Bilirubin encephalopathy is a severe complication of hyperbilirubinemia in the newborn. It involves damage to the central nervous system. Severe sequelae or even a fatal outcome are possible.
What is bilirubin encephalopathy?
Bilirubin encephalopathy is characterized by severe central nervous system (CNS) damage caused by elevated bilirubin levels in the neonatal period. Hyperbilirubinemia can cause a condition called kernicterus (jaundice with brain intoxication) of the infant. Free unconjugated bilirubin is insoluble in water. It dissolves only in fats. However, it is normally bound by certain albumins in the blood and transported to the liver. For various reasons, however, the binding capacity of the albumins may be overtaxed, resulting in bilirubin accumulation in the blood. This results in neonatal jaundice, which can become dangerous in rare cases. If bilirubin crosses the blood–brain barrier, it can enter the nuclear areas of the brain and exert neurotoxic effects there. This gives rise to the term kernicterus. The basal ganglia, which are composed of the putamen, globus pallidus and caudate nucleus, are particularly affected by the damage. Severe bilirubin encephalopathy is often fatal. This complication occurs in 0.4 to 2.7 cases per 100,000 live births in the Western world. Because of less medical care, kernicterus is 100 times more common in some developing countries.
Causes
The cause of bilirubin encephalopathy is damage to specific nuclear areas in the newborn’s brain from intoxication with unconjugated bilirubin. Unconjugated bilirubin is very commonly found free in the blood of newborns. About 60 percent of all infants show symptoms of neonatal jaundice, but it usually resolves within four days. Because of the immature liver, bilirubin often cannot be broken down as quickly. However, these symptoms are usually not worrisome. In rare cases, however, the bilirubin concentration becomes so high that free unconjugated bilirubin can cross the blood-brain barrier. There it has a neurotoxic effect and damages important core areas of the brain. Normally, unconjugated fat-soluble bilirubin is bound to albumins, transported to the liver and broken down there. In the case of increased formation of bilirubin due to hemolysis in blood group incompatibilities with the mother, the binding capacity of albumin is overtaxed. Thus, the bilirubin concentration in the blood increases very much and can cross the blood-brain barrier. Various drugs also lower the binding capacity of bilirubin to albumin by displacement processes. These include, for example, diazepam, sulfonamides, furosemide, and others. Even with normal concentrations of bilirubin in the blood, the blood-brain barrier can become permeable to bilirubin. This often occurs with oxygen deprivation (hypoxia), hypoglycemia, hyperacidity (acidosis), or hypothermia. Bilirubin can also cross the blood-brain barrier if the albumin concentration is too low (hypalbuminemia).
Symptoms, complaints, and signs
Acute bilirubin encephalopathy usually progresses in three phases:
- Initially, the infant is noted to have a reluctance to drink, flaccid muscle tone, drowsiness, and lack of movement.
- In a second phase, the newborn begins to scream shrilly. Increasingly, consciousness becomes cloudy (stupor). Furthermore, increased muscle tension appears, with hyperextension of the neck or spine.
- Eventually, muscle tension may increase, with convulsions occurring. The stupor may progress to coma. Often, the condition is fatal. However, if the infant survives the acute phase, late sequelae often present with numbness, extrapyramidal motor movement disorders, and psychosomatic developmental disorders.
The extrapyramidal-motor movement disorders are called athetosis and are manifested in involuntary slow extending screwing movements of the feet and hands. The joints become overstretched. The gait is stumbling and overshooting. The cause of these bizarre movements lies in the disturbance of the interaction between antagonists and agonists.
Diagnosis and course
Elevated bilirubin levels are very common in the first days of life. Therefore, screening is performed in maternity hospitals to avert the risk of bilirubin encephalopathy as early as possible by detecting possible hyperbilirubinemia. When the infant turns yellow, the first signs of elevated bilirubin levels are present. In this case, bilirubin levels are determined through the skin using a multispectral device during the first 20 hours. If the values are critical, a blood test for hyperbilirubinemia must be performed. It has been shown that neurological disorders can occur at levels as low as 20 mg/dl. If not treated in time at this level, motor dysfunction can occur by the age of seven. At bilirubin concentrations above 25 mg/dl, there is already a great risk of developing kernicterus.
Complications
Elevated bilirubin levels in infants initially result in a yellowish coloration of the infant (neonatal icterus), which is usually not serious and resolves without any complications. However, in the worst cases, bilirubin can accumulate in the brain in the basal ganglia, leading to kernicterus; bilirubin encephalopathy is the result. The infant is initially characterized by generalized weakness and muscle weakness. This results in a reluctance to drink, whereupon the baby may become dehydrated (exsiccosis). As a result, the skin becomes more cracked and the baby becomes more susceptible to infections. In addition, in the worst case, the heart can fail. In addition, the newborn’s reflexes are weakened. Furthermore, the baby may suddenly start screaming shrilly in pain. In addition, there is a clouding of consciousness and cramping of the muscles, especially of the neck and spine (opisthotonus), so that the baby overstretches its head. In addition, the infant may manifest the sunset phenomenon, which means that the eye turns downward when it opens, limiting the range of vision. In the worst cases, the child develops cerebral deficits, which can have various consequences such as deafness. In addition, there are usually further seizures and a mental developmental disorder. The disease can also lead to death of the child via coma.
When should you see a doctor?
In most cases, bilirubin encephalopathy is diagnosed before birth or immediately after birth. For this reason, no additional diagnosis or treatment by another doctor is necessary. However, treatment in the hospital must be immediate, otherwise bilirubin encephalopathy can lead to the death of the affected person in the worst case. In most cases, an examination should be performed when the child shows no muscle tone or is very sleepy and does not move. The child’s consciousness also becomes clouded, which may indicate the disease. In severe cases, children fall into a coma during this process. To avoid complications or death later, a doctor should be alerted immediately if these symptoms occur. The diagnosis and treatment of bilirubin encephalopathy is usually carried out directly in the hospital. Parents usually do not need to see an additional physician for this. A positive course of the disease cannot be guaranteed in every case.
Treatment and therapy
If bilirubin levels are very high, above 20 mg/dl, treatment must be initiated immediately to prevent bilirubin encephalopathy. Treatment is given within the first 72 hours by phototherapy with blue light. The wavelength of blue light is between 425 and 475 nanometers. Phototherapy converts the unconjugated water-insoluble bilirubin into water-soluble lumirubin. This is then excreted from the body via the bile or kidneys. When bilirubin levels exceed 30 mg/dl, phototherapy is of no help. A blood transfusion should then be given.
Outlook and prognosis
The prognosis of bilirubin encephalopathy depends on how quickly therapy is initiated after the first symptoms of the disease appear or when bilirubin concentrations are elevated. Even before the onset of the disease, the infant must be constantly monitored for rapid response if the concentration of unconjugated bilirubin exceeds 15 mg/dl.When unconjugated bilirubin crosses the blood-brain barrier into the brain, it destroys nerve cells there by blocking phosphorylation reactions. These processes are potentially irreversible. They can therefore no longer be reversed, or only partially. The water-insoluble unconjugated bilirubin is transformed into water-soluble conjugated bilirubin by blue light during treatment and can thus be eliminated from the body via blood exchange transfusions. If no treatment is given, late sequelae may develop, the symptoms of which can only be alleviated by symptomatic therapies. These late effects include motor disturbances, deafness, constant seizures, and mental retardation. The motor disorders are manifested, among other things, by screw-like movements of the extremities. The late damage is more severe the later treatment begins. However, treatment starting immediately after the onset of the disease does not guarantee that there will be no late damage. Because elevated bilirubin levels are very common in newborns, early screening after birth is very important to detect and treat hyperbilirubinemia (elevated bilirubin concentration in the blood) in a timely manner.
Prevention
Bilirubin encephalopathy can be prevented only by early screening after birth. If bilirubin levels are severely elevated, blue light treatment must be given immediately or, if levels are extremely high, a blood exchange transfusion must be given. If jaundice appears only after a few days at home and the child becomes lethargic, the physician should be consulted immediately.
Follow-up
There are usually no special means of follow-up available to the individual with bilirubin encephalopathy. In the worst case scenario, this condition can also have a fatal outcome, with the child dying. Early diagnosis and therapy have a very positive effect on the further course of the disease and can prevent various complications. As a rule, the patient is dependent on radiation with blue light to alleviate the symptoms. If treatment is not given, the child often dies immediately. Further follow-up for bilirubin encephalopathy most often involves the newborn child and not the mother. The child is dependent on special support to treat the mental retardation and further delayed development. Seizures can also be alleviated with the help of various medications. In this case, the parents must ensure that the medication is taken regularly, and interactions with other medications should also be taken into account. After birth, the child is dependent on regular examinations. Since bilirubin encephalopathy can also lead to psychological discomfort for the parents and the child’s relatives, intensive discussions and contact with other people affected by bilirubin encephalopathy are also very helpful here.
What you can do yourself
The options for self-help are very limited in bilirubin encephalopathy. The condition occurs in newborns. By its very nature, they cannot take any action to improve their situation. Therefore, the consequences of the disease are usually borne by relatives and parents. These see themselves exposed to helplessness due to the circumstances and must regulate their own emotional states. If this cannot be achieved on their own, psychological assistance should be sought. Immediate medical care for the newborn is important. A close exchange with the attending physicians and nurses is necessary so that a reaction can be made as quickly as possible in the event of changes in the state of health. In addition, relatives should be educated about the disease to a sufficient degree as well as inform themselves. The consequences and disturbances are individual, but on a severely life-impairing scale. Calmness should be maintained so that good and optimal decisions can be made that are in the best interest of the offspring. Unity and mutual reinforcement among family members is advisable, so that no conflict of interests arises and offices or authorities have to be involved. Disputes, self-interest or power games ultimately harm the well-being of the newborn and lead to time delays when doctors need the parents’ consent for treatment methods.