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Introduction: Jaundice and Kernicterus

Jaundice

About 60% of newborn infants in the United States are jaundiced, that is they look yellow. Jaundice is the yellow coloring of the skin and other tissues. Jaundice can often be seen well in the sclera, the "whites" of the eyes, which look yellow. Many babies look jaundiced (60%), 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, 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 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 develop fever, may arch their heads back into a very contorted position known as opisthotonus or retrocollis.

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Information for Parents: The Jaundiced Baby

Jaundice in Newborns and its Treatment

About 60% 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 gets too high, it can be treated. Norms exist for bilirubin in term and nearly term babies based on the 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.

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 or other hemolytic diseases of the newborn, a more extreme treatment may be used, exchange transfusion, to rapidly remove toxic bilirubin from the blood.

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

When signs of acute kernicterus occur in a jaundiced baby, permanent brain damage is occurring. Immediate treatment should be done to prevent further damage, and because perhaps some of the damage is 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 probably be tube fed an elemental infant formula. 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 bilirubin, and the baby improves before the blood is ready for an exchange transfusion.

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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 Bhutani Nomogram to see what percentile it is in. 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") might be prescribed, but levels must be closely followed since the amount of phototherapy delivered by home systems is relatively small.

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:

  1. abnormalities of tone, including increased tone (hypertonia), decreased tone (hypotonia), or a variation in tone from hypertonia to hypotonia,
  2. lethargy, difficulty in arousing the baby,
  3. a high-pitched cry,
  4. arching the back and spine (retrocollis or opisthotonus), and
  5. 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 in-adequate feeding.

Experts 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 9 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, a lethargic baby who is difficult to rouse and falls back to sleep, a comatose baby responsive to only deep painful stimuli, and a comatose unresponsive baby. 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 is reduced, the better, the less permanent brain damage will occur. THIS IS A TRUE MEDICAL 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.

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

  1. 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. If the bilirubin drops rapidly to a relatively safe level, and the child is asymptomatic (no symptoms), the exchange transfusion can be cancelled.
  2. Delaying treatment or interrupting phototherapy for diagnostic testing to determine the risk of an exchange. If a sepsis workup or LP is needed, or an echocardiogram etc., 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.
  3. Not examining the baby for signs of acute kernicterus
  4. Using the indirect (or unconjugated) bilirubin instead of the total serum bilirubin to make treatment decisions. Use the total bilirubin.
  5. 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.
  6. 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 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 Bhutani Nomogram, although some may use their own normal values.

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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 of brainstem nuclei in auditory (hearing), oculomotor (eye movement), 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: 1) specific movement disorders, 2) hearing loss or deafness, 3) impairment of eye movements especially upward gaze, and 4) abnormal staining of the enamel of baby teeth. Children with kernicterus have a "dystonic" or "athetoid" form of cerebral palsy. An "athetoid" form of cerebral palsy is classic and 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 now called auditory neuropathy or auditory dys-synchrony. Auditory brainstem response (ABR) tests (also known as BAEP, BAER or BSER) are often abnormal, whereas other "hearing" tests, such as otoacoustic emissions (OAEs) and cochlear microphonic responses are normal.

Kernicterus is fortunately a very rare occurrence. Other forms of bilirubin-induced neurological damage may exist, including cognitive problems and auditory processing problems, one form of which is called auditory neuropathy or auditory dys-synchrony.

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Caveats

The opinions in this article are solely mine except where I've cited others. I'm 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. Many things are very well established about how bilirubin toxicity damages the brain, but unfortunately, many other things are conjecture. Usually conservative in my clinical practice, in this area 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 the concern, then I'd err on the side of over- treating while there is still uncertainty because the cost is a few days or so of a very safe treatment, and the cost of not treating could be a lifetime of a neurological problem.

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Kernicterus Clinic and Kernicterus Center of Excellence

I received 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 phone at (816) 234-3490. You may be seen in consultation with recommendations for treatment to be carried out locally, or receive ongoing care at our clinic.

  • 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 (ABR, SEP, VEP); EMG, EEG, video EEG, sleep studies, metabolic and genetic testing, auditory, and neuropsychological testing
  • 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.

To schedule appointments and arrange to have medical records sent call (816) 234-3090 and leave a message for Amy Wolf.

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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.pickonline.org

Newbornjaundice - Newborn Jaundice and Kernicterus

This is an excellent yahoo discussion list, started in July 2001 by Melissa Li, mother of a child with auditory-predominant kernicterus. Parents and sometimes professional discuss a wide range of topics. You may receive e-mails individually or in digest form. This list is a treasure trove of information and practical advice about kernicterus and newborn jaundice hyper-bilirubinemia. You can sign up for this at http://groups.yahoo.com/group/newbornjaundice/.

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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:

  1. Click Here to Donate Online. (To designate your gift to the Kernicterus Center, choose Other in the dropdown menu underneath Direct my gift to: and type Kernicterus in the Comments text field.)
  2. Contact Lauren Davis at (816) 346-1361 to discuss mailing a check or other donation methods.

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Contact Information

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

Dr. Steven Shapiro, Children's Mercy Hospitals and Clinics

Dr. Steven M. Shapiro MD, MSHA
Chief, Section of Neurology, Children's Mercy Hospitals and Clinics
Professor of Pediatrics, University of Missouri-Kansas City School of Medicine
Professor of Neurology, University of Kansas School of Medicine

Mailing Address:

Steven M. Shapiro MD, MSHA
Attn: Amy Wolf
2401 Gillham Road
Kansas City, Missouri 64108
Phone: (816) 234-3090
E-mail: kernicterus@cmh.edu

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Bhutani Nomogram

The widely used nomogram, first published in 1999 an article by Dr. Vinod Bhutani, Dr. Lois Johnson, and Emedio Sivieri in the medical journal Pediatrics, volume 103, issue #1, pages 6 to 14, was reprinted in "Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation", the current guideline for the management endorsed by the American Academy of Pediatrics, published in Pediatrics in 2004, volume 114, issue 1, pages 297 to 316.

nomogram
Click Here to view larger image.
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References

Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004;114(1):297-316.

Bhutani VK, Johnson L, Sivieri EM. Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns. Pediatrics 1999;103(1):6-14.

Shapiro SM. Bilirubin toxicity in the developing nervous system. Pediatric Neurology 2003;29(5):410-21.

Shapiro SM. Definition of the clinical spectrum of kernicterus and bilirubin-induced neurologic dysfunction (BIND). Journal of Perinatology 2005;25(1):54-9.

Shapiro SM, Bhutani VK, Johnson L. Hyperbilirubinemia and kernicterus. Clinics in Perinatology 2006;33(2):387-410.

Shapiro SM, Nakamura H. Bilirubin and the auditory system. Journal of Perinatology 2001;21 Suppl 1:S52-5; discussion S59-62.

Gieger, A. S., Rice, A.C., Shapiro, S. M., Minocycline blocks acute bilirubin induced neurological dysfunction in jaundiced Gunn rats. Neonatology 92:219-226, 2007.

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