Page 68 - 16Neonatal Jaundice_compressed

3 Factors that influence

hyperbilirubinaemia and

kernicterus

Introduction
Some disorders cause red cells to be more fragile than normal and to break down more easily
(haemolysis), and this process can add significantly to the bilirubin load. Some of these
disorders are inherited. Other problems include increased destruction of red cells by circulating
antibodies directed against them. Historically, Rhesus haemolytic disease (involving Rhesus
blood group antibodies) was a major cause of kernicterus but, thanks to effective prevention and
treatment of Rhesus incompatibility, other causes of haemolysis, such as ABO incompatibility,
have assumed increasing importance. Large areas of bruising with extravasated and damaged
red blood cells can also contribute to the bilirubin load requiring clearance by the liver. For
reasons that are not understood, babies who are breastfed have higher bilirubin levels than
those who are ‘formula’-fed.
This chapter examines the evidence for and against the factors that have been suggested as
candidates for identifying babies at higher risk of developing significant hyperbilirubinaemia,
and therefore kernicterus.

Clinical question
What are the factors associated with an increased risk of hyperbilirubinaemia? Which factors
affect the relationship between neonatal hyperbilirubinaemia and kernicterus or other
adverse outcomes (neurodevelopmental, auditory)?

A common literature search was conducted for both of the sub-questions and 1865 abstracts and
titles were identified from the electronic databases. After primary screening, hard copies of 98
articles were retrieved. There were many studies that had evaluated the association between
various demographic, maternal and neonatal factors with increased or decreased risk of
hyperbilirubinaemia, but most did not control for confounding variables and were therefore
excluded. For the second sub-question, few good-quality studies were identified.
This review includes 16 studies: ten studies evaluating the risk factors for development of
hyperbilirubinaemia and 3 studies each for the risk factors of kernicterus and adverse sequelae.

3.1 Factors that influence hyperbilirubinaemia

Description of included studies

Of the ten studies 9-18 included under this section, eight are from the USA 9-12;14;16-18 and two from
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Israel. 13;15 Except for one cross-sectional survey of EL III, all studies are comparative
observational studies, all of EL II. The results of all comparative studies on risk factors are
presented in Table 3.1.

Review findings
A nested case–control study was carried out at 11 hospitals of a health maintenance
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organisation in the USA to investigate predictors of hyperbilirubinaemia and evaluate the

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