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Am Fam Physician. 2005;71(5):947-948

What are the effects of treatments for unconjugated hyperbilirubinemia in term and preterm infants?


Exchange Transfusion. We found no randomized controlled trials (RCTs) on the effects of exchange transfusion versus no treatment or versus phototherapy. There is general consensus that exchange transfusion is effective in reducing serum bilirubin levels and in preventing neurodevelopmental sequelae. In most of the RCTs comparing other interventions, exchange transfusion was used successfully to reduce serum bilirubin levels when those interventions failed to control the rise of serum bilirubin.

Phototherapy. Two RCTs found that conventional phototherapy and fiberoptic phototherapy reduced neonatal jaundice more effectively than no treatment. One systematic review (which included quasirandomized and randomized controlled trials) and one subsequent RCT found that conventional phototherapy was more effective than fiberoptic phototherapy, although subgroup analysis in the systematic review found no significant difference between groups in preterm infants. No trials included in the review evaluated the impact of either phototherapy method on parent–infant bonding. One RCT found a greater effect with double-conventional compared with single-conventional phototherapy, but another RCT found no significant difference between double-fiberoptic and single-conventional phototherapy. One systematic review (which included quasirandomized and randomized controlled trials) found no significant difference between fiberoptic plus conventional and conventional phototherapy alone in additional phototherapy, exchange transfusion, or percentage change in bilirubin after 24 hours, although it noted a trend favoring the fiberoptic plus conventional group. Most trials did not report kernicterus as an outcome. We found insufficient evidence on the adverse effects of phototherapy.


Albumin Infusion. We found no RCTs on the effects of albumin infusion versus no treatment or versus other treatment.

Home Versus Hospital Phototherapy. We found no RCTs on the effects of home phototherapy versus no treatment or versus hospital phototherapy.


Neonatal jaundice refers to the yellow coloration of the skin and sclera of newborn infants that results from hyperbilirubinemia.


Jaundice is the most common condition requiring medical attention in newborn infants. About 50 percent of term and 80 percent of preterm infants develop jaundice in the first week of life.1 Jaundice also is a common cause of readmission to the hospital after early discharge of newborn infants.2 Jaundice usually appears two to four days after birth and disappears one to two weeks later, usually without the need for treatment.

Etiology/Risk Factors

In most infants with jaundice, there is no underlying disease and the jaundice is termed physiologic. Physiologic jaundice occurs when there is accumulation of unconjugated bilirubin in the skin and mucous membranes. It typically presents on the second or third day of life and results from the increased production of bilirubin (caused by increased circulating red cell mass and a shortened red cell lifespan) and the decreased excretion of bilirubin (caused by low concentrations of the hepatocyte binding protein, low activity of glucuronyl transferase, and increased enterohepatic circulation) that normally occur in newborn infants. In some infants, unconjugated hyperbilirubinemia may be associated with breastfeeding (breast milk jaundice), and this typically occurs after the third day of life. Although the exact cause of breast milk jaundice is not clear, it is believed to be caused by an unidentified factor in breast milk. Nonphysiologic causes include blood group incompatibility (Rhesus or ABO problems), other causes of hemolysis, sepsis, bruising, and metabolic disorders. Gilbert’s and Crigler-Najjar syndromes are rare causes of neonatal jaundice.


In the newborn infant, unconjugated bilirubin can penetrate the blood–brain barrier and is potentially neurotoxic. Unconjugated hyperbilirubinemia can, therefore, result in neurodevelopmental sequelae including the development of kernicterus. Kernicterus is brain damage arising from the deposition of bilirubin in brain tissue. However, the exact level of bilirubin that is neurotoxic is unclear, and kernicterus at autopsy has been reported in infants in the absence of markedly elevated levels of bilirubin.3 Recent reports suggest a resurgence of kernicterus in countries in which this complication had virtually disappeared.4 This has been attributed primarily to early discharge of newborns from the hospital.

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