Jaundice and Kernicterus

Jaundice is a common and easily-diagnosed condition in newborns caused by elevated bilirubin levels. If jaundice is not properly handled, it can lead to kernicterus, a dangerous and permanent form of brain damage. Doctors can conduct diagnostic testing to determine a child’s bilirubin levels and take appropriate action depending on the severity of jaundice. They can treat jaundice using phototherapy, blood transfusions, or by addressing any underlying causes. Because jaundice is so easily diagnosed and treated, kernicterus is highly preventable.

Neonatal jaundice is extremely common, although it usually appears in a mild form. About 60% of full-term infants and 80% of preterm infants develop jaundice (1). In many infants, jaundice goes away on its own. However, some infants need extra help removing this excess bilirubin.

While very mild levels of jaundice are not dangerous, more intense degrees of jaundice can be cause for concern. Jaundice is typically most noticeable within 2 to 4 days of age, and goes away within a couple of weeks. Whether treatment is needed, and what kind of treatment, depends on the following factors (2):

• Level of bilirubin
• Speed at which the level of bilirubin has been rising
• Prematurity (preemies are more likely to be treated at lower levels of bilirubin)
• Age of the baby

It is very important that medical professionals know when to treat jaundice as a medical emergency — for example, if jaundice emerges in the first 24 hours of life, or if the baby’s palms and soles appear yellow (3).

Additionally, it is important to note that mild cases of jaundice may still warrant careful monitoring and intervention.

Bilirubin is a byproduct of the body breaking down red blood cells. Newborns have a higher concentration of red blood cells than adults because they need to transport higher oxygen levels inside the womb than they do after birth (4). Newborns’ livers are also slower at clearing away bilirubin. In the womb, the mother’s placenta removes bilirubin, but after birth, the baby’s liver must adjust to removing the bilirubin, which can take some time (2). Additionally, babies’ livers may be ineffective in processing bilirubin, which causes it to build up.

High levels of bilirubin, also known as hyperbilirubinemia, can cause the baby to have yellow-looking skin and eyes (jaundice) (1).

Risk factors and causes of jaundice and elevated bilirubin levels include the following, among others (2, 5, 6, 7, 8, 9):

• Premature birth
• Insufficient nutrition (not getting enough breast milk or formula)
• Blood type mismatch (Rh incompatibility) between mother and baby
• Bruising or internal bleeding from birth trauma
• Hypoxic-ischemic encephalopathy (HIE)
• Cephalohematoma (bleeding under the scalp caused by difficult delivery, often involving vacuum extractors or forceps)
• Liver conditions such as cystic fibrosis or hepatitis
• A lack of certain important enzymes, e.g. G6PD deficiency
• High red blood cell counts (polycythemia), which is more common in babies who are small for gestational age or twins
• Sickle cell anemia
• Low levels of oxygen (hypoxia)
• Infection such as sepsis
• Macrosomic (large) babies of diabetic mothers are predisposed to blood cell problems.
• Certain medications
• Having a sibling with jaundice
• Mediterranean or East Asian descent

Every baby is different and therefore may experience different symptoms at different times.  However, there are certain signs and symptoms that may mean that a baby has jaundice. Jaundice is often characterized by a yellowing of the baby’s skin (usually starting on the face and moving down the body) and the whites of the eyes. This may be more apparent after pressing a finger to the baby’s nose or forehead. It is important to note that changes in skin color can be more difficult to spot in babies with darker skin tones — the yellowing may be more noticeable in the whites of the eyes, inside the mouth, or on the palms and soles of the feet (1).

Other signs of newborn jaundice include the following (1, 2, 5, 10, 11):

• Poor feeding
• Lethargy, tiredness
• Inability to gain weight
• Dark yellow urine
• Pale stools
• Arching the neck or body backwards
• Irritability

According to the American Academy of Pediatrics, all babies should be checked for high bilirubin levels before being discharged from the hospital, and again at 3-5 days of life (12).

In many cases, jaundice is diagnosed based solely on the baby’s appearance. However, to glean more precise information on the severity of jaundice, it is necessary to perform diagnostic tests to measure levels of bilirubin in the blood. Bilirubin levels can be checked using either a serum bilirubin blood test or a transcutaneous bilirubinometer device (this is done noninvasively by shining a light through the skin) (10).

If jaundice persists for longer than normal, additional tests can be performed to determine the underlying cause and any associated conditions that may need to be addressed. These tests may include (5):

• Blood type (for Rh incompatibility)
• Complete blood count
• Coombs test (to check for increased breakdown of red blood cells)

Babies with jaundice should be fed frequently (up to twelve times a day), which will encourage defecation and help to remove bilirubin from the bloodstream. In some cases, extra fluids may be given via IV.

Additionally, some common treatments for jaundice include (5, 13):

• Phototherapy. The baby is exposed to a special blue-spectrum light that decreases the bilirubin levels.  Blood tests are performed afterward to check bilirubin levels to ensure the phototherapy is working.
• Fiber optic blanket. This is another form of phototherapy. The blanket is placed underneath the infant and can be used alone or along with regular phototherapy.
• Blood transfusion to increase the red blood cell count and reduce the levels of bilirubin.
• Treatment of any underlying causes of hyperbilirubinemia, such as infection.

If jaundice is severe and improperly treated, it can lead to a form of brain damage known as bilirubin encephalopathy, which can progress to a more serious injury known as chronic bilirubin encephalopathy or kernicterus.

“Bilirubin encephalopathy” and “kernicterus” are sometimes used as synonyms, although the American Academy of Pediatrics (AAP) recommends that the term acute bilirubin encephalopathy (ABE) be used to describe symptoms manifesting in the first few weeks of life, while kernicterus (or kernicterus spectrum disorder) be reserved for more chronic manifestations of ABE.

ABE has been categorized into three phases:

• Phase 1 typically begins around 3-5 days of life, and may involve decreased alertness, feeding problems, hypotonia, and a weak Moro reflex.
• Phase 2 typically begins later in the first week, and may involve stupor, irritability, changes in muscle tone/movement, and a high-pitched cry.
• Phase 3 typically begins after the first week, and may involve hypotonia, coma, spasms, “sun setting eyes,” fever, feeding problems, and apnea. The rate of mortality has been estimated to be at least 21%.

In premature babies, nervous system immaturity can mask clinical conditions and make the signs of ABE appear more subtle.

Kernicterus is a more permanent effect of hyperbilirubinemia that can develop in babies who survive ABE. In the first year of life, it typically manifests with abnormalities in muscle tone, persistence of tonic neck reflex, and delayed developmental milestones. After the first year of a child’s life or sooner, the effects can vary widely, but may include the following:

• Vision and hearing impairments
• Cognitive impairments
• Dental issues
• Motor control issues such as cerebral palsy,  dystonia, athetosis, and chorea (14)

Sometimes, children may develop subtle neurodevelopmental disabilities in the absence of classical signs of kernicterus. However, after careful medical testing, their symptoms are attributed to bilirubin toxicity (15). This can be called subtle kernicterus, bilirubin-induced neurologic dysfunction (BIND), or subtle bilirubin encephalopathy (SBE).

There are two types of bilirubin: unconjugated and conjugated bilirubin. Unconjugated bilirubin is processed by the liver into conjugated bilirubin. Unconjugated bilirubin can cross the blood-brain barrier to cause kernicterus. An excess in conjugated bilirubin can also lead to serious health problems, including a liver disease known as cholestasis, which involves impairment in the excretion of bile. Infants who still show signs of jaundice at two weeks after birth should be evaluated for conjugated hyperbilirubinemia and cholestasis. Conjugated hyperbilirubinemia is treated very differently than physiologic jaundice; it is key that medical professionals distinguish between the two.