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Cholestasis in the Newborn

By

William J. Cochran

, MD, Geisinger Clinic

Last full review/revision Aug 2021| Content last modified Aug 2021
Click here for the Professional Version
Topic Resources
  • Cholestasis has numerous causes, including infections, metabolic problems, genetic defects, and blockages.

  • The most common symptoms are jaundice and dark urine.

  • The diagnosis is made by blood tests, and then other blood tests, imaging tests, and sometimes liver biopsy are done to determine the specific cause.

  • Treatment depends on the cause.

Bilirubin is a yellow substance formed when hemoglobin (the part of red blood cells that carries oxygen) is broken down as part of the normal process of recycling old or damaged red blood cells. Bilirubin is carried in the bloodstream to the liver and processed so that it can be excreted out of the liver as part of bile (the digestive fluid produced by the liver). Bilirubin processing in the liver involves attaching it to another chemical substance in a process called conjugation.

  • Processed bilirubin in the bile is thus called conjugated bilirubin.

  • Unprocessed bilirubin is called unconjugated bilirubin.

Bile is transported through the bile ducts into the beginning of the small intestine (duodenum). If bilirubin cannot be processed and excreted by the liver and bile ducts quickly enough, it builds up in the blood (hyperbilirubinemia Jaundice in the Newborn Jaundice is a yellow color to the skin and/or eyes caused by an increase in bilirubin in the bloodstream. Bilirubin is a yellow substance formed when hemoglobin (the part of red blood cells... read more Jaundice in the Newborn ). The excess bilirubin settles in the skin, the whites of the eyes, and other tissues, causing them to turn yellow (jaundice Jaundice in the Newborn Jaundice is a yellow color to the skin and/or eyes caused by an increase in bilirubin in the bloodstream. Bilirubin is a yellow substance formed when hemoglobin (the part of red blood cells... read more Jaundice in the Newborn ).

In cholestasis, the liver cells process bilirubin properly, but the excretion of bile is impaired at some point between the liver cells and the duodenum. This results in an increase in conjugated bilirubin in the blood and a decrease in bile delivered to the small intestine.

Another effect of bile not being excreted normally into the small intestine is that digestion is impaired. Bile is important for digestion because it helps the body absorb fats and the fat-soluble vitamins Overview of Vitamins Vitamins are a vital part of a healthy diet. The recommended dietary allowance (RDA)—the amount most healthy people need each day to remain healthy—has been determined for most vitamins. A safe... read more A, D, E, and K. When there is not enough bile in the intestine, fat absorption is impaired, which can lead to vitamin deficiency, inadequate nutrition, and a failure to grow and gain weight.

View of the Liver

View of the Liver and Gallbladder

Causes of Cholestasis in Newborns

Cholestasis in the newborn can be caused by

  • Biliary atresia (blockage of the bile ducts)

  • Biliary cysts

  • Infection

  • An immune disorder

  • Metabolic disorders

  • Genetic defects

  • Toxic causes

Biliary atresia Biliary Atresia Biliary atresia is a birth defect in which the bile ducts progressively narrow and become blocked after birth, preventing bile from reaching the intestine. This defect causes bile to collect... read more is a blockage of the bile ducts that starts in the fetus near the end of the pregnancy or in the first several weeks of life. It is more common among full-term infants than premature infants. Affected infants typically develop jaundice in the first several weeks of life.

Biliary cysts or bile duct cysts are enlargements of parts of the bile ducts. These rare cysts are typically caused by a birth defect in the area where the bile duct and the pancreatic duct meet (see figure View of the Liver View of the Liver Cholestasis is a reduction of bile formation or bile flow. As a result, bilirubin backs up into the bloodstream (hyperbilirubinemia), leading to a yellow to yellow-green discoloration of the... read more ). Biliary cysts are more common among infants who have polycystic kidney disease Polycystic Kidney Disease(PKD) Polycystic kidney disease is a hereditary disorder in which many fluid-filled sacs (cysts) form in both kidneys. The kidneys grow larger but have less functioning tissue. Polycystic kidney disease... read more (PKD). PKD is an inherited disorder that causes cysts to form in the kidneys.

Infections can lead to cholestasis in the newborn. Some infecting organisms are

Gestational alloimmune liver disease is a disorder that begins before birth. In this disease, antibodies from the mother cross the placenta and attack the fetus's liver.

Metabolic disorders Overview of Hereditary Metabolic Disorders Hereditary metabolic disorders are inherited genetic conditions that cause metabolism problems. Heredity is the passing of genes from one generation to the next. Children inherit their parents'... read more that cause cholestasis are numerous and include alpha-1 antitrypsin deficiency Alpha-1 Antitrypsin Deficiency Alpha-1 antitrypsin deficiency is a hereditary disorder in which a lack or low level of the enzyme alpha-1 antitrypsin damages the lungs and liver. Alpha-1 antitrypsin deficiency is caused by... read more Alpha-1 Antitrypsin Deficiency , galactosemia Galactosemia Galactosemia (a high blood level of galactose) is a carbohydrate metabolism disorder that is caused by a lack of one of the enzymes necessary for metabolizing galactose, a sugar that is part... read more , tyrosinemia Tyrosinemia Tyrosinemia is a disorder of amino acid metabolism that is caused by a lack of the enzyme needed to metabolize tyrosine. The most common form of this disorder mostly affects the liver and the... read more , bile acid defects, and fatty acid oxidation disorders Fatty Acid Oxidation Disorders Fatty acid oxidation disorders are lipid metabolism disorders that are caused by a lack or deficiency of the enzymes needed to break down fats, resulting in delayed mental and physical development... read more . These disorders occur when the newborn is missing an enzyme that is needed to break down a certain substance, allowing toxic substances to accumulate and damage the liver.

Genetic defects, such as Alagille syndrome and cystic fibrosis Cystic Fibrosis (CF) Cystic fibrosis is a hereditary disease that causes certain glands to produce abnormally thick secretions, resulting in tissue and organ damage, especially in the lungs and the digestive tract... read more , may cause cholestasis in the newborn. Genetic defects and other gene mutations can disrupt normal bile production and removal, which causes cholestasis.

Neonatal hepatitis syndrome is the term used to describe inflammation in the newborn's liver for which there is no identified cause. This diagnosis is being made less frequently due to advances in tests that can determine an exact cause.

Symptoms of Cholestasis in Newborns

Symptoms of cholestasis typically develop during the first 2 weeks of a newborn's life. Infants with cholestasis have jaundice and often have dark urine, light-colored stools, and/or an enlarged liver. Bilirubin in the skin can cause itching, which makes infants irritable. Because infants with cholestasis may not properly absorb fats and vitamins, they may not grow well.

Diagnosis of Cholestasis in Newborns

  • Blood tests

  • Imaging tests

  • Sometimes biopsy of the liver

Almost all newborns have higher bilirubin levels in their blood (hyperbilirubinemia) during the first week of life than they do later on. This normal jaundice (physiologic jaundice) resolves over a week or two, and the bilirubin level returns to normal. For infants who remain jaundiced at 2 weeks of age, doctors check to see if the elevated bilirubin is conjugated or unconjugated. A high level of conjugated bilirubin indicates liver dysfunction and possible cholestasis. A high level of unconjugated bilirubin is not caused by liver dysfunction. If that test indicates cholestasis is present, infants have additional blood tests to determine if the liver is inflamed or not functioning normally (see Liver Blood Tests Liver Blood Tests Liver tests are blood tests that represent a noninvasive way to screen for the presence of liver disease (for example, hepatitis in donated blood) and to measure the severity and progress of... read more ). Doctors do other tests to determine the cause of cholestasis.

Doctors do ultrasonography Ultrasonography Imaging tests of the liver, gallbladder, and biliary tract include ultrasonography, radionuclide scanning, computed tomography (CT), magnetic resonance imaging (MRI), endoscopic retrograde cholangiopancreatography... read more of the abdomen to assess the size of the liver and view the gallbladder and major bile duct. In another type of imaging test called cholescintigraphy Imaging tests of the liver, gallbladder, and biliary tract include ultrasonography, radionuclide scanning, computed tomography (CT), magnetic resonance imaging (MRI), endoscopic retrograde cholangiopancreatography... read more (hepatobiliary scintigraphy or scan), doctors inject a radioactive substance into the infant's vein. They then follow the movement of the radioactive substance as it is secreted from the liver and passes into the gallbladder and through the bile ducts into the duodenum.

Prognosis for Cholestasis in Newborns

Biliary atresia Biliary Atresia Biliary atresia is a birth defect in which the bile ducts progressively narrow and become blocked after birth, preventing bile from reaching the intestine. This defect causes bile to collect... read more can result in progressively worsening liver disease even if it is appropriately diagnosed and treated. Infants who are not treated frequently die of liver failure by 1 year of age.

Cholestasis caused by intravenous nutrition will correct itself if the intravenous nutrition is stopped before the infant develops severe liver disease. If intravenous nutrition cannot be stopped, then a different formulation containing fish oil can be used to relieve the cholestasis.

Gestational alloimmune liver disease that is not treated early typically has a poor prognosis.

Treatment of Cholestasis in Newborns

  • Treatment of the specific cause

  • Supportive care, including good nutrition

Treatment of the cause

Infants who have biliary atresia are treated with a surgical procedure called portoenterostomy (Kasai procedure). Ideally, this procedure should be done in the first 1 to 2 months of life. During this procedure, a part of the small intestine is attached to an area of the liver so that bile can drain into the small intestine. Infants who do not respond well to this procedure ultimately require a liver transplant Liver Transplantation Liver transplantation is the surgical removal of a healthy liver or sometimes a part of a liver from a living person and then its transfer into a person whose liver no longer functions. (See... read more .

Some metabolic diseases such as galactosemia can be treated. Galactosemia is treated Treatment Galactosemia (a high blood level of galactose) is a carbohydrate metabolism disorder that is caused by a lack of one of the enzymes necessary for metabolizing galactose, a sugar that is part... read more by eliminating milk and milk products (which contain the sugar galactose) from the infant's diet. Typically, infants are given a soy formula.

Infants who have gestational alloimmune liver disease may be treated with immune globulin (antibodies obtained from the blood of people with a normal immune system) given by vein or by withdrawing a large amount of the infant's blood and replacing it with transfused blood (exchange transfusion).

Supportive care

It is important to promote good nutrition and give supplements for any deficiencies in vitamins A, D, E, and K. Infants with cholestasis typically do not absorb fat well, so using formulas that contain specialized fat (medium-chain triglycerides) improves their fat absorption and growth. Some infants are not able to drink enough formula to achieve normal growth and may need a concentrated formula that contains more calories per ounce.

Infants who do not have biliary atresia may be given ursodeoxycholic acid to increase bile flow and improve their liver disease.

Drugs Mentioned In This Article

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Gammagard S/D
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