Bilirubin nomograms for identification of neonatal hyperbilirubinemia in healthy term and late-preterm infants: a systematic review and meta-analysis

World J Pediatr. 2014 Aug;10(3):211-8. doi: 10.1007/s12519-014-0495-8. Epub 2014 Aug 15.


Background: Hyperbilirubinemia occurs in most healthy term and late-preterm infants, and must be monitored to identify those who might develop severe hyperbilirubinemia. Total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) nomograms have been developed and validated to identify neonatal hyperbilirubinemia. This study aimed to review previously published studies and compare the TcB nomograms with the TSB nomogram, and to determine if the former has the same predictive value for significant hyperbilirubinemia as TSB nomogram does.

Methods: A predefined search strategy and inclusion criteria were set up. We selected studies assessing the predictive ability of TSB/TcB nomograms to identify significant hyperbilirubinemia in healthy term and late-preterm infants. Two independent reviewers assessed the quality and extracted the data from the included studies. Meta-Disc 1.4 analysis software was used to calculate the pooled sensitivity, specificity, and positive likelihood ratio of TcB/TSB nomograms. A pooled summary of the receiver operating characteristic of the TcB/TSB nomograms was created.

Results: After screening 187 publications from electronic database searches and reference lists of eligible articles, we included 14 studies in the systematic review and meta-analysis. Eleven studies were of medium methodological quality. The remaining three studies were of low methodological quality. Seven studies evaluated the TcB nomograms, and seven studies assessed TSB nomograms. There were no differences between the predictive abilities of the TSB and TcB nomograms (the pooled area under curve was 0.819 vs. 0.817).

Conclusions: This study showed that TcB nomograms had the same predictive value as TSB nomograms, both of which could be used to identify subsequent significant hyperbilirubinemia. But this result should be interpreted cautiously because some methodological limitations of these included studies were identified in this review.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Bilirubin / blood*
  • Biomarkers / blood
  • Evidence-Based Medicine
  • Humans
  • Hyperbilirubinemia, Neonatal / blood
  • Hyperbilirubinemia, Neonatal / diagnosis*
  • Hyperbilirubinemia, Neonatal / etiology
  • Infant
  • Infant, Newborn
  • Infant, Premature / blood*
  • Neonatal Screening* / methods
  • Nomograms*
  • Predictive Value of Tests
  • Prognosis
  • Risk Assessment
  • Risk Factors
  • Sensitivity and Specificity
  • Term Birth / blood*


  • Biomarkers
  • Bilirubin