ARTICLEPEDIATRICS Volume 138 , number 3 , September 2016 :e 20160907

Differences Between Transcutaneous and Serum Bilirubin Measurements in Black African NeonatesBolajoko O. Olusanya, FRCPCH, PhD, a Donald O. Imosemi, MBBS, FWACS, b Abieyuwa A. Emokpae, MBBS, FMCPaedc

abstractBACKGROUND AND OBJECTIVE: Transcutaneous bilirubin (TcB) correlates positively with total

serum bilirubin (TSB) across different racial populations. However, little is known

about the pattern of divergence between TcB and TSB at individual patient-level and the

relationship with TcB measuring techniques among African neonates. This study, therefore,

investigates TcB–TSB discrepancies and the contribution of 2 models of transcutaneous

bilirubinometers to the observed divergence in a black African population.

METHODS: Medical records were retrieved for late preterm and term infants with 1 to 3 pairs

of TcB and TSB measurements between December 2011 to June 2015 in Nigeria. Divergence

between TcB and TSB values for each infant was determined and the associated factors

explored with generalized estimating equations for logistic regression. Contributions

of BiliChek and JM-103 transcutaneous bilirubinometers to the divergence were further

explored through linear regression and Bland-Altman analysis.

RESULTS: Overall, 2107 TcB/TSB measurements from 1553 infants were analyzed. TSB was

overestimated by ≥2 mg/dL in 64.5%, ≥3 mg/dL in 42.7%, and ≥4 mg/dL in 25.7% of all

measurements. In contrast, TSB was underestimated by ≥2 mg/dL in 1.1%, ≥3 mg/dL in

0.5%, and ≥4 mg/dL in 0.3% of all recordings. Postnatal age, feeding mode, and type of TcB

instrument were predictive of TSB overestimation. The JM-103 was associated with greater

imprecision than BiliChek at all TSB levels.

CONCLUSIONS: BiliChek and JM-103 bilirubinometers significantly overestimate TSB in black

African neonates and may result in unnecessary or excessive treatments. Additional

development of appropriate bilirubin determination devices for this racial group, especially

in resource-limited settings, is warranted.

aCentre for Healthy Start Initiative, Ikoyi, Lagos, Nigeria; bLagos Island Maternity Hospital, Lagos, Nigeria; and cMassey Street Children’s Hospital, Lagos, Nigeria

Dr Olusanya conceived and designed the study, analyzed the data, drafted the manuscript,

and fi nalized the manuscript; Drs Imosemi and Emokpae participated in data collection and

the interpretation of the data and critically reviewed the revised manuscript; and all authors

approved the fi nal manuscript as submitted.

DOI: 10.1542/peds.2016-0907

Accepted for publication Jun 30, 2016

Address correspondence to Bolajoko O. Olusanya, FRCPCH, PhD, Centre for Healthy Start Initiative,

286A Corporation Dr, PO Box 75130 VI, Dolphin Estate, Ikoyi, Lagos, Nigeria. E-mail: bolajoko.

olusanya@uclmail.net

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2016 by the American Academy of Pediatrics

To cite: Olusanya BO, Imosemi DO, Emokpae AA. Differ-

ences Between Transcutaneous and Serum Bilirubin

Measure ments in Black African Neonates. Pediatrics.

2016;138(3):e20160907

WHAT’S KNOWN ON THIS SUBJECT: Transcutaneous

bilirubin (TcB) is highly correlated with total serum

bilirubin (TSB) across ethnic populations. TcB is a

useful screening tool or indication for treatment

in infants with severe hyperbilirubinemia where

facilities for TSB are limited or lacking.

WHAT THIS STUDY ADDS: Approximately 1 in 3 black

African neonates with hyperbilirubinemia may be

prone to TcB overestimation (≥3 mg/dL), resulting in

unnecessary treatments where confi rmatory TSB is

not readily available. Improved bilirubin measuring

devices are needed for this racial population,

especially in resource-limited settings.

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OLUSANYA et al

Studies among neonates of African-

American ancestry have so far shown

that the black race is unusually

associated with a decreased risk

of severe hyperbilirubinemia but

an increased risk of kernicterus, 1, 2

underpinned by glucose-6-phosphate

dehydrogenase (G6PD) deficiency. 3

As a high-risk population, routine,

predischarge bilirubin screening

is warranted in this racial group to

minimize the risk of kernicterus. 4

The excellent correlation between

transcutaneous bilirubin (TcB) and

total serum bilirubin (TSB) tests5, 6

has made TcB a valuable screening

tool for TSB in the management of

hyperbilirubinemia worldwide. 4, 7, 8

However, TcB tends to underestimate

TSB in whites or neonates with

light or medium skin color and

overestimate TSB in non-whites or

neonates with dark skin color.9 – 11

Such discrepancies may compromise

the effective management of infants

at risk for bilirubin encephalopathy. 12

Limited evidence exists on the

pattern and predictors of individual

TcB–TSB divergence, especially

in settings with predominantly

dark-skinned infants or limited

access to timely and reliable TSB

measurements. 13– 15 This study,

therefore, set out to determine

the prevalence and correlates of

significant TcB overestimation in a

black African population to facilitate

optimal decisions for appropriate

clinical intervention.

METHODS

This prospective, observational study

was conducted at Island Maternity

Hospital, a leading specialist

maternity hospital in Nigeria owned

by the Lagos State Government.

This 180-bed public hospital is a

referral center for over 300 private

and public hospitals in the Lagos

metropolis and its environs.

All healthy late preterm and term

neonates (gestational age ≥35 weeks

or birth weight ≥2.2 kg) delivered

between December 2011 and June

2015 with 1 to 3 pairs of TcB–TSB

measurements in the first 120

hours of life were enrolled. Only

measurements recorded before

receiving phototherapy were eligible

for analysis. All sick infants were

excluded. The study was conducted

under institutional ethical approval

from the Lagos State Health Service

Commission.

Infants of consenting mothers were

screened routinely for jaundice by

using the BiliChek transcutaneous

bilirubinometer (Philips Healthcare

North America, Monroeville, PA)

or the JM-103 transcutaneous

bilirubinometer (Draeger Medical,

Telford, PA). Measurements were

derived from the infant’s sternum

by specially trained nurse assistants.

The BiliChek was used from

December 2, 2011 to November 26,

2012 and the JM-103 was used from

November 27, 2012 to June 23, 2015.

Two units of each piece of equipment

were available to provide back-up

for maintenance. Both instruments

were used in accordance with the

manufacturers’ instructions for

quality control and calibration.

The algorithms and other technical

features of the 2 devices are well

described. 5, 6, 9 Infants whose bilirubin

levels at screening exceeded 3 mg/dL

below the recommended postnatal

age threshold for phototherapy

based on the American Academy of

Pediatrics (AAP) guidelines were

assessed for TSB within ∼1 hour.

This criterion was adopted because

of the high prevalence of G6PD

deficiency in this population. 16 TSB

measurements were performed on

capillary blood samples drawn by

heel puncture and analyzed by direct

spectrophotometry by using the

Advanced Bilirubin Stat-Analyzer

(model BR2; Advanced Instruments,

Inc, Norwood, MA).

The choice of putative predictor

variables was guided by relevant

literature, 9 – 15 and included infant’s

sex, birth weight, estimated

gestational age (in completed weeks,

based on maternal history of last

menstrual period correlated with

ultrasound scan by using Siemens

Sonoline SI-450 as documented

in the hospital records), postnatal

age at screening, maternal self-

report of ethnicity (based on the

3 most predominant tribes in

Nigeria: Hausa, Ibo, and Yoruba,

as well as others), skin color (light

brown, medium brown, or dark

brown), mode of feeding at the

time of TcB screening (formula

only, exclusive breastfeeding, or

mixed feeding), G6PD status, and

TcB model. Skin color was classified

as previously reported in this

population, 14 and recorded by the

trained nurse assistants as shown

in a color guide (Supplemental Fig

5). G6PD evaluation was based on

the fluorescent blood spot for all

infants by using methods described

by Beutler et al, 17 as previously

reported.18 Lack of fluorescence

after 10 minutes was indicative of

deficient levels.

Three levels of significant

overestimation or underestimation

were computed from the TcB–TSB

pairs: TcB–TSB ≥2 mg/dL, ≥3 mg/dL,

or ≥4 mg/dL. Because of the small

amount of TSB underestimation

by TcB, further analysis was not

considered necessary. Univariate

associations between the

predictor variables and bilirubin

overestimation (each defined as a

binary outcome) were then explored

with Pearson’s χ2. Strength of

association was estimated by odds

ratios (OR) and the corresponding

95% confidence intervals (CI) as

an approximation of the relative

risk. Statistical significance was set

at a critical level of P < .05. Factors

significantly associated with each

outcome in the univariate analysis

were entered into the respective

multivariable logistic regression

model. The generalized estimating

equation method was used for the

regression modeling to account for

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PEDIATRICS Volume 138 , number 3 , September 2016

repeated measurements on the same

infant. All models were adjusted

for TSB level. Plausible interaction

between TSB and each predictor

variable was also investigated.

The contributions of BiliChek and

JM-103 to TSB overestimation were

examined further with Pearson’s

correlation coefficients (r), scatter

plots, and linear regression analyses.

Because of the limitations of

Pearson’s coefficients in determining

the variability and linear correlation

between 2 continuous variables, we

explored the degree of agreement

(bias) between TcB and TSB for

each device using the Bland-Altman

method. 19 The mean bias was defined

as the mean difference between each

pair of TcB and TSB measurement

obtained from each enrolled infant.

TcB imprecision or variability

compared with TSB was defined as

2 SD from the mean difference. The

limits of agreement (LOA) of the

mean differences and their 95% CIs

were also determined. Additionally,

the discriminatory power of the

TcB devices in predicting infants

who required phototherapy was

determined by using receiver

operating curve analysis. 20 The

criteria for phototherapy were based

on the appropriate age-specific

thresholds in the AAP guidelines. 4

The interinstrument variability

in a sample of infants tested

simultaneously with BiliChek and

JM-103 was also computed. IBM SPSS

Statistics for Windows software,

version 21.0 (IBM Corporation,

Armonk, NY) was used for all

statistical analyses.

RESULTS

A total of 1553 infants with

2107 paired TcB–TSB measure-

ments were enrolled for the study.

The infants had a mean TcB of 10.04

(SD, 3.40) mg/dL and a mean TSB of

7.28 (SD, 2.66) mg/dL. TcB ranged

from 2.1 to 19.9 mg/dL, whereas TSB

ranged from 0.3 to 19.5 mg/dL.

The characteristics of the infants are

presented in Table 1. Some 54.9%

(853/1553) of the infants were

male, 5.7% (89/1551) weighed

<2.5 kg, and 9.8% (150/1533) had

a gestational age of <37 weeks. The

infants were predominantly of the

Yoruba tribe (71.2%), had light or

medium brown skin (91.6%), and

were exclusively breastfed (69.1%).

A total of 263 (16.9%) infants were

G6PD deficient.

TcB recordings in 79.1% of the

infants were with the JM-103. TSB

was overestimated by ≥2 mg/dL

in 64.5% (1358/2107), ≥3 mg/

dL in 42.7% (899/2107), and

≥4 mg/dL in 25.7% (542/2107)

of all measurements. TSB was

overestimated by ∼8 mg/dL 32 times

(19 neonates). In contrast, TSB was

underestimated by ≥2 mg/dL in

1.1% (23/2107), ≥3 mg/dL in 0.5%

(10/2107), and ≥4 mg/dL in 0.3%

(7/2107) of all measurements. Of

the 1774 (84.2%) overestimated TSB

values ≥1 mg/dL, phototherapy was

required in only 55 (3.1%) cases.

In the univariate logistic regression

analysis, 4 factors (postnatal age,

G6PD status, feeding mode, and

TcB equipment) were significantly

associated with the 3 levels of

overestimation. Ethnicity or

skin color was not significantly

associated with overestimation.

The independent predictors of

significant bilirubin overestimation

after multivariable logistic regression

are presented in Table 2. Increasing

postnatal age and use of the JM-103

were predictive of all levels of

overestimation, whereas exclusive

breastfeeding was only associated

with ≥2 mg/dL overestimation.

TSB level had a modifying effect

on feeding mode, which prompted

our adjusting all models with the

interaction term, feeding mode*TSB.

The correlation between TcB and TSB

was linear and significant for BiliChek

(Pearson’s r = 0.83, R2 = 0.69, P <

.001) or JM-103 (Pearson’s r = 0.85,

R2 = 0.72, P < .001) as presented in

Fig 1. The combined measurements

also showed significant correlation

(Pearson’s r = 0.81, R2 = 0.66,

P < .001). As shown in Fig 2, the

discriminatory power of JM-103

(area under the curve = 0.725; 95%

CI, 0.665–0.786) was slightly higher

than the value for BiliChek (area

under the curve = 0.706; 95% CI,

0.625–0.787) in predicting the need

for phototherapy. JM-103 had an

optimal combination of sensitivity

(64%) and specificity (72%) at a

cut-off of 12.1 mg/dL in detecting

infants who required phototherapy,

compared with BiliChek, which had

a sensitivity of 60% and a specificity

of 74% at a cut-off of 10.3 mg/dL.

JM-103 was associated with 100%

sensitivity for TcB values up to 4.8

mg/dL, compared with 1.6 mg/dL for

BiliChek.

The Bland-Altman plots are

presented in Fig 3. The mean bias for

JM-103 was 3.04 (SD, 1.89) mg/dL

(95% LOA: –0.66 to 6.74 mg/dL)

compared with 1.28 (SD, 1.77) mg/dL

(95% LOA: –2.20 to 4.76 mg/dL) for

BiliChek. The pattern of mean bias

at various levels of TSB for all paired

measurements is presented in Fig 4.

The mean bias between JM-103 and

BiliChek widens as TSB increases,

with BiliChek underestimating TSB

from roughly 13.5 mg/dL. The index

of consistency based on the average

measures of intraclass correlation

between BiliChek and JM-103 in a

sample of 276 neonates was 0.818

(95% CI, 0.769–0.856), which

is indicative of a high degree of

reliability.

DISCUSSION

Principal Findings

TcB has strong positive linear

correlation with TSB regardless

of the choice of bilirubinometer.

However, TcB is likely to overestimate

TSB by at least 2 mg/dL in ∼6 out

of every 10 black African neonates

screened in the first 120 hours of

life by either BiliChek or JM-103.

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OLUSANYA et al

Increasing postnatal age, exclusive

breastfeeding, and type of

bilirubinometer are predictive of

significant overestimation. Ethnicity,

G6PD status, and skin color are

not significantly associated with

overestimation in this population. TSB

underestimation by both TcB devices

is also minimal. However, JM-103 is

4

TABLE 1 Profi le of Infants With Signifi cant Bilirubin Overestimation in an African Population

Factors No. of Infants Pairs of TcB–TSB Readings (n = 2107)

n = 1553 TcB–TSB ≥2 mg/dL;

n = 1358a (%)

TcB–TSB ≥3 mg/dL;

n = 899a (%)

TcB–TSB ≥4 mg/dL;

n = 542a (%)

Sex

Male 853 757 (65.1) 491 (42.2) 305 (26.2)

Female 700 601 (63.7) 408 (43.2) 237 (25.1)

Birth weight

<2.5 kg 89 83 (68.0) 58 (47.5) 36 (29.5)

≥2.5 kg 1462 1274 (64.2) 840 (42.4) 506 (25.5)

Missing data 2 1 (50.0) 1 (50.0) 0 (0)

Mean (± SD) 3.19 ± 0.50 3.17 ± 0.49 3.15 ± 0.48 3.16 ± 0.49

Gestational age

<37 wk 150 136 (70.5) 96 (49.7) 57 (29.5)

≥37 wk 1383 1208 (63.9) 792 (41.9) 476 (25.2)

Missing data 20 14 (60.9) 11 (47.8) 9 (39.1)

Mean (± SD) 38.18 ± 1.62 38.18 ± 1.71 38.16 ± 1.80 38.14 ± 1.65

Postnatal age, h

0–48 1146 710 (54.2) 384 (29.3) 194 (14.8)

48.1–96 369 583 (81.0) 462 (64.2) 313 (43.5)

96.1–120 38 65 (85.5) 53 (69.7) 35 (46.1)

Ethnicity

Yoruba 1106 981 (65.5) 656 (43.8) 404 (27.0)

Hausa 72 61 (68.5) 34 (38.2) 20 (22.5)

Igbo 198 166 (59.1) 108 (38.4) 57 (20.3)

Other 177 150 (62.8) 101 (42.3) 61 (25.5)

Skin color

Light brown 645 521 (62.0) 356 (42.3) 227 (27.0)

Medium brown 778 718 (66.1) 475 (43.7) 275 (25.3)

Dark brown 130 119 (66.5) 68 (38.0) 40 (22.3)

G6PD-defi cient

No 1290 1103 (63.9) 723 (41.9) 431 (25.0)

Yes 263 255 (67.1) 176 (46.3) 111 (29.2)

Feeding mode

Formula only 276 258 (58.4) 162 (36.7) 78 (17.6)

Exclusive breast milk 1073 902 (65.2) 594 (43.0) 364 (26.3)

Breast milk with formula 204 198 (70.2) 143 (50.7) 100 (35.5)

TcB equipment

BiliChek 325 130 (35.0) 45 (12.1) 20 (5.4)

JM-103 1228 1228 (70.7) 854 (49.2) 522 (30.1)

a n refers to number of infants.

TABLE 2 Predictors of Infants With Signifi cant Bilirubin Overestimation in an African Population After Multivariate Logistic Regression

Factors TcB–TSB ≥2 mg/dL; Adjusted OR

(95% CI)

TcB–TSB ≥3 mg/dL; Adjusted OR

(95% CI)

TcB–TSB ≥4 mg/dL; Adjusted OR

(95% CI)

Postnatal age, h

0–48 Reference Reference Reference

48.1–96 1.41 (1.16–1.66) 1.49 (1.23–1.75) 1.51 (1.20–1.81)

96.1–120 2.00 (1.32–2.68) 1.91 (1.31–2.51) 1.70 (1.10–2.30)

Feeding mode

Formula Reference Reference Reference

Exclusive breast milk 1.96 (1.18–2.74) 1.66 (0.94–2.37) 1.62 (0.71–2.53)

Breast milk with formula 1.90 (0.68–3.12) 1.80 (0.74–2.85) 1.56 (0.37–2.75)

TcB equipment

BiliChek Reference Reference Reference

JM-103 1.55 (1.28–1.81) 2.00 (1.65–2.35) 2.00 (1.51–2.49)

OR adjusted for all factors including G6PD status, TSB level, and interaction term: feeding mode*TSB. All models based on 2107 measurements from 1553 infants by using generalized

estimating equations.

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PEDIATRICS Volume 138 , number 3 , September 2016

associated with higher imprecision

(mean bias) than BiliChek, which

increases as TSB levels increase.

Comparison With Other Studies

In general, the high and positive

correlation between TcB and TSB is

consistent with the findings in

several studies from racially diverse

populations. 9, 10, 14, 15, 21 – 23 The TSB

overestimation is also corroborated

by several studies among multiracial

populations 10, 13, 24 and black

neonates. 14, 15 For example, although

Maisels et al 10 found a close

correlation between TcB and TSB

values among 849 neonates across

all ethnic groups, by using JM-103,

TSB was overestimated by ≥2 mg/

dL in 37.9% of blacks, compared

with 1.8% of whites or 5.4% of other

races. Among black infants, TSB was

overestimated by ≥3 mg/dL in 17.4%

and by ≥4 mg/dL in 6.7%. TcB was

also consistently higher than TSB

in the black population whenever

the difference between TcB and

TSB was ≥3 mg/dL. Similarly, in a

multicenter study of 769 racially and

ethnically diverse newborns with

at least 1 TcB–TSB pair, Taylor et al

found that African-American race

was independently associated with a

higher chance of TSB overestimation

by at least 2 mg/dL (OR, 2.19; 95%

CI, 1.09–4.39). 13 In a predominantly

black population, 1 study from

Malawi reported TSB overestimation

in term neonates not receiving

phototherapy as indexed by a mean

bias of 1.5 (SD, 4.2) mg/dL in the TcB

measurements.15

JM-103 overestimated TSB in

this population by a greater

magnitude than BiliChek. Studies

comparing BiliChek and JM-103 in

predominantly black populations

are rare. However, the significantly

higher mean measurement bias

associated with JM-103 compared

with BiliChek appears consistent

with findings in other studies among

multiracial populations. 10, 25 –28 For

example, based on a limited sample

of black infants, Maisels et al 10

suggested that although JM-103

correlated with BiliChek, it had a

higher tendency to overestimate TSB.

In another multiracial population

in the United Kingdom, JM-103 was

also found to overestimate TSB in

black infants (mean difference, 1.6

mg/dL; 95% CI, 1.0–2.3 mg/dL) and

underestimate TSB in white infants

(mean difference, –2.2 mg/dL; 95%

CI, –2.7 to –1.7 mg/dL). 25 However,

despite the comparable correlations

between BiliChek and JM-103 in an

Asian population, the former had a

higher tendency to overestimate TSB. 27

To date, only 1 study is known to

have explored the independent

predictors of TcB–TSB divergence. 13

In that study, a postnatal age

5

FIGURE 1Linear regression plots showing the relationship between TSB and TcB measured by BiliChek and JM-103.

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OLUSANYA et al

of <48 hours was independently

associated with TSB overestimation

by ≥2 mg/dL (OR, 0.36; 95% CI,

0.22–0.59) and ≥3 mg/dL (OR, 0.38;

95% CI, 0.20–0.72). These findings

are in agreement with our study,

which showed that a postnatal age

>48 hours was associated with

higher odds of TSB overestimation

at all levels. This may be due to

the gradual reduction in the total

blood flow through the skin and

muscle during the first 7 days of

life within the neonatal period. 29

The study by Taylor et al 13 also

showed that TcB had a tendency

to be less accurate at higher TSB

levels, regardless of the type of

bilirubinometer ( Fig 4). Other studies

among whites seem to support this

finding, 30 suggesting that it was not

race dependent. This observation

may possibly be attributable to the

dynamic processes, such as changes

in hemoglobin concentration, in the

early hours of life. 13

The association between

exclusive breastfeeding and TSB

overestimation appears to be

supported by other reports on

TcB patterns in relation to feeding

mode. 31 – 33 Itoh and colleagues, 33 for

example, proposed that increased

unconjugated bilirubin in breastfed

infants may be underpinned by

the high enterohepatic circulation

of unconjugated bilirubin from

deconjugation by β-glucuronidase of

the conjugated bilirubin in meconium.

The resultant increase in circulating

unconjugated bilirubin may therefore

be related to the observed higher

TcB/TSB discrepancy. The observed

TSB overestimation by at least ≥4

mg/dL in this population warrants

additional investigation.34

Our study also suggests that tribe

or shades of skin color in the

black race has little or no effect

on TcB performance. This is in

accordance with an earlier study that

demonstrated strong correlations

between TcB and TSB regardless of

the degree of skin pigmentation. 14

Clinical Implications of Key Findings

To optimize its utility, high TcB

levels from any instrument should

precipitate a valid concern about the

risk of severe hyperbilirubinemia or

kernicterus in the tested infant that

6

FIGURE 2Receiver operating characteristic curves for BiliChek and JM103 for predicting infants who require phototherapy based on AAP 2004 guidelines. AUC, area under the curve.

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PEDIATRICS Volume 138 , number 3 , September 2016

requires a follow-up blood sampling

for TSB or provide assurance where

such risk does not exist. Within

this context, the strong correlation

between TcB and TSB confers some

merit on the former as a screening

tool as well as a potential alternative

to TSB in resource-limited settings.

TcB should, for example, be preferred

to the highly subjective visual

assessment that prevails in such

settings. However, the evidence

from the current study and similar

reports 10, 13 would suggest some

caution in placing sole reliance on

TcB as a basis for clinical decisions

to guide phototherapy or exchange

transfusions in black African neonates.

Perhaps more notable is the ample

evidence that the commonly reported

satisfactory statistical correlation

between TcB and TSB masks clinically

significant discrepancies between

the 2 measures at the individual

patient level. TSB should therefore

continue to be regarded as an

absolute necessity, notwithstanding

the common challenges in ensuring

its availability routinely. In settings

where a high proportion of infants

are born outside hospitals and late

presentation of high-risk infants is

frequent, the utility of TcB is likely

to be severely limited considering

the significant imprecision of

measurements at high TSB levels.

This is without prejudice to studies

that suggest improved predictive

utility of TcB when combined with

clinical risk factors. 5 It may be argued

that the divergence between TcB and

TSB should not be unexpected after

all, because the former measures

the extravascular rather than the

intravascular bilirubin concentration,

and possibly better reflects the risk

of kernicterus. 35 However, additional

studies are warranted to establish

more precisely the clinical value of

TcB as a predictor of kernicterus.

Our study also underscores the

need to consider the performance

and cost-effectiveness of available

TcB equipment. Of the 3 predictors

in this population, choice of TcB

device is the most modifiable factor.

Available cost estimates suggest

that BiliChek is more expensive than

JM-103 because of the added running

cost for consumables. However,

a more robust cost-effectiveness

analysis should be considered for

the latest models of all commercially

available instruments to guide the

expected trade-off among devices.

To our knowledge, no instrument

has been developed specifically to

address TSB overestimation in the

black population. Although there

is a need to explore technological

7

FIGURE 3Bland-Altman plots of agreement between TcB and TSB for BiliChek and JM-103.

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OLUSANYA et al

improvement for TcB devices for

this racial group, efforts to develop

low-cost, point-of-care TSB devices

are currently in progress and, if

successful, hold promise for low-

and middle-income countries. 8 It

may also be helpful to consider the

development of equipment-specific

TcB nomograms in this population.

Strengths and Limitations of Study

A major strength of this study is

the large sample of exclusively

black African neonates. This is the

first study, to our knowledge, to

characterize the pattern and the risk

factors of the divergence between

TcB and TSB in this population. Unlike

previous studies, we were able to

compare the performance of 2 common

TcB equipment models. However, only

2 TcB models were evaluated, which

may restrict generalization to other

TcB instruments. It was also unclear if

the use of BiliChek for a significantly

shorter duration impacted the findings.

We could not determine the effect

of deriving TcB measurements from

the forehead compared with the

sternum. It was unclear how the

finding on skin color and ethnicity

would have been moderated by

comparison with white infants.

Additionally, this study was conducted

among inborn infants and may not

provide an accurate picture of the

pattern of divergence among outborn

infants that are frequently exposed to

hemolytic infant care products in this

population. 16 Notwithstanding, our

study has provided valuable and rare

insights to the potential limitations of

TcB as a screening tool or proxy for

TSB among black African neonates to

inform clinical decisions and additional

technological development of TcB

devices for the optimal care of infants

at risk for avoidable kernicterus.

CONCLUSIONS

TcB is noninvasive, simple to

perform, less expensive, and

has a satisfactory correlation

with TSB. However, current TcB

devices are highly sensitive only

at lower TSB levels and are more

likely to overestimate TSB with

increasing age by at least 2 mg/dL

in ∼6 out of every 10 black African

neonates and up to 9 mg/dL in

some neonates. The LOA depend

on the type of bilirubinometer

used, with JM-103 having a greater

tendency to overestimate TSB than

BiliChek. This divergence should

be recognized in the management

of infants at risk for kernicterus to

avoid unnecessary blood sampling or

excessive treatments where routine

confirmatory TSB is impracticable.

Technological advancement for

improved bilirubin determination is

warranted for this population.

ACKNOWLEDGMENTS

We thank Tina Slusher for the

provision of the bilirubinometers and

G6PD test kits used in this study. We

also thank the research team at the

Centre for Healthy Start Initiative

for assistance in data retrieval and

management.

8

ABBREVIATIONS

AAP:  American Academy of

Pediatrics

CI:  confidence interval

G6PD:  glucose-6-phosphate

dehydrogenase

LOA:  limits of agreement

OR:  odds ratio

TcB:  transcutaneous bilirubin

TSB:  total serum bilirubin

FINANCIAL DISCLOSURE: The transcutaneous bilirubin devices used in this study were provided by Philips Healthcare North America (Monroeville, PA) and

Draeger Medical (Telford, PA). The authors have indicated they have no other fi nancial relationships relevant to this article to disclose.

FUNDING: No external funding.

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential confl icts of interest to disclose.

FIGURE 4Pattern of TcB–TSB differences at various levels of TSB between BiliChek and JM-103. Data shown are mean values of TcB–TSB differences with 95% CI error bars.

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PEDIATRICS Volume 138 , number 3 , September 2016

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