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Neonatal jaundice
subsequently developed hearing loss. One of the included studies reported on IQ at 6 years and
found that IQ decreased at higher B/A ratios (r = −0.12; P = 0.06). A study of autopsies in 398
babies identified 27 (6.8%) with kernicterus. These 27 babies were compared with 103
autopsied babies matched for birthweight and gestational age. There was no difference in mean
serum bilirubin between the kernicteric and non-kernicteric babies. Serum albumin and the
reserve albumin binding capacity were lower in the kernicteric babies but where B/A ratios
could be calculated there was no difference. The final included study found that the bilirubin-
binding capacity expressed as the molar B/A ratio was lower in kernicteric than non-kernicteric
babies (P < 0.05). [EL 1++]
A case series in India 115 reported the correlation between the B/A ratio and free bilirubin. The
study included 53 babies with hyperbilirubinaemia with a mean gestational age of
37.9 ± 2.3 weeks and mean birthweight of 2780 ± 620 g. The reported mean serum bilirubin
was 227 ± 80 micromol/litre, mean free bilirubin 8.7 ± 5.6 nmol/l and mean albumin levels
3.6 ± 0.7 g/dl. The mean B/A ratio was 3.7 and the correlation between free bilirubin and B/A
ratio was 0.74 (P < 0.001). [EL 3]
A Canadian case series 116 examined the relationship between albumin levels and free bilirubin.
A total of 55 plasma samples from 46 jaundiced babies were used. Diagnoses included preterm
birth, birth asphyxia, respiratory distress syndrome and idiopathic hyperbilirubinaemia. The
mean gestational age was 36 ± 4 weeks and the mean birthweight was 2453 ± 813 g. No other
demographic details were reported. There was a correlation between free bilirubin and the
bilirubin/albumin molar ratio (r = 0.75; P < 0.001) [EL 3]
6.1.6 Relationship between circulating free bilirubin and unconjugated bilirubin
Review findings
A case series from Brazil 117 examined the correlation between free bilirubin and unconjugated
bilirubin in 43 term babies with non-haemolytic hyperbilirubinaemia. Inclusion criteria were
birthweight > 2500 g, negative DAT, gestational age 37–41 weeks, postnatal age < 7 days,
and negative maternal history and serology for syphilis. The babies had no history of perinatal
hypoxia, had Apgar score > 8 at 1 and 5 minutes, did not receive any substances competing for
albumin binding sites and had not received phototherapy, exchange transfusions or human
albumin. Over half of the sample (25; 58.1%) were male but no other demographic data were
reported. The correlation between free bilirubin and indirect bilirubin was 0.69 (P < 0.01).
[EL 3]
6.1.7 Medical co-morbidity identified by measuring conjugated bilirubin, routine
haematology or urinalysis
Review findings
A retrospective case series in the USA 118 looked at the usefulness of measuring conjugated
bilirubin in jaundiced term babies. Preterm babies were excluded. Testing rates were different in
the two units: in one, serum bilirubin and conjugated bilirubin were measured in 55% and 53%
of the term babies and in the second unit in 16% and 5%, respectively. Abnormal results were
defined as the top 5% of conjugated bilirubin measurements in each unit so in the first unit an
abnormal score was > 39 micromol/litre while in the second it was > 17 micromol/litre. Of
149 babies with high conjugated bilirubin levels, 40 (26.8%) had associated conditions but
identifying conjugated hyperbilirubinaemia contributed to the diagnosis in only four of these.
Over half, 78 (52.3%), of the cases with high conjugated bilirubin were unexplained while 24
(16.1%) were laboratory errors. Associated diagnoses included isoimmunisation in 19 (12.7%)
babies, sepsis or pneumonia in five (3.6%), congestive heart failure in five (3.6%), multiple
anomalies in two (1.3%), pyloric stenosis in two (1.3%), extreme growth restriction (possible
rubella) in one (0.7%), hypothyroidism in one (0.7%) and choledochal cyst in one (0.7%). [EL 3]
119
A retrospective case series in the USA looked at the usefulness of laboratory tests in babies
with hyperbilirubinaemia. Only babies (n = 447) with a birthweight of > 2500 g were included.
The mean birthweight was 3440 ± 485 g. No other demographic details were reported. Routine
tests included total and conjugated bilirubin, blood type, complete blood count, differential cell
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