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Jaundice in Newborns

(Hyperbilirubinemia)

by Arthur E. Kopelman, MD

In jaundice, the skin and whites of the eyes look yellow. Jaundice is common in newborns. It occurs when the level of bilirubin (a yellow pigment produced during the normal breakdown of red blood cells) in the blood rises. When the bilirubin level gets too high, bilirubin can be deposited in the skin, the whites of the eyes, and other tissues. As bilirubin levels increase, the whites of the eyes turn yellow first, followed by the skin. Slightly more than half of all full-term newborns develop jaundice during the first week of life. Jaundice is even more common among premature infants.

Newborns normally have a high red blood cell count at birth, and their red blood cells have a shorter life span than adult red blood cells. The high red blood cell count and shorter life span mean that more of the newborn's red blood cells undergo the normal daily breakdown of aging red blood cells (a process called hemolysis). Aging red blood cells are normally removed by the spleen. Hemoglobin (the substance in red blood cells that carries oxygen) is broken down and recycled. One portion of the hemoglobin molecule is converted into bilirubin, which is carried by the blood to the liver. The liver chemically changes the bilirubin by binding it to another substance, creating conjugated bilirubin. The conjugated bilirubin passes into the bile, which is then excreted into the digestive tract. In adults, bilirubin is further broken down by the bacteria that normally reside in the digestive tract. This form of bilirubin is excreted in the stool and gives stool its typical brown color. However, newborns do not yet have these bacteria or other digestive enzymes needed to process bilirubin. Thus, because newborns produce more bilirubin than older children and adults and eliminate bilirubin at a slower rate than older children and adults, high levels of bilirubin can build up in their blood relatively quickly. This disorder is called hyperbilirubinemia.

Complications

Whether jaundice is dangerous depends on what is causing it, how high the bilirubin level is, and how quickly the bilirubin level rises. Some disorders that cause jaundice are dangerous regardless of what the bilirubin level is. However, an extremely high bilirubin level, regardless of cause, is dangerous.

The most serious consequence of a high bilirubin level is kernicterus—a disorder in which bilirubin is deposited in the brain and causes brain damage. Kernicterus occurs only when the level of bilirubin is high. The risk of this disorder is higher for newborns who are premature, seriously ill, or who are given certain drugs. If untreated, kernicterus may lead to unresponsiveness (stupor) or lethargy, loss of muscle tone, a high-pitched cry, poor feeding, and seizures. Later, children can have cerebral palsy, hearing loss, a permanent upward gaze, or other signs of brain damage. Kernicterus is now rare because of increased screening for hyperbilirubinemia and early treatment.

Causes

Common causes

The most common causes of jaundice in the newborn are

  • Physiologic jaundice (most common)

  • Breastfeeding jaundice

  • Breast milk jaundice

  • Excessive breakdown of red blood cells (hemolysis)

Physiologic jaundice occurs in most newborns. It develops because the red blood cells in newborns normally break down at a slightly increased rate and because the digestive tract and liver function in newborns are immature. As the digestive tract and liver mature, bilirubin is processed faster, and jaundice quickly disappears. Physiologic jaundice typically appears 2 to 4 days after birth (jaundice that appears in the first 24 to 48 hours after birth is usually due to a disorder). Physiologic jaundice usually causes no other symptoms and resolves within 1 to 2 weeks.

Breastfeeding jaundice is common. It develops in 1 of 6 breastfed infants a few days after birth. It occurs in newborns who do not consume enough breast milk (often because the mother's milk has not yet come in well). Newborns who consume less breast milk have fewer bowel movements and thus eliminate less bilirubin. As newborns continue to breastfeed and consume more milk, the jaundice usually disappears on its own.

Breast milk jaundice is less common. It develops in only 1 to 2% of breastfed newborns. It occurs when breast milk contains a high level of a substance that slows bilirubin excretion and thus causes the bilirubin level to increase. Breast milk jaundice appears when newborns are 5 to 7 days old, peaks at about 2 weeks, and can last for 3 to 12 weeks.

Excessive breakdown of red blood cells can overwhelm the liver with more bilirubin than it can process. There are several causes of excessive breakdown of red blood cells. In hemolytic disease of the newborn, the newborn’s blood type is incompatible with the mother’s (as occurs in Rh incompatibility—see Rh Incompatibility). Because their blood types are different, antibodies from the mother can cross the placenta and attack the newborn’s red blood cells, rapidly breaking them down. This causes a sudden rise in bilirubin level. Less common 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 severe alpha-thalassemia (see Thalassemias). Events during delivery sometimes lead to excessive breakdown of red blood cells. 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 or this blood can also cause jaundice.

Less common causes

Less common disorders that cause jaundice include

  • Severe infections

  • An underactive thyroid gland (hypothyroidism)

  • Certain hereditary liver disorders

  • Obstruction of bile flow from the liver

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 virus or rubella virus.

Hypothyroidism may be present at birth or shortly thereafter (see Hypothyroidism in the Newborn), and up to 10% of affected newborns have jaundice for weeks to months.

Hereditary liver disorders that can cause jaundice include 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), pyloric stenosis, or because a disorder such as cystic fibrosis has damaged the liver.

Risk factors

Major risk factors for jaundice include prematurity (35 to 36 weeks' gestation), blood type incompatibility with the mother, jaundice that begins soon after birth (high levels occur in the first 24 hours), birth-related bruising, and family history of jaundice. Also at major risk of jaundice are newborns who are exclusively breastfed and who have lost a significant amount of weight and have a high-risk bilirubin level before discharge from the hospital.

Newborns who have a low-risk level of bilirubin before discharge from the hospital, who are postmature (over 41 weeks' gestation), and who are exclusively bottle-fed are at low risk of jaundice.

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.

Warning signs

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

  • Jaundice that appears in the first 24 hours of life

  • Jaundice in newborns over 3 weeks old

  • Lethargy, poor feeding, irritability, or difficulty breathing

  • Jaundice that rapidly worsens

  • A fever

Doctors are also concerned when the bilirubin level is very high or is 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 bilirubin level should be done before discharge. A follow-up visit to measure the bilirubin level should be scheduled within 2 days of discharge. Newborns with risk factors for a high jaundice level or who had a high level before discharge may need to be seen at least twice after discharge from the hospital.

Once at home, if the newborn had not been jaundiced before but parents now 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. Information about how much urine and stool the newborn produces can help doctors evaluate whether the newborn is being fed enough.

Doctors ask the mother whether she has had infections or disorders that can cause jaundice, what her blood type is, and what drugs she is 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, and thyroid disease.

Testing

The bilirubin level is measured to confirm the diagnosis of jaundice and determine its severity. The level 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 include

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

  • Examination of a blood sample under a microscope

  • 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

  • Albumin (a protein that binds bilirubin, keeping it from being able to enter the brain) level

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 infection and measuring levels of red blood cell enzymes to check for unusual causes of red blood cell breakdown.

Treatment

When a disorder is identified, it is treated if possible (for example, doctors may give immune globulin to infants with hemolytic disease of the newborn). A high bilirubin level itself may also require treatment.

Physiologic jaundice usually does not require treatment. More frequent feedings (for breastfed newborns, nursing at least 8 to 12 times per day and similar or slightly fewer feedings for formula-fed newborns) 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. Newborns should not be fed water or sugar water because these liquids do not prevent the bilirubin level from rising, do not provide nutrition, and will decrease the amount of milk or formula the newborn drinks.

Breastfeeding jaundice may also be prevented or reduced by increasing the frequency of feedings to at least 8 to 12 times per day. If the bilirubin level continues to increase, temporarily supplementing breast milk feedings with formula or expressed breast milk may help.

Breast milk jaundice is not relieved by more frequent nursing because the breast milk contains a substance that worsens jaundice. In some cases, mothers may be advised to stop breastfeeding for 1 or 2 days and to express breast milk regularly during this break from breastfeeding. They can resume breastfeeding as soon as the newborn's bilirubin level starts to decrease. In most cases, mothers are advised to breastfeed as usual because the benefits of breastfeeding are greater than the risk of developing kernicterus with breast milk jaundice.

A high bilirubin level may be treated with

  • Exposure to light (phototherapy)

  • Exchange transfusion

Phototherapy

This treatment is most commonly used. It uses bright light to change unconjugated bilirubin into forms that can be eliminated rapidly through the urine. Blue light is the most effective light, and most doctors use special commercial phototherapy units. Newborns are undressed to expose as much skin as possible. They are turned frequently and left under the lights until the bilirubin level comes down and stays low. The lights may be needed for as few as 2 days to a week. Intensive phototherapy can prevent kernicterus if started early when the bilirubin level is rising. However, it is useful only for a high level of bilirubin that has not been changed (conjugated) by the liver. To determine how well the treatment is working, doctors periodically measure the bilirubin level in the blood. Skin color is not a reliable guide. Light therapy is relatively safe for newborns. However, newborns need eye shields to protect their eyes from the bright light.

Exchange transfusion

This treatment is used when the bilirubin level is very high and continues to rise despite use of intensive phototherapy. It 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 an equal amount of donor blood. The procedure usually takes 2 to 4 hours. Typically, the total amount of blood that is removed and replaced is equal to twice the newborn's total blood volume.

Exchange transfusions may need to be repeated if the bilirubin level continues to rise. 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 early bilirubin screening has become the normal practice and because phototherapy (and immune globulin treatment for hemolytic disease of the newborn) has become increasingly effective.

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, how high the bilirubin level is, and how quickly the bilirubin level rises.

  • Doctors check newborns for risk factors, do bilirubin tests before newborns leave the hospital, and follow up within 2 to 3 days after discharge from the hospital to identify newborns who may need treatment.

  • 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, parents should call their doctor right away.

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

  • If a high bilirubin level requires treatment, it is typically treated with phototherapy and sometimes with exchange transfusions.