Acute Bilirubin Encephalopathy

How bilirubin damages the brain

Bilirubin is a yellow substance made when red blood cells break down. Newborns produce a lot because they have many red cells with a short lifespan, and their immature liver clears it slowly. That is why most babies develop some newborn jaundice.

Most bilirubin travels bound to albumin in the blood. When levels rise very high, or albumin binding is reduced (in prematurity, acidosis, infection or some medicines), free unbound bilirubin crosses the blood-brain barrier. It is toxic to nerve cells, particularly in the globus pallidus, subthalamic nucleus, hippocampus, brainstem hearing nuclei and nerves controlling eye movement.

ABE is the acute phase of this injury. If it progresses or is not reversed, it leads to chronic bilirubin encephalopathy, also called kernicterus.

Phases and symptoms

Doctors sometimes use a BIND score (bilirubin-induced neurologic dysfunction) that rates mental status, muscle tone and cry to judge severity and response to treatment. Early-phase changes are usually reversible with prompt treatment. Intermediate and advanced phases carry a high risk of permanent damage.

Causes and risk factors

ABE results from severe hyperbilirubinemia. Factors that raise bilirubin quickly or make the brain more vulnerable include:

• Hemolysis (red cell breakdown): ABO incompatibility, Rh disease, G6PD deficiency, hereditary spherocytosis
• Prematurity, including late preterm babies born at 35 to 37 weeks
• Poor feeding and dehydration, especially in the first week of exclusive breastfeeding when feeding is not yet established
• Bruising or a large scalp hematoma from a difficult delivery
• Infection (sepsis), acidosis and low albumin
• Genetic conditions such as Crigler-Najjar syndrome
• Previous sibling who needed phototherapy
• East Asian ancestry, associated with higher bilirubin levels

Early discharge from hospital without a follow-up check is a known contributor to missed severe jaundice.

Diagnosis

• Total serum bilirubin (TSB): a blood test, plotted on age-in-hours charts with neurotoxicity risk factors to decide on treatment thresholds
• Direct (conjugated) bilirubin to exclude liver disease
• Blood group and Coombs test (direct antiglobulin test) for immune hemolysis
• Blood count, reticulocytes and smear, G6PD level, albumin
• Neurological exam for tone, cry and alertness
• Hearing test (auditory brainstem response), which can be abnormal early
• MRI later may show changes in the globus pallidus

Treatment

ABE is treated as an emergency. The 2022 AAP guideline advises an escalation of care when bilirubin approaches the exchange transfusion threshold.

• Intensive phototherapy: special blue-green light converts bilirubin into forms that are excreted without needing the liver. It is started immediately while other treatment is arranged.
• Exchange transfusion: the baby's blood is gradually replaced with donor blood through an umbilical catheter, rapidly lowering bilirubin and removing antibodies. It is recommended urgently for any baby showing signs of ABE, even if bilirubin is falling.
• IV immunoglobulin (IVIG) in immune hemolysis to slow red cell breakdown.
• Fluids and feeding support to correct dehydration.
• Treating infection and acidosis.

Outcome and complications

Babies treated during the early phase often recover completely. Delayed treatment can lead to kernicterus, which causes:

• athetoid (dyskinetic) cerebral palsy with writhing movements
• hearing loss or auditory neuropathy
• limited upward gaze
• dental enamel defects
• intellectual function is often relatively preserved

All babies who had ABE need hearing tests and developmental follow-up.

Prevention

• Check every newborn for jaundice before discharge with a skin or blood bilirubin measurement.
• Arrange a follow-up visit within 1 to 2 days of discharge for babies leaving hospital early.
• Support frequent feeding: 8 to 12 breastfeeds every 24 hours.
• Know the warning signs: jaundice in the first day, spreading jaundice, sleepiness, poor feeding.
• Test for G6PD deficiency in at-risk babies.
• Give Rh immunoglobulin to Rh-negative mothers in pregnancy to prevent Rh disease.

Frequently asked questions

What are the early signs of bilirubin encephalopathy?

Early signs in a jaundiced newborn are unusual sleepiness, poor sucking and feeding, and low muscle tone. Later signs include a high-pitched cry, arching of the neck and back, fever and seizures. Any jaundiced baby who is hard to wake or not feeding needs emergency care.

Is acute bilirubin encephalopathy reversible?

Often, if treated early. Prompt intensive phototherapy and exchange transfusion during the early phase can reverse the signs. Once a baby reaches the intermediate or advanced phases, permanent brain damage (kernicterus) is much more likely.

What is the difference between ABE and kernicterus?

Acute bilirubin encephalopathy describes the acute signs of bilirubin toxicity in the first weeks of life. Kernicterus is the chronic, permanent result, with movement disorders, hearing loss and eye movement problems that become clear over the first year.

What bilirubin level causes brain damage?

There is no single level. Risk depends on the baby's age in hours, gestational age and risk factors such as hemolysis, infection and low albumin. Doctors use age-specific charts from the American Academy of Pediatrics to decide when to start phototherapy and when exchange transfusion is needed.

Can breastfeeding cause bilirubin encephalopathy?

Normal breastfeeding does not. However, when breastfeeding is not well established in the first days, babies may get too little milk, become dehydrated and clear bilirubin more slowly. Feeding support and early jaundice checks prevent this.