Page 94 - 16Neonatal Jaundice_compressed

Early prediction of serious hyperbilirubinaemia

GDG translation from evidence
Current evidence does not support measuring umbilical cord blood bilirubin levels for the
prediction of subsequent hyperbilirubinaemia in healthy babies.

Recommendations

See the end of Section 4.2.
End-tidal carbon monoxide measurement (ETCOc)

Description of included studies
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Two studies 32;33 with EL II have been included in this section. The first study had a large
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sample size of both term and near-term babies while the second, smaller, study included only
term babies. In both studies, ROC curves were developed to evaluate the accuracy of end-tidal
carbon monoxide (CO) production corrected for ambient CO (ETCOc) in predicting
hyperbilirubinaemia.

Review findings
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The first study was an international study carried out at nine sites (four in the USA, two in
China, two in Israel and one in Japan). All newborn babies with gestational age ≥ 35 weeks
were enrolled in the first 36 hours of life. Of the 1895 babies enrolled, 1370 (72%) completed
the study. All babies had measurements of ETCOc and serum bilirubin performed at
30 ± 6 hours, and serum bilirubin only at 96 ± 12 hours. Between these times, serum bilirubin
could be measured for clinical reasons. ETCOc was measured using a breath analyser with
single-use disposable nasal sampler. Hyperbilirubinaemia was defined as laboratory serum
bilirubin ≥ 95th centile at any time during the study period. Threshold centile values were
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taken as those defined by Bhutani et al. and adopted by the AAP. Inclusion and exclusion
criteria were well defined. Babies with age-specific serum bilirubin ≥ 95th centile at up to
96 ± 12 hours were withdrawn from the study. About 9% (120 of 1370) of babies had serum
bilirubin levels ≥ 95th centile at 30 ± 6 hours or at 96 ± 12 hours. The mean ETCOc levels in
this group were statistically significantly higher than the mean levels in the non-
hyperbilirubinaemic group (P < 0.001). Logistic regression analysis was conducted with
variables found to be associated with hyperbilirubinaemia (serum bilirubin percentile at
30 hours, bruising, maternal blood type, race, maternal diabetes, feeding type, gravidity and
ETCOc). Models to evaluate diagnostic accuracy of ETCOc, laboratory serum bilirubin and their
combination in predicting hyperbilirubinaemia were developed. ETCOc at 30 ± 6 hours with a
threshold value above the population mean (1.48 ± 0.49 ppm) predicted hyperbilirubinaemia
with 13% positive predictive value (PPV) and 96% negative predictive value (NPV), while
laboratory serum bilirubin levels > 75th centile showed 17% PPV and 98% NPV. When both
tests were combined, NPV increased to 99% but PPV decreased to only 6%. It was concluded
that serum bilirubin measurement before discharge (at 30 ± 6 hours) may provide some
assistance in predicting risk of hyperbilirubinaemia, but the addition of ETCOc does not
improve its predictive accuracy. [EL II]
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In the second study, from Japan, ETCOc levels were measured every 6 hours during the first
3 days of life in 51 healthy, full-term babies. The Minolta JM-102 was used to record
transcutaneous bilirubin measurements every 12 hours during the first 5 days and serum
bilirubin levels were measured if the JM-102 index was ≥ 22 reflectance units. An ROC curve
was developed to evaluate the accuracy of ETCOc at different ages in predicting
hyperbilirubinaemia, which was defined as serum bilirubin ≥ 257 micromol/litre.
Hyperbilirubinaemia occurred in seven babies, while 44 babies had serum bilirubin levels
< 257 micromol/litre. There were no statistically significant differences between the
hyperbilirubinaemic and non-hyperbilirubinaemic babies in terms of sex, gestational age, mode
of delivery, Apgar score at 1 minute, age at peak transcutaneous bilirubin, or mode of feeding.
Moreover, the mean levels of ETCOc were similar for the two groups from 6 to 36 hours of age,
but the hyperbilirubinaemic group had higher mean levels at 42, 48, 54 and 66 hours. The ROC
curve indicated that ETCOc at 42 hours of age showed the best accuracy in predicting

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