埼玉医科大学雑誌 第29巻第4号 (2002年10月) 245-249頁 (C) 2002 The Medical Society
of Saitama Medical School
Clinical Evaluation of a New Device for Transcutaneous
Bilirubin Measurement in Japanese Infants
Toshihiko Nakamura, Daigo Yamada, Yukino Itakura, Yunosuke Ogawa
Department of Pediatrics, and Division of Neonatal medicine, Center for
Maternal, Fetal and Neonatal Medicine, Saitama Medical Center, Saitama Medical
School, Kawagoe, Saitama 350-8550, Japan.
Background: The advantages of using noninvasive techniques of bilirubin
measurement are the avoidance of pain and of local infection as well as real-time
results. Recently the accurate measurement of total serum bilirubin by transcutaneous
bilirubin using a reflectance spectrophotometer, the BiliCheckTM,
has been introduced in a heterogeneous newborn population. But there is limited
data on the use of BiliCheckTM on Oriental babies including
Japanese newborn infants.
Methods: A total of 240 transcutaneous bilirubin measurements were taken
from the three body sites (forehead, chest, and left or right upper arm) of 52
Japanese neonates and compared with simultaneous total serum bilirubin measurements
determined by the direct spectrophotometric method. Of 240 occasions, 206 measurements
were taken before starting phototherapy and 34 were during phototherapy. A phototherapy
eye-patch was placed over the measurement site on the forehead prior to the start
Results: As a preliminary study, total serum bilirubin concentrations measured
by the direct spectrophotometric method and by the bilirubin oxidase method were
compared. There was a good correlation between the values obtained by these 2
methods ( r＝0.980, y＝1.05 x＋0.176, p＜0.0001). The precision of the device was
expressed as a mean coefficient of variation of less than 5 % and operator difference
was small as coefficient of variation below 5 %.
Before phototherapy, the correlations between the transcutaneous bilirubin measurements
by the BiliCheckTM and total serum bilirubin by the direct spectrophorometric
method were high; r＝0.925 on forehead, 0.848 on chest and 0.822 on upper arm,
respectively. However, the correlation became less during phototherapy (on forehead
Conclusion: These data indicate that accurate measurements of total serum
bilirubin by transutaneous bilirubinometry with BiliCheckTM
are applicable in Japanese infants. But the use of the device for infants who
receive phototherapy needs further study.
Keywords: transcutaneous bilirubinometer, total serum bilirubin concentration,
phototherapy, Japanese infants
J Saitama Med School 2002;29:245-249
(Received September 2, 2002)
More than 80 % of Japanese newborn infants develop visible physiologic jaundice
in the first week after birth. The incidence of hyperbilirubinemia is reported
to be especially higher in Japanese infants1). It has been a routine
procedure in every nursery to screen the degree of individual jaundice by noninvasive
transcutaneous bilirubin measurements with Minolta transcutaneous bilirubin meter
and to measure the serum concentration with blood sampled from the heel of each
infant when the reading is high2). However, the device available at
present only shows the reading values of the device, and the values do not correspond
directly to the values of serum bilirubin concentration3). Therefore,
many infants, especially sick neonates and smaller infants, still require unnecessary
invasive serum bilirubin measurements.
The BiliCheckTM is a new transcutaneous bilirubin measurement
device that uses spectral reflectance analysis algorithms based on recent studies
of the dermal light scattering and light absorption characteristics of neonatal
skin and corrects for the interfering pigments4). In contrast to the
Minolta transcutaneous bilirubin meter, the BiliCheckTM provides
absolute values of the total serum bilirubin. Recently in a mixed population,
the applicability of the BiliCheckTM has been examined5).
But the number of Asian infants was too small in comparison to white and black
subjects. The aim of this study is to determine the accuracy and reliability of
the BiliCheckTM device in the measurement of transcutaneous
bilirubin in Japanese infants.
We measured transcutaneous bilirubin using the BiliCheckTM
on 52 Japanese infants who were born in Saitama Medical Center, Saitama Medical
School during the period of 6 months, from June to November 1998. Infants were
sequentially enrolled as many as possible in the study from both the well-baby
nursery and the neonatal intensive care unit. The gestational age was between
33.4 and 41.7 weeks (average: 35.5 weeks). The newborns weighed between 1064 g
and 3410 g (average: 2138 g). Preterm infants were＜37 weeks of gestational age.
No infant had clinical manifestations of sepsis, heart or circulatory disease,
respiratory distress, or clinical evidence of hemoglobinopathy. The same physician
took BiliCheckTM measurements on each patient after obtaining
parental informed consent.
The measurements were made on three of the following sites ; forehead, chest,
and right or left upper arm within 30 minutes of the blood withdrawal via heel
stick for conventional laboratory measurement. During phototherapy, the BiliCheckTM
measurement was taken only on the forehead that had been completely protected
by the round patch (approximately 3 cm in diameter) made from photo-opaque material.
Total serum bilirubin level was measured using bedside bilirubinometer (Nakamura
Medical, Tokyo, Japan) that uses the direct spectrophotometric method. In order
to confirm the accuracy of bedside bilirubinometer, 50 stocked serum samples from
neonates were simultaneously checked for serum bilirubin concentration by 2 different
methods; bilirubin oxidase method using automatic analyser (Hitachi 717) and direct
specrophotometric method using bedside bilirubinometer, as a preliminary experiment.
The precision of BiliCheckTM was tested on five different newborn
infants with total serum bilirubin concentrations ranging from 1.2 to 17.3 mg/dL.
In each instance, the same test was performed on the same infant, on the same
body site, by the same physician.
For the survey on operator difference in transcutaneous bilirubin measurement,
all of the four authors performed the measurements on the other 5 infants and
observed for the difference.
Regression analysis according to Pearson was used to test the correlation between
two variables. A p value of ＜0.05 was considered to be significant.
Preliminary study on 50 stocked serum samples revealed an excellent correlation
between the values of total serum bilirubin obtained by the direct spectrophotometiric
method and the bilirubin oxidase method as shown in Fig. 1 (r＝0.980, y＝1.05x＋0.576,
p＜0.0001). Thus the accuracy and reliability of the BiliCheckTM
was tested by comparison with measurements on withdrawn blood samples using the
The precision of the device was shown in Table 1. The 20-test sampling for precision
produced coefficients of variation ranging from 2.11 to 4.80 %.
Table 2 summarizes the operator difference in transcutaneous bilirubin measurement.
The coefficients of variation ranged from 1.14 to 4.33 %.
A total of 240 measurements ( 37 preterm infants and 15 term infants ) were taken
between 0 and 10 days after birth and 206 measurements were taken before phototherapy
and 34 were during phototherapy.
The correlation between the transcutaneous bilirubin measurements by the BiliCheckTM
on the forehead and total serum bilirubin by the direct spectrophotometric method
before phototherapy was excellent as shown in Fig. 2. The transcutaneous bilirubin
levels ranged from 1.4 to 19.9 mg/dL, while the total serum bilirubin levels ranged
from 0.0 to 20.9 mg/dL. The coefficient of correlation was 0.925, with regression
line; y＝0.932x＋1.757 (N＝204, p＜0.0001). There were no differences in correlation
among the gestational maturity. Table 3 shows the correlation of the values between
the total serum bilirubin and the transcutaeous bilirubin measured on 3 different
body sites. Measurement on the forehead revealed the best correlation, and those
on the upper arm and chest were less accurate. When the transcutaneous bilirubin
measurement was performed on the forehead, the 95 % confidence limits against
bedside bilirubinometer was±1.758 mg/dL.
There were no apparent differences in correlation among the birth weight groups
The correlation between the transcutaneous bilirubin measurements by the BiliCheckTM
and the total serum bilirubin by bedside bilirubinometer during phototherapy was
also good, but less than that of before phototherapy (r＝0.803, y＝0.79x＋3.937,
p＜0.001) (Fig. 3). The transcutaneous bilirubin level tended to be higher than
the total serum bilirubin level in the lower range during phototherapy, and lower
in the higher range. The 95 % confidence limits against bedside bilirubinometer
The transcutaneous bilirubinometer has been evaluated in a number of studies2,3,6-8)
and has been proposed as a valuable screening device that might aid in decreasing
length of stay at hospital after birth. These products also provide rapid, point-of-care
bilirubin measurement as a replacement for traditional clinical chemistry methods.
These results are achieved with no trauma to the patient, no risk of infection,
and potentially reduced cost of monitoring serum bilirubin by minimizing the use
of hospital personnel and supplies. In addition, as Knudsen et al 9)
has suggested, transcutaneous bilirubin measurement could be a somewhat better
predictor of kernicterus than total serum bilirubin measurement. But concerns
exist regarding linearity of transcutaneous measurement 9-12).
The BiliCheckTM works by directing white light into the skin
of the newborn and measuring the intensity of the specific wavelengths, which
are returned. The major skin components, which impact the spectral reflectance
in newborns, are dermal maturity, melanin, hemoglobin, and bilirubin13).
Each of these four components has been considered in the development of the algorithm
used to compute the bilirubin measurement. Measuring the intensity of the relaxant
light at 137 individual wavelengths performs a spectral analysis. By subtracting
the special contribution of the known components, the bilirubin absorbance can
be quantified and is then correlated to the laboratory gold standard high performance
liquid chromatography. So the measurement can indicate the result in clinical
units of mg/dL or μmol/L.
Previous report shows there was no significant difference in accuracy of transcutaneous
bilirubin assays in black and white babies5). In their report, however,
there are a few Asian people, which are enrolled in subjects. So to determine
the clinical accuracy of the device for measuring transcutaneous bilirubin in
Asians, additional data with sufficient number of infants are indispensable. Our
data indicate that accurate measurement of total serum bilirubin by transcutaneous
bilirubin assay with this device is possible in a heterogeneous newborn population
including Japanese infants.
There are limited data on use of the BiliCheckTM on infants
under the phototherapy11,14). Our results demonstrate that transcutaneous
bilirubin measurement using the BiliCheckTM correlates less
with total serum bilirubin level during phototherapy. The use of phototherapy
to decrease the serum bilirubin level has been rapidly reduce the concentration
of bilirubin in the skin through photo-conversion of the bilirubin molecule and
subsequent washout into the blood15). This intentional alteration in
the blood-skin relationship decreases the skin bilirubin concentration and introduces
an error in transcutaneous measurement without protection of the measurement site
by a photo-opaque material16). It is suspected that in our study the
measurement site, forehead, was not protected completely because of head position,
which was changed every three hours. So accurate measurements of transcutaneous
bilirubin techniques in babies receiving phototherapy require continued study.
In conclusion, our data indicate that accurate measurements of total serum
bilirubin by transcutaneous bilirubin assay with the BiliCheckTM
are possible also in Japanese infants. Accurate measurements of total serum bilirubin
by transcutaneous technique in babies receiving phototherapy require continued
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中村 利彦，山田 大悟，板倉 敬乃，小川 雄之亮
埼玉医科大学総合医療センター 総合周産期母子医療センター 新生児部門
(C) 2002 The Medical Society of Saitama Medical School