Kernicterus is a form of brain damage caused by excessive jaundice. The substance which causes jaundice, bilirubin, is so high that it can move out of the blood into brain tissue. When babies begin to be affected by excessive jaundice, when they begin to have brain damage, they become
excessively lethargic. They are too sleepy, and they are difficult to arouse – either they don’t wake up from sleep easily like a normal baby, or they don’t wake up fully, or they can’t be kept awake. They may have a high-pitched cry, and decreased muscle tone, becoming hypotonic or floppy with episodes of increased muscle tone (hypertonic) and arching of the head and back backwards. As the damage continues they may arch their heads back into a very contorted position
known as opisthotonus or retrocollis, they may develop fever, and they may even develop seizures (convulsions). Kernicterus is from the Greek “kern” or kernel plus “icterus” or yellow. Kernicterus refers to the yellow staining of the deep nuclei (i.e., the kernel) of the brain namely, the basal ganglia. Kernicterus involves a specific part of the basal ganglia, the globus pallidus. It also includes lesions (damage) to brainstem nuclei in auditory (hearing), oculomotor (eye movement), and vestibular (balance) systems and the cerebellum (coordination). Abnormalities of the globus pallidus can be seen on MRI scan of infants with kernicterus.
Clinically, classic kernicterus involves:
• Specific movement disorders of abnormal tone and involuntary movements
• Auditory processing disturbance with or without hearing loss or deafness
• Impairment of eye movements especially upward gaze
• Abnormal staining of the enamel of baby teeth
Children with kernicterus have a “dystonic” or “athetoid” form of cerebral palsy. The “athetoid” form of cerebral palsy is classic and athetosis refers to the slow, writhing involuntary movements that occur. Dystonia, or abnormal muscle tone and position, is more common, and may occur with or without athetosis.
Some children with kernicterus are deaf, some have normal hearing, and some with or without deafness have an auditory processing problem called auditory neuropathy, auditory dyssynchrony or by it’s new name, auditory neuropathy spectrum disorder (ANSD). Auditory brainstem responses, ABRs also known as BAEPs, BAERs or BSERs are often abnormal, whereas other “hearing” tests, such as otoacoustic emissions (OAEs) and cochlear microphonic responses are
normal. An abnormal ABR with a normal cochlear microphonic response is the “gold standard” way to diagnose ANSD, and requires recording electrical activity (brain waves) from a few electrodes pasted on the scalp in response to sounds played through insert earphones, usually when the child is asleep or sedated
Kernicterus is, fortunately, a very rare occurrence. Other forms of more subtle bilirubin-induced neurological damage may exist, including auditory processing problems, one form of which is ANSD, and other problems of sensorimotor integration.
Most newborn Infants are temporarily jaundiced in the first week or two of life. That is, 60 to 80% of newborns have visible jaundice in the first week or two of life.
Jaundice is yellow coloring of the skin and other tissues because of a high level of bilirubin in the blood (hyperbilirubinemia). Bilirubin is a normal breakdown product of red blood cell hemoglobin. Babies are normally born with a large part of their blood composed of red blood cells, about 60%, that is, about 60% is red blood cells, and 40% is plasma. The red cell volume of the blood, called the hematocrit, is higher in the newborn than at any other time of life.
Red blood cells are made constantly at all ages. Mature red blood cells survive for about 2 months in newborns and about 3 months in older children and adults and therefore must constantly be replaced. When red cells break down, the hemoglobin which gives blood its red color is released and broken down into bilirubin. This bilirubin is unconjugated bilirubin (UCB) or also called indirect bilirubin.
Bilirubin. The unconjugated bilirubin (UCB) cannot dissolve in water, that is to say, it is not soluble in water or in blood. If it is free to move out of the blood into tissue, UCB can be toxic to specific parts of the brain. However, in blood UCB binds tightly to albumin and other proteins, and this keeps it from moving out of the blood into tissue. The albumin-bound UCB then goes to the liver where a sugar molecule (called a glucuronide) is attached or conjugated onto it forming conjugated bilirubin (also called direct bilirubin). This conjugated bilirubin is soluble in blood and water, it is non-toxic, and it is excreted into the gut where it is eliminated with the stool.
When does bilirubin become toxic to the brain, i.e., when does bilirubin neurotoxicity occur?
The simple answer is that bilirubin become neurotoxic when it: 1) exceeds the capacity of the blood to hold it inside the blood vessels and it escapes into the tissue, and 2) exceeds the capacity of the tissue (i.e., the brain) to get rid of it.
A more complex answer is that bilirubin (or UCB) is held in the blood bound to protein, especially albumin in the blood, and when it exceeds the capacity of albumin to bind it, it can escape into tissue. When this happens varies for different babies, depending on their maturity (gestational age), size, health (or sickness), amount of albumin in their blood, and amount of feeding and stooling which is how the bilirubin is eliminated from the body.
When UCB starts to leave the blood and go into brain tissue, it starts to cause neurological signs and symptoms. Early on it’s hard to tell when symptoms start, it may just be increased sleepiness. But then lethargy, abnormal decreased and/or increased muscle tone, abnormal high-pitched (high-sounding cry), backward arching of the trunk and spine (opisthotonus), download deviation of the eyes (sun-setting sign), and even worse – seizures and cardiovascular collapse. I’ve described the worst case scenario, a progression of worsening signs and symptoms that progresses to become a neurological emergency requiring immediate treatment. But, we talk more about in this website in the section title Acute Bilirubin Encephalopathy (ABE) also called Acute Kernicterus.
Back to hyperbilirubinemia and jaundice caused by high levels of bilirubin in the blood. Jaundice can be seen in 60-80% of babies, and can sometimes be seen in the sclera, the “whites” of the eyes, which look yellow. Although many babies look jaundiced, they are not deeply jaundiced, i.e., not jaundiced below their abdomen, and they act normal – they nurse, they are not too sleepy, they have normal muscle tone, their cry is normal, and they don’t arch their backs or have any of the worst-case-scenerio signs I’ve mentioned above. Importantly, they continue to nurse, gain weight, and wake up easily and normally from sleep (i.e. they are not lethargic).
Jaundice and levels of bilirubin
Most pediatricians and physicians and nurses who take care of babies can recognize jaundice when the level of bilirubin in the blood reaches about 6 milligrams per deciliter (also written 6 mg/dL or 6 mg%). Most guidelines to prevent brain damage and kernicterus recommend treating hyperbilirubinemia in an infant 5 days of age or older at a level of about 21 mg/dL in a healthy, term infant without risk factors, 18 mg/dL in an infant at medium risk, and 15 mg/dL at high risk (for example see Figure 2). But, there is no way to know the difference between a “safe” level of bilirubin and one that is high enough to be treated without measuring it.
To be clear, once the baby becomes jaundiced, it is hard to tell the difference between a bilirubin level that is concerning versus a bilirubin level not to worry about without measuring it even for experienced professionals. Therefore, many pediatricians and most so-called “bilirubinologists” believe in hour-specific universal screening of infants to predict those that will rise to a level at which treatment will be recommended.
How to determine bilirubin levels?
That’s easy – there are two ways: 1) a blood bilirubin level, usually a total bilirubin (TB) also sometime called total serum bilirubin (TSB) which is almost always predominantly the toxic, unconjugated form if bilirubin (UCB) in newborn infants, or 2) a transcutaneous bilirubin (TcB) measurment. The blood level takes a drop of blood, usually from a “heel stick” and is the gold standard. Transcutaneous bilirubin (TcB) is done with an instrument that has a light that is pressed on the skin, shines a light on the skin and reads the color of the light that is reflected back from the tissue, and calculates the bilirubin. The TcB correlates very well with the total bilirubin up to a level of about 15 mg/dL. Above 15 mg/dL it read "greater than 15 mg/dL" and a blood level is then recommended. This is very important to do because it could be much higher than 15 mg/dL, and one may not be able to tell be looking
The blood or TcB can be plotted on an hour-specific nomogram (e.g., the bilirubin nomogram, Figure 1) or via an computer App (e.g., BiliTool™ at www.bilitool.org) that predicts how likely the bilirubin will rise to a level that might need to be treated (17 mg/dL), but does not predict the likelihood of brain damage. Note for some high-risk babies with Rh or ABO blood type mismatches, G6PD deficiency, or other rare causes of hemolysis (conditions which lead to abnormal breakdown of red blood cells) this nomogram should not be used because these babies may have bilirubin levels that rise faster than the nomogram predicts. More on Rh, ABO, G6PD and other causes of hemolysis later.