Understanding how hypoxic-ischaemic encephalopathy is identified is essential for families facing this serious brain condition. Early and accurate diagnosis can make a significant difference in determining the best course of treatment and support for affected newborns.

Introduction: Who Should Undergo Diagnostics

Diagnosing hypoxic-ischaemic encephalopathy, often called HIE, is a process that typically begins immediately after birth, especially when there have been complications during labor and delivery. This condition occurs when a baby’s brain does not receive enough oxygen and blood flow before, during, or shortly after birth. Because brain cells are extremely sensitive to oxygen deprivation, quick identification is critical to start treatment as soon as possible and prevent further damage.^[1]

Healthcare providers usually suspect HIE when certain warning signs appear during delivery or in the first hours of a newborn’s life. These situations include problems like prolonged labor, abnormal fetal heart rate patterns, low blood pressure in the mother, complications with the umbilical cord or placenta, or if the baby requires significant resuscitation efforts at birth. Additionally, if a baby shows symptoms such as seizures, difficulty breathing, unusual muscle tone, or does not respond normally to stimulation, doctors will consider HIE as a possible diagnosis.^[2]

In some cases, the full extent of HIE may not become apparent until weeks, months, or even years later. Parents might first notice developmental delays when their child misses important milestones like crawling or walking. Some children may not show obvious difficulties until they start school and struggle with learning or coordination. For this reason, any baby who experienced oxygen deprivation or significant complications at birth should be monitored closely for signs of brain injury, even if they seem healthy at first.^[1]

Diagnostic Methods: How Doctors Identify HIE

Diagnosing HIE involves multiple steps and different types of tests. Doctors begin with a careful review of what happened during pregnancy, labor, and delivery. They look at medical records to see if there were events that could have restricted oxygen or blood flow to the baby’s brain. This includes examining whether there were complications like placental abruption, umbilical cord problems, uterine rupture, or episodes of low blood pressure in the mother. The medical team also reviews how the baby responded immediately after birth, including whether resuscitation was needed and how quickly the baby began breathing on their own.^[3]

A thorough physical examination is a crucial part of diagnosing HIE. Doctors carefully observe the baby’s level of alertness and responsiveness. They check muscle tone, which might be either too floppy or too stiff in babies with HIE. The examination includes testing reflexes like grasping, sucking, and the Moro reflex, which may be weak or absent. Healthcare providers also look at eye movements, as babies with HIE might have unusual eye movements, dilated pupils, or poor response to light. The baby’s breathing pattern, heart rate, and blood pressure are continuously monitored because irregularities can indicate brain injury.^[7]

The severity of HIE is typically classified into three categories based on symptoms. Mild HIE involves behavioral changes like irritability, poor feeding, excessive crying or sleeping, and slightly increased muscle tone. These symptoms often resolve within about 24 hours. Moderate HIE presents with lethargy, significant low muscle tone, poor reflexes, and seizures that typically occur within the first 24 hours after birth. Babies might have periods of apnea, which means brief pauses in breathing. Severe HIE is the most serious category, where the baby may be in a coma or stupor, showing little or no response even to painful stimulation. Seizures can be frequent and difficult to control. These babies often need help breathing with a ventilator and may have very low or absent reflexes.^[7]

Blood Tests and Laboratory Analysis

Blood tests provide important information about how oxygen deprivation has affected the baby’s body. One key measurement is blood gas analysis, which shows the levels of oxygen, carbon dioxide, and acids in the blood. Babies with HIE often have too much acid in their blood, a condition called acidosis, which develops when cells don’t get enough oxygen and switch to less efficient ways of producing energy. Doctors also measure blood sugar levels because both low and high blood sugar can worsen brain injury. Additional blood tests check kidney and liver function, as these organs may also be affected when oxygen supply is reduced throughout the body.^[1]

Brain Imaging Studies

Imaging tests that create pictures of the brain are essential for confirming HIE and understanding which areas of the brain have been affected. Magnetic resonance imaging, or MRI, is considered the most helpful imaging test for HIE. MRI uses powerful magnets and radio waves to create detailed images of the brain’s soft tissues. It can show patterns of injury that are typical of oxygen deprivation and can help doctors predict how severe the long-term effects might be. However, MRI is not always performed immediately because moving a critically ill newborn to the MRI machine carries risks, and babies must be very still during the scan.^[9]

Ultrasound of the brain, performed through the soft spot on a baby’s head, is often done first because it can be performed right at the bedside without moving the baby. While not as detailed as MRI, ultrasound can quickly identify serious problems like bleeding in the brain or severe swelling. Computed tomography, or CT scan, uses X-rays to create cross-sectional images of the brain. CT scans are faster than MRI and can be useful in urgent situations, though they provide less detail about the specific patterns of brain injury seen in HIE.^[10]

Electroencephalogram (EEG)

An electroencephalogram, abbreviated as EEG, measures the electrical activity of the brain using small sensors placed on the baby’s scalp. This test is particularly important because many babies with HIE have seizures, which may not always be obvious from the outside. Some seizures cause visible movements, but others are “silent” and can only be detected through brain wave patterns on the EEG. Continuous EEG monitoring helps doctors identify seizures so they can be treated promptly, as seizures can cause additional brain damage. The EEG pattern itself can also provide information about the severity of brain injury. In severe HIE, the EEG might show very little activity or a pattern called “burst suppression,” where periods of activity alternate with periods of near-silence.^[7]

Additional Diagnostic Considerations

Because HIE can affect multiple organs beyond the brain, doctors perform tests to check the function of the heart, kidneys, liver, and lungs. Heart function is assessed through physical examination and sometimes echocardiography, which uses ultrasound to visualize the heart’s structure and pumping action. Kidney function tests look at urine output and blood levels of waste products. Liver function tests measure specific enzymes and proteins in the blood. These additional assessments help doctors provide comprehensive care and anticipate complications.^[1]

It’s important to understand that diagnosing HIE is not always straightforward. Doctors must distinguish HIE from other conditions that can cause similar symptoms in newborns, such as infections, stroke, bleeding in the brain from trauma, or metabolic disorders. Sometimes multiple conditions may be present at the same time. The diagnostic process involves piecing together information from the birth history, physical examination, laboratory tests, and imaging studies to arrive at the most accurate diagnosis.^[3]

Diagnostics for Clinical Trial Qualification

When researchers conduct clinical trials to test new treatments for HIE, they use specific diagnostic criteria to determine which babies can participate. These criteria help ensure that the trial includes babies who are most likely to benefit from the experimental treatment and that the results can be interpreted accurately. The goal is to create a group of participants who have similar characteristics so researchers can determine whether the treatment makes a meaningful difference.^[16]

Most clinical trials for HIE treatment focus on babies born at or near full term who have moderate to severe encephalopathy. To qualify for these trials, specific diagnostic findings must be present. Typically, researchers require evidence that the baby experienced a significant oxygen-depriving event at or near birth. This might include documentation of problems like a low Apgar score, which is a quick assessment done at one and five minutes after birth that evaluates heart rate, breathing, muscle tone, reflexes, and skin color. A low score suggests the baby was not doing well immediately after birth.^[11]

Blood gas measurements showing acidosis are often required for trial enrollment. Researchers usually look for a specific pH level in blood samples taken from the umbilical cord or from the baby shortly after birth. The pH is a measure of acidity, and a low pH indicates that too much acid has built up in the blood due to oxygen deprivation. Many trials require a pH below a certain threshold, such as 7.0 or 7.1, as evidence of significant oxygen deprivation.^[11]

Clinical examination findings are another key enrollment criterion. Babies must show specific neurological signs consistent with moderate or severe HIE. These signs include altered consciousness or responsiveness, abnormal muscle tone and reflexes, and sometimes seizures. Some trials use standardized scoring systems to classify the severity of encephalopathy based on these physical findings. Only babies meeting specific severity criteria are enrolled, as those with very mild symptoms may recover without treatment, while those with the most severe injury may not benefit significantly from experimental therapies.^[13]

Timing is crucial for many HIE clinical trials. Because some treatments work by interrupting the cascade of injury that unfolds in the hours after oxygen deprivation, trials often require that babies be identified and enrolled within a specific time window, typically within six hours of birth. This urgency means that diagnostic tests must be completed quickly. Babies who arrive at the hospital too late after the oxygen-depriving event or who cannot complete the diagnostic evaluation in time may not be eligible for the trial, even if they otherwise meet the criteria.^[11]

Some clinical trials investigating newer treatments or combination therapies may include additional diagnostic requirements beyond the standard criteria. For example, trials testing medications that work through specific biological pathways might require certain blood markers to be measured to ensure the baby’s body is capable of responding to the treatment. Trials may also mandate that specific imaging studies, such as MRI or continuous EEG monitoring, be performed to document the baseline severity of brain injury and track changes over time.^[16]

The use of therapeutic hypothermia, also called cooling therapy, has become the standard treatment for moderate to severe HIE. This treatment involves carefully lowering the baby’s body temperature to about 33-34 degrees Celsius for 72 hours, which can help reduce the progression of brain injury. Because cooling therapy is now standard care, many newer clinical trials test experimental treatments that would be given in addition to cooling, not instead of it. Therefore, the diagnostic criteria for these trials ensure that babies qualify for both the standard cooling treatment and the experimental therapy being tested.^[13]