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Formal assessment for the causes of neonatal hyperbilirubinaemia

count, reticulocyte count, platelet count, red blood cell morphological examination, and a
urinalysis. No cause was identified in 214 (47.8%) cases of hyperbilirubinaemia. A possible
cause of hyperbilirubinaemia was identified only from patient history, physical examination or
routine haematocrit (at 4 hours) in 145 (32.4%) cases. Thirteen cases (2.9%) had other causes
related to hyperbilirubinaemia that were not identified by the routine tests. Seventy-five cases
(16.8%) were diagnosed from the routine tests. These included isoimmunisation alone in 58
cases (12.9%) and isoimmunisation accompanied by preterm birth, bruising, cephalohaematoma,
bacterial infection, viral infection or maternal diabetes in 17 cases (3.8%). [EL 3]

Overall evidence summary (6.1.5–6.1.7)
A number of poor-quality studies and one good-quality review were identified. The good-quality
review identified six studies that showed a link between the B/A ratio and various indices of
bilirubin encephalopathy (abnormal ABR, IQ at 6 years). Two poor-quality studies showed a
moderately positive correlation between free bilirubin and both the B/A ratio and the B/A molar
ratio (r = 0.74 and r = 0.75, respectively). There was also a moderately positive correlation
between unconjugated bilirubin and free bilirubin (r = 0.69).
Similarly, two studies have been carried out to determine the diagnostic yield from additional
tests, including direct bilirubin, to help in the investigation of early jaundice or prolonged
jaundice. The value of these additional tests was variable, and they were often non-contributory.
Overall GDG translation from evidence (6.1.5–6.1.7)

The evidence does not support changing current clinical practice in the UK, which does not
routinely include the calculation of the B/A ratio in determining treatment thresholds for
jaundice. Furthermore, expert advice received by the GDG is that most commonly used
laboratory methods overestimate albumin, especially at low concentrations. External quality
assurance data from October 2009 (www.birminghamquality.org.uk) shows that the affected
methods are used by virtually all NHS laboratories. The GDG is aware of an ongoing RCT in the
Netherlands which is examining the use of the B/A ratio alongside serum bilirubin in jaundiced
babies as an indicator for treatment with phototherapy.

Poor-quality evidence did not show a clinically useful correlation between unconjugated
bilirubin and free bilirubin. Previous advice advocated subtracting direct bilirubin from the total
serum bilirubin when deciding on management in babies with hyperbilirubinaemia. The GDG
agrees with the AAP that this practice should cease, and total bilirubin levels should be used to
guide management. The GDG is aware of rare cases of kernicterus with high conjugated
bilirubin levels, and there is a theoretical risk that conjugated bilirubin can elevate free bilirubin
levels by displacing unconjugated bilirubin from the binding sites. Specialist advice should be
sought for the exceptional cases in which the conjugated bilirubin is more than 50% of the total.
The GDG considers that total serum bilirubin should be used to guide the management of
jaundiced babies less than 14 days old.

Recommendations – 6.1 Tests to detect underlying disease in all babies with
significant hyperbilirubinaemia
In addition to a full clinical examination by a suitably trained healthcare professional, carry
out all of the following tests in babies with significant hyperbilirubinaemia as part of an
assessment for underlying disease (see threshold table (Section 1.3) and treatment threshold
graphs (Section 1.6)):
• serum bilirubin (for baseline level to assess response to treatment)
• blood packed cell volume
• blood group (mother and baby)
• DAT (Coombs’ test). Interpret the result taking account of the strength of reaction, and
whether mother received prophylactic anti-D immunoglobulin during pregnancy.

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