Accuracy of transcutaneous bilirubin measurement NEMC Evidence Report

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Accuracy of transcutaneous bilirubin measurement
NEMC Evidence Report

• Rebecca Flynn OBrien, MD
• Division of General Pediatrics and Adolescent
  Medicine
• The Floating Hospital for Children
• Tufts-New England Medical Center

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Terms

• TcB Transcutaneous bilirubin
• TSB Total serum bilirubin
• HPLC High Performance Liquid Chromatography

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Description of included studies

• 47 qualifying studies in 50 publications
  evaluated test performance and/or correlation of
  TcB to TSB
• Minolta Airshields bilirubinometer (41 studies
  6,779 subjects)
• BiliCheck (3 studies 809 subjects)
• Ingram Icterometer (4 studies 245 subjects)
• Colormate III (1 study 900 subjects )

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Minolta AirShields Bilirubinometer

• Minolta Airshields Jaundice Meter TM (2002)
• Handheld, fiberoptic techniques to illuminate
  skin and subcutaneous tissue
• Spectrophotometric analysis of intensity of
  yellow color
• Requires development of correlation curves at
  each institution relating TcB index and TSB
• Daily calibration of instrument

Manufactured by Minolta/Hill-Rom Air-Shield,
Hatbro, PA
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Accuracy of Minolta AirShields

• Studied over 20 years, diverse populations
• 22 of 41 studies reported test performance,
  sensitivity, and specificity of TcB
• Threshold TcB index to predict threshold TSB
• Measurement sites forehead, mid-sternum or mixed

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Test Performance (Sensitivity/Specificity)Minolta
AirShields Bilirubinometer

• Studies varied as to TSB threshold levels used
• Limits ability to combine data across studies
  (Evidence Report Table 3.21, p 76)
• META-ANALYSIS
• 3 studies reported test performance of TcB index
  to predict TSB gt 11 (10-11.7)
• 11 studies reported test performance of TcB index
  to predict TSB gt 13 (12.5-13)
• 3 studies reported test performance of TcB index
  to predict TSB gt 15 (14.5-15.2)

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Pooled Sensitivity and Specificity of Minolta
AirShields predicting TSB gt 11mg/dl

• 3 studies, 502 paired TcB and TSB measures at
  forehead
• Random Effects Model pooled estimates

Study, Year n Threshold TcB index Sens (95 CI) Spec (95 CI)
Knudsen, 1992 138 9 0.75 (0.55-0.89 0.65 (0.56-0.74)
Knudsen, 1990 207 10.2 0.72 (0.61-0.80) 0.81 (0.73-0.88)
Maisels, 1982 157 20 0.91(0.70-0.98) 0.90 (0.83-0.94)
Overall 502 0.76 (0.64-0.85) 0.80 (0.63-0.91)
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Pooled sensitivity and specificity of Minolta
AirShields predicting TSBgt13

• 11 studies, 1560 paired TcB and TSB measures
• Cutoff TcB index ranged from 13-24
• SROC curve shows heterogeneity across studies
  that is due to more than just a threshold effect
• Random Effects Model pooled estimates
• Sensitivity 0.85 (0.77-0.91)
• Specificity 0.77 (0.66-0.85)

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SROC curve Minolta AirShields asScreening Tool
for TSBgt13
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Pooled Sensitivity and Specificity Minolta
AirShields predicting TSBgt15

• 3 studies, 299 paired TcB and TSB forehead
  measures
• All 3 studies had sensitivity of 100 (SROC
  curve not appropriate, no threshold effect)

Study n Threshold TcB index Sens. (95 CI) Spec. (95 CI)
Dai, 1996 40 17 1.00 (0.63-1.00) 0.66 (0.47-0.81)
Sheridan-,1982 57 20 1.00 (0.40-1.00) 0.75 (0.61-0.86)
Fok, 1986 202 22 1.00 (0.79-1.00) 0.66 (0.58-0.72
Overall 299 0.95 (0.77-0.99) 0.67 (0.61-0.73)
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Meta-analysis of correlation coefficients for
Minolta Airshields

• 38 of 41 studies linear regression analysis of
  Pearsons correlation coefficient (r)
• TcB versus TSB
• r values ranged from 0.52 to 0.96
• Pooled r 0.84 (95 CI 0.81-0.87)
• Evidence Report Fig S3, p241

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Limitations of meta-analysis of correlation
coefficients

• Correlation coefficient does not provide
  information as to clinical utility of diagnostic
  test
• Correlation coefficient (r) is highly dependent
  on distribution of serum bilirubin
• Correlation measures ignore bias
• Measures relative rather than absolute agreement

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Factors affecting test accuracy of Minolta
AirShields Bilirubinometer

• Study designs varied as to study population
• All infants versus jaundiced infants
• Racial background
• Measurement site
• Age at measurement
• Type of assay for TSB reference gold standard
• Subgroup analysis was done in some studies

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Factors affecting test accuracy of Minolta
Airshield Bilirubinometer

• Higher correlation of TcB with TSB
• Sternum or forehead vs other sites
• Term vs. Near term
• White vs. Black
• No phototherapy vs. phototherapy

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Measurement Sites-Minolta Airshieldsmeta-analysis
of correlation coefficients
Body site (studies) n Pooled r 95 CI
Forehead (12) 1,936 0.87 0.82-0.90
Sternum (11) 1,815 0.90 0.86-0.92
Abdomen (3) 477 0.85 0.73-0.92
Upper back (6) 612 0.84 0.77-0.90
Lower back (3) 477 0.82 0.59-0.92
Sole (3) 477 0.67 0.40-0.84
Palm (2) 141 0.61 0.27-0.82
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Gestational age or birthweight Minolta
AirShields Bilirubinometer

• 5 studies reported separate correlation
  coefficients
• Term (GAgt37 wk or BW gt 2500g)
• Near term infants (GA 34-37 wk or BW lt 2500 g)
• No significant differences, trend lower in near
  term

n Pooled r 95 CI
Term 425 0.81 0.75-0.86
Near Term 308 0.74 0.64-0.82
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Race or skin color Minolta AirShields
Bilirubinometer

• 6 studies compared correlation coefficients
  across race or skin color at forehead
• 3 studies at sternum site
• 2 studies in US found significant differences in
  White vs Black infants
• Other racial groups studied included Malay,
  Chinese, Indian
• No Hispanic subgroups were analyzed

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Race or skin color at forehead meta-analysis
Minolta AirShields Bilirubinometer
Race (studies) N Pooled r 95 CI
Black (3) 258 0.59 0.42-0.71
Chinese (3) 392 0.81 0.47-0.94
Indian (2) 150 0.75 0.49-0.88
Malay (3) 310 0.85 0.82-0.88
White (3) 564 0.75 0.48-0.89
Overall 1674 0.76 0.68-0.83
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Phototherapy Minolta Airshields

• 6 studies reported on effect of phototherapy
• All studies had lower correlation coefficients if
  had received phototherapy, significant in 2
  studies
• Meta-analysis of correlation coefficient
• No PhotoRx (n870) r 0.85 (0.79-0.89)
• PhotoRx (n213) r 0.78 (0.72-0.83)

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Ingram Icterometer

• Transparent Plexiglas with 5 painted transverse
  strips of precise and graded hue
• Used since 1925
• Press Plexiglas against infants nose until skin
  blanches and color compared with yellow stripes
  and jaundice score applied
• Advantage is low cost

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Test accuracy of Ingram Icterometer

• 4 studies reported correlation coefficient r of
  TcB to TSB
• Turkey (n96) r0.78
• US Black (n55) r0.96
• India (n11) r0.97
• India (n77) r0.97
• US White (n106) r0.63
• Pooled correlation coefficient
• r0.92 (95 CI 0.72-0.98)

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Test Perfomance (Sensitivity/Specificity)Ingram
Icterometer

• 3 of 4 studies reported test performance
• 2 studies reported TSB threshold gt 12.9 mg/dl
• 1 study reported TSB threshold gt 10 mg/dl

Study Country n Sens. () Spec. () Threshold Ict Threshold TSB
Bilgen,1998 Turkey 96 100 48 3 12.9
Schumacher,1985 US 106 82 74 3 12.9
Gupta, 1991 India 77 97 71 3 10
Preterm 11 50 86 3 10
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BilicheckTM

• Handheld device uses in vivo multiwavelength
  spectral reflectance technique
• Allows for individual optical densities (ODs)
  attributed to bilirubin, Hg, melanin
• Theoretically improves TcB measurement by
  accounting for skin thickness, blood content and
  flow, maturity and pigmentation (Bhutani,
  Gourley, Adler et al, 2000)
• Fiberoptic probe on forehead with light source
  triggered after appropriate contact

SpectRX Inc., Norcross, GA
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Accuracy of BilicheckTM
Study, Year Country Race (n) Reference Standard
Bhutani, 2000 US Mixed race (490) HPLC
Lodha, 2000 India Indian (109) Lab TSB
Rubaltelli, 2001 Europe Mixed Race (210) HPLC
Twin beam Microbilimeter (Ginveri Technologie
Biomediche)
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Test Performance BilicheckTM
Study r Sens. () Spec. () Threshold TcB Threshold TSB
Bhutani 0.91 100 88 gt 75th ile gt 95th ile
Lodha 0.83 69 47 20 89 99 100 13 15 18 13 15 18
Rulbatelli 0.87-0.89 97-66 92-52 90-50 64-89 71-95 87-99 10-13 12-15 14-17 13 15 17
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Accuracy of BilicheckTM

• Bhutani, Gourley, Adler et al., 2000
• n1788 samples in 490 healthy term/near term
  infants predischarge
• 59 White 29 Black 3 Hispanic, 4 Asian
• 11 devices
• Correlation of TcB with HPLC TSB
• r0.91

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Accuracy of BilicheckTM
Bhutani VK, Gourley GR et al. Pediatrics
2000106(2)
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Error distribution paired HPLC TSB and TcB
Bhutani VK, Gourley GR et al. Pediatrics 2000
106(2)
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Accuracy of Bilicheck

• Rulbatelli, Gourley, Loskamp 2001
• Multicenter, 6 European hospitals, n35 each site
• Newborn infants undergoing TSB as part of care
• Multiple users TcB and multiple lab TSB methods
  compared to gold standard HPLC
• Single independent lab for HPLC TSB
• r0.89 forehead and r0.88 sternum TcB/HPLC
• Lab TSB/HPLC r0.93

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Accuracy of Bilicheck compared to Lab TSB
HPLC TSB-Bilicheck
Lab TSB-Bilicheck
HPLC TSB-Lab TSB
Rulbatelli, Gourley, Loskam et al. Pediatrics
20011071264-1271
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Accuracy of Bilicheck-Error Plot
HPLC TSB - Bilicheck
Lab TSB -Bilicheck
Lab TSB - HPLC TSB
Rulbatelli, Gourley, Loskam et al. Pediatrics
20011071264-1271
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TcB or Lab TSB compared with HPLC TSB
HPLC gt 15
HPLC gt 17
HPLC gt 13
Rulbatelli, Gourley, Loskam et al. Pediatrics
20011071264-1271
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Accuracy of Bilicheck

• Lodha R, Deorari AK, Jatan V et al. 2000
• 109 jaundiced term Indian infants (TSBgt8)
• TSB by twin beam microbilimeter
• Correlation coefficient r0.8 overall
• Subgroup (n 46, TSBgt13) r0.64

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Direct comparison accuracyMinolta Airshields vs
Bilicheck

• Robertson, Kazmierczak, Vos, 2002
• Compared the Jaundice Meter JM 102
  (Minolta/Hill-ROM Air-Shields) to SpectRx
  BilicheckTM
• n101 jaundiced term infants not on phototherapy
• TcB by both methods compared to lab TSB
• Bilicheck performed superiorly r0.937
• Jaundice Meter r0.704
• Skin color was significant for Jaundice Meter

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Bilicheck vs Minolta Airshields (JM Meter)
Robertson 2002
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Colormate III

• Hand held colorimeter with Xenon flash tube and
  light sensors connected to portable computer
• Measures band of wavelengths from 400-700 nm with
  filters to assess reflectance of specific
  wavelengths
• Data processed by computer to assess luminosity
  (lightness), redness and yellowness
• Baseline measure prior to jaundiced, measure 3 of
  4 sites

Chromatics Color Sciences International, Inc.,
New York, NY
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Accuracy of Colormate III

• 2441 infants enrolled at birth, 2 sites
• Term and Preterm
• TcB within 30 h birth and every 6-8 h
• 900 infants had TSB
• 72 B, 110 W, 615 H, 103 A
• Mean BW 3135 g
• 53 lt 2000g
• 19 lt 1500g

N1600 measurements in 900 infants
Tayaba R et al, Pediatrics 1998 102 (3)
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Visual Inspection vs Chromatics III TcB
N1470 measures in 851 infants
N1600 measures in 900 infants
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Chromatics III Phototherapy
N284 measures in 61 patients
Tayaba et al, 1998
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Conclusions/Limitations

• TCB measurements by all 3 devices have a linear
  correlation to TSB
• Correlation coefficient does not provide
  information as to clinical utility of diagnostic
  test, however many of the studies reported only
  correlation of TcB with TSB
• Correlation coefficient (r) is highly dependent
  on distribution of serum bilirubin
• All of the devices perform less well as screening
  tests at higher levels of bilirubin

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Conclusions/Limitations

• Minolta Airshields bilirubinometer
• Performs best at sternum or forehead site
• Performs less well in Black vs White infants
• As a screening test, it does not perform
  consistently across studies as evidenced by SROC
• Ingram icterometer
• Small number of studies
• Lacks objectivity of other methods as depends on
  observer visualization

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Conclusions/Limitations

• Newer BilicheckTM device that theoretically
  correct effects of melanin and hemoglobin appears
  to be an improvement over older devices
• Future research should confirm these findings in
  larger sample sizes of diverse populations and
  include effects of phototherapy