Hyperbilirubinemia

Many newborns develop jaundice, which is the yellowish discoloration of skin caused by bilirubin. Fortunately, in most instances the condition improves in a few days and there are no long-term consequences. In a few cases, a condition known as hyperbilirubinemia develops, which is normally defined as having a total serum or plasma bilirubin (TB) level >95th percentile on the Bhutani nomogram. Hyperbilirubinemia may occur in as many as 80 percent of preterm babies born before 29 weeks gestation and the rate of occurrence rapidly decreases to less than 1 percent of term babies. Hyperbili rubinemia is associated with an increased risk for bilirubin induced neurologic dysfunction, which is known as BIND.

BIND is a concern because it only arises when the bilirubin crosses the blood-brain barrier and binds to brain tissue. In its acute stage it is referred to as acute bilirubin encephalopathy (ABE). If severe enough, permanent brain damage can occur and this is known as Kernicterus. This condition typically develops in the baby's first year. The major symptoms of Kernicterus may include: (1) cerebral palsy; (2) hearing loss; (3) gaze abnormalities; and (4) dental enamel abnormalities. In most cases of hyperbilirubinemia occurring in term and late preterm infants, Kernicterus is an avoidable condition.

Studies have shown that the following correctable factors may cause Kernicterus.

Discharge before 48 hours after birth without appropriate follow-up.

Failure to measure the total serum or plasma bilirubin (TB) concentration in an infant with jaundice within 24 hours of age.

Failure to recognize risk factors for hyperbilirubinemia.

Lack of concern regarding the presence of jaundice.

Delayed measurement of TB in infants with severe jaundice.

Delayed initiation of phototherapy in infants with elevated TB.

Lack of response to parental concerns regarding jaundice, lethargy, or poor feeding. ii

In light of these known correctable factors, medical authorities believe that Kernicterus can be prevented in term and late preterm infants if "a systemic approach were in place that identified and treated infants at risk for severe hyperbilirubinemia." iii These authorities have identified the following major and minor risk factors for the development of severe hyperbilirubinemia in infants of 35 or more weeks' gestation.

Major risk factors include:

  • Predischarge TB or TcB level in the high-risk zone.
  • Jaundice observed in the first 24 hours.
  • Blood group incompatibility with positive direct antiglobulin test, other known hemolytic disease, elevated ETCO.
  • Gestational age 35-356 weeks.
  • Previous sibling received phototherapy.
  • Cephalohematoma or significant bruising.
  • Exclusive breastfeeding, particularly if nursing is not going well and weight loss is excessive.
  • East Asian race. iv

Minor risk factors include:

  • Predischarge TB or TcB level in the high intermediate-risk zone.
  • Gestational age 37-38 weeks.
  • Jaundice observed before discharge.
  • Previous sibling with jaundice.
  • Macrosomic infant of a diabetic mother.
  • Maternal age ≥ 25 years.
  • Male gender." v

The leading cause of hyperbilirubinemia in infants is hemolytic disease, of which fetomaternal blood group incompatibilities (Rh and ABO) are the most common. vi As noted in other sections of this website, the American College of Obstetricians and Gynecologists (ACOG) has noted that protocols have been developed which, if followed, are dramatically successful in reducing Rh alloimmunization. vii Therefore, if a child develops hyperbilirubinemia newborn injury as a result of a Rh incompatibility, there is an excellent chance that this could have been avoided if proper protocols were followed.

If your child develops hyperbilirubinemia and Kernicterus, particularly as a result of Rh incompatibility, you may wish to have your child's medical records reviewed by an experienced medical malpractice law firm.


i. Iams JD, Preterm Birth, Chapter 23, Figure 23-8, Obstetrics Normal and Problem Pregnancies, edited by Gabbe S, Niebyl JR, Simpson JL. 4th Ed. 2002.

ii. Wong RJ, Bhutani VK, Evaluation of Unconjugated Hyperbilirubinemia in Term and Late Preterm Infants, 2013 UpToDate.

iii. Id.

iv. Id. at Table.

v. Id.

vi. Rosenberg AA, The Neonate, Chapter 20, p. 677, Obstetrics Normal and Problem Pregnancies, edited by Gabbe S, Niebyl JR, Simpson JL. 4th Ed. 2002.

vii. In May of 1999, ACOG published Practice Bulletin No. 4, Prevention of Rh D Alloimmunization. This bulletin noted that "before the introduction of anti-D immune globulin, hemolytic disease of the fetus and newborn affected 9-10% of pregnancies and was a major cause of perinatal morbidity and mortality." The bulletin further noted that the administration of the anti-D immune globulin is successful in reducing the rate of developing antibodies. ACOG instructs its members that protocols have been developed which are "responsible for the dramatic decrease in alloimmunization and subsequent hemolytic disease in the past two decades." Despite the development of these protocols, ACOG noted that " Rh D alloimmunization remains a clinical concern, with many cases due to failure to follow established protocols. "