Neonatal Encephalopathy

Neonatal encephalopathy is a serious condition affecting newborns that occurs when the brain does not function normally in the earliest days of life, often marked by altered consciousness, seizures, poor muscle tone, and breathing difficulties.

Table of contents

• What is Neonatal Encephalopathy?
• What Causes Neonatal Encephalopathy?
• Risk Factors
• Signs and Symptoms
• How is it Diagnosed?
• Severity Levels
• Treatment Options
• Outcomes and Prognosis
• Infection and Neonatal Encephalopathy

What is Neonatal Encephalopathy?

Neonatal encephalopathy is a complex condition of the newborn characterized by disturbed brain function in the earliest days of life. It affects infants born at or beyond 35 weeks of pregnancy.^[2] The condition shows itself through an altered level of consciousness or seizures, and is often accompanied by difficulty starting or maintaining breathing and weakness in muscle tone and reflexes.^[2]

Encephalopathy means a disorder or disease of the brain. In newborns, this condition ranks among the top 10 neurological conditions worldwide with the highest disability-adjusted life years and is increasingly recognized as a major cause of death and lifelong disability.^[6] The condition is also associated with problems in multiple organs beyond the brain.^[2]

The incidence of neonatal encephalopathy is estimated at 3 per 1,000 live births.^[2] In the United States, one type of neonatal encephalopathy called hypoxic-ischemic encephalopathy (HIE) affects an estimated 1 to 6 infants out of every 1,000 births, which equals about 9,000 to 12,000 newborns each year.^[4]

birth asphyxia, neonatal hypoxic-ischemic encephalopathy, perinatal hypoxia, perinatal asphyxia, acute neonatal encephalopathy

What Causes Neonatal Encephalopathy?

Neonatal encephalopathy can have many different causes. These causes can occur before birth, during birth, or shortly after birth. Understanding that there are multiple causes is important for proper treatment and prevention.^[2]

One common cause is when a baby’s brain does not get enough oxygen and blood flow. This is called hypoxic-ischemic encephalopathy (HIE). Hypoxic means not enough oxygen, and ischemic means not enough blood flow.^[3] When brain tissue does not receive oxygen for even a few minutes, brain cells can be damaged or die. Just 5 minutes without oxygen can cause permanent problems.^[17]

Other factors that have been linked to neonatal encephalopathy include infections, problems with the placenta, blood clotting disorders, and metabolic disorders.^[2] Maternal infections and a condition called chorioamnionitis (infection of the membranes around the baby) have also been documented as contributing factors.^[6] In many cases, the exact cause of neonatal encephalopathy is unknown.^[3]

Problems during fetal development can also lead to neonatal encephalopathy. These include abnormal development or function of the baby’s heart or lungs, infections during pregnancy, blood pressure that is too high or too low in the pregnant mother, or low oxygen levels in the mother.^[4]

Complications during labor and delivery are another important group of causes. The umbilical cord may drop out of place before the baby is born, the cord may be compressed, or blood flow in the cord may stop. The placenta may separate from the uterus too early, the uterus may tear open, or the placenta may block the cervix.^[4]

Risk Factors

Many factors can raise a baby’s risk for developing neonatal encephalopathy. Some of these factors are related to the pregnant parent, while others are related to health problems in the developing baby.^[3]

Risk factors related to the baby include low birth weight, contamination of the amniotic fluid, delayed fetal development where certain organs like the lungs did not develop completely, and heart problems in the baby.^[3][4] Fetal stroke can occur for many reasons, such as the pregnant parent’s blood pressure level, pelvic infection, or impaired blood flow in the placenta.^[3]

Risk factors in the pregnant parent include very low or high blood pressure, preeclampsia (a serious condition involving high blood pressure during pregnancy), gestational diabetes (diabetes that develops during pregnancy), prolonged labor, and substance use disorder.^[4]

Problems with the uterus or placenta, problems during labor and delivery such as injury from the umbilical cord, emergency cesarean section, lack of blood flow to the baby’s brain during birth, poor oxygen supply during pregnancy, and trauma all increase the risk of neonatal encephalopathy.^[3]

Signs and Symptoms

The symptoms of neonatal encephalopathy can vary from baby to baby and depend on which part of the brain is damaged. Symptoms can range from mild to severe.^[3]

Common symptoms include an unusual state of being awake and aware, such as being highly alert or having very low energy. Babies may have trouble breathing or not be able to breathe on their own. They may have difficulty eating and problems with hearing or vision.^[3]

Babies with neonatal encephalopathy may experience seizures or other neurological problems. They often have muscle or reflex problems, with muscles that are either too floppy (weak muscle tone or hypotonia) or too tense (hypertonia).^[3][4] A weak cry, a slow heart rate, and organ failure can also occur.^[3]

At birth, some babies need help to breathe and maintain a heartbeat, which is called resuscitation. The baby’s skin color may be bluish, gray, or lighter than normal. There may be too much acid in the blood, a condition called acidosis.^[15]

In severe cases, a baby may have delays in growth or development. They may also develop cerebral palsy or a mental disability. The severity of these symptoms may not be fully seen until ages 3 to 4.^[3]

How is it Diagnosed?

In many cases, doctors suspect neonatal encephalopathy in a newborn shortly after birth. The diagnosis is often based on the baby’s symptoms, such as seizures, and any problems that occurred during labor and delivery.^[3]

At birth, doctors and nurses check the baby carefully and rate their condition from 0 to 10 using a scoring system called an Apgar score. The Apgar score rates skin color, heart rate, muscle tone, reflexes, and breathing effort. A very low Apgar score (0 to 5) lasting longer than 10 minutes may be a sign of neonatal encephalopathy.^[15]

To confirm the diagnosis, doctors may use several tests. Blood tests are used to check the amount of oxygen in the blood and can show the levels of electrolytes, enzymes, certain nutrients like calcium, and other parts of the blood that may help with diagnosis.^[3] The doctor will look for signs of a high level of acid in the blood by taking a sample of the baby’s blood or cord blood at the time of birth or soon after.^[15]

Testing the blood from the umbilical cord or examining the placenta may help figure out the cause of neonatal encephalopathy.^[3] A lumbar puncture (also called a spinal tap) may be done, where a long needle is put into the lower back to take a sample of cerebrospinal fluid. The fluid is then checked for infection.^[3]

Imaging tests help doctors see what is happening in the baby’s brain. An ultrasound of the head can show if a baby has bleeding or a buildup of fluid in the brain. Magnetic resonance imaging (MRI) scans use magnets and radio waves to create detailed pictures of the brain’s soft tissues.^[3]

An electroencephalography (EEG) test checks the electrical activity of the brain and can detect abnormal brain function or seizures.^[3] Doctors will also examine the baby for signs of abnormal brain function. All these tests together help doctors understand the severity of the condition and plan treatment.^[15]

Severity Levels

Neonatal encephalopathy is graded based on how severe it is and the baby’s outlook for recovery. Healthcare providers classify the condition as mild, moderate, or severe. These grades can affect neurological outcomes and help guide treatment decisions.^[4]

The severity of neonatal encephalopathy depends on how long the baby’s brain was without enough oxygen and blood flow. The longer the brain goes without oxygen, the more severe the damage can be.^[3] All grades of neonatal encephalopathy require emergency medical attention to prevent life-threatening complications.^[4]

Two stages of injury can happen with neonatal encephalopathy. The first stage happens within minutes if blood flow is low and cells do not get enough oxygen. The second stage is called reperfusion injury and can last for days or even weeks. After the brain starts getting normal levels of blood and oxygen, damaged cells release chemicals that cause additional harm.^[15]

Treatment Options

At present, therapeutic hypothermia (also called cooling therapy or whole-body cooling) is the only treatment available for moderate to severe neonatal encephalopathy, regardless of the specific cause.^[2][10] This treatment involves carefully lowering the baby’s body temperature to help protect the brain from further damage.

Therapeutic hypothermia is indicated for infants with moderate to severe neonatal encephalopathy. Following initial resuscitation and stabilization, treatment includes hypothermia therapy as well as supportive measures focusing on adequate oxygen delivery, proper breathing support, and careful blood flow management.^[8]

Treatment must be started quickly. Based on current recommendations, therapeutic hypothermia must be initiated within 6 hours after birth to be effective.^[8] The cooling treatment lowers the baby’s body temperature to about 33.5 degrees Celsius and typically continues for a specific period before the baby is slowly warmed back to normal temperature.^[9][16]

Supportive management is critical to prevent additional injury. This includes treatment of seizures, careful management of fluids and electrolytes, avoiding both low blood sugar (hypoglycemia) and high blood sugar (hyperglycemia), and avoiding high body temperature. Ensuring adequate oxygenation, breathing support, and stable blood pressure are also essential.^[8]

If the baby has signs of infection along with neonatal encephalopathy, antibiotics are used. However, the dosing of certain antibiotics like gentamicin may need to be adjusted during cooling therapy because the medicine is cleared from the body differently when the baby’s temperature is lowered.^[8]

Physical therapy and developmental evaluations are needed before the baby is discharged from the hospital. Close monitoring and regular follow-ups are essential to optimize outcomes. Referring the baby to early intervention programs is recommended at the time of discharge.^[8]

Researchers are exploring other treatments that might be used along with cooling therapy. One such treatment being studied is erythropoietin (EPO), a substance that may help protect brain cells. Studies in animals and early human trials suggest that combining EPO with hypothermia may lead to better outcomes, though more research is needed.^[9]

Outcomes and Prognosis

Neonatal encephalopathy is a life-threatening condition that is associated with high rates of death and disability. The condition can be fatal or cause permanent brain damage in severe cases.^[4] After a diagnosis of neonatal encephalopathy, 40% to 60% of infants either do not survive past two years of age or suffer severe intellectual disabilities, such as mental retardation, epilepsy, or cerebral palsy.^[6]

The outcome depends on several factors, including the severity of the condition and how quickly treatment begins. Babies with mild or moderate neonatal encephalopathy may recover fully if cells did not go without oxygen for too long.^[15] However, if cells did not get enough oxygen for a longer time, a baby may have permanent injury affecting their brain, heart, lungs, kidneys, or other organs.^[15]

The amount of harm depends on how long the baby did not get enough oxygen and how quickly the baby received the right treatment.^[15] At this time, whole-body cooling is the only treatment that can improve outcomes for babies born after 35 weeks of pregnancy who have moderate or severe neonatal encephalopathy.^[15]

Long-term outcomes may include delays in growth or development, learning difficulties, movement problems, or cerebral palsy. Some children may also have epilepsy or other neurological problems. The severity of these symptoms may not be fully apparent until ages 3 to 4.^[3]

Caring for a child with neonatal encephalopathy can be emotionally challenging for families. Parents often experience cumulative loss and grief throughout the crisis period, the critical first days in the hospital, and when the child misses developmental milestones. Parents also find themselves balancing the needs of the affected child with broader family interests and often evolve into becoming advocates for their child.^[13]

Infection and Neonatal Encephalopathy

The relationship between infection and neonatal encephalopathy is increasingly recognized as important. The incidence of early culture-positive infections is much higher in babies with neonatal encephalopathy, increased 20 to 40 times over newborns without the condition.^[6] The rate of confirmed early infection in babies with neonatal encephalopathy is 23 per 1,000 compared to rates of early onset sepsis in term and near-term infants of 0.5 to 1.0 per 1,000 live births.^[6]

Maternal infections, including chorioamnionitis, have been well documented as contributing to worse outcomes in babies with neonatal encephalopathy.^[6] Chorioamnionitis is associated with brain injury and worse developmental outcomes including cerebral palsy, even in the absence of neonatal encephalopathy.^[6]

Some studies have suggested that therapeutic hypothermia might be less effective in infants with both sepsis and neonatal encephalopathy, though other research has shown that culture-positive sepsis was not a barrier to improved outcomes from cooling treatment.^[6] Despite the evidence linking infection with neonatal encephalopathy outcomes, this has not yet changed treatment guidelines, and cooling therapy is still recommended for babies with moderate to severe neonatal encephalopathy who also have risk factors for infection.^[6]

Understanding the role of infection in causing or worsening neonatal encephalopathy is important for optimal management. Recognizing when infection may be involved helps guide investigations such as metabolic workups and sepsis evaluations to ensure babies receive appropriate treatment.^[2]