Outcomes among newborns with total serum bilirubin levels of 25 mg per deciliter or more

Department of Pediatrics, University of California, San Francisco, San Francisco, California, United States
New England Journal of Medicine (Impact Factor: 54.42). 06/2006; 354(18):1889-900. DOI: 10.1056/NEJMoa054244
Source: PubMed

ABSTRACT The neurodevelopmental risks associated with high total serum bilirubin levels in newborns are not well defined.
We identified 140 infants with neonatal total serum bilirubin levels of at least 25 mg per deciliter (428 micromol per liter) and 419 randomly selected controls from a cohort of 106,627 term and near-term infants born from 1995 through 1998 in Kaiser Permanente hospitals in northern California. Data on outcomes were obtained from electronic records, interviews, responses to questionnaires, and neurodevelopmental evaluations that had been performed in a blinded fashion.
Peak bilirubin levels were between 25 and 29.9 mg per deciliter (511 micromol per liter) in 130 of the newborns with hyperbilirubinemia and 30 mg per deciliter (513 micromol per liter) or more in 10 newborns; treatment involved phototherapy in 136 cases and exchange transfusion in 5. Follow-up data to the age of at least two years were available for 132 of 140 children with a history of hyperbilirubinemia (94 percent) and 372 of 419 controls (89 percent) and included formal evaluation at a mean (+/-SD) age of 5.1+/-0.12 years for 82 children (59 percent) and 168 children (40 percent), respectively. There were no cases of kernicterus. Neither crude nor adjusted scores on cognitive tests differed significantly between the two groups; on most tests, 95 percent confidence intervals excluded a 3-point (0.2 SD) decrease in adjusted scores in the hyperbilirubinemia group. There was no significant difference between groups in the proportion of children with abnormal neurologic findings on physical examination or with documented diagnoses of neurologic abnormalities. Fourteen of the children with hyperbilirubinemia (17 percent) had "questionable" or abnormal findings on neurologic examination, as compared with 48 controls (29 percent; P=0.05; adjusted odds ratio, 0.47; 95 percent confidence interval, 0.23 to 0.98; P=0.04). The frequencies of parental concern and reported behavioral problems also were not significantly different between the two groups. Within the hyperbilirubinemia group, those with positive direct antiglobulin tests had lower scores on cognitive testing but not more neurologic or behavioral problems.
When treated with phototherapy or exchange transfusion, total serum bilirubin levels in the range included in this study were not associated with adverse neurodevelopmental outcomes in infants born at or near term.

1 Follower
  • [Show abstract] [Hide abstract]
    ABSTRACT: AimTo investigate whether infants with neonatal hyperbilirubinaemia but without intermediate or advanced bilirubin encephalopathy develop long-term sequelae, with impairment of motor development, executive function, or hearing.Method This nested double-cohort study included 167 exposed children (107 males, 60 females) born in Denmark 2000 to 2005 at gestational age ≥35 weeks with a total serum bilirubin ≥450 μmol/L (26.3mg/dL) and 163 age-, sex-, and gestational age-matched unexposed children (103 males, 60 females). The children were examined at a mean age of 7.7 years (SD 1.7y) using the Movement Assessment Battery for Children–Second Edition (MABC-2), pure tone audiometry, and the Behavioural Regulation Inventory of Executive Function (BRIEF) questionnaire.ResultsThe follow-up rate was 70% of the eligible infants in the exposed group and 45% in the unexposed group. Mean difference was −0.2 (95% confidence interval [CI] −1.1 to 0.8) in adjusted standard score for MABC-2 and 0.3 (95% CI −2.9 to 3.5) in adjusted BRIEF executive composite standard score. No children had significant hearing impairment or a diagnosis of cerebral palsy, attention-deficit–hyperactive disorder, or autism spectrum disorder recorded in national registries.InterpretationNo evidence was found of an increased risk of deficits in motor development, executive function, or hearing in children with extreme hyperbilirubinaemia who did not have intermediate or advanced bilirubin encephalopathy.
    Developmental Medicine & Child Neurology 10/2014; 57(4). DOI:10.1111/dmcn.12603 · 3.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Physiological jaundice is a common problem faced by neonates affecting approximately 60% full term and 80% preterm infants. If left untreated bilirubin levels continue to rise and can lead to bilirubin encephalopathy and kernicterus. There are many controversies within the literature around the management and treatment of hyperbilirubinaemia creating uncertainty around when to commence phototherapy treatment. This paper will discuss what clinical indicators should be considered when deciding to initiate phototherapy.MethodsA critical review of five research papers was performed in an attempt to explore the clinical uncertainties and reach a conclusion. Each paper was analysed in relation to methodological content to establish the quality of the paper before comparing findings to consider implications for practice.ResultsThe strongest study was Sarici et al. (2004) who clearly showed that near term newborns was a significant clinical risk for hyperbilirubinaemia. Bhutani et al. (1999) and Sarici et al. (2004) showed the usefulness of predictive nomograms to identify infants at risk of significant hyperbilirubinaemia. Gartner et al. (1998) and Petrova et al. (2006) highlighted uncertainties among practitioners in relation to the management and treatment of hyperbilirubinaemia. The weakest study was the RCT by Leite and Facchini (2004) these results were both inconsistent with previous studies and indicated flaws in the methods.Implications for PracticeNew guidelines are required and should incorporate individual guidance for near term newborns as they have been shown to be at increased risk of developing significant hyperbilirubinaemia. Further research into when phototherapy treatment should be initiated is required to provide evidence-based practice for neonates of all gestations.
    Journal of Neonatal Nursing 06/2011; 17(3):92-102. DOI:10.1016/j.jnn.2010.08.003
  • [Show abstract] [Hide abstract]
    ABSTRACT: In the first days of life, low grade jaundice is essentially universal. The source of the elevated bilirubin level giving rise to "physiological jaundice of the newborn" is only partly known. We hypothesized that it is, at least in part, the result of active and specific hemolysis involving a physiological mechanism to lower the high fetal hematocrit, appropriate for the relatively low oxygen environment in utero, to a lower level appropriate for the state of oxygen abundance after birth. We tested this by quantifying end tidal carbon monoxide (ETCO) as a marker of the rate of heme metabolism to bilirubin. We found that ETCO values of 20 neonates and children with known hemolytic disorders were higher than 20 age-matched healthy controls (p<0.0001), indicating that this instrumentation recognizes hemolysis in neonates and children. We also found that ETCO reference intervals were indeed higher in healthy neonates during the first three days after birth (5th to 95th percentile reference range, 1.4 to 1.7ppm) than after 1month of age (all ≤1.0ppm, p<0.0001). These results suggest to us that hemolysis is physiological during the first days after birth. The cellular and molecular mechanisms responsible for transient hemolysis after birth are topics of current investigation. Copyright © 2014 Elsevier Inc. All rights reserved.
    Blood Cells Molecules and Diseases 11/2014; 54(3). DOI:10.1016/j.bcmd.2014.11.018 · 2.33 Impact Factor

Full-text (2 Sources)

Available from
May 22, 2014