Neurodevelopmental Outcomes of Newborns with Severe Neonatal Jaundice

Abstract

Source: Newman TB, Lijestrand P, Jeremy RJ, et al. Outcomes among newborns with total serum bilirubin levels of 25 mg per deciliter or more. N Engl J Med. 2006;354:1889–1900; doi:10.1056/NEJMoa054244Although newborns with severe hyperbilirubinemia (those whose serum bilirubin levels reach 25 mg per deciliter or more) are aggressively treated, long-term outcomes are poorly defined. A prospective study was performed by investigators from the University of California, San Francisco and the Division of Research at Kaiser Permanente Medical Care Program in Oakland, Calif. to determine whether neurodevelopmental outcomes were affected in term and near term newborns whose total serum bilirubin reached 25 mg per deciliter or greater. A total of 140 infants with severe hyperbilirubinemia were compared to 419 randomly selected controls. Perinatal data were collected from paper and electronic records. Formal evaluation of neurologic development at approximately 5 years of age was performed per parental consent by an examiner masked to the group. Fifty-nine percent of parents of children in the hyperbilirubinemia group agreed to formal evaluation versus 40% for the control group. For infants who did not have a formal neurological assessment, outcome was assessed using parental questionnaires and a search of electronic medical records for neurological diagnosis codes.A formal evaluation, completed parental questionnaire, or record of an outpatient visit at the age of 5 years or more was available for 94% of the subjects in the hyperbilirubinemia group, and 89% of those in the control group (P=.06). Very few infants (10) had serum bilirubin measurements of greater than 30 mg per deciliter, and only 5 were treated with an exchange transfusion. The study identified no significant differences between the hyperbilirubinemia and control groups with regard to intelligence testing, verbal-motor skills, or parental report of behavioral problems at ~5 years of age. However, lower IQs were observed in the very small number of children (9) who had positive direct antiglobulin tests. Neither the degree nor duration of hyperbilirubinemia or gestational age at birth had a significant effect on outcome.Dr. Eichenwald has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of a commercial product/device. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.This study is 1 of only 2 available that has prospectively followed a group of term and near term newborns with severe hyperbilirubinemia and compared them to a control group without elevated bilirubin levels.1 Recent identification of the re-emergence of kernicterus makes this study timely and important in understanding treatment recommendations for neonatal jaundice.2 Although limited by the inability to perform formal neurological assessments on all the enrolled infants, the study was able to accomplish some assessment of outcome beyond 2 years of age, when cerebral palsy should be evident, in the majority of infants. Very few of the subjects with hyperbilirubinemia had bilirubin levels that exceeded 30 mg per deciliter, and most had short periods with a documented bilirubin level over 25 mg per deciliter. Despite these limitations, the results of this study should provide reassurance to pediatricians and families that total serum bilirubin values between 20 and 25 mg per deciliter are unlikely to cause long-term sequelae with adequate treatment. The lower IQs in the small sample of infants with positive direct antiglobulin tests, while too limited to draw firm conclusions, do suggest that more aggressive treatment of newborns with jaundice and evidence of hemolysis is warranted.2