Introduction 

Acute Bilirubin Encephalopathy (ABE) is a rare but serious neurological complication resulting from jaundice, which occurs due to high levels of bilirubin in the infant’s body. Unconjugated Bilirubin is a yellow fat-soluble pigment formed from haemoglobin, which gives rise to yellow discolouration of the skin (jaundice) in newborns. In the early days of a newborn's life, when bilirubin levels in the blood get too high, it can lead to acute bilirubin encephalopathy (ABE).

Only 60-80% of newborns experience neonatal jaundice during their first few days, but less than 2% reach dangerously high bilirubin levels that could result in serious neurodevelopmental issues like Acute Bilirubin Encephalopathy.¹

Therefore, it is important to look out for the early warning signs and symptoms of Acute Bilirubin Encephalopathy in your child in order to avoid any risks of long-term complications to the brain.

What causes acute bilirubin encephalopathy? 

Bilirubin metabolism basics

In newborns, excessive red blood cells will break down in a natural process called hemolysis, resulting in the release of haemoglobin, which will be converted to unconjugated bilirubin. This bilirubin is then processed in the liver into conjugated bilirubin, which is a water-soluble form that can be easily excreted by the body.

High bilirubin levels (also known as hyperbilirubinaemia) will give rise to jaundice, which generally appears on the second day of life. It is clinically visible when serum bilirubin reaches 5 mg/dl and increases in severity until day 4–5 before gradually disappearing by day 10.⁷ This is known as physiological jaundice, which is generally harmless and does not usually require any treatment.

In some newborns, however, unconjugated bilirubin can be significantly high due to increased red blood cell destruction, impaired bilirubin processing in the liver or decreased excretion.

This unconjugated bilirubin may cross the blood-brain barrier and deposit in the brain, particularly in the basal ganglia, because of its lipid solubility. If this toxicity continues over time, it can result in a permanent condition known as kernicterus.³ 

Risk factors

Lipid-soluble, unconjugated bilirubin is toxic to the developing brain, especially when its concentrations are high. Any condition which increases the bilirubin level in the blood above 20 mg/dL predisposes the baby to Acute Bilirubin Encephalopathy.³ These risk factors include:

• Premature birth-Babies born at less than 38 weeks of pregnancy
• Blood group incompatibility (e.g., Rh or ABO incompatibility)-If your baby has a brother or sister who had jaundice that needed treatment as a baby
• Bruising during birth or cephalohematoma
• Bilirubin-displacing drugs
• Infections or genetic disorders-Factors include hypothyroidism and infections, particularly meningitis

Early signs and symptoms of ABE 

Clinically, bilirubin encephalopathy progresses through three phases.³ In the first 2–3 days, the baby might appear to be lethargic and hypotonic(low muscle tone) and sucks weakly. Then the symptoms will progress to increased muscle tone, arching of the back, fever, and high-pitched crying, etc. In the final phase, the baby would have low muscle tone and floppy limbs for several days, and then gradually the muscle tone will increase.

Phase 1-Early-stage ABE (also called “acute phase”)

The acute phase of the disease spans over the first 3-5 days, and presents as non-specific symptoms such as:

• Lethargy-Unusual sleepiness 
• Poor feeding-A lack of interest in feeding or trouble latching on.
• Hypotonia (low muscle tone or floppy limbs)
• High-pitched crying
• Fuzzy or irritability

These signs indicate that bilirubin may be affecting the baby's nervous system. They can be subtle and overlap with other conditions such as low blood sugar, asphyxia, hypoxia(decreased oxygenation of the baby), hypothermia, and sepsis.³ Therefore, every jaundiced baby should be carefully assessed to exclude other causes.

Phase 2-Intermediate phase symptoms of ABE

Towards the end of the 1st week, the symptoms can progress into

• Arching of the back and neck
• Fever
• Shrill or high-pitched crying
• Seizures or fits-Sudden jerking movements, stiffening, or loss of consciousness-seizures usually go away on their own after the acute phase 

Neurological signs

• Muscles alternating between stiff and floppy
• Reduced responsiveness or coma

The child may also appear to have a scared or anxious facial appearance, which is the so-called “kernicterus facies”, which can even last up to at least 2-3 weeks after acute bilirubin encephalopathy.¹ Signs of kernicterus facies include:

• Abnormal facial movements-Infants have a tendency to have involuntary twitching, blinking
• Upward gaze with eyelid retraction-” Sun setting sign”

Phase 3-Advanced symptoms of ABE

Kernicterus is usually noted when the bilirubin level is excessively higher than the levels seen in physiological jaundice. If unrecognised and untreated, it may result in death or severe disabilities in the brain development of the baby. These disabilities include:

• Cerebral palsy- A child may develop Choreoathetoid cerebral palsy
• Significantly floppy limbs with low muscle tone
• Hearing loss
• Visual abnormalities
• Developmental delays
• Intellectual disabilities
• Difficulty with movement and coordination

FAQs

1: How ABE Is diagnosed?

If the jaundice appears on the first day of life, even in preterm babies, it is deemed abnormal and severe enough to require intervention. The same applies if it persists beyond the usual period of 2-10 days.

Clinical observation

The initial diagnosis of hyperbilirubinaemia is based on the appearance of jaundice during physical examination. The child is often placed by an open light source, such as a window, so that he/she may be checked in natural light. This is done in the first 3 days after birth, and the child’s behaviour, muscle tone, and feeding are also monitored along with this.⁴

Diagnostic tests

The bilirubin level in a baby's blood is measured through blood samples if jaundice appears within the first 24 hours of life.⁴

ABE and Kernicterus are associated with unconjugated bilirubin levels close to 20 mg/dL, and the incidence increases as serum bilirubin levels exceed 25 mg/dL. However, if the baby is premature and has other conditions and risk factors, kernicterus may be noted even at bilirubin levels less than 20 mg/dL.

Neurological assessment

Along with neurological symptoms and blood tests, an MRI of the brain is the most effective imaging technique for confirming the diagnosis.MRI is useful for distinguishing between the changes that occur in the acute phase and the chronic phase of the condition by visualising changes in the basal ganglia.³ Usually it is rarely used and reserved for severe cases or when lab tests are inconclusive.

2: How ABE Is treated?

ABE and Kernicterus may be prevented by avoiding excessively high unconjugated bilirubin levels and by avoiding conditions or drugs that may increase the bilirubin levels in the blood. 

The treatment modality is guided by the serum bilirubin levels and other coexisting conditions.

Phototherapy and exchange transfusion are the mainstay of treatment, and may be needed for several days before bilirubin levels in the blood normalise.

Phototherapy

Phototherapy is a treatment where the baby is kept under Ultraviolet light. The baby's skin absorbs this light, which changes bilirubin into a form that can be removed through urine. It is important to ensure that the baby is well hydrated since dehydration can increase bilirubin levels in the blood.

The effectiveness of phototherapy can be maximised by increasing the intensity of light or by maximising the exposure of the body surface. The baby’s eyes are shielded to prevent the optic nerves from absorbing too much light, which can permanently damage the retina.⁵ Phototherapy can also be done using a unique fiberoptic blanket. This approach doesn't require covering the baby's eyes, and it can be administered at home.

Exchange transfusion

Early signs of ABE may occasionally be reversed by beginning an exchange transfusion immediately. Exchange transfusion is effective for rapidly reducing the serum bilirubin levels to half of what they were before the procedure.

Exchange transfusion is usually performed through a catheter placed in the baby’s belly button, where the baby’s blood will be exchanged with blood from a matched donor with the same blood compatibility. Nowadays, the need for exchange transfusion has been decreasing due to the effectiveness of phototherapy.⁶

Summary

ABE is a preventable and treatable condition if recognised in time, and can protect your baby from harm. Understanding how ABE can differ from newborn jaundice can make all the difference when it comes to spotting the early symptoms and preventing the condition from progressing into more severe forms. Therefore, staying informed, trusting your instincts and being vigilant in seeking early treatment can lead to better outcomes and a healthier future for the child.