An early (sixth-hour) serum bilirubin measurement is useful in predicting the development of significant hyperbilirubinemia and severe ABO hemolytic disease in a selective high-risk population of newborns with ABO incompatibility

Pediatrics. 2002 Apr;109(4):e53. doi: 10.1542/peds.109.4.e53.


Objective: In the era of early discharge of newborns from the hospital, newborns with ABO incompatibility are at especially greater risk for developing a subsequent significant hyperbilirubinemia because some of these infants also may present with some degree of ABO isoimmune disease. In this study, we aimed to determine prospectively the critical serum total bilirubin level to predict significant hyperbilirubinemia and severe hemolytic disease in healthy term newborns with ABO incompatibility based on a serum bilirubin measurement made at a postnatal age at which all newborns are at the hospital before discharge and at which any therapeutic intervention, if necessary, could be started as early as possible.

Methods: A total of 136 healthy term newborns with ABO (O-A or O-B) blood group incompatibility were followed prospectively with daily serum total bilirubin measurements for the first 5 days of life. Newborns with serum total bilirubin levels of > or =5 mg/dL and an increase in serum total bilirubin concentration of >0.5 mg/dL/h in the first 24 hours, > or =12 mg/dL on day 2, > or =15 mg/dL on day 3, and > or =17 mg/dL on days 4 and 5 were defined to have significant hyperbilirubinemia and were started on phototherapy treatment. Additional treatment modalities, including intense phototherapy, intravenous immunoglobulin treatment, and exchange transfusion, were used when serum bilirubin concentrations exceeded 20 mg/dL or increased by >1 mg/dL/h despite a phototherapy treatment of at least 4 hours. The additional assessment of the predictive ability of the sixth-hour serum total bilirubin value in determining the development of significant hyperbilirubinemia was made on the basis of the placement of any of the first 5 days' serum bilirubin measurements in the > or =90th percentile of the study population. On the basis of the percentile tracks constructed from the 10th, 35th, 50th, 60th, and 90th percentiles of serum total bilirubin values, a nomogram demonstrating the 3 percentile tracks as risk zone demarcators with divided risk zones was produced.

Results: Twenty-nine newborns (21.3%) had significant hyperbilirubinemia. There were significant differences between the newborns who did and the newborns who did not develop significant hyperbilirubinemia with respect to the reticulocyte count (4.39 +/- 3.46% vs 2.95 +/- 1.63) and the presence of a direct antiglobulin test positivity (6 of 23 vs 0 of 107) and a sibling with neonatal jaundice (6 of 23 vs 5 of 102). A mean serum bilirubin level of > or =4 mg/dL at the sixth hour of life was determined to have the highest sensitivity (86.2%) and negative predictive value (94.5%) and a positive predictive value of 39.7% to predict the newborns who would develop significant hyperbilirubinemia. At the mean serum bilirubin level of 6 mg/dL, the sensitivity, specificity, and negative and positive predictive values were 100%, 91.5%, 100%, and 35.3%, respectively, in diagnosing 6 cases of severe ABO hemolytic disease. On the hour (age)-specific percentile-based nomogram, the zone above the 90th percentile was determined as high risk and that below the 35th percentile as low risk.

Conclusions: The reticulocyte count, a positive direct antiglobulin test, and the presence of a sibling with neonatal jaundice were determined to be the good predictors for the development of significant hyperbilirubinemia and severe hemolytic disease of the newborn. A serum bilirubin measurement and the use of the critical bilirubin levels of 4 mg/dL and 6 mg/dL at the sixth hour of life will predict nearly all newborns who will have significant hyperbilirubinemia and those who will develop severe hemolytic disease of the newborn, respectively. An hour (age)-specific percentile-based nomogram can be used to predict which newborn is at high risk (> or =90th percentile), intermediate risk (35th-90th percentiles), and low risk (<35th percentile) for developing significant hyperbilirubinemia. The 35th and 90th percentile tracks, approximating the serum bilirubin levels of 3.3 mg/dL and 6.5 mg/dL at the sixth hour of life, respectively, can be used as safe risk demarcators in deciding about the time of discharge of ABO-incompatible newborns from the hospital.

Publication types

  • Clinical Trial

MeSH terms

  • ABO Blood-Group System*
  • Bilirubin / blood*
  • Erythroblastosis, Fetal / complications*
  • Humans
  • Hyperbilirubinemia / blood*
  • Hyperbilirubinemia / complications
  • Hyperbilirubinemia / diagnosis*
  • Infant, Newborn
  • Predictive Value of Tests
  • Prospective Studies
  • ROC Curve


  • ABO Blood-Group System
  • Bilirubin