Introduction 

Kernicterus is defined as a rare but serious neurological complication of untreated jaundice in newborn babies.¹ Jaundice is the yellowing of the skin and whites of the eyes, and can range from being harmless to dangerous, in cases such as kernicterus.¹ It is important to diagnose kernicterus early, as bilirubin, which is the substance in the body which yellows the skin, can damage the brain and spinal cord, which can be life-threatening.1 Risk factors for jaundice, and therefore kernicterus, include being born premature, breastfeeding, an underactive thyroid gland (hypothyroidism), blood group incompatibility with the mother, infection, and several other conditions.¹ Although kernicterus is relatively rare, if significant brain damage occurs before treatment, a child can develop cerebral palsy,² hearing loss and learning disabilities, again highlighting the importance of early diagnosis. The methods of diagnosis of kernicterus are visual examination, a bilirubin test and further laboratory tests, such as the baby’s blood group, to diagnose infection or other underlying cause for the raised levels of bilirubin.¹ However, several brain scans can detect whether the brain has been affected by elevated bilirubin levels, including Magnetic Resonance Imaging (MRI), Magnetic Resonance Spectroscopy (MRS) and Diffusion Tensor Imaging (DTI).¹⁰

Pathophysiology

Jaundice is caused by the buildup of a substance called bilirubin in the blood.1 It is a substance produced when red blood cells are broken down.¹ Jaundice is common in newborn babies because they have a high amount of red blood cells, which are broken down and replaced frequently.¹ Bilirubin is removed from the blood via the liver, and if a baby’s liver is not fully developed (i.e. if they are premature), it is less effective at clearing bilirubin from the blood, leading to a yellowish colour of the skin and eyes.1 In newborn babies with extremely high levels of bilirubin in the blood for a prolonged period of time, the bilirubin can cross the barrier that separates the brain from the blood and cause kernicterus, which is a rare consequence of high levels of bilirubin in babies.¹

Risk factors 

Neonatal risk factors 

If a baby is born with low birth weight (<2500g at birth)⁴ or premature (before 37 completed weeks of gestation),⁵ they are at risk for developing kernicterus due to an immature liver being unable to process extra bilirubin.³

Maternal and perinatal factors

 The most common cause of severely high levels of bilirubin in a baby’s blood is breakdown of red blood cells due to blood cell incompatibility with the mother. This means the mother’s immune system recognises the baby’s blood cells (which are shared in the womb) as foreign due to being of a different blood type, thereby attacking and destroying them, after which the breakdown products cause jaundice and kernicterus.³

Other risk factors

A newborn should show signs of jaundice within 72 hours,¹ of being born as part of the newborn examination. If a newborn is discharged from the hospital or is not delivered by a medical professional in a healthcare facility and checked for jaundice, this can lead to kernicterus.³

Clinical findings

Initial signs of jaundice

Jaundice is the initial phase of kernicterus; however, only a few babies with jaundice will progress to having kernicterus if left untreated.¹ Early signs of jaundice are yellowing of the skin, eyes, inside the mouth, on the soles of the feet, and on the palms of the hands.¹ A newborn with jaundice may also be excessively sleeping, have dark yellow pee and pale poo.¹

Initial signs of kernicterus

Jaundice progresses to kernicterus, which involves the baby’s brain.¹ Signs of kernicterus are: 

• Poor feeding
• Rritability
• A high-pitched cry
• No startle reflex (when a baby spreads its arms and legs when given fright)⁶
• Fatigue
• Brief cessation of breathing 
• Muscles are becoming floppy¹

Late (chronic) symptoms
Later signs include:

• Fits (seizures) and muscle spasms
  • This can look like arching of the back and neck¹ 
  • If left untreated, a child can develop serious and permanent complications such as hearing loss, learning disabilities, involuntary twitching, problems with eye movements, poor teeth development and cerebral palsy⁷

Imaging findings

Clinical findings are the initial first line of detection of jaundice, and a bilirubin test can also be used.¹ This test can be conducted using a small device which shines a light on the baby’s skin to detect the level of bilirubin in the blood.¹ A blood sample can also be taken, whereby bilirubin can be measured.¹ However, bilirubin that progresses to kernicterus requires medical imaging.

Role of magnetic resonance imaging (MRI)

MRI is the imaging modality of choice and typically shows the areas that have excess amounts of bilirubin in the brain. Of these areas, an area of the brain called the globus pallidus seems to be the most sensitive region in the brain for detecting anomalies associated with kernicterus.⁹ The pattern of abnormalities demonstrated is usually both sides of the brain and symmetrical.¹⁰ 

Typical MRI patterns in kernicterus include T1, T2 and DWI regions.⁹ In the early/subacute phases (days or weeks after brain damage due to encephalopathy), high T1-signal regions have variable signal abnormalities, leading to false positive or negative results due to the presence of a substance called myelin in the brain.10 Thus, early MRI has limited predictive value.¹⁰ T2 regions may initially be normal, then develop into high signal intensity as the disease progresses, and DWI regions are normal.⁹ It is now understood that the nature of these abnormalities varies with time.¹⁰ A chronic increased T2 signal in the globus pallidus and subthalamic nucleus (another area of the brain) of an infant with previous high bilirubin levels and chronic brain damage due to this remains the neuroimaging hallmark of kernicterus.¹⁰ 

Advanced imaging techniques:

Magnetic resonance spectroscopy (MRS) and Diffusion tensor imaging (DTI) are new diagnostic techniques which show promise in the detection of kernicterus.¹⁰ MRS has previously been reported to be useful in the detection of early kernicterus.¹⁰ Increased levels of glutamine and glutamate are present with decreased levels of choline and N-acetyl-aspartate, which are brain metabolites, in areas of the brain affected by kernicterus.⁹  

DTI measures water diffusion along white matter tracts. While MRI detects end-stage T2 signs of kernicterus, DTI and MRS offer early, quantitative measures of both the cause and severity of kernicterus,¹⁰ but are still evolving modalities.

Differential diagnosis

Other conditions with similar symptoms include hypoxic ischaemic encephalopathy, hypoglycaemia, carbon monoxide poisoning, encephalitis, inborn errors of metabolism, demyelinating disorders and various degenerative diseases.⁹

Summary

While neonatal jaundice is extremely common, it can range from being completely harmless and resolving spontaneously within a few days to having dire long-term consequences if left undetected and untreated.¹ One such consequence is kernicterus, which is damage to the newborn’s brain due to high levels of bilirubin.¹ The first signs of high levels of bilirubin will be yellowing of the skin and eyes, restlessness and poor feeding.1 As the condition worsens, the baby may display neurological signs of kernicterus, such as seizures and stiffness. These are urgent signs for medical care. The gold standard for diagnosing kernicterus on scan is T2 MRI; however, MRS, DTI, and evolving diagnostic methods can detect kernicterus earlier and can measure the severity and cause thereof.^9,10 As kernicterus can cause long-term developmental complications such as cerebral palsy, hearing loss and visual problems, it is vital to detect neonatal jaundice and kernicterus early.¹

FAQs

Can kernicterus be cured?

As kernicterus is long-term brain damage, it cannot be reversed; however, early stages of brain damage can be treated if caught in time.¹

Is all jaundice dangerous?

No, mid jaundice is common in newborns; however, very high levels of bilirubin, especially if left untreated, can lead to kernicterus.¹

When should parents worry about jaundice?

If the baby’s skin or eyes are yellow, especially within the first two days, or shows signs of poor feeding, muscle weakness, or a high-pitched cry, medical attention should be sought.¹