Kernicterus

Kernicterus is a preventable life-long neurologic syndrome caused by severe and untreated hyperbilirubinemia during the neonatal period. High levels of bilirubin are toxic to the developing newborn. In full-term infants, hyperbilirubinemia symptoms include severe jaundice, lethargy, and poor feeding. Features of kernicterus may include choreoathetoid cerebral palsy, mental retardation, sensorineural hearing loss, and gaze paresis. Kernicterus is not a reportable condition in the United States, and its prevalence is unknown; however, a pilot registry at a Pennsylvania hospital documented 90 cases in 21 states from 1984 to June 2001 (L. Johnson, Pennsylvania Hospital, Philadelphia, personal communication, 2001). This report summarizes case histories off our full-term, healthy infants who developed kernicterus and underscores that to prevent kernicterus, newborns must be screened and promptly treated for hyperbilirubinemia [1].

In early 2001, a national support group for parents of children with kernicterus conducted a survey on kernicterus. A convenience sample of 15 families was identified by word-of-mouth or through the Internet, and a self-administered questionnaire was mailed. For this report, a case was defined as a child in whom kernicterus (International Classification of Diseases, Ninth Revision, Clinical Modification, codes 773.4, 774.6, and 774.7) was diagnosed since 1994, who was [greater than]37 weeks' gestational age, and who weighed at birth [greater than]5 lbs, 5 oz ([greater than]2500 g). Among the sample families, seven did not complete the questionnaire, four had children who did not meet the case definition, and the remaining four had children who did meet the case definition.

Case Reports

Case 1. In 1994, an apparently healthy white boy was born at 37 weeks' gestation weighing 6 lbs, 13 oz (3090 g). Delivery was uncomplicated. His 1 minute and 5 minute Apgar scores were eight and nine, respectively (normal range: seven-10). His mother's blood type was 0+, and the newborn was A+, Coombs negative. On discharge at 20 hours, he was alert and nursing well; a 2-week follow-up appointment was scheduled at a pediatric clinic. On day 9, the infant was taken to a pediatric clinic with jaundice. The condition was thought to be the result of breastfeeding. That evening, he exhibited lethargy, was not nursing, and had "pumpkin orange" skin coloration. On day 10, the parents notified their physician about the infant's lethargy and poor eating and were given an appointment for the following morning. During a pediatric appointment on day 11, the infant weighed 5 lbs, 10 oz (2552 g), was dehydrated, and jaundiced. A tested serum sample revealed an elevated bilirubin of 41.5 mg/dL (normal range at age [greater than]72 hours: [less than]17 mg/dL). Despite treatment with phototherapy and two double-volume exchange transfusions, on day 11, he developed athetosis, oral-motor dysfunction requiring a gastrostomy tube, and dental dysplasia. Kernicterus was diagnosed at age 6 months.

Case 2. In 1995, an apparently healthy white boy was born at 37 weeks' gestation weighing 6 lbs. 5 oz (2863 g). Apgar scores were eight and nine at 1 and 5 minutes, respectively. At 17,23, and 33 hours, jaundice was noted. No serum bilirubin level or ABO or Rh status was disclosed. Examination revealed normal neurologic and physical findings, and he was discharged after 36 hours; a follow-up appointment at a pediatric clinic was scheduled at 1 week. On day 4, the patient exhibited lethargy and poor breastfeeding. On days, he was admitted to a hospital. Laboratory findings included a bilirubin level of 34.6 mg/dL, and phototherapy was started. Later that day, the patient developed opisthotonus, a high-pitched cry, and poor suckling and later developed athetoid cerebral palsy, hearing loss, and gaze paresis. Kernicterus was diagnosed at age 18 months.

Case 3. In 1997, an apparently healthy white boy was born at 37 weeks' gestation weighing 8 lbs. 2 oz (3686 g). His Apgar scores were nine at 1 and 5 minutes. On discharge at 22 hours, a cephalohematoma and heart murmur were noted. The following day, the infant was taken to a pediatric clinic where examination found jaundice but no heart murmur. Fifteen minutes of sunlight per day was recommended as treatment. During the next 4 days, the infant developed lethargy and poor breastfeeding. On day 6, he was taken to a pediatric clinic where a serum sample was drawn and tested. Results included a bilirubin level of 27 mg/dL; phototherapy was started. By 11 p.m., the patient's bilirubin peaked at 33.4 mg/dL, and he received an exchange transfusion. During the next 4 months, he developed athetoid cerebral palsy, oral-motor dysfunction requiring a gastrostomy tube, and gaze paresis. Kernicterus was diagnosed at age 4 months.

Case 4. In 1998, an apparently healthy white boy was born at 39 weeks' gestation weighing 9 lbs. 8 oz (4313 g). Pregnancy was unremarkable but delivery required vacuum extraction. His Apgar scores were eight and nine at 1 and 5 minutes, respectively. AO blood incompatibility was noted and Rh status was unknown. At 22 hours, he appeared jaundiced; at 52 hours, he was discharged with the treatment recommendation that he receive sunlight. The infant was alert and nursed well during the next 11 days. However, at his follow-up examination on day 12, he appeared jaundiced. The initial serum bilirubin level was 23.6 mg/dL, which peaked at 29.4 mg/dL. The same day, the infant was admitted to a hospital for phototherapy. During the next 4 months, he developed athetoid cerebral palsy, hearing loss, and enamel hypoplasia, and kernicterus was diagnosed at age 4 months.

Reported by: K Carter, MD, Emory Univ School of Medicine, Atlanta, Georgia. K Dixon, Parents of Infants and Children with Kernicterus, Birmingham, Alabama. National Center on Birth Defects and Developmental Disabilities; and an EIS Officer, CDC.

Editorial Note: These cases illustrate that hyperbilirubinemia in full-term, otherwise healthy infants can lead to kernicterus. Each of these white male infants was nursing normally when discharged but shortly after developed feeding problems. A historic cohort study suggests boys are more susceptible than girls to adverse outcomes from hyperbilirubinemia [2.] At follow-up, initial serum bilirubin levels in all the infants exceeded maximum levels (mean: 34.7 mg/dL) specified for treatment by the American Academy of Pediatrics practice guideline, which currently is under revision [3.]

Treating hyperbilirubinemia with phototherapy and exchange transfusions prevents kernicterus if treatment is initiated promptly and is continued until bilirubin levels normalize. By the 1970s, such therapy was implemented effectively, and kernicterus virtually disappeared in full-term infants until the early 1990s [4], when physicians began to debate the need to identify and treat hyperbilirubinemia in healthy, full-term infants without risk factors for hemolysis [5-7].

Increases in breastfeeding and early hospital discharge after delivery coincided with this debate [8,9]. Although mild jaundice occasionally is associated with breastfeeding, it provides optimum nutrition. In the full-term newborn, serum bilirubin levels peak at 48-72 hours. Healthy, full-term infants often are discharged from hospitals before this peak. Some health-care providers rely on visual assessment to detect pathology; however, this method can be unreliable. Hyperbilirubinemia can be reduced if heath-care providers recognize risk factors and remember the acronym "JAUNDICE" (see box). Another useful tool is the May 2, 2001, Sentinel Event Alert issued by the Joint Commission on Accreditation of Healthcare Organizations.

The findings in this report are subject to at least two limitations. First, a small number of case reports has inherent limitations that include lack of representativeness. No inference can be made about risks for disease or trends. Second, these cases reflect self-reported data and are subject to potential reporting bias.

Early hyperbilirubinemia detection is critical to the prevention of the irreversible effects of kernicterus. Health-care providers, parents, and other caretakers should be aware of risk factors for hyperbilirubinemia, and treatment should begin immediately after hyperbilirubinemia is diagnosed. Verbal and written information received before the infant is discharged may be useful in gaining an understanding of risk factors for and signs and treatment of jaundice and hyperbilirubinemia. Bilirubin levels before discharge may provide quantitative measurement that could aid management [5,10]. Infants discharged <48 hours after birth should be examined by a health-care provider within 2 to 3 days to receive routine follow-up visits and a jaundice assessment. In addition, CDC, along with other agencies, researchers, and partners, plans to initiate surveillance and the systematic evaluation of trends and prevalence rate that will provide the data necessary to target prevention activities.

References

(1.) Joint Commission on Accreditation of Healthcare Organizations. Sentinel event alert issue 18: kernicterus threatens healthy newborns; May 2, 2001. Available at http://www.jcaho.org. Accessed June 2001.

(2.) Johnson LH, Sivieri E, Bhutani V. Neurologic outcome of singleton [greater than or equal to]2500 g CORE project babies not treated for hyperbilirubinemia. [Abstract]. Pediatr Res 1999;45:203A.

(3.) American Academy of Pediatrics. Management of hyperbilirubinemia in the healthy term newborn. Pediatrics 1994;94:558-65. Available at http://www.aap.org/policy/hyperb.htm. Accessed June 2001.

(4.) Brown AK, Johnson L. Loss of concern about jaundice and the reemergence of kernicterus in full-term infants in the era of managed care. In: Fanaroff AA, Klaus MH, eds. Yearbook of neonatal and perinatal medicine. St. Louis, Missouri: Mosby Yearbook; 1996:xvii-xxviii.

(5.) Maisels MJ, Newman TB. Kernicterus in otherwise healthy, breast-fed term newborns. Pediatrics 1995;96:730-3.

(6.) Newman TB, Maisels MJ. Evaluation and treatment of jaundice in the term newborn: a kinder, gentler approach. Pediatrics 1992;89:809-18.

(7.) Newman TB, Maisels MJ. Less aggressive treatment of neonatal jaundice and reports of kernicterus: lessons about practice guidelines. Pediatrics 2000;105:242-5.

(8.) Ryan AS. The resurgence of breastfeeding in the United States. Pediatrics 1997;99:e12. Available at http://www.pediatrics.orgfcgi/content/full/99/4/e12. Accessed June 2001.

(9.) Seidman DS, Stevenson DK, Ergaz Z, Gale R. Hospital readmission due to neonatal hyperbilirubinemia. Pediatrics 1995;96:727-9.

(10.) Liu LL, Clemens CJ, Shay DK, Davis RL, Novack AH. The safety of newborn early discharge: the Washington state experience. JAMA 1997;278:293-8.

Major Risk Factors for Hyperbilirubinemia in Full-Term Newborns

* Jaundice within first 24 hours after birth.

* A sibling who was jaundiced as a neonate.

* Unrecognized hemolysis such as ABO blood type incompatibility or Rh incompatibility.

* Nonoptimal sucking/nursing.

* Deficiency in glucose-6-phosphate dehydrogenase, a genetic disorder.

* Infection.

* Cephalohematomas/bruising.

* East Asian or Mediterranean descent.

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