Introduction: Jaundice and Kernicterus Jaundice

About 60% to 80% of newborn Infants in the United States are jaundiced, that is they look yellow. Jaundice is yellow coloring of the skin and other tissues. Jaundice can often be seen in the sclera, the "whites'' of the eyes, which look yellow. Although many babies look jaundiced, but they are not deeply jaundiced, not jaundiced below the abdomen, and they act OK - they nurse, they aren't too sleepy, they have normal muscle tone, their cry is normal, and they don't arch their backs. 

Kernicterus

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).

Information for Parents: The Jaundiced Baby

 

Jaundice in Newborns and its Treatment

About 60% to 80% of newborn infants in the United States are jaundiced, that is they look yellow. Excessive jaundice in newborn infants may cause brain damage. Jaundice is caused by a high level of bilirubin in the blood (hyperbilirubinemia) and tissues. When bilirubin in the blood (hyperbilirubinemia) gets too high, babies can be treated to lower the bilirubin level. Norms exist for bilirubin in term and near-term premature babies based on their age in hours after birth. Other factors, such as prematurity, blood group incompatibilities between infant and mother including Rh and ABO blood types, and bruising, especially cephalohematomas and caputs (bleeding under the skin of the scalp), can increase bilirubin production and lead to excessive jaundice and hyperbilirubinemia.

Babies with high bilirubin levels can be effectively treated. Phototherapy (treatment with light) is usually very effective. It is the blue color in visible light that alters the bilirubin from a toxic form to a water soluble, non-toxic form that can be eliminated. At higher, more dangerous levels of bilirubin, or in certain situations where the bilirubin is expected to rise very rapidly, such as Rh disease or other hemolytic diseases of the newborn, a more extreme treatment may be used, such as a blood exchange transfusion to rapidly remove toxic bilirubin from the blood. 

The Jaundiced Baby with Signs of Acute Kernicterus: A Medical Emergency

When signs of acute kernicterus occur in a jaundiced baby, brain damage is starting to occur. Immediate treatment should be done to prevent further damage or the damage may become permanent, because at the earliest times some of the damage may be reversible.

Treatment should be immediate triple-bank phototherapy lights put as close as possible to the baby. A STAT measurement of blood bilirubin should be sent, but the phototherapy should be started before the bilirubin results come back. The baby should be hydrated with fluids and if the baby is not too sick should probably be given an elemental infant formula via a tube from the nose or mouth into the stomach. The baby should be blood typed for a possible exchange transfusion, which should be done as soon as possible unless there is a large drop in the hyperbilirubinemia and the baby improves before the blood is ready for an exchange transfusion. 

Introduction: The Jaundiced Baby with a high Bilirubin and NO Signs of Acute Kernicterus

The bilirubin should be plotted on a nomogram such as the Bilirubin Nomogram (see Figure) to see what percentile it is in. This gives the risk that the bilirubin will rise to a level that should be treated, generally 17 mg/dL (=17 mg% or 290 µM). The cause of the jaundice should be determined. Measures to increase feeding and hydration, e.g. lactation counseling and increased breast-feeding and/or temporary supplementation should be considered. Home phototherapy with a phototherapy blanket ("biliblanket") may be prescribed, but levels must be closely followed since the amount of phototherapy delivered by home systems is relatively small. Putting the baby in the sunlight is not recommended because the dose of phototherapy is small due to the risk of sunburn.

Jaundice and Preventing Brain Damage

When infants have signs of brain dysfunction from bilirubin toxicity, immediate treatment is needed to minimize permanent brain damage. The signs of acute bilirubin toxicity are:

  • Abnormalities of tone, including increased tone (hypertonia), decreased tone (hypotonia), or a variation in tone from hypertonia to hypotonia.
  • Lethargy, difficulty in arousing the baby.
  • A high-pitched cry,
  • Arching the back and spine (retrocollis or opisthotonus), and fever.

Feeding or nursing is decreased, which makes matters worse not only because of dehydration, but because bilirubin is eliminated via the stool, and decreased feeding prevents bilirubin from being eliminated from the body. Expert neonatologists say that the most common cause of bilirubin levels rising high enough after discharge from the hospital to require readmission is inadequate feeding.

We and others have proposed a clinical scale called the BIND scale, for Bilirubin-Induced Neurological Dysfunction. Babies are scored from 0-3 on each of three characteristics, tone, cry and mental status, with 0 being normal and 3 being the worst. Overall, 0 is normal and 9 is the worst score. Degrees of severity of mental status, for example, would include with a normal awake baby or a sleeping baby who is easily roused (score 0), a lethargic baby who is difficult to rouse and falls back to sleep (score 1), a comatose baby responsive to only deep painful stimuli (score 2), and a comatose unresponsive baby (score 3). In any event, jaundice with any of abnormal signs such as lethargy, abnormal tone, arching, high-pitched cry, or fever, is a cause for IMMEDIATE concern, and an URGENT visit to a physician or hospital emergency room is required.

Some physicians have asked me, when the signs occur, isn't it too late to treat? No! Although damage may have occurred, when the infant is jaundiced and signs are occurring, damage is continuing to occur. The sooner the bilirubin level in the blood is reduced, the better, the less permanent brain damage will occur. This is a true emergency. Delay will make the damage worse.

With an excessively high bilirubin level, and with signs of acute kernicterus, arrangements should immediately be made for a double volume exchange transfusion. This may take a few hours, even in the best of medical centers. In the meantime, the baby should be given double or triple phototherapy with the lights as close as possible to the baby with maximal surface area exposed (and the eyes covered), and the baby should be fed orally or by gavage tube with Nutramigen or another elemental formula, to eliminate bilirubin via the gut. Dehydration may be corrected by intravenous infusion, but gastrointestinal feeding should not be ignored unless the baby is having a seizure or severely ill.

When bilirubin is very high do not make or let your child's physicians make any of the following mistakes in care:

 

  • Not believing the bilirubin level from the lab, and delaying treatment while it is repeated. There is no problem in repeating the test, but don't delay treatment for an instant while waiting for the repeat. You have nothing to lose by treating with a huge dose of phototherapy, gavage feeding, hydrating, ordering a type and cross match and blood for a possible exchange transfusion. If the bilirubin drops rapidly to a relatively safe level, and the child is asymptomatic (no symptoms), the exchange transfusion can be cancelled.

  • Delaying treatment or interrupting phototherapy for diagnostic testing to determine the risk of an exchange. If a sepsis workup or lumbar puncture (LP, a.k.a. spinal tap) or an echocardiogram (ultrasound study of the heart) etc. is needed, do it under the lights. If it's not possible, keep the lights on every possible minute. If the baby needs to go for a test out of the unit, the lights go with him or her.
  • Not examining the baby for signs of acute kernicterus.

  • Using the indirect (or unconjugated) bilirubin level instead of the total bilirubin level to make treatment decisions. Experts agree, use the total bilirubin.

  • Allowing the bilirubin to reach potentially dangerous levels. Obtaining a transcutaneous bilirubin level or measuring blood bilirubin is very easy to do. It is much easier to prevent bilirubin from rising too high than to treat it when it does.

  • Measuring the bilirubin and not comparing it to hour-specific norms. This is very important. A bilirubin level in a one-day-old may be normal or dangerously high depending on whether the baby is 24 or 47 hours old. A level of 8.5 mg/dL would be in a high-risk zone (95th percentile) in a 24h old baby, and in a low risk zone (40th percentile) in a 47h old baby. Most use the Bilirubin Nomogram (see Figure), which is used in the American Academy of Pediatrics (AAP) guidelines (see References) although some may use their own normal values. The nomogram predicts the risk of the baby’s bilirubin rising to a level of 17 mg/dL, a level at which a term infant should be treated in phototherapy to prevent the bilirubin from rising higher.

 

Kernicterus: Brain Damage due to Excessive Jaundice

Kernicterus is the name given to the severe form of brain damage that is caused by excessive jaundice in newborn infants. 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
  • 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 dys-synchrony 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. 

Caveats

The opinions in this article are solely mine except where I've cited others. I am a child neurologist and medical researcher. I've been studying brain damage due to jaundice since 1982. I care very deeply about preventing brain damage, and kernicterus is a preventable form of brain damage that occurs in newborn infants. There are many well established scientific facts known about how bilirubin toxicity damages the brain, but unfortunately, there is much that is not known. Usually conservative in my clinical practice, in a baby with excessive hyperbilirubinemia I would err on the side of treatment that is more aggressive. For example, if there is a possibility that subtle cognitive processing problems are caused by levels of bilirubin lower than are usually treated, and if it will take time for new studies to resolve this concern, then I'd err on the side of over- treating while there is still uncertainty because the cost of treating is a few days or so of a very safe treatment, whereas the cost of not treating might be a lifetime of a neurological problem.

Kernicterus Clinic and Kernicterus Center of Excellence

Our department receives many requests to evaluate patients. I currently see patients in the inpatient and outpatient services of Children's Mercy Hospitals and Clinics' Neurology Department. We make and coordinate referrals by email at kernicterus@cmh.edu or by phone at (816) 234-9398. You may be seen in consultation with recommendations for treatment to be carried out locally, or you may receive ongoing care at our clinic, or may opt for a combination of the two.

Diagnosis - New patients fill out a questionnaire, and then undergo a carefully history-taking, physical and neurological examination. We review past medical records. Patients are routinely videotaped for documentation of movements.

Testing -A full range of routine and specialty diagnostic testing is available, including MRI and PET scans, evoked potentials (e.g., ABR); EMG, EEG, video EEG, sleep studies, metabolic and genetic testing, auditory, and neuropsychological testing.

Consultations – with experts in Pediatric Movement Disorders, Orthopedics, Neurosurgery, Gastroenterology (GI), Sleep Disorders Specialists, Opthalmology, Otolaryngology Audiology, Speech and Language Therapy, Physical and Occupational Therapy, Feldenkrais Therapy, Gait Analysis, Neuropsychology and Vision Assessment, Hematology.

Referrals -To physician specialists in areas including pediatric genetics, neurosurgery, neuromuscular and movement disorders specialists; physical medicine rehabilitation; audiology; otolaryngology; speech, physical and occupational therapy, gait analysis and neuropsychology.

Education - Educational consultants experienced in evaluating the educational needs of children with neurological problems.

Treatment - When treatment is necessary, our clinic offers pharmacological and non-pharmacological treatments and referrals.

Pharmacological treatments (medication)

Non-pharmacological treatments which might include referrals to speech, physical and/or occupational therapy, rehab and/or assistive technology, educational recommendations, botulinum toxin injections, baclofen pumps, cochlear implants, or deep brain stimulators.

Additional Information and Support for Parents

 

PICK, Parents of Infants and Children with Kernicterus

One excellent source of information for parents (or grandparents, other relatives, friends, or older people who have neurological problems that might be related to hyperbilirubinemia) is PICK, Parents of Infants and Children with Kernicterus, a parent's organization dedicated to preventing and treating kernicterus. I have known many of the parents in this organization and served on its medical advisory board since its inception in the year 2000. Their website is www.pic-k.org

Kernicterus Research Fund

Kernicterus, hyperbilirubinemia and BIND do not appear to be current funding priorities of the major sources of funding for medical research, such as the NIH (National Institutes of Health).

PICK members and others have contributed to our Kernicterus Research Fund. If you (or your friends or relatives) care to make a charitable contribution to support research on kernicterus and the neurological effects of newborn jaundice and hyperbilirubinemia, please consider a gift to our Kernicterus Research Fund to support research on kernicterus, hyperbilirubinemia and BIND. The fund is administered by Children's Mercy. Any amount is welcome.

Donations to the Kernicterus Research Fund supporting clinical and basic science research to detect, prevent and treat kernicterus and bilirubin-induced neurological disorders, can be made as follows:
Donate Online »

To designate your gift to the Kernicterus Center, go to “*Gift Designation” and choose "Other, Specify below" in the dropdown menu

Then underneath in the “Comments” field “Kernicterus”.

You may also contact Lauren Davis by email at lmdavis@cmh.edu or by phone at (816) 346-1361 to discuss mailing a check or other donation methods. 

Contact Information

If you have any questions or comments, please feel free to contact me:

Dr. Steven M. Shapiro MD, MSHA

Chief, Division of Neurology,

Children's Mercy Hospitals and Clinics

Professor of Pediatrics, University of Missouri-Kansas City School of Medicine

Professor of Neurology and Pediatrics, University of Kansas School of Medicine

If you have any other questions or have any trouble reaching us, please contact me via email at: sshapiro@cmh.edu. Please put “kernicterus” or “newborn jaundice” in the subject line.

Mailing Address:

Steven M. Shapiro MD,

2401 Gillham Road

Kansas City, Missouri 64108

Phone: (816) 234-3090, option #4

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