Hypothermia or Brain Cooling for the Treatment of HIE:

The only brain-specific therapy for HIE that has been proven to reduce the risk of long-term neurodevelopmental handicaps is brain or whole body hypothermia (cooling the infant’s body temperature by 3-4 degrees to approximately 33.5 degrees Celsius or 92 degrees Fahrenheit)

What infants qualify for cooling?

  1. Infants with moderate to severe HIE, not mild cases
  2. The infant cannot have another cause of brain dysfunction such as a brain malformation or bleeding into the brain.
  3. Only infants that are less than 6 hours old. Laboratory studies show that after 6 hours of life, there appears to be no benefit in cooling for HIE.

Where is brain cooling performed?

Cooling is only performed in selective, experienced tertiary neonatal intensive care units (this is the highest level of medical care for infants).

How is cooling performed?

  1. Infants are either cooled using a cooling blanket that tightly regulates the infant’s body temperature, or a cooling cap that is placed directly on the infant’s head.
  2. Both cooling techniques have been shown to be beneficial for treating infants with HIE. The method used is dependent on the hospital treating the infant. See the pictures below of the cooling blanket and cool cap.
  3. Cooling occurs over 72 hours or 3 days. After that time, the infant’s body temperature is re-warmed slowly to a normal temperature value.

Does cooling help all infants with HIE?

Unfortunately, cooling only helps approximately 1 in 8 babies with moderate to severe HIE. At this time, when a physician starts the cooling process it is impossible to know which babies will benefit from cooling and which babies will not. Further research is currently ongoing in this area.

Is cooling safe?

To date, clinical trials involving more than 550 infants have been published to assess the benefit of cooling for HIE. These trials have demonstrated that cooling for brain protection in infants with moderate to severe HIE is both beneficial and safe. However, in these trials, some noted potential side effects of cooling were skin changes that resolved in time, more use of blood pressure medications, and a slight decrease in the blood’s ability to clot.

What is the prognosis (outcome) for infants with HIE?

The outcome for infants with HIE is usually determined by the severity or classification of HIE; mild, moderate or severe. Other indicators such as MRI and EEG results can help predict outcome as well.

Prognosis based on clinical classification is as follows:

  1. Mild HIE: Less than 5% of these infants will have a severe handicap.
  2. Moderate HIE: 25% to 75% of these infants will have a severe handicap or potentially die early in life.
  3. Severe HIE: 75% or more of these infants will have a severe handicap or potentially die early in life.

How can parents help their child with HIE once they go home?

One of the most important aspects in caring for an infant with HIE is talking to your child’s doctor and understanding your child’s needs when he/she is discharged from the hospital. The following may help guide parents when preparing for discharge home:

  1. Understand your infant’s feeding plan: type of formula or breast milk, amount your child needs to grow, how often are the feeds, does your child feed completely by mouth or does your child have a feeding tube?
  2. Does your baby need a special care seat? Child may need a special car seat at the time of discharge.
  3. What medications does your baby need? The amount or dose, time medications are given, how the medications are given and why these medications are used.
  4. What follow-up appointments does your baby have? The following are some common appointments needed for babies with HIE: Pediatrician, Pediatric Neurologist if your baby has seizures, occupation and/or physical therapy, hearing and vision evaluation.
  5. Babies with HIE are at a higher risk to develop movement problems such as Cerebral Palsy. Early rehabilitation with a pediatric occupational and physical therapist is recommended to help your baby reach their full potential.
  6. The therapist can teach the infant’s family home-based exercises and therapy that will further enhance the infant’s development.

What research is being done to cure or prevent HIE?

There is a large amount of research being conducted in the area of HIE. Multiple studies are evaluating the use of different medications that may protect the infant’s brain prior to birth and once HIE has occurred. Currently, the only therapeutic option for brain protection is hypothermia/cooling if used in the first 6 hours of birth as mentioned above. However, clinical trials are underway to evaluate the possible effect of cooling if started after 6 hours of life.

There is also a clinical trial in the United States evaluating a medication called Erythropoietin as a neuroprotective (brain protective) agent. This medication has been used for many years in medicine to help treat anemia and is naturally present in our bodies. More recent evidence is available showing that Erythropoietin has neuroprotective effects and is safe. A study from China in 2009 demonstrated Erythropoietin to have a beneficial effect for infants with moderate HIE if administered in the first 48 hours of life. Although these results are promising, more evidence will be required before this medication is approved for the treatment of HIE in the United States.