Journal of Perinatology (2014) 34, 209–212 & 2014 Nature America, Inc. All rights reserved 0743-8346/14 www.nature.com/jp
ORIGINAL ARTICLE
Interscapular site for transcutaneous bilirubin measurement in preterm infants: a better and safer screening site A Yaser, L Tooke and N Rhoda OBJECTIVE: To prevent bilirubin induced brain injury in the newborn, repeated blood withdrawals are necessary to ascertain bilirubin levels and institute care. Noninvasive, painless and bloodless screening using transcutaneous bilirubinometry is the standard of care for term and near term neonates but there is still debate about its use with preterm neonates. The aims of this study were to determine how transcutaneous bilirubin (TcB) level measured from the interscapular site related to total serum bilirubin (TSB) level and to compare performance of TcB from the forehead, sternum and interscapular sites in identifying preterm neonates in need of phototherapy. STUDY DESIGN: This was a cross sectional study conducted at Groote Schuur level III neonatal unit. Over a 5-month period 122 consecutive preterm neonates o35 weeks gestational age were enrolled. TcBs were measured over the forehead, sternum and interscapular area. Pearson’s correlation coefficients and differences between TSB and TcBs were computed. P-value o0.05 was considered significant. RESULT: The median gestational age of the study participants was 31 weeks (range: 24 to 34 weeks), the median TSB level was 81.5 mmol l 1 (range: 25 to 229 mmol l 1) and 45% had a TSB at the phototherapy threshold. The correlation coefficients for TcBs ranged from 0.859 to 0.929 (Po0.001). The difference between TSB and TcBs ranged from 86 to þ 51 mmol l 1. With respect to initiating phototherapy, the interscapular site had the highest sensitivity of 94% and lowest false negative rate of 6%. CONCLUSION: Using transcutaneous bilirubinometry, the interscapular site is superior and safer for screening preterm neonates. Journal of Perinatology (2014) 34, 209–212; doi:10.1038/jp.2013.167; published online 9 January 2014 Keywords: preterm neonates; transcutaneous bilirubin; interscapular transcutaneous bilirubin
INTRODUCTION Neonatal jaundice is one of the most common clinical sign encountered among newborn babies. Immaturity of the liver enzyme system among neonates is the main factor predisposing them to developing jaundice.1–4 Unconjugated bilirubin can cross the blood-brain barrier and induce encephalopathy acutely and in the long-term survivors’ possible cerebral palsy.4–7 The need to prevent these complications necessitates repeated blood withdrawal to ascertain bilirubin levels and institute early care. Noninvasive, painless screening for jaundice by use of transcutaneous bilirubinometry is the standard of care for term and near term neonates.8,9 Whereas, some studies have shown good correlation between serum (TSB) and transcutaneous bilirubin (TcB) among preterm neonates10–12 due to their susceptibility to bilirubin encephalopathy at lower bilirubin levels; The National Institute of health and Clinical Excellence and the American Academy of Pediatrics guidelines at present do not advocate using TcB in neonates of o35 weeks gestational age.8,9 Considering the fact that unconjugated bilirubin is lipophilic and the interscapular site is among the earliest sites for fat deposition in the fetus,13 we considered this site to be a logical site for transcutaneous bilirubinometry and yet no study has previously looked at it. The majority of studies using transcutaneous bilirubinometry have used the forehead and the sternum. The purpose of this study was to establish the accuracy of interscapular TcB (TcBi) in identifying preterm neonates o35weeks gestational age in need of phototherapy and how the TcBi predicts total serum bilirubin (TSB).
Ethical approval Ethical approval was obtained from the Human Research and Ethics Committee of the University of Cape Town and written consent was obtained from parents of study participants. METHODS Setting This study was conducted at Groote Schuur Hospital, which is a level III neonatal care unit in Cape Town, South Africa. The unit admits over 500 babies per year who weigh less than 1500 g at birth.
Study population Preterm neonates of gestational age o35 weeks who were o8 days old in whom serum bilirubin had been requested and phototherapy had not been initiated were eligible. Eligible neonates who had poor perfusion (capillary refill 43 s) were excluded.
Sample size Sample size for positive and negative predictive value assuming TcB had a sensitivity of 80% in predicting the need to start phototherapy was generated. The sample size need to demonstrate this with a power of 90% was 122.
Procedure A cross-sectional study was conducted between May 2012 and September 2012. Of the 306 preterm neonates o35 weeks gestational age admitted to the unit, 122 were enrolled in the study.
Department of Neonatal Medicine, Groote Schuur Hospital, University of Cape Town, Cape Town, Republic of South Africa. Correspondence: Dr A Yaser, Department of Neonatal Medicine, Groote Schuur Hospital, University of Cape Town, Rm 63, H46, OMB, Observatory, 7925 Cape Town, Republic of South Africa. E-mail: [email protected] Received 29 July 2013; revised 26 October 2013; accepted 20 November 2013; published online 9 January 2014
Interscapular site for TcB measurement A Yaser et al
210 Table 1.
Table of correlation and difference between TSB and TcB from the three body sites
Test TcB forehead TcB chest TcB interscapular
Correlation co-efficienta(Cr)
Difference (TSB–TcB)
Percentage over estimated/under estimated by 420 mmol l 1
0.904 (Po0.001) 0.929 (Po0.001) 0.859 (Po0.001)
86 to 44 mmol l 1 52 to 48 mmol l 1 80 to 51 mmol l 1 one outlier excluded
17.2/19.7 7.3/26.2 37.7/9.0
Abbreviations: TcB, transcutaneous bilirubin; TSB, total serum bilirubin. a Spearman’s correlation.
TcB was measured on the forehead, chest (sternum) and interscapular area by the principal investigator using a JM103 bilirubinometer (Draeger Medical Systems, Telford, PA, USA). These measurements were obtained within 30 min of blood withdrawal to establish TSB levels. The bilirubinometer was calibrated once daily and used according to the manufacturer’s instruction. An average of three measurements was recorded for each site. Study subjects with jaundice were managed in accordance to the South African guidelines.14 These guidelines take into account the infant’s gestational age, birth weight and age in hours. The need for phototherapy is determined by consulting the charts for each particular infant and starting phototherapy if indicated. Photo line is the TSB threshold levels generated at which phototherapy should be commenced. Infants with TSB at and above photo line and those with TSB of 20 mmol l 1 within photo line are commenced on phototherapy.14 Study subjects with TSB warranting commencement of phototherapy according to the South African guidelines were categorized as being in need of phototherapy.
Data management Baseline characteristics of study participants (gestational age estimated by early antenatal ultrasound or Ballard score, birth weight and gender) were captured. Time of blood drawing for measuring serum bilirubin level, TcB measurements, TSB level and phototherapy line were entered into data capturing sheet. Data were entered into Microsoft excel 2010 package and then transferred to STATA version 11 for analysis. P-valueo0.05 was considered significant.
Table 2. Table of correlation and difference between TSB and TcB from the three body sites with respect to gestational age Test
Correlation coefficient (Cr)
Difference (TSB–TcB)
TcB forehead p30 weeks 430 weeks
0.923 (Po0.001) 0.894 (Po0.001)
86–43 mmol l 1 76–44 mmol l 1
TcB chest p30 weeks 430 weeks
0.965 (Po0.001) 0.908 (Po0.001)
51–45 mmol l 1 52–48 mmol l 1
TcB Interscapular p30 weeks 430 weeks
0.892 (Po0.001) 0.844 (Po0.001)
80–51 mmol l 1 76–37 mmol l 1 (one outlier 118 mmol l 1)
Abbreviations: TcB, transcutaneous bilirubin; TSB, total serum bilirubin.
Statistical methods Shapirow–Wilk w-test was used to classify distribution of data. Spearman’s correlation was computed for the different TcBs, and using 2 2 tabulation with point of interest being initiation of phototherapy the sensitivity, specificity, positive and negative predictive values were computed. Receiver operating curve was also generated.
RESULTS The median gestational age of the study participants was 31 weeks (range: 24 to 34 weeks), the median birth weight was 1242 grams (range: 608 to 2560 grams), 32 (26.2%) of the study participants were small for gestational age (weight o10th centile for gestational age). The median age when blood was drawn for serum bilirubin measurement was 21 h (range: 4 to 136 h), 65.5% of these were obtained within the first 24 h, and the median serum bilirubin was 81.5 mmol l 1 (range: 25 to 229 mmol l 1). Although most of the mothers are of African or mixed-race descent, 94% of study participants’ skin color was described as pink and the rest as red. TcB from sites studied (forehead, chest and interscapular) had statistically significant correlation with the TSB. Table 1 shows the correlation and difference between TSB and the TcBs. In one study participant (outlier) TcBi underestimated TSB by 118 mmol l 1; this was an 84 h old preterm neonate of 32 weeks gestational age weighing 1420 grams. The correlation coefficients did not differ significantly between study participants of gestational age p30 weeks and those 430 weeks. (See Table 2) Figure 1 shows the correlation of TcB and TSB at different TSB levels. From the graph it is evident that there was a tendency for Journal of Perinatology (2014), 209 – 212
Figure 1. Correlation between serum and TcB with line of best fit intersecting the graph.
TcB to underestimate TSB at low TSB levels and to overestimate at high levels. Table 3 shows how TcBs from the three sites identified preterm neonates in need of phototherapy. With respect to initiating phototherapy, the TcBi had the highest sensitivity (94%). Table 4 shows sensitivity, specificity and false-negative rates of the TcBs. A receiver operating curve was generated to determine whether a cutoff value would improve sensitivity of TcBi. Figure 2 shows the receiver operating curve of TcBi; the area under the curve is 0.731. & 2014 Nature America, Inc.
Interscapular site for TcB measurement A Yaser et al
211 Table 3. Table showing performance of TcB in identifying study subjects needing phototherapy TcB
Forehead (TcBf ) Chest (TcBc) Interscapular (TcBi)
Number needing phototherapy (67/122) true positive
Number not needing phototherapy (55/122) true negative
Needing phototherapy but labeled as not needing false negative
Not needing phototherapy but labeled as needing false positive
54
48
13
7
47 63
53 40
20 4
2 15
Abbreviation: TcB, transcutaneous bilirubin.
Table 4. Table of sensitivity, specificity and false-negative rate of TcB from the three body site with respect to initiation of phototherapy p30 weeks
430 weeks
Overall
Sensitivity TcBf TcBc TcBi
69.2% 69.2% 92.3%
87.8% 70.7% 97.5%
80.6% 70.1% 94.0%
Specificity TcBf TcBc TcBi
83.3% 95.8% 83.3%
90.3% 96.7% 64.5%
87.3% 96.4% 72.7%
False negative rate TcBf 30.7% TcBc 30.7% TcBi 7.7%
12.2% 29.3% 4.9%
19.4% 30.0% 6.0%
Test
Abbreviations: TcBc, transcutaneous bilirubin chest; TcBf, transcutaneous bilirubin forehead; TcBi, transcutaneous bilirubin interscapular. 95% CI.
0.859 (Po0.001), but for one of the study participants TcBi significantly underestimated TSB by 118 mmol l 1. We do not have an explanation for the underestimation observed in this study participant. Although Knupfer et al.17 using Bilicheck, found an increased incoherence between serum bilirubin and forehead TcB with lower gestational ages, Ebbesen et al.16 using Minolta JM 103 found no association, whereas Schmidt et al.11 demonstrated an increase correlation of sternal TcB with decreasing gestational age. Our study did not demonstrate significant difference in correlation coefficients from the three sites after stratifying study subjects by gestational ages. The discrepancy in correlation of forehead and TSB may be due to the fact that the forehead is continuously exposed to ambient light. The difference between TSB and TcBf in this study was 88 to þ 44, whereas TSB and TcBc was 52 to þ 48; these are comparable with the findings from other studies using different transcutaneous bilirubinometers11,15,17,18 with an overall tendency of TcBf and TcBc to underestimate the TSB. The difference between TSB and TcBi in this study was 80 to þ 51 mmol l 1 with one outlier in whom the TcBi underestimated TSB by 118 mmol l 1. Forty-six (37.7%) of TcBi overestimated, whereas 11 (9.0%) underestimated TSB by 420 mmol l 1. It is apparent that the TcBi tends to overestimate TSB with fewer cases underestimated compared with the TcBf and TcBc. The sensitivity of TcBf in identifying study participants in need of phototherapy was 80.8% and comparable with Knupfer et al. who found a sensitivity of 86.8% using the Bilicheck on the forehead. From this study it seems that the chest was the poorest site of choice as many participants would not receive phototherapy when they actually needed it (30.3%). No study that we came across looked at sensitivity and specificity of the TcBc in determining need to initiate phototherapy without setting a cutoff value. The TcBi had the highest sensitivity in identifying study participants in need of phototherapy (94%) and it wrongly mislabeled 6% of those in need of phototherapy. The four study subjects labeled as not needing phototherapy included three whose TSBs were 62, 64 and 68 mmol l 1 all done within first 24 h of age and the fourth one had TSB of 105 mmol l 1 at 53 h of age. None of them had TSBs at exchange transfusion level. Using TcBi for screening preterm neonates would have enabled early initiation of phototherapy in 63/67 (94%), it would prevent unnecessary blood sampling of 40/55 (70%) preterm neonates not needing phototherapy. Study limitations
Figure 2.
ROC for interscapular TcB.
DISCUSSION The correlation coefficient of forehead TcBf of 0.904 (Po0.001) found in this study was higher than that described by other studies,15–18 whereas the correlation coefficient of chest TcBc of 0.929 (Po0.001) is comparable with the finding of Schmidt et al.11 0.79 to 0.92 (Po0.001). The correlation coefficient of TcBi was & 2014 Nature America, Inc.
1. TcB measurements were obtained by the principal investigator who ensured that the Draeger JM 103 bilirubinometer was calibrated and followed the manufacturer’s instruction. Under daily clinical practice if these are not observed the results might be highly varied. 2. Highest TSB obtained was 229 mmol l 1, so the performance of this device at much higher serum bilirubin levels is not known and cannot be extrapolated. 3. These results only reflect the Draeger JM 103 bilirubinometer and these results cannot be applied when using a different bilirubinometer type. CONCLUSION For TcB screening of preterm neonates o35 weeks gestational age, the interscapular site is superior to the forehead and sternal sites as it misses the fewest neonates who need phototherapy. We postulate that this is due to the fat deposition at this site as well as the lack of exposure to ambient light. Journal of Perinatology (2014), 209 – 212
Interscapular site for TcB measurement A Yaser et al
212 CONFLICT OF INTEREST The authors declare no conflict of interest.
ACKNOWLEDGEMENTS We would like to thank the staff of Groote Schuur Hospital for all the support rendered that enabled completion of this piece of work.
AUTHORS CONTRIBUTION Dr Abdallah Yaser was the principle investigator; he did the literature search, data collection, entry and the writing up of this work. Dr Natasha Rhoda and Dr Lloyd Tooke were involved in study design and methodology; they reviewed the wright-up, data analysis and interpretation of findings.
REFERENCES 1 Kawade N, Onishi S. The prenatal and postnatal development of UDP-glucuronyltransferase activity towards bilirubin and the effect of premature birth on this activity in the human liver. Biochem J 1981; 196(1): 257–260. 2 Ronald JW, David KS, Charles EA, Hendrik JV. Neonatal jaundice: bilirubin physiology and clinical chemistry. NeoReviews 2007; 8: e58–e67. 3 Watchko JF, Maisel MJ. Jaundice in low birthweight infants: pathobiology and outcome. Arch Dis Child Fetal Neonatal Ed 2003; 88(6): F455–F458. 4 McDonagh AF, Lightner DA. ’Like a shrivelled blood orange’--bilirubin, jaundice, and phototherapy. Pediatrics 1985; 75(3): 443–455. 5 Worssam AR. The sequelae of kernicterus. Br Med J 1957; 2(5046): 683–684. 6 Ernster L, Herlin L, Zetterstrom R. Experimental studies on the pathogenesis of kernicterus. Pediatrics 1957; 20(4): 647–652.
Journal of Perinatology (2014), 209 – 212
7 Turkel SB, Miller CA, Guttenberg ME, Moynes DR, Godgman JE. A clinical pathologic reappraisal of kernicterus. Pediatrics 1982; 69(3): 267–272. 8 American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004; 114(1): 297–316. 9 Rennie J, Burman-Roy S, Murphy MS. Guideline Development Group. Neonatal jaundice: summary of NICE guidance. BMJ 2010; 340: c2409. 10 Ahmed M, Mostafa S, Fisher G, Reynolds TM. Comparison between transcutaneous bilirubinometry and total serum bilirubin measurements in preterm infants o35 weeks gestation. Ann Clin Biochem 2010; 47(Pt 1): 72–77. 11 Schmidt ET, Wheeler CA, Jackson GL, Engle WD. Evaluation of transcutaneous bilirubinometry in preterm neonates. J Perinatol 2009; 29(8): 564–569. 12 Stillova L, Matasova K, Zibolen M, Stilla J, Kolarovszka H. Transcutaneous bilirubinometry in preterm neonates. Indian Pediatr 2009; 46(5): 405–408. 13 Poissonnet CM, Burdi AR, Garn SM. The chronology of adipose tissue appearance and distribution in the human fetus. Early Hum Dev 1984; 10(1-2): 1–11. 14 Horn AR, Kirsten GF, Kroon SM, Henning PA, Mo¨ller G, Pieper C et al. Phototherapy and exchange transfusion for neonatal hyperbilirubinaemia: neonatal academic hospitals’ consensus guidelines for South African hospitals and primary care facilities. S Afr Med J 2006; 96(9): 819–824. 15 De Luca D, Zecca E, de Turris P, Barbato G, Marras M, Romagnoli C. Using BiliCheck for preterm neonates in a sub-intensive unit: diagnostic usefulness and suitability. Early Hum Dev 2007; 83(5): 313–317. 16 Ebbesen F, Vandborg PK, Trydal T. Comparison of the transcutaneous bilirubinometers BiliCheck and Minolta JM-103 in preterm neonates. Acta Paediatr 2012; 101(11): 1128–1133. 17 Knu¨pfer M, Pulzer F, Braun L, Heilmann A, Robel-Tillig E, Vogtmann C. Transcutaneous bilirubinometry in preterm infants. Acta Paediatr 2001; 90(8): 899–903. 18 Willems WA, van den Berg LM, de Wit H, Molendijk A. Transcutaneous bilirubinometry with the Bilicheck in very premature newborns. J Matern Fetal Neonatal Med 2004; 16(4): 209–214.
& 2014 Nature America, Inc.
ORIGINAL ARTICLE
Interscapular site for transcutaneous bilirubin measurement in preterm infants: a better and safer screening site A Yaser, L Tooke and N Rhoda OBJECTIVE: To prevent bilirubin induced brain injury in the newborn, repeated blood withdrawals are necessary to ascertain bilirubin levels and institute care. Noninvasive, painless and bloodless screening using transcutaneous bilirubinometry is the standard of care for term and near term neonates but there is still debate about its use with preterm neonates. The aims of this study were to determine how transcutaneous bilirubin (TcB) level measured from the interscapular site related to total serum bilirubin (TSB) level and to compare performance of TcB from the forehead, sternum and interscapular sites in identifying preterm neonates in need of phototherapy. STUDY DESIGN: This was a cross sectional study conducted at Groote Schuur level III neonatal unit. Over a 5-month period 122 consecutive preterm neonates o35 weeks gestational age were enrolled. TcBs were measured over the forehead, sternum and interscapular area. Pearson’s correlation coefficients and differences between TSB and TcBs were computed. P-value o0.05 was considered significant. RESULT: The median gestational age of the study participants was 31 weeks (range: 24 to 34 weeks), the median TSB level was 81.5 mmol l 1 (range: 25 to 229 mmol l 1) and 45% had a TSB at the phototherapy threshold. The correlation coefficients for TcBs ranged from 0.859 to 0.929 (Po0.001). The difference between TSB and TcBs ranged from 86 to þ 51 mmol l 1. With respect to initiating phototherapy, the interscapular site had the highest sensitivity of 94% and lowest false negative rate of 6%. CONCLUSION: Using transcutaneous bilirubinometry, the interscapular site is superior and safer for screening preterm neonates. Journal of Perinatology (2014) 34, 209–212; doi:10.1038/jp.2013.167; published online 9 January 2014 Keywords: preterm neonates; transcutaneous bilirubin; interscapular transcutaneous bilirubin
INTRODUCTION Neonatal jaundice is one of the most common clinical sign encountered among newborn babies. Immaturity of the liver enzyme system among neonates is the main factor predisposing them to developing jaundice.1–4 Unconjugated bilirubin can cross the blood-brain barrier and induce encephalopathy acutely and in the long-term survivors’ possible cerebral palsy.4–7 The need to prevent these complications necessitates repeated blood withdrawal to ascertain bilirubin levels and institute early care. Noninvasive, painless screening for jaundice by use of transcutaneous bilirubinometry is the standard of care for term and near term neonates.8,9 Whereas, some studies have shown good correlation between serum (TSB) and transcutaneous bilirubin (TcB) among preterm neonates10–12 due to their susceptibility to bilirubin encephalopathy at lower bilirubin levels; The National Institute of health and Clinical Excellence and the American Academy of Pediatrics guidelines at present do not advocate using TcB in neonates of o35 weeks gestational age.8,9 Considering the fact that unconjugated bilirubin is lipophilic and the interscapular site is among the earliest sites for fat deposition in the fetus,13 we considered this site to be a logical site for transcutaneous bilirubinometry and yet no study has previously looked at it. The majority of studies using transcutaneous bilirubinometry have used the forehead and the sternum. The purpose of this study was to establish the accuracy of interscapular TcB (TcBi) in identifying preterm neonates o35weeks gestational age in need of phototherapy and how the TcBi predicts total serum bilirubin (TSB).
Ethical approval Ethical approval was obtained from the Human Research and Ethics Committee of the University of Cape Town and written consent was obtained from parents of study participants. METHODS Setting This study was conducted at Groote Schuur Hospital, which is a level III neonatal care unit in Cape Town, South Africa. The unit admits over 500 babies per year who weigh less than 1500 g at birth.
Study population Preterm neonates of gestational age o35 weeks who were o8 days old in whom serum bilirubin had been requested and phototherapy had not been initiated were eligible. Eligible neonates who had poor perfusion (capillary refill 43 s) were excluded.
Sample size Sample size for positive and negative predictive value assuming TcB had a sensitivity of 80% in predicting the need to start phototherapy was generated. The sample size need to demonstrate this with a power of 90% was 122.
Procedure A cross-sectional study was conducted between May 2012 and September 2012. Of the 306 preterm neonates o35 weeks gestational age admitted to the unit, 122 were enrolled in the study.
Department of Neonatal Medicine, Groote Schuur Hospital, University of Cape Town, Cape Town, Republic of South Africa. Correspondence: Dr A Yaser, Department of Neonatal Medicine, Groote Schuur Hospital, University of Cape Town, Rm 63, H46, OMB, Observatory, 7925 Cape Town, Republic of South Africa. E-mail: [email protected] Received 29 July 2013; revised 26 October 2013; accepted 20 November 2013; published online 9 January 2014
Interscapular site for TcB measurement A Yaser et al
210 Table 1.
Table of correlation and difference between TSB and TcB from the three body sites
Test TcB forehead TcB chest TcB interscapular
Correlation co-efficienta(Cr)
Difference (TSB–TcB)
Percentage over estimated/under estimated by 420 mmol l 1
0.904 (Po0.001) 0.929 (Po0.001) 0.859 (Po0.001)
86 to 44 mmol l 1 52 to 48 mmol l 1 80 to 51 mmol l 1 one outlier excluded
17.2/19.7 7.3/26.2 37.7/9.0
Abbreviations: TcB, transcutaneous bilirubin; TSB, total serum bilirubin. a Spearman’s correlation.
TcB was measured on the forehead, chest (sternum) and interscapular area by the principal investigator using a JM103 bilirubinometer (Draeger Medical Systems, Telford, PA, USA). These measurements were obtained within 30 min of blood withdrawal to establish TSB levels. The bilirubinometer was calibrated once daily and used according to the manufacturer’s instruction. An average of three measurements was recorded for each site. Study subjects with jaundice were managed in accordance to the South African guidelines.14 These guidelines take into account the infant’s gestational age, birth weight and age in hours. The need for phototherapy is determined by consulting the charts for each particular infant and starting phototherapy if indicated. Photo line is the TSB threshold levels generated at which phototherapy should be commenced. Infants with TSB at and above photo line and those with TSB of 20 mmol l 1 within photo line are commenced on phototherapy.14 Study subjects with TSB warranting commencement of phototherapy according to the South African guidelines were categorized as being in need of phototherapy.
Data management Baseline characteristics of study participants (gestational age estimated by early antenatal ultrasound or Ballard score, birth weight and gender) were captured. Time of blood drawing for measuring serum bilirubin level, TcB measurements, TSB level and phototherapy line were entered into data capturing sheet. Data were entered into Microsoft excel 2010 package and then transferred to STATA version 11 for analysis. P-valueo0.05 was considered significant.
Table 2. Table of correlation and difference between TSB and TcB from the three body sites with respect to gestational age Test
Correlation coefficient (Cr)
Difference (TSB–TcB)
TcB forehead p30 weeks 430 weeks
0.923 (Po0.001) 0.894 (Po0.001)
86–43 mmol l 1 76–44 mmol l 1
TcB chest p30 weeks 430 weeks
0.965 (Po0.001) 0.908 (Po0.001)
51–45 mmol l 1 52–48 mmol l 1
TcB Interscapular p30 weeks 430 weeks
0.892 (Po0.001) 0.844 (Po0.001)
80–51 mmol l 1 76–37 mmol l 1 (one outlier 118 mmol l 1)
Abbreviations: TcB, transcutaneous bilirubin; TSB, total serum bilirubin.
Statistical methods Shapirow–Wilk w-test was used to classify distribution of data. Spearman’s correlation was computed for the different TcBs, and using 2 2 tabulation with point of interest being initiation of phototherapy the sensitivity, specificity, positive and negative predictive values were computed. Receiver operating curve was also generated.
RESULTS The median gestational age of the study participants was 31 weeks (range: 24 to 34 weeks), the median birth weight was 1242 grams (range: 608 to 2560 grams), 32 (26.2%) of the study participants were small for gestational age (weight o10th centile for gestational age). The median age when blood was drawn for serum bilirubin measurement was 21 h (range: 4 to 136 h), 65.5% of these were obtained within the first 24 h, and the median serum bilirubin was 81.5 mmol l 1 (range: 25 to 229 mmol l 1). Although most of the mothers are of African or mixed-race descent, 94% of study participants’ skin color was described as pink and the rest as red. TcB from sites studied (forehead, chest and interscapular) had statistically significant correlation with the TSB. Table 1 shows the correlation and difference between TSB and the TcBs. In one study participant (outlier) TcBi underestimated TSB by 118 mmol l 1; this was an 84 h old preterm neonate of 32 weeks gestational age weighing 1420 grams. The correlation coefficients did not differ significantly between study participants of gestational age p30 weeks and those 430 weeks. (See Table 2) Figure 1 shows the correlation of TcB and TSB at different TSB levels. From the graph it is evident that there was a tendency for Journal of Perinatology (2014), 209 – 212
Figure 1. Correlation between serum and TcB with line of best fit intersecting the graph.
TcB to underestimate TSB at low TSB levels and to overestimate at high levels. Table 3 shows how TcBs from the three sites identified preterm neonates in need of phototherapy. With respect to initiating phototherapy, the TcBi had the highest sensitivity (94%). Table 4 shows sensitivity, specificity and false-negative rates of the TcBs. A receiver operating curve was generated to determine whether a cutoff value would improve sensitivity of TcBi. Figure 2 shows the receiver operating curve of TcBi; the area under the curve is 0.731. & 2014 Nature America, Inc.
Interscapular site for TcB measurement A Yaser et al
211 Table 3. Table showing performance of TcB in identifying study subjects needing phototherapy TcB
Forehead (TcBf ) Chest (TcBc) Interscapular (TcBi)
Number needing phototherapy (67/122) true positive
Number not needing phototherapy (55/122) true negative
Needing phototherapy but labeled as not needing false negative
Not needing phototherapy but labeled as needing false positive
54
48
13
7
47 63
53 40
20 4
2 15
Abbreviation: TcB, transcutaneous bilirubin.
Table 4. Table of sensitivity, specificity and false-negative rate of TcB from the three body site with respect to initiation of phototherapy p30 weeks
430 weeks
Overall
Sensitivity TcBf TcBc TcBi
69.2% 69.2% 92.3%
87.8% 70.7% 97.5%
80.6% 70.1% 94.0%
Specificity TcBf TcBc TcBi
83.3% 95.8% 83.3%
90.3% 96.7% 64.5%
87.3% 96.4% 72.7%
False negative rate TcBf 30.7% TcBc 30.7% TcBi 7.7%
12.2% 29.3% 4.9%
19.4% 30.0% 6.0%
Test
Abbreviations: TcBc, transcutaneous bilirubin chest; TcBf, transcutaneous bilirubin forehead; TcBi, transcutaneous bilirubin interscapular. 95% CI.
0.859 (Po0.001), but for one of the study participants TcBi significantly underestimated TSB by 118 mmol l 1. We do not have an explanation for the underestimation observed in this study participant. Although Knupfer et al.17 using Bilicheck, found an increased incoherence between serum bilirubin and forehead TcB with lower gestational ages, Ebbesen et al.16 using Minolta JM 103 found no association, whereas Schmidt et al.11 demonstrated an increase correlation of sternal TcB with decreasing gestational age. Our study did not demonstrate significant difference in correlation coefficients from the three sites after stratifying study subjects by gestational ages. The discrepancy in correlation of forehead and TSB may be due to the fact that the forehead is continuously exposed to ambient light. The difference between TSB and TcBf in this study was 88 to þ 44, whereas TSB and TcBc was 52 to þ 48; these are comparable with the findings from other studies using different transcutaneous bilirubinometers11,15,17,18 with an overall tendency of TcBf and TcBc to underestimate the TSB. The difference between TSB and TcBi in this study was 80 to þ 51 mmol l 1 with one outlier in whom the TcBi underestimated TSB by 118 mmol l 1. Forty-six (37.7%) of TcBi overestimated, whereas 11 (9.0%) underestimated TSB by 420 mmol l 1. It is apparent that the TcBi tends to overestimate TSB with fewer cases underestimated compared with the TcBf and TcBc. The sensitivity of TcBf in identifying study participants in need of phototherapy was 80.8% and comparable with Knupfer et al. who found a sensitivity of 86.8% using the Bilicheck on the forehead. From this study it seems that the chest was the poorest site of choice as many participants would not receive phototherapy when they actually needed it (30.3%). No study that we came across looked at sensitivity and specificity of the TcBc in determining need to initiate phototherapy without setting a cutoff value. The TcBi had the highest sensitivity in identifying study participants in need of phototherapy (94%) and it wrongly mislabeled 6% of those in need of phototherapy. The four study subjects labeled as not needing phototherapy included three whose TSBs were 62, 64 and 68 mmol l 1 all done within first 24 h of age and the fourth one had TSB of 105 mmol l 1 at 53 h of age. None of them had TSBs at exchange transfusion level. Using TcBi for screening preterm neonates would have enabled early initiation of phototherapy in 63/67 (94%), it would prevent unnecessary blood sampling of 40/55 (70%) preterm neonates not needing phototherapy. Study limitations
Figure 2.
ROC for interscapular TcB.
DISCUSSION The correlation coefficient of forehead TcBf of 0.904 (Po0.001) found in this study was higher than that described by other studies,15–18 whereas the correlation coefficient of chest TcBc of 0.929 (Po0.001) is comparable with the finding of Schmidt et al.11 0.79 to 0.92 (Po0.001). The correlation coefficient of TcBi was & 2014 Nature America, Inc.
1. TcB measurements were obtained by the principal investigator who ensured that the Draeger JM 103 bilirubinometer was calibrated and followed the manufacturer’s instruction. Under daily clinical practice if these are not observed the results might be highly varied. 2. Highest TSB obtained was 229 mmol l 1, so the performance of this device at much higher serum bilirubin levels is not known and cannot be extrapolated. 3. These results only reflect the Draeger JM 103 bilirubinometer and these results cannot be applied when using a different bilirubinometer type. CONCLUSION For TcB screening of preterm neonates o35 weeks gestational age, the interscapular site is superior to the forehead and sternal sites as it misses the fewest neonates who need phototherapy. We postulate that this is due to the fat deposition at this site as well as the lack of exposure to ambient light. Journal of Perinatology (2014), 209 – 212
Interscapular site for TcB measurement A Yaser et al
212 CONFLICT OF INTEREST The authors declare no conflict of interest.
ACKNOWLEDGEMENTS We would like to thank the staff of Groote Schuur Hospital for all the support rendered that enabled completion of this piece of work.
AUTHORS CONTRIBUTION Dr Abdallah Yaser was the principle investigator; he did the literature search, data collection, entry and the writing up of this work. Dr Natasha Rhoda and Dr Lloyd Tooke were involved in study design and methodology; they reviewed the wright-up, data analysis and interpretation of findings.
REFERENCES 1 Kawade N, Onishi S. The prenatal and postnatal development of UDP-glucuronyltransferase activity towards bilirubin and the effect of premature birth on this activity in the human liver. Biochem J 1981; 196(1): 257–260. 2 Ronald JW, David KS, Charles EA, Hendrik JV. Neonatal jaundice: bilirubin physiology and clinical chemistry. NeoReviews 2007; 8: e58–e67. 3 Watchko JF, Maisel MJ. Jaundice in low birthweight infants: pathobiology and outcome. Arch Dis Child Fetal Neonatal Ed 2003; 88(6): F455–F458. 4 McDonagh AF, Lightner DA. ’Like a shrivelled blood orange’--bilirubin, jaundice, and phototherapy. Pediatrics 1985; 75(3): 443–455. 5 Worssam AR. The sequelae of kernicterus. Br Med J 1957; 2(5046): 683–684. 6 Ernster L, Herlin L, Zetterstrom R. Experimental studies on the pathogenesis of kernicterus. Pediatrics 1957; 20(4): 647–652.
Journal of Perinatology (2014), 209 – 212
7 Turkel SB, Miller CA, Guttenberg ME, Moynes DR, Godgman JE. A clinical pathologic reappraisal of kernicterus. Pediatrics 1982; 69(3): 267–272. 8 American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004; 114(1): 297–316. 9 Rennie J, Burman-Roy S, Murphy MS. Guideline Development Group. Neonatal jaundice: summary of NICE guidance. BMJ 2010; 340: c2409. 10 Ahmed M, Mostafa S, Fisher G, Reynolds TM. Comparison between transcutaneous bilirubinometry and total serum bilirubin measurements in preterm infants o35 weeks gestation. Ann Clin Biochem 2010; 47(Pt 1): 72–77. 11 Schmidt ET, Wheeler CA, Jackson GL, Engle WD. Evaluation of transcutaneous bilirubinometry in preterm neonates. J Perinatol 2009; 29(8): 564–569. 12 Stillova L, Matasova K, Zibolen M, Stilla J, Kolarovszka H. Transcutaneous bilirubinometry in preterm neonates. Indian Pediatr 2009; 46(5): 405–408. 13 Poissonnet CM, Burdi AR, Garn SM. The chronology of adipose tissue appearance and distribution in the human fetus. Early Hum Dev 1984; 10(1-2): 1–11. 14 Horn AR, Kirsten GF, Kroon SM, Henning PA, Mo¨ller G, Pieper C et al. Phototherapy and exchange transfusion for neonatal hyperbilirubinaemia: neonatal academic hospitals’ consensus guidelines for South African hospitals and primary care facilities. S Afr Med J 2006; 96(9): 819–824. 15 De Luca D, Zecca E, de Turris P, Barbato G, Marras M, Romagnoli C. Using BiliCheck for preterm neonates in a sub-intensive unit: diagnostic usefulness and suitability. Early Hum Dev 2007; 83(5): 313–317. 16 Ebbesen F, Vandborg PK, Trydal T. Comparison of the transcutaneous bilirubinometers BiliCheck and Minolta JM-103 in preterm neonates. Acta Paediatr 2012; 101(11): 1128–1133. 17 Knu¨pfer M, Pulzer F, Braun L, Heilmann A, Robel-Tillig E, Vogtmann C. Transcutaneous bilirubinometry in preterm infants. Acta Paediatr 2001; 90(8): 899–903. 18 Willems WA, van den Berg LM, de Wit H, Molendijk A. Transcutaneous bilirubinometry with the Bilicheck in very premature newborns. J Matern Fetal Neonatal Med 2004; 16(4): 209–214.
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