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Jaundice in the Newborn

(Hyperbilirubinemia)

By William J. Cochran, MD, Associate, Department of Pediatrics GI and Nutrition;Clinical Professor, Department of Pediatrics, Geisinger Clinic, Danville, PA;Temple University School of Medicine

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Jaundice is a yellow color to the skin and/or eyes caused by an increase in bilirubin in the bloodstream (hyperbilirubinemia). 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). 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. As bilirubin levels in the blood increase, the whites of the eyes turn yellow first, followed by the skin. During the first week of life, the majority of full-term newborns develop jaundice that normally resolves within a week or two (physiologic jaundice). Jaundice is even more common among premature infants.

Complications of jaundice

Whether jaundice is dangerous depends on what causes it and how high the bilirubin levels are. Some disorders that cause jaundice are dangerous whatever the bilirubin level is. Extremely high bilirubin levels regardless of cause are dangerous.

The most serious consequence of high bilirubin levels is

  • Kernicterus

Kernicterus is brain damage due to accumulation of bilirubin in the brain. The risk of this disorder is higher for newborns who are premature, who are seriously ill, or who are given certain drugs. If untreated, kernicterus may lead to significant brain injury resulting in developmental delay, cerebral palsy, hearing loss, seizures, and even death. Although now rare, kernicterus still occurs, but it can nearly always be prevented by early diagnosis and treatment of hyperbilirubinemia. Once brain injury has occurred, there is no treatment to reverse it.

Causes

Common causes of jaundice

The most common causes of jaundice in the newborn are

  • Physiologic jaundice (most common)

  • Breastfeeding

  • Excessive breakdown of red blood cells (hemolysis)

Physiologic jaundice occurs for two reasons. First, the red blood cells in newborns break down faster than in older infants resulting in increased bilirubin production. Second, the newborn's liver is immature and cannot process bilirubin and get it out of the body as well as in older infants. Almost all newborns have physiologic jaundice. It typically appears 2 to 3 days after birth (jaundice that appears in the first 24 hours after birth may be due to a serious disorder). Physiologic jaundice usually causes no other symptoms and resolves within 1 week. If the infant remains jaundiced at 2 weeks of age, doctors evaluate the infant for other causes of hyperbilirubinemia besides physiologic jaundice.

Breastfeeding can cause jaundice in two ways, which are called

  • Breastfeeding jaundice (more common)

  • Breast milk jaundice

Breastfeeding jaundice develops in the first few days of life and typically resolves in the first week. It occurs in newborns who do not consume enough breast milk, for example, when the mother's milk has not yet come in well. Such newborns have fewer bowel movements and thus eliminate less bilirubin. As newborns continue to breastfeed and consume more, the jaundice disappears on its own.

Breast milk jaundice differs from breastfeeding jaundice in that it occurs towards the end of the first week of life and may resolve by 2 weeks of age or persist for several months. Breast milk jaundice is caused by substances in breast milk that interfere with the liver getting rid of bilirubin from the body.

Excessive breakdown of red blood cells (hemolysis) can overwhelm the newborn's liver with more bilirubin than it can process. There are several causes of hemolysis, which are categorized by whether they are caused by an

  • Immune disorder

  • Nonimmune disorder

Immune disorders cause hemolysis when there is an antibody in the infant's blood that attacks and destroys the infant's red blood cells. This destruction can occur when the fetus's blood type is incompatible with the mother's, or, less commonly, can result from Rh incompatibility (see also Hemolytic Disease of the Newborn).

Nonimmune causes of excessive red blood cell breakdown include hereditary deficiency of the red blood cell enzyme glucose-6-phosphate dehydrogenase (G6PD) and hereditary red blood cell disorders such as the thalassemias. Newborns who were injured during birth sometimes have a collection of blood (hematoma) under their skin. The breakdown of blood in a large hematoma may cause jaundice. If the umbilical cord was not clamped quickly, newborns may get excess blood from the placenta. The breakdown of this blood can also cause jaundice. Breakdown of transfused blood cells can cause increased bilirubin.

Less common causes of jaundice

Less common causes of jaundice include

  • Severe infections

  • An underactive thyroid gland (hypothyroidism)

  • An underactive pituitary gland (hypopituitarism)

  • Certain hereditary disorders

  • Obstruction of bile flow from the liver

Most of these disorders involve cholestasis, which is a reduction in bile flow.

Overwhelming bacterial infection (sepsis) acquired during or shortly after birth can cause jaundice. Infections acquired by the fetus in the womb are sometimes the cause. Such infections include toxoplasmosis and infections with cytomegalovirus or the herpes simplex or rubella viruses.

Some hereditary disorders that can cause jaundice include cystic fibrosis, Dubin-Johnson syndrome, Rotor syndrome, Crigler-Najjar syndrome, and Gilbert syndrome.

Bile flow may be reduced or blocked because of a birth defect of the bile ducts such as biliary atresia or because of a disorder such as cystic fibrosis damages the liver.

Evaluation

While newborns are in the hospital, doctors periodically check them for jaundice. Jaundice is sometimes obvious in the color of the whites of the newborn's eyes or skin. But most doctors also measure the newborn's bilirubin level before discharge from the hospital. If the newborn has jaundice, doctors focus on determining whether it is physiologic and, if not, identifying its cause so that any dangerous causes can be treated. It is particularly important for infants to be evaluated for serious disorders if jaundice persists after 2 weeks of age.

Warning signs

In newborns with jaundice, the following symptoms are cause for concern:

  • Jaundice that appears on the first day of life

  • Jaundice in newborns over 2 weeks old

  • Lethargy, poor feeding, irritability, and difficulty breathing

  • A fever

Doctors are also concerned when bilirubin levels are very high or are increasing rapidly and when blood tests suggest that the flow of bile is reduced or blocked.

When to see a doctor

Newborns with warning signs should be evaluated by a doctor right away. If the newborn is discharged from the hospital on the first day after birth, a follow-up visit to measure the bilirubin level should be scheduled within 2 days of discharge.

Once at home, if parents notice that their newborn’s skin or eyes look yellow, they should contact their doctor immediately. The doctor can decide how urgently to evaluate the newborn based on whether the newborn has any symptoms or risk factors such as prematurity.

What the doctor does

Doctors first ask questions about the newborn’s symptoms and medical history. Doctors then do a physical examination. What they find during the history and physical examination often suggests a cause and the tests that may need to be done.

Doctors ask when the jaundice started, how long has it been present, and whether the newborn has other symptoms such as lethargy and poor feeding. Doctors ask what, how much, and how often the newborn is being fed. They ask how well the newborn is latching onto the breast or taking the nipple of the bottle, whether the mother feels that her milk has come in, and whether the newborn is swallowing during feedings and seems satisfied after feedings. The doctor also asks about stool color. Information about how much urine and stool the newborn produces can help doctors evaluate whether the newborn is being fed enough. Stool that is pale and not the normal yellow-gold color suggests there may be cholestasis.

Doctors ask the mother whether she had infections or disorders during pregnancy (such as diabetes) that can cause jaundice in the newborn, what her blood type is, and what drugs she has been taking. They also ask whether family members have had any of the hereditary disorders that can cause jaundice.

During the physical examination, doctors check the newborn's skin to see how far jaundice has spread. They also look for other clues suggesting a cause, particularly signs of infection, injury, thyroid disease, or pituitary failure.

Testing

Bilirubin levels are measured to confirm the diagnosis of jaundice and determine its severity. Levels may be measured in a sample of blood or by using a sensor placed on the skin.

If the bilirubin level is high, other blood tests are done. They typically include

  • Hematocrit (the percentage of red blood cells in blood)

  • Examination of a blood sample under a microscope to look for signs of red blood cell breakdown

  • Reticulocyte count (the number of newly formed red blood cells)

  • Direct Coombs test (which checks for certain antibodies attached to red blood cells)

  • Measurement of different types of bilirubin

  • Blood type and Rh status (positive or negative) of the newborn and mother

Other tests may be done depending on results of the history and physical examination and on the newborn's bilirubin level. They may include culturing samples of blood, urine, or cerebrospinal fluid to check for sepsis, measuring levels of red blood cell enzymes to check for unusual causes of red blood cell breakdown, doing blood tests of thyroid and pituitary function, and doing tests for liver disease.

Treatment

When a disorder is identified, it is treated if possible. High bilirubin levels themselves may also require treatment.

Physiologic jaundice usually does not require treatment and resolves within 1 week. For newborns being fed formula, frequent feedings can help prevent jaundice or reduce its severity. Frequent feedings increase the frequency of bowel movements and thus eliminate more bilirubin in stool. The type of formula does not seem to matter.

Breastfeeding jaundice may also be prevented or reduced by increasing the frequency of feedings. If the bilirubin level continues to increase, rarely, infants may need to be supplemented with formula.

In breast milk jaundice, mothers may be advised to stop breastfeeding for only 1 or 2 days and to express breast milk regularly during this break from breastfeeding to keep their milk supply up. Then they can resume breastfeeding as soon as the newborn's bilirubin level starts to decrease. While breastfeeding, mothers are usually advised not to give the newborn water or water containing sugar because doing so may decrease how much milk the newborn drinks and may disrupt the mother's milk production. However, breastfed infants who are dehydrated despite efforts to increase breastfeeding may need additional fluids.

High bilirubin levels may be treated with

  • Exposure to light (phototherapy)

  • Exchange transfusion

Phototherapy or "bili lights"

This treatment is most commonly used, but it is not effective for all types of hyperbilirubinemia. For example, phototherapy is not used for infants with cholestasis. Phototherapy uses bright light to change bilirubin into a form that can be eliminated rapidly from the body. Blue light is the most effective, and most doctors use special commercial phototherapy units. Newborns are placed under the unit and undressed to expose as much skin as possible. They are turned frequently and left under the lights for variable periods of time (typically about 2 days to a week) depending on how much the bilirubin levels in the blood need to be lowered. Phototherapy can help prevent kernicterus. To determine how well the treatment is working, doctors periodically measure bilirubin levels in blood. Skin color is not a reliable guide.

Exchange transfusion

This treatment is used when bilirubin levels are very high and phototherapy is not sufficiently effective. An exchange transfusion can rapidly remove bilirubin from the bloodstream. A small amount of the newborn's blood is gradually removed (one syringe at a time) and replaced with equal volumes of donor blood. The procedure usually takes about 2 hours.

Exchange transfusions may need to be repeated if bilirubin levels remain high. Also, the procedure has risks and complications, such as heart and breathing problems, blood clots, and electrolyte imbalances in the blood.

The need for exchange transfusion has decreased since phototherapy has become so effective and since doctors have become better able to prevent problems resulting from incompatible blood types.

Key Points

  • In many newborns, jaundice develops 2 or 3 days after birth and disappears on its own within a week.

  • Whether jaundice is of concern depends on what is causing it and how high the bilirubin levels are.

  • Jaundice may result from serious disorders, such as incompatibility of the newborn’s and mother’s blood type, excessive breakdown of red blood cells, or a severe infection.

  • If jaundice develops in a newborn at home, parents should call their doctor right away.

  • If jaundice is caused by a specific disorder, that disorder is treated.

  • If high bilirubin levels require treatment, infants are typically treated with phototherapy and sometimes with exchange transfusions.