The Turkish Journal of Pediatrics
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The joint use of human and electronic eye: visual assessment of jaundice and transcutaneous bilirubinometry
Daniele De Luca, Enrico Zecca, Antonio Alberto Zuppa, Costantino Romagnoli
Division of Neonatology, Department of Pediatrics, Catholic University of the Sacred Heart, Rome, Italy
|De Luca D, Zecca E, Zuppa AA, Romagnoli C. The joint use of
human and electronic eye: visual assessment of jaundice and transcutaneous
bilirubinometry. Turk J Pediatr 2008; 50: 456-461.
Our aim was to study the usefulness of jaundice visual assessment combined
with skin bilirubin determination in 517 healthy newborns. Yellowness
assessment was made and babies were included in three different bilirubin
classes. Skin bilirubin and total serum bilirubin were determined within
10 minutes from the visual assessment. This latter led to underestimation of
serum bilirubin in 16.7-40.4% and overestimation in 4.9-35.7% of newborns.
Skin bilirubin measurement after the visual assessment decreased the risk of
underestimation to 0-9.2% and the risk of overestimation to 2.1-11.1%. The
majority of visual assessment errors were performed in the more lighted hours
of the morning (75%), while the smallest number (39%) occurred during the
afternoon. Skin bilirubin measurement significantly corrected these diagnostic
errors (p<0.001, p<0.02) without differences during the day. Clinical estimate
is unreliable for evaluating the need for serum bilirubin assay. Using the
addition of skin bilirubin determination is a more advisable approach.
jaundice, yellowness, neonate, transcutaneous bilirubinometry.
|Nearly 60% of term newborns become visibly
jaundiced in the first week of life and total
serum bilirubin (TSB) assay is actually one of
the most frequent laboratory tests performed
in healthy neonates. In many centers, the
diagnostic process is initially based on jaundice
visual assessment (VA) by nurses and/or
pediatricians. Guidelines by the American
Academy of Pediatrics (AAP) advise clinicians
to measure TSB when the jaundice “appears
excessive for the infant's age”. Unfortunately,
no additional definition of clinically significant
jaundice is given, and the AAP also states
“visual estimation of bilirubin levels from
the degree of jaundice can lead to errors”.
This happens because measurement of the
skin yellowness, as a method to predict TSB
levels, is unreliable. The complexity of bilirubin
transfer from vascular space to the skin seems
to be the main cause of this unreliability[2-4].
Moreover, concentration of bilirubin in the skin
capillary beds and tissue is only one of the
factors affecting the skin color: it also depends
on the presence of other skin pigments, like
melanin and hemoglobin. Because of the poor
correlation between visually estimated jaundice
and TSB, Moyer et al. suggested that TSB
testing should be based on risk factors for
severe hyperbilirubinemia rather than on the
clinical observation. Nevertheless, in a recent
study, the reliability of mothers in examining
their infants for jaundice was surprisingly high,
whether determining the yellowness extent or
using an Ingram icterometer.
Various transcutaneous devices have been proposed
to evaluate the skin yellowness. Accuracy
of first-generation bilirubinometers, based on a
two-wavelength technique, was affected by skin
pigmentation and other factors[7-12]. Many authors
recently studied the accuracy of BiliCheckTM (BC;
Respironics, Marietta, GA), a new transcutaneous
bilirubinometer based on a multiwavelength
spectral reflectance technology[7-10]. BC may
provide an accurate measurement of skin bilirubin
(SB), independent of the presence of other skin
pigments, providing an automatic subtraction of
the light reflected by skin chromogens among
the whole spectrum of visible light[7-10]. Compared
with the Ingram's icterometer, the BC provides a
“real” SB measurement and not a generic estimate
The aim of this study was to verify if the
combined use of yellowness VA and SB
determination can be a reliable indicator for
TSB measurement and a useful tool in the
management of neonatal jaundice.
|Material and Methods |
|This observational study was conducted in a
maternity unit, randomly enrolling healthy term
white newborns that had a TSB assayed for
any reason. The Ethics Board of our University
approved the study and informed consent was
obtained from all parents. TSB was routinely
measured if a baby appeared icteric; otherwise,
TSB was determined in all babies just prior to
hospital discharge. All babies had a postnatal age
<72 hours and were full- or near-term (gestational
age ≥35 weeks), appropriate for gestational age
infants. Study neonates were delivered after an
uneventful pregnancy, without asphyxia (Apgar
score >7 at 1 minute and 5 minutes) and with
no Rh or major ABO isoimmunization. Infants
with previous TSB determinations or receiving
phototherapy were excluded from the study to
prevent observer bias.
For each neonate, we performed jaundice VA,
SB determination and TSB measurement within
10 minutes. Blood samples (150 µl) were drawn
by heel puncture into two heparinized capillary
tubes for micro-assay and were protected
from light exposure to avoid bilirubin photo
conversion. After centrifugation at 3000 rpm for
5 minutes, samples were analyzed with the direct
spectrophotometer (Microbilimeter Twin Beam
Plus mod.11144A73, Ginevri, Rome, Italy),
routinely used for TSB assay in our Division.
Direct spectrophotometry is a simple and accurate
method for TSB assaying, requiring a small blood
volume, which analyzes serum absorbance at
two wavelengths (455 and 575 nm), making
automatic subtraction of absorbance due to
hemoglobin. Spectrophotometer was calibrated
before each determination according to the
manufacturer's recommendations. The same
laboratory technician, who was blinded to
both yellowness VA and SB values, did all
TSB determinations. Skilled pediatric nurses
performed blood samplings and VA of jaundice,
whereas a fellow-neonatologist measured SB.
According to the AAP guidelines, yellowness
was evaluated in a well-lighted room, blanching
the skin of a naked newborn to reveal the
To evaluate jaundice, nurses recorded their
VA, subdividing yellowness in three classes.
Class A: estimated TSB value 6-8 mg/dl; class
B: estimated TSB value 8.1-12 mg/dl; class
C: estimated TSB value 12.1-15 mg/dl. These
estimated TSB levels were chosen for their
usefulness in the management of physiological
jaundice in term newborns. All SB measurements
were made according to the manufacturer's
recommendations: BC was calibrated before
each measurement and all SB determinations
were performed with five readings in different
points of the neonatal forehead while the infant
was in a quiet state. Locations of the readings
were distanced from the hairline and free of
any bruising, nevus, hemangioma or other
skin anomalies. For each yellowness class, we
calculated the number of VA underestimates
and overestimates when a nurse ascribed a baby
into an incorrect yellowness class, respectively
below or above the real TSB value. Thereafter,
we computed the number of errors corrigible
by using SB measurement; we considered the
SB measurement as true and we corrected the
VA diagnostic error when SB was not in accord
with VA but in the same class of TSB.
Sensitivity and specificity were calculated
in order to evaluate the accuracy of both
techniques for predicting different TSB ranges.
Proportions were compared by χ 2 or McNemar's
test, when appropriate. Continuous variables
were contrasted by Student's t test. Data were
analyzed with the statistical software SPSS
for Windows, rel. 11.01 (SPSS Inc., Chicago,
IL, USA) and p values <0.05 were considered
to be statistically significant.
|Baseline characteristics of the study population
are shown in Table I. A total of 517 neonates
underwent TSB measurement, jaundice VA and
SB determination during a period of six months
ending in July 2005. A slight predominance
of males was observed. Subdividing the
study population by VA yellowness classes,
general characteristics were similar apart from
| ||Table I. Details of Study Population [Data shown as mean ± SD or as number (%)]|
Table II shows the diagnostic usefulness of
jaundice evaluation: this was initially performed
by means of VA alone and then by adding
the SB measurement. Assessing jaundice only
visually led to underestimation of TSB in 16.7-40.4% and to overestimation in 4.9-35.7% of
newborns. SB measurement after yellowness
VA decreased the risk of underestimation to
0-9.2% and that of overestimation to 2.1-11.1%.
SB determination significantly reduced both
diagnostic errors when the estimated bilirubin
level was ≤8 mg/dl (p<0.001) and significantly
decreased the risk of underestimation when
the estimated bilirubin level was 8.1-12 mg/
dl (p<0.001). SB determination zeroed the
underestimation and decreased the risk for
overestimation in the highest yellowness
range, although statistical significance was
| ||Table II. Diagnostic Usefulness of VA Alone and Corrected by SB Measurement
[Data shown as number (%)]|
Table III reports the number of diagnostic
errors of jaundice VA alone and jointly with
SB, considering three different daily periods of
observation. The vast majority of measurements
were made in the morning (from 7:00 to
13:00) when rate of incorrect VAs was 61-75%, while less than 40% of errors occurred
in the afternoon. The number of errors was
significantly different between the three periods.
SB measurement significantly reduced the
number of VA diagnostic errors, independently
from the daily hours of observation.
| ||Table III. Diagnostic Errors of VA Alone and with SB Measurement by Hours of Determination
[Data shown as number (%)]|
Table IV reports the diagnostic accuracy of
either jaundice VA alone and VA corrected
by SB. Sensitivity was high for both methods
when TSB ranged from 6 to 8 mg/dl, while
the specificity increased from 35.5% to 75.3%
using SB determination after the jaundice
VA. For TSB levels higher than 8 mg/dl,
sensitivity decreased and specificity increased
with increasing TSB level for both methods
of evaluation. Correction made by the SB
measurement gave very good sensitivity and
specificity at each TSB range.
| ||Table IV. Diagnostic Accuracy of Jaundice VA Alone and Corrected by SB Measurement, for Predicting
TSB Ranges [Data shown as percent (%)]|
|In the last 10 years, four studies have
examined the accuracy of clinical estimate
and its usefulness in the diagnosis of neonatal
jaundice[5,16-18]. Although clinicians usually
assume that jaundice is a reliable clinical
finding, existing data do not support this
hypothesis. Madlon-Kay found that the
correlation between jaundice VA and TSB is
less than optimal if estimates were performed
by physicians or nurses (r=0.55 and r=0.52,
respectively). Level of correlation seems to
increase when parents perform VA but it
remains too low (r maximum=0.7) to be
clinically useful. Riskin et al. stated that
VA performed by an experienced clinician is
a reliable method to estimate the jaundice.
However, Pearson's coefficient between VA and
TSB was 0.68 with high inter- and intra-observer
variations. This paper has also been criticized
because VA accuracy could be significantly
affected by the observer's experience and this
training should be strictly defined. Moreover,
because of the well-known variation of color
perception among individuals, it seems
unreasonable to expect two observers to agree.
The low inter-observer agreement has been
confirmed by a recent comparative work by
Szabo et al.. Clinical assessment was easily
affected by skin color and ambient lighting
and these authors described the jaundice
VA as significantly worse for predicting TSB
compared to transcutaneous bilirubinometry.
Indeed, Moyer et al. definitively demonstrated
that agreement between observers is not much
better than would be predicted by chance. Since
no observer performed better than others for
predicting TSB, this study confirmed that the
variability between yellowness and TSB level
is peculiar to each infant and mainly depends
on bilirubin transfer to the skin and on skin
BiliCheckTM (BC) method has been described
as unaffected by both inter/intra-observer
variability and different skin structure, and
our data show that its use coupled with
jaundice VA can improve the accuracy of
clinical estimate. We only enrolled healthy
term white infants in our study, with SB
measurements made solely on the forehead,
and our considerations may only concern this
population. One limitation of our study could
be that TSB measurements were performed
by direct spectrophotometry and not by high
performance liquid chromatography (HPLC),
which is considered the gold standard for TSB
assay. However, some authors recently reported
that direct spectrophotometry provides a better
agreement with HPLC than other techniques.
Moreover, Bhutani et al. demonstrated that the
agreement between SB and TSB determined by
a variety of laboratory methods is similar to
the agreement between SB and HPLC.
In our study, the observers were pediatric
nurses with several years of full-time experience
in the well-baby nursery, and we asked them to
categorize yellowness within TSB ranges that are
useful in our routine management of neonatal
jaundice. Nevertheless, we found a significant
number of diagnostic errors, confirming that
clinical estimate is an inaccurate method to
evaluate neonatal jaundice. The main concern
can be raised about the underestimation rate.
In fact, to ascribe a neonate into the yellowness
class B leads to an underestimate risk of
more than 40%, meaning that 40% of babies
with TSB >12 mg/dl would be unrecognized,
underestimating jaundice that could be no
more physiological. Surprisingly, a lot of VA
errors were found in the more lighted hours of
the morning (about 75% of errors from 9:00
to 13:00), while the lowest number of errors
(39%) occurred from 15:00 to 18:00. Even
though the number of neonates sampled in the
afternoon is small, a better room illumination
does not seem to improve the jaundice VA.
Diagnostic errors are fewer in the highest
yellowness class (TSB >12 mg/dl) in which
the vast majority of yellow babies are correctly
identified as severely jaundiced. This is due to
the fact that the gap between TSB levels and
yellowness decreases with the increase of large
amounts of bilirubin in the skin.
The use of BC after the jaundice VA can correct
the diagnostic error, significantly reducing the
underestimation rate and decreasing the number
of overestimates in the lowest yellowness class.
An improvement can also be observed at higher
bilirubin levels but it does not reach statistical
significance, probably due to the small number
As we chose yellowness classes in function
of TSB levels useful for the management of
physiological jaundice, it has to be emphasized
that the major improvement in the jaundice
estimate was obtained in classes A and B (from 6
to 12 mg/dl). In these classes, SB determination
after the nurses' VA reduced the underestimate
rate of 77-84% and the overestimate rate of
57-80%. Avoiding the bilirubin underestimation
within these levels could easily help to identify
physiological jaundice and those babies who
need a TSB determination. The improvement
of jaundice estimate due to SB determination
is unrelated to the hour of observation and it
demonstrates that BC is not affected by different
room illumination, and sets BC apart from the
Improving the diagnosis of neonatal jaundice
is actually an urgent need[22,23]. It demands
a reduction both in the management costs
and in the kernicterus incidence that is now
BiliCheck is useful to assess the need for TSB
Assay[1,24], whereas clinical estimate cannot be
recommended as the only method to evaluate
this need. Our study is the first to demonstrate
the usefulness of the joint use of jaundice VA
We are grateful to all nurses of our maternity
unit and to the laboratory technician, for
performing blood samplings and analysis.
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