Page 83 - 16Neonatal Jaundice_compressed

Neonatal jaundice

4.1 Tests that predict hyperbilirubinaemia

Serum bilirubin levels in the first 24 hours of life (serum bilirubin–day 1)

Description of included studies
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One EL Ib study and three EL II studies 13;26;28 have been included. They were conducted in
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Spain, India, Turkey and Israel. The study population in three studies 13;26;28 included
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healthy term babies (≥ 37 weeks) and serum bilirubin was measured within 24 hours of birth.
The Indian study included healthy babies with gestational age > 35 weeks and serum
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bilirubin was measured at 24 ± 6 hours of age. In three studies, 26-28 the ability of serum
bilirubin–day 1 (threshold value ≥ 102 micromol/litre) to predict hyperbilirubinaemia (defined
as serum bilirubin ≥ 290 micromol/litre on day 3–5) was calculated, and results from these
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studies were pooled to obtain the summary results. Since the Spanish study was conducted in
two phases, data have been given separately for both phases. The fourth study, from Israel,
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used multiple regression analysis to investigate the association of various factors (maternal age,
education, O blood group, breastfeeding, serum bilirubin–day 1 and change in serum bilirubin
levels) with hyperbilirubinaemia.
Review findings
In three studies 26-28 used in the meta-analysis, hyperbilirubinaemia was defined as serum
bilirubin levels ≥ 290 micromol/litre and its prevalence ranged from 2.9% to 12.0%. The
pooled sensitivity of serum bilirubin–day 1 in predicting hyperbilirubinaemia was 94% (95% CI
88% to 97%), with values in individual studies ranging from 90% to 100%, and the results were
statistically homogeneous (Figure 4.1). On the other hand, there was strong evidence of
statistical heterogeneity for specificity, with the pooled value being 62% (95% CI 59% to 65%)
and individual values ranging from 46% to 71% (Figure 4.2).
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The study from Israel showed serum bilirubin value > 85 micromol/litre on day 1 to have a
sensitivity of 63% and specificity of 94%, while the model with all other variables (except
serum bilirubin on day 1) showed 58% sensitivity and 90% specificity. The addition of serum
bilirubin > 85 micromol/litre on day 1 to the model with all other variables increased the
sensitivity to 82% but the specificity decreased to 80%.
Evidence summary

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Evidence from one EL 1b and two EL II studies 26;28 indicates that serum bilirubin
≥ 102 micromol/litre on day 1 is a sensitive predictor of later hyperbilirubinaemia. In another
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study, combining serum bilirubin > 85 micromol/litre at less than 24 hours with maternal
variables (blood group O, age, exclusive breastfeeding and education) resulted in an increase in
sensitivity but a decrease in specificity.
GDG translation from evidence

Evidence shows that serum bilirubin > 102 micromol/litre in the first 24 hours of life is
predictive of serum bilirubin > 290 micromol/litre between days 3 and 5. This supports the
evidence reviewed in Chapter 3 on risk factors, that visible jaundice in the first 24 hours is a risk
factor for later significant hyperbilirubinaemia and underlies the recommendation in Table 7.1.
In babies with light skin tones, jaundice is usually visible at levels of bilirubin
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> 90 micromol/litre. Some studies show that the sensitivity can be improved using a model
combining serum bilirubin with maternal variables.
The GDG is of the opinion that visible jaundice in the first 24 hours remains an important
predictor of later clinically important hyperbilirubinaemia. Any visible or suspected jaundice in
the first 24 hours requires urgent medical review (within 2 hours), which must include serum
bilirubin measurement and an investigation of the underlying causes (see Chapter 6 on formal
assessment).

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