A NON-INVASIVE METHOD OF BILIRUBIN MEASUREMENTS IN TERM AND PRETERM

INFANTS
Kuznik Boris Ilyich, M.D.
Chita State Medical Academy, Chita, Russia

Summary. Comparative studies of bilirubin measurements using a non-invasive technology

with the BiliCare device (Gerium Medical Ltd) and invasive methods using total serum bilirubin
measurements obtained by venipuncture were conducted in 144 newborns with a gestational age
ranging from 25 to 41 weeks. Within these patient populations described, strictly conterminous results
(Р <0.0001, r 0.91-0.96) have been obtained.
The proposed and tested non-invasive method for determining bilirubin concentration described
here is a screening one, and it allows the bedside clinician to make an indirect judgement on the
presence or absence of jaundice in newborns.

Keywords: BiliCare, transcutaneous bilirubin, invasive and non-invasive research method, term
and preterm infants

Hyperbilirubinemia in newborns is the most widespread and common condition requiring

medical intervention and treatment for infants within the first 2 weeks of life. Many newborns are
discharged within 48 hours, prior to reaching their peak bilirubin level, which occurs between 3-5 days
of age [1], making diagnosis and medical management of neonatal jaundice challenging. By utilizing a
non-invasive method of bilirubin measurements in newborns as a screening tool prior to discharge
and in community settings, the clinician can better assess risk and provide enhanced care to the
newborn.

Transcutaneous bilirubin (TcB) is a measurement of the yellow color of the blanched skin and
subcutaneous tissue, not of the serum, and is used as a screening tool to help determine at risk
infants and whether the TSB should be measured. TcB measurements are being used with increasing
frequency in hospital nurseries and in some outpatient settings. They have the advantage of providing
instantaneous information and probably reduce the likelihood of missing the diagnosis of significant
hyperbilirubinemia or kernicterus [1,2,3,4]. The shortening of newborn hospital stays after birth and
the observation that kernicterus is still occurring [5,6,7] has drawn attention to the importance of
identifying and monitoring the jaundiced newborn infant. The use of TcB screening is deemed to be
more accurate than visual assessment and reduces the number of blood tests for bilirubin
determination, without compromising detection of infants with elevated TSB values.

The American Academy of Pediatrics (AAP) [2] and the National Institute for Health and Clinical
Excellence (NICE) [3] have approved the use of invasive (TSB) and non-invasive (TcB) methods for
determining a general bilirubin level in blood for the purpose of identifying infants with significant
hyperbilirubinemia who may subsequently require repeat testing or phototherapy.

BiliCare device

BiliCare is a new device developed by Gerium Medical Ltd1 for the screening of infants’ TcB

1
Gerium Medical Ltd. www.geriumltd.com
1
levels. This high-precision system allows clinicians to determine a predicted bilirubin level according
to the absorbance of the light using transmission technology with LED’s and immediately display the
measured results on the device. The device is very easy to operate, and measurement is performed
in just a few seconds without causing disturbance to the baby. Calibration of the device may be
checked at any time at the discretion of the user.

The BiliCare Non-invasive Bilirubin Meter uses the ear of the neonate as the measuring site. It emits
light in two visible wavelengths to the ear tissue and measures the light transmitted through the ear
tissue. On its way through the ear’s tissue, the light path is obstructed by bilirubin molecules which
absorb some of the light.

Fig. 1. Non-invasive method of bilirubin measurement using the BiliCare device.

The main advantage of BiliCare over other models for non-invasive bilirubin measurements in
newborns is the use of transmission spectroscopy allowing the application of less complex modeling
assumptions, reducing dependence upon changes of object geometry, increasing measuring
sensitivity of moving objects and reducing the number of unknowns by measuring tissue thickness at
each individual recording site. Blood depletion in the measurement site, required to take a
measurement of bilirubin in the transcutaneous tissue, is carried out automatically by application of
subtle pressure, with a spring fixture being an integral part of the device and providing fixed pressure
independent of the user. Therefore, the principle action, based on the measurement of a light-
transmission coefficient of the investigated medium, provides results that are more stable and more
robust than those based on evaluation of object reflective power.

Each result of the transcutaneous bilirubin measurement is calculated on the base of 1-3
independent measurements that can be chosen by the user. The device carries out measurements
within a few seconds and then displays the result on the LCD screen.

The bilirubin level is calculated with use of an algorithm developed by Gerium Medical, by
formula BR = F (TG, TB, D), where:
BR – bilirubin concentration in mg/dl;
TG – green light transmission factor;
TB – dark blue light transmission factor;
D– tissue thickness (mm);
F– function used by Gerium Medical.

Our research objective has been to evaluate the performance of the BiliCare device for both
term and preterm newborns by means of comparative bilirubin measurements using the non-invasive
(TcB) and invasive (TSB) methods.
2
 Research method and statistical analysis.

Clinical studies were performed in the perinatal city center of Chita (Russia) in 144 newborns –
70 boys and 74 girls with a distribution as noted below. One hundred and seven (107) newborns (55
girls and 52 boys) had a gestational age of more than 35 weeks and birth weight from 2,175 up to
4,240 g; 37 newborns (19 girls and 18 boys) had a gestational age of 25-35 weeks and birth weight
from 785 up to 2,700 g.

Characteristic Value
gestational age (weeks, mean±SD) 37.23±3.62

weight (grams, mean±SD) 2816±712

male 70 (48.6%)
gender
female 74 (51.4%)

skin Caucasian 128 (88.8%)

type Asians 17 (11.2%)

TSB bilirubin <8 (mg/dl) 69 (47.9%)

TSB bilirubin 8-12 (mg/dl) 44 (30.5%)

TSB bilirubin >12 (mg/dl) 31 (21.6%)

Age ranges were 1-78 days. The distribution of neonate ages according to number of
performed measurements can be observed in the graph below.

Fig. 2. Distribution of neonate ages according to number of performed measurements

All together 432 measurements were executed: 321 measurements – in term infants, and 111
measurements – in preterm infants.
The criterion of including an infant into the study was a gestational age of not less than 24
weeks.
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 Exclusion criteria:

1. Bruising at the point of measurement on both ears;

2. Birthmarks at the point of measurement on both ears;
3. Hematomas at the point of measurement on both ears;
4. Excessive hairiness at the point of measurement on both ears.

The studies were verified by means of three BiliCare devices (fig. 1) and recordings taken
within 30 min. after extracting blood in order to determine the bilirubin concentration using the
invasive (TSB) method. Drawing of blood samples was carried out by hospital personnel within the
scope of common procedures. Since no essential difference was revealed among measurements
performed with different BiliCare devices, STD among each pair was less than 1 mg/dl and correlation
of 0.98, we considered it possible to unite all measurements in one general group.

Observation results

Our observations have shown (Table. 1) that bilirubin measurements using the non-invasive
and invasive methods demonstrated similar results. The obtained data reveal that the newborn’s
gestational age is practically of no significance to the research results. High significance (Р <0,0001)
show BiliCare to be effective in accuracy for the general study group, as well as for preterm infants
who were born to mothers at a gestational age of 25-35 weeks.

Based on the study, the correlation and standard deviation between invasive and noninvasive
methods were calculated for all study population and preterm infants groups. The standard deviation
for all study population group was found 1.55 mg/dl, high Pearson correlation coefficient was found
between the methods (r=0.93, p<0.0001, n=432). The standard deviation for preterm neonate group
was found 1.36 mg/dl, high Pearson correlation coefficient was found between the methods (r=0.96,
p<0.0001, n=111).

Table 1
Comparative results of bilirubin measurements (mg/dl) using invasive and non-invasive
methods in term and preterm newborns
Study cohort Research method Mean-square R, P
Invasive Non-invasive deviation (δ)
(M±SD) (M±SD)
All study population 8.51±4.21 8.50 ± 3.67 1.55 0.93 (0.0001)

Preterm infants 8.30 ± 5.12 8.08± 4.51 1.36 0.96 (0.0001)

High correlation coefficients have been detected between indexes of bilirubin level (r=0.9-0.96)
using the non-invasive and invasive methods (Fig. 3 A and B). At that, data variations (top and bottom
percentiles) practically coincide or are similar to each other using both the invasive and non-invasive
measurement methods.

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 r=0.93 r=0.96

A B

Fig. 3. Correlation of the invasive and non-invasive methods for determining of

bilirubin concentration for the whole population (A) and for preterm newborns (B)

The proposed non-invasive method for determination of bilirubin concentration is a screening

one, and it allows the clinician to make an indirect judgment on the presence or absence of jaundice
in newborns.

We found the advantages of the transmission technology in the BiliCare device verses other
devices that measure transcutaneous bilirubin on the forehead and sternum using reflection method
to be as follows:
1. Can accurately define a level of bilirubin in preterm infants at a gestational age of 24
weeks and more.
2. The method is extremely simple; it does not require long training of personnel and can
be carried out by staff nurses. The device can be operated with one hand, both by
right- and left-handers.
3. Long-term storage of results provides trending of patient data.
4. An optional single-use tip is provided with the BiliCare device for infection control
purposes. Customers can take measurements with or without the tip, per their protocol
or use environment dictates.
5. Unlike xenon and tungsten lamps used for other device models, where radiation
intensity decreases in due course and periodic calibrations are required, the specified
parameters of the BiliCare device do not change over time since BiliCare uses LED
technology. The consistency of power and radiation spectrum with LED technology
means routine calibration is not necessary. Nevertheless, users can carry out a device
calibration check as per hospital protocol if required.
6. The BiliCare device can be used on all skin tones and bilirubin measurements in
newborns do not depend upon thickness of the ear.
7. Since the location of the measurement is neonatal ear, the measurement can be
performed without disturbing the baby if sleeping. This is especially essential for the
preterm neonates who may be nested on their side or nursed prone making it difficult
to perform transcutaneous bilirubin test on the forehead or sternum without turning and
waking the baby.

All the presented data demonstrate that the proposed non-invasive method of bilirubin level
study in preterm and term infants using the BiliCare device can successfully and safely be applied in
clinical practice.
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 References

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2. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of

hyperbilirubinemia in the neonate infant 35 or more weeks of gestation. Pediatrics. 2004;114(1):297.
3. NICE Clinical guidelines, CG98 Neonatal jaundice - Issued: May 2010.
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Bilirubin measurement for neonates: comparison of 9 frequently used methods, Pediatrics Vol. 117
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Data on Author

Kuznik Boris Ilyich, M.D., Professor, Honored Scientist of the RF, Professor of the Department of
Human Physiology of the Chita State Medical Academy. 672000, Chita, Gorkogo 39a, Medical
Academy, Department of Human Physiology. Tel.: 8.3022-35-31-33 (of.), 8.924-486-59-10 (mob.). E-
mail: Bi_kuznik@mail.ru