Introduction

Our bodies are constantly renewing themselves, even down to our blood. As part of this process, old red blood cells are broken down and recycled, producing a yellow substance called bilirubin.¹

In both adults and children, bilirubin is quickly processed and removed by the liver without any issues. However, in newborns, things work a little differently. Their bodies are still adjusting to life outside the womb, and sometimes bilirubin can build up to dangerous levels. When this happens, it can lead to kernicterus (ker-nick-ter-us), a form of brain damage caused by very high levels of bilirubin.²

In this article, we’ll explore what bilirubin is, why newborns are more vulnerable to it, and how it can cause kernicterus. Most importantly, we’ll learn how kernicterus can almost always be prevented with early care.

Understanding bilirubin

What is bilirubin?

Bilirubin is a natural yellow waste product created by the breakdown of red blood cells. Bilirubin metabolism reflects liver function and its ability to clear metabolic waste: high bilirubin levels in the blood (hyperbilirubinaemia) may suggest that something is wrong in the liver.¹ 

How is bilirubin created?

To understand how bilirubin may cause disease, let's break down how it is formed in the body. Red blood cells (RBCs) are responsible for transporting oxygen around the body and have a lifespan of around 120 days. When old, damaged RBCs are ready to be removed from the circulation, they are broken down by a process called haemolysis (hee-mo-ly-sis). Old RBCs are filtered through the spleen, where they are phagocytised (engulfed) by white blood cells called macrophages, and degraded.¹

Our RBCs contain a protein called haemoglobin, which carries oxygen and carbon dioxide through the body. Haemoglobin is digested into heme and globin (oxygen-binding protein). Heme is further broken down into iron, which can be recycled back into the body, and biliverdin (a green pigment). Biliverdin is then converted to bilirubin and released into the blood as unconjugated (free) bilirubin.^1,3

Unconjugated bilirubin is fat-soluble, meaning it mixes with fat (not water) and therefore cannot be passed out of the body. To safely travel through the watery bloodstream to the liver for processing, unconjugated bilirubin must bind to a carrier protein called albumin.

The liver’s role: making bilirubin safe

Once unconjugated bilirubin reaches the liver, enzymes convert unconjugated bilirubin into conjugated bilirubin, a water-soluble version that can be transported without the need for albumin. Conjugated bilirubin then moves into the digestive system as bile and is further converted by bacteria in the intestine into waste that is excreted in urine (urobilinogen) and faeces (stercobilin).^3,4

Why are babies more vulnerable?

In a healthy adult, the breakdown and excretion of bilirubin work smoothly. However, newborn babies are more susceptible to potential problems. Newborn RBCs have a considerably shorter lifespan of 80-100 days (60-80 days if premature) compared to that of an adult (adult RBCs can survive up to 140 days). As a result, newborn RBCs regenerate at a higher rate, producing more bilirubin when they are broken down. Newborn babies also have less albumin in the blood to bind to unconjugated bilirubin for transportation to the liver.^4,5

Furthermore, the developing liver and digestive systems may not remove bilirubin quickly enough. This can be due to various reasons, including:⁴

• Decreased uptake of unconjugated bilirubin into the liver
• Fewer enzymes are made by the liver for bilirubin conjugation 
• Underdeveloped gut bacteria in the intestines, slowing the breakdown of conjugated bilirubin into excretable forms

These combinations mean that bilirubin can build up in their bodies faster than it can be removed, leading to neonatal (newborn) jaundice, characterised by yellowing of the skin and eyes.⁴

Unless present in the first 24 hours of life, neonatal jaundice is common and usually harmless. Around 60% of babies develop jaundice in the first week after birth, rising to 80% for babies born prematurely. This often resolves without causing harm by 14 days post-birth, when a baby’s liver is more effective at processing bilirubin. However, prolonged elevated jaundice levels pose serious health risks if left untreated.^6,7

When bilirubin becomes dangerous 

Hyperbilirubinaemia (hyp-er-bili-rubin-eemia) is a medical term used to describe when there is too much bilirubin in the blood, leading to jaundice. Usually, this can be managed easily, but it can become dangerous without intervention. At very high levels, bilirubin may cross into the brain and harm delicate brain tissue, leading to kernicterus.² 

What is kernicterus?

Kernicterus (also known as bilirubin encephalopathy) is a form of permanent brain damage caused by prolonged high bilirubin levels. Severe hyperbilirubinemia (> 20 mg/dL) that could potentially lead to kernicterus is extremely rare, affecting less than 2% of newborns. However, if left untreated, it can cause lifelong disabilities.^2,8 

How bilirubin enters the brain

Normally, albumin holds bilirubin safely in the blood. If unconjugated bilirubin levels cross 25mg/dL in the blood, there is not enough albumin to bind to it, creating free unconjugated bilirubin. This is fat-soluble and can cross the protective layers around the brain called the blood-brain barrier. In newborns, the blood-brain barrier isn’t fully developed, and free bilirubin may accumulate in the brain, particularly in the basal ganglia responsible for movement, decision making and emotions.^2,4,9

Bilirubin causes toxicity to brain cells by attaching to the surface of the messenger cells in your brain called neurons (nerve cells). It damages the mitochondria of the cells, preventing the cells from producing energy and causing calcium release that promotes cell death. It also affects the growth of axons and dendrites, both key structures in nerve cell function and communication. Overall, this interferes with the normal functioning of brain cells and leads to irreversible damage that worsens with longer exposure.^2,8

Commonly affected areas include, but aren’t limited to:^2,8,10 

Warning signs

Initial (acute) symptoms of kernicterus in babies include:

• High-pitched crying
• Irritability
• Poor feeding
• Lethargy (sleepiness)
• Apnoea (brief pauses in breathing)
• Less responsive or floppy muscles

As kernicterus progresses, symptoms can include seizures and muscle spasms that can cause arching of the back and neck. Late-stage kernicterus is very serious and can be fatal, with most deaths occurring in low-middle-income countries (LMICs).¹¹

Complications

If left untreated, chronic kernicterus can develop, causing long-term conditions such as:^2,8 

• Cerebral palsy (a condition affecting movement and coordination)
• Learning disabilities
• Mild to severe hearing loss
• Vision and dental problems

These effects are irreversible, which is why early diagnosis and treatment are crucial to get the best outcome. If severe brain damage caused by kernicterus does occur, families face long-term challenges. Babies with this condition often need physical therapy, speech therapy, and other forms of support as they grow. Some may require assistive devices for mobility or communication.^2,8

FAQs

Which babies are at risk of kernicterus?

Healthy babies can develop jaundice due to too much bilirubin. However, certain factors can disrupt the metabolism of bilirubin and increase the chance of significant hyperbilirubinaemia, leading to kernicterus. These include:^2,8

• Premature birth (before 38 weeks)
• Previous sibling with neonatal jaundice requiring phototherapy (phototherapy)
• Feeding difficulties

• Blood type incompatibilities causing the mother’s immune cells to break down the baby’s red blood cells
• Bruising or birthing injuries
• Certain genetic conditions (e.g. Gilbert’s Syndrome, G6PD Deficiency)

All of these can either increase bilirubin production, reduce liver processing, or weaken albumin binding, leading to more free bilirubin in the blood. In addition, yellowing of the skin may be harder to spot in babies with a darker skin tone, meaning the initial signs of jaundice may be missed. To prevent this, healthcare professionals must ensure that the whites of the eyes, gums, palms of hands and soles of feet are checked.^2,8

How can kernicterus be prevented?

With early diagnosis and treatment, kernicterus is preventable. The most important factor in preventing kernicterus is timing, as bilirubin levels can rise rapidly. Most babies with jaundice don’t develop kernicterus, but all babies should be monitored so that hyperbilirubinaemia can be treated before bilirubin reaches the brain.^2,8

Summary

Bilirubin is a natural substance produced by the breakdown of old, damaged RBCs, but too much bilirubin can be harmful to newborns and can lead to kernicterus if it passes the underdeveloped blood-brain barrier. Understanding how bilirubin is made, how it’s supposed to be processed, and what happens when the system fails is key to preventing harm. Modern medicine makes kernicterus very rare and almost entirely preventable with good monitoring and treatment. 

Safe bilirubin levels today may be unsafe tomorrow. Parents should never hesitate to ask their doctors about jaundice, bilirubin levels, or treatment options. It is important to speak up if you are concerned about potential jaundice in your baby, as knowing what to look for can truly make a difference.