Page 74 - 16Neonatal Jaundice_compressed

Factors that influence hyperbilirubinaemia and kernicterus

Research recommendations

What are the factors that underlie the association between breastfeeding and jaundice?
Why this is important
Evidence: Breastfeeding has been shown to be a factor in significant hyperbilirubinaemia. The
reasons for this association have not yet been fully elucidated. Population: Infants in the first
28 days of life. Exposure: Feeding type (breast milk, formula feeds or mixed feeds).
Comparison: Infants who do not develop significant hyperbilirubinaemia will be compared
with infants with significant hyperbilirubinaemia. Outcome: Factors to be analysed include I)
maternal factors, II) neonatal factors, III) blood analyses. Time stamp: Sept 2009

What is the comparative effectiveness and cost-effectiveness of universal pre-discharge
transcutaneous bilirubin screening alone or combined with a risk assessment in reducing
jaundice-related neonatal morbidity and hospital readmission?

Why this is important
Evidence: There is good evidence that a risk assessment that combines the result of a timed
transcutaneous bilirubin level with risk factors for significant hyperbilirubinaemia is effective
at preventing later significant hyperbilirubinaemia.Population: Babies in the first 28 days of
life. Subgroups should include near-term babies and babies with dark skin tones. Exposure: A/
Timed pre-discharge transcutaneous bilirubin level. B/ Timed pre-discharge transcutaneous
bilirubin level combined with risk assessment. Comparison: Standard care (discharge without
timed transcutaneous bilirubin level). Outcome: i) Significant hyperbilirubinaemia, ii) Cost-
effectiveness, III) Parental anxiety. Time stamp: Sept 2009

3.2 Risk factors for kernicterus and/or adverse sequelae

Description of included studies
Three studies 20-22 were identified that examined the association between risk factors and the
development of kernicterus: two comparative studies 21;22 [EL II] and one descriptive study.
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[EL III]
For adverse sequelae, two studies 23;24 [EL II] looked at the association between
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hyperbilirubinaemia and neurodevelopmental outcomes (one in term babies and the other in
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extremely low birthweight babies ) and one study [EL II] evaluated risk factors for hearing loss.
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Review findings
A prospective study conducted over a 1 year period in a tertiary referral neonatal unit in India
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sought to determine the risk factors for the development of kernicterus in term babies with non-
haemolytic jaundice. The inclusion criteria were total serum bilirubin levels
> 308 micromol/litre, absence of haemolysis and absence of major malformations. Laboratory
investigations were carried out to rule out haemolysis, meningitis, intracranial haemorrhage and
other pathology. Exchange transfusions were done whenever serum bilirubin levels reached
342 micromol/litre. There were 64 babies eligible for the study, of whom 14 (21.9%) had
kernicterus. In all cases, stage II encephalopathy was reported: all the babies with kernicterus
had stage II bilirubin encephalopathy characterised by presence of opisthotonos, rigidity and
paralysis of upward gaze. There was no statistically significant difference between affected and
unaffected babies in gender, mean gestational age, mean birthweight, proportion exclusively
breastfed and postnatal weight. Mean peak serum bilirubin levels, free bilirubin levels,
bilirubin/albumin ratio and free fatty acid levels were statistically significantly higher in cases
than in babies without kernicterus. Multiple logistic regression analyses showed birth asphyxia
(OR 8.3, 95% CI 1.2 to 111.8; P = 0.03), serum bilirubin levels (OR 1.15, 95% CI 1.04 to1.3;
P < 0.01) and free bilirubin levels (OR 1.1, 95% CI 1.04 to 2.2; P < 0.01) to be statistically
significantly associated with the development of kernicterus. [EL II]

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