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Formal assessment for the causes of neonatal hyperbilirubinaemia

A sensitivity analysis of these prevalence rates (Figure 6.4) shows the varying importance of
idiopathic hyperbilirubinaemia in different world regions. In Africa no known cause was found
in over 9.0% of cases at each level of serum bilirubin and in cases of kernicterus. In Asia no
cause could be found for 27% of cases with serum bilirubin between 255 micromol/litre and
399 micromol/litre and 29.9% of cases of exchange transfusion or serum bilirubin
> 400 micromol/litre. In the Middle East no cause was found for 62.3% of cases of serum
bilirubin > 400 micromol/litre and 16.7% of cases of kernicterus. In Europe and North America
27.3% of babies with serum bilirubin > 400 micromol/litre and 33.3% of cases of kernicterus
had no cause identified.
Overall evidence summary (6.1.1– 6.1.4)

These meta-analyses indicate that blood group incompatibility and G6PD deficiency are the
most commonly associated conditions in babies with hyperbilirubinaemia
> 255 micromol/litre. Infection was less commonly found at this serum bilirubin level but was
more often found in cases of kernicterus, and in many cases no cause was ever found.
Further examination of the data demonstrates that among jaundiced babies in Europe and North
America blood group incompatibility was the most prevalent underlying factor leading to higher
bilirubin levels (> 400 micromol/litre), whereas G6PD deficiency was more common in
kernicterus cases.
G6PD deficiency is the most common associated condition in cases of jaundice of any severity
among African babies while blood group incompatibility was the second most common factor
in this group. Amongst jaundiced babies in Asia, both blood group incompatibility and G6PD
deficiency were the two most common causes and they were identified more frequently in
babies with more severe hyperbilirubinaemia. Data from studies in the Middle East were too
sparse to allow any meaningful sensitivity analysis.
Overall GDG translation from evidence (6.1.1–6.1.4)

Only poor-quality evidence (EL 2− and EL 3) was available to inform our recommendations
regarding the formal assessment of babies with hyperbilirubinaemia. The evidence supports
current clinical practice, which includes investigations targeted at detecting haemolysis due to
blood group incompatibility and G6PD deficiency in appropriate ethnic groups.
The evidence shows that blood group incompatibility remains an important cause of
hyperbilirubinaemia and kernicterus in Europe and worldwide. Although the evidence did not
support the routine use of DAT (Coombs’ test) in healthy babies, this finding emphasises the
conclusions reached in Chapter 4 on prediction (see Section 4.2.3), namely that a positive DAT
(Coombs’ test) in a baby born to a mother who did not receive prophylactic anti-D
immunoglobulin during pregnancy should be taken into account when considering the cause of
jaundice. Any information about the presence of maternal blood group antibodies should be
transferred from the mother’s notes to those of the baby.
Sepsis was an important co-morbidity in some reported series. No co-morbidity was identified in
a significant minority of the babies in the included studies.
Recommendations

See the end of Section 6.1.
6.1.5 Bilirubin/albumin ratio

Review findings
The usefulness of the B/A ratio in predicting bilirubin-induced neurotoxicity in preterm babies
(gestational age < 32 weeks) with unconjugated hyperbilirubinaemia was examined in a
systematic review. 114 Studies were included if the B/A ratio was measured and outcome data on
neurotoxicity or neurodevelopmental outcome were reported. Six studies were included. One
study reported a trend suggesting that the B/A ratio was better than serum bilirubin in predicting
abnormal auditory brainstem response (ABR) maturation (P = 0.19 versus P = 0.98) while a
second reported that higher B/A ratios were present in babies with abnormal ABR who

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