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Is it worthwhile using a transcutaneous bilirubinometer in the nursery?
Early Human Development 88S2 (2012) S25–S26
Contents lists available at ScienceDirect
Early Human Development j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / e a r l h u m d ev
Is it worthwhile using a transcutaneous bilirubinometer in the nursery? L. Capasso, C. Parrella, A.C. Borrelli, R. Maffucci, P. Milite, A. Sodano, T. Ferrara, F. Raimondi* Division of Neonatology, Department of Pediatrics, Universit` a “Federico II” di Napoli, Naples, Italy
article info
summary
Keywords: Hyperbilirubinaemia Jaundice Neonate Preterm Bilirubin BiliCheck
Jaundice is a potential threat to neonatal health and/or life. The advantages and limitations of transcutaneous determination of bilirubin concentration and current devices are briefly discussed in this paper.
1. Introduction Hyperbilirubinaemia is one of the most common diagnoses in the neonatal period. Extreme neonatal hyperbilirubinaemia, a potential cause of mortality or of permanent neurological damage (i.e. kernicterus), is a rare but apparently resurgent condition in developed countries [1]. In 2004 the American Academy of Pediatrics (AAP) has revised the official guidelines for management of hyperbilirubinaemia in neonates with gestational age (GA) ≥35 weeks with the declared intent to prevent kernicterus. The strategy of AAP guidelines includes universal bilirubin screening before hospital discharge and planning of a tailored follow-up. In order to properly assess the risk of significant hyperbilirubinaemia, the AAP recommends to measure either the serum bilirubin with a spectrophotometric method (TSB) or the transcutaneous bilirubin (TcB); both values should be plotted on an appropriate nomogram that takes birthweight, post-natal age and a list of risk factors into account [2]. TcB is advantageous over TSB as it spares pain and blood to the baby and time to the nurse. TcB is a powerful tool to clinically screen relevant neonatal hyperbilirubinaemia although several issues remain open. 2. Transcutaneous bilirubinometer in term and late preterm neonates In term or late preterm neonates, several TcB devices have been individually validated versus spectrophotometric or high pressure liquid chromatography (HPLC) determination of TSB. The first generation of bilirubinometers showed an accuracy * Corresponding author. Francesco Raimondi MD PhD. Assistant Professor of Pediatrics, Division of Neonatology, Department of Pediatrics, Universita` “Federico II” di Napoli, 80131 Naples, Italy. Tel.: +39 0817462908. E-mail address: [email protected] (F. Raimondi). 0378-3782/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved.
© 2012 Elsevier Ireland Ltd. All rights reserved.
strongly limited by skin pigmentation. More recently, a new generation of bilirubinometers has overcome the problem. At present, the most widely used devices are BiliCheck and JM-103, which use different algorithms but somewhat similar principles of operation. BiliCheck (SpectRX, Norcross, GA) scans the whole spectrum of visible light and automatically subtracts the beam reflected by confounding factors like haemoglobin, dermal thickness or melanin; it isolates the absorption of light due to bilirubin in the capillary bed and subcutaneous tissue, therefore calculating the concentration of bilirubin; it needs to be calibrated using a disposable “BiliCal” before each measurement. JM-103 (Draeger Medical Systems, Inc., Telford, PA) uses two wavelengths and a dual optical path system. The principle of operation includes the formation of two beams, one of which reaches only the shallow areas of the subcutaneous tissue, while the other penetrates the deeper layers. The differences between the optical densities are detected by blue and green photocells. Measurement of bilirubin primarily accumulated in the deeper subcutaneous tissue should decrease the influence of other pigments in the skin, such as melanin and haemoglobin. JM-103 does not need to be calibrated with a disposable item before each determination [3]. Whatever the device, transcutaneous bilirubinometry measures the bilirubin in the subcutaneous tissue and therefore TcB is related to serum bilirubin but it is NOT the same value. The available literature demonstrated excellent linear correlation between TSB and TcB for these two devices in term and late preterm neonates. In particular JM-103 and BiliCheck reach almost a 100% sensitivity to predict hyperbilirubinaemia up to a TcB value of 11 mg/dl [4,5]. It is therefore often recommended to perform a TSB when TcB is higher than 11 mg/dl. In the past few years, specific nomograms for transcutaneous bilirubin have been published. Maisels et al. published a nomogram based on 3984 healthy North American neonates (GA ≥35 weeks) from 6 to 96 h of age using the JM-103; they found that infants requiring additional monitoring were
S26
L. Capasso et al. / Early Human Development 88S2 (2012) S25–S26
those whose TcB concentrations were ≥95th percentile, i.e., those whose TcB is increasing at a rate >0.22 mg/dl/h in the first 24 hours, >0.15 mg/dl/h between 24 and 48 h, or >0.06 mg/dl/h after 48 h [6]. Furthermore, combining pre-discharge TcB levels with two clinical risk factors such as gestational age and exclusive breastfeeding, significantly improved the prediction of subsequent hyperbilirubinaemia [7]. Recently, an hour-specific nomogram for the Italian population was developed; the 75th percentile of this TcB nomogram used as a cut off value efficiently excludes any subsequent severe hyperbilirubinaemia from 48 h of life ahead [8]. Definitely, transcutaneous bilirubinometry in term and late preterm infants, as reassumed by Schumacher, seems “to have useful diagnostic accuracy when used as a mass-screening device. It can help establish a risk estimate and answer the question: – Should I worry about this infant? –. If this is the way one practices, then this might be the right job for the tool” [9]. 3. Transcutaneous bilirubinometers and ethnicity As already mentioned, accuracy of the first generation of bilirubinometers was influenced by skin pigmentation, an issue that had to be solved for practical use in most multi-racial societies. Furthermore, De Luca et al., in a systematic review of population differences and analysis of bilirubin kinetics, confirmed that hyperbilirubinaemia trends and kinetics are different among ethnic groups [10]. Though the majority of published studies validated TcB meters on Caucasian neonates, some authors investigated these technologies also on mostly homogeneous populations of Asian, African and Hispanic infants. Sanpavat et al. [11] compared BiliCheck vs JM-103 on Thai neonates and found similar correlation of the two devices with TSB but a better accuracy for JM-103. Engle et al. [12] showed a lower sensitivity of BiliCheck on Hispanic compared with nonHispanic neonates; in order to have an almost 100% sensitivity in predicting a TSB >10 mg/dl and >15 mg/dl, a TcB cut off of 8 and 9 mg/dl had to be chosen. This was probably due to the higher incidence of hyperbilirubinaemia in the Hispanic population and to the tendency of TcB to underestimate TSB. In African-American infants, the correlation between BiliChek TcB and HPLC measurements of the TSB was as good as in Caucasian infants [13]. To provide useful clinical information, our group (Raimondi et al., submitted) compared the performance of three transcutaneous bilirubinometers – BiliCheck, JM-103 and BiliMed – on a Caucasian and African population of term and late preterm neonates. We also provided the first direct comparison of Bilicheck and JM-103 in a mixed African and Caucasian population, as previous authors investigated these technologies on Asian or Caucasian infants. We showed that BiliCheck and JM-103 but not BiliMed are reliable screening tools for moderate neonatal hyperbilirubinaemia. Considering the whole population we demonstrated the poor accuracy of BiliMed compared to BiliCheck and JM-103, which had a similar performance; within the African subgroup, BiliMed lost further ground to JM-103 and BiliCheck. 4. Transcutaneous bilirubinometer and preterm infants Few data are available on very preterm neonates. Schmidt et al. [14] demonstrated a sensitivity >90% using a cut off of
6 mg/dl of TcB to predict a TSB >8 mg/dl in preterm >29 wk of GA but the sensitivity decreased for preterm <29 wk of GA. A study on 340 Italian preterm infants between 30 and 36 weeks showed that BiliCheck has a good reliability although not as good as in healthy term babies, and its tendency to overestimate suggests its use only for screening purposes. The authors, considering the whole time for serum bilirubin measurement, showed that transcutaneous bilirubinometry is a faster but more expensive technique with a cost of about 5 euro/ measurement. Nevertheless, using BiliCheck as a screening device they could safely avoid 58–79% of blood samples and this would allow a cost reduction of 1555–2120 euro/year [15]. 5. Conclusions There is today considerable evidence to recommend transcutaneous bilirubin measurement as a non-invasive technology that spares working time to nurses and blood and pain to neonates. Transcutaneous bilirubin measurement results should not be confused with bilirubin concentration in the serum. The former can (and perhaps should) be used as a safe surrogate in term and late preterm neonates older than 48 h for moderate hyperbilirubinaemia. Conflict of interest statement The authors have no conflicts of interest to declare. References 1. Raimondi F, Maffucci R, Milite P, Ferrara T, Borrelli AC, Sodano A, et al. Why should we care about neonatal hyperbilirubinemia in 2011? J Matern Fetal Neonatal Med 2011;24(Suppl 1):83–84. 2. AAP. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004;114;297–316. 3. Maisels MJ. Historical perspectives: transcutaneous bilirubinometry. Neoreviews 2006;7;e217–25. 4. Maisels MJ, Ostrea EM Jr, Touch S, Clune SE, Cepeda E, Kring E, et al. Evaluation of a new transcutaneous bilirubinometer. Pediatrics 2004;113;1628. 5. Rubaltelli F, Gourley GR, Loskamp N, Modi N, Roth-Kleiner M, Sender A, et al. Transcutaneous bilirubin measurement: a multicenter evaluation of a new device. Pediatrics 2001;107;1264. 6. Maisels MJ, Kring E. Transcutaneous bilirubin level in the first 96 hours in a normal newborn population of ≥35 weeks’ gestation. Pediatrics 2006;117: 1169–73. 7. Maisels MJ, Deridder JM, Kring EA, Balasubramaniam M. Routine transcutaneous bilirubin measurements combined with clinical risk factors improve the prediction of subsequent hyperbilirubinemia. J Perinatol 2009;29(9):612–7 8. Romagnoli C, Tiberi E, Barone G, De Curtis M, Regoli D, Paolillo P, et al. Validation of transcutaneous bilirubin nomogram in identifying neonates not at risk of hyperbilirubinaemia: a prospective, observational, multicenter study. Early Hum Dev 2012;88(1):51–5. 9. Schumacher RE. Transcutaneous bilirubinometry and diagnostic tests: “the right job for the tool”. Pediatrics 2002;110;407. 10. De Luca D, Jackson GL, Tridente A, Carnielli VP, Engle WD. Transcutaneous bilirubin nomograms. Arch Pediatr Adolesc Med 2009;163(11):1054–9. 11. Sanpavat S, Nuchprayoon I. Comparison of two transcutaneous bilirubinometers – Minolta AirShields Jaundice Meter JM103 and Spectrx Bilicheck – in Thai neonates. Southeast Asian J Trop Med Public Health 2005;36(6):1533–7. 12. Engle WD, Jackson GL, Sendelbach D, Manning D, Frawley WH. Assessment of transcutaneous device in the evaluation of neonatal hyperbilirubinemia in a primarily Hispanic population. Pediatrics 2002;110(1 Pt 1):61–7. 13. Bhutani V, Gourley GR, Adler S, Kreamer B, Dalman C, Johnson LH. Noninvasive measurement of total serum bilirubin in a multiracial predischarge newborn population to assess the risk of severe hyperbilirubinemia. Pediatrics 2000;106: e17. 14. Schmidt ET, Wheeler CA, Jackson GL, Engle WD. Evaluation of transcutaneous bilirubinometry in preterm neonates. J Perinatol 2009;29:564–9. 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;83:313–7.
Contents lists available at ScienceDirect
Early Human Development j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / e a r l h u m d ev
Is it worthwhile using a transcutaneous bilirubinometer in the nursery? L. Capasso, C. Parrella, A.C. Borrelli, R. Maffucci, P. Milite, A. Sodano, T. Ferrara, F. Raimondi* Division of Neonatology, Department of Pediatrics, Universit` a “Federico II” di Napoli, Naples, Italy
article info
summary
Keywords: Hyperbilirubinaemia Jaundice Neonate Preterm Bilirubin BiliCheck
Jaundice is a potential threat to neonatal health and/or life. The advantages and limitations of transcutaneous determination of bilirubin concentration and current devices are briefly discussed in this paper.
1. Introduction Hyperbilirubinaemia is one of the most common diagnoses in the neonatal period. Extreme neonatal hyperbilirubinaemia, a potential cause of mortality or of permanent neurological damage (i.e. kernicterus), is a rare but apparently resurgent condition in developed countries [1]. In 2004 the American Academy of Pediatrics (AAP) has revised the official guidelines for management of hyperbilirubinaemia in neonates with gestational age (GA) ≥35 weeks with the declared intent to prevent kernicterus. The strategy of AAP guidelines includes universal bilirubin screening before hospital discharge and planning of a tailored follow-up. In order to properly assess the risk of significant hyperbilirubinaemia, the AAP recommends to measure either the serum bilirubin with a spectrophotometric method (TSB) or the transcutaneous bilirubin (TcB); both values should be plotted on an appropriate nomogram that takes birthweight, post-natal age and a list of risk factors into account [2]. TcB is advantageous over TSB as it spares pain and blood to the baby and time to the nurse. TcB is a powerful tool to clinically screen relevant neonatal hyperbilirubinaemia although several issues remain open. 2. Transcutaneous bilirubinometer in term and late preterm neonates In term or late preterm neonates, several TcB devices have been individually validated versus spectrophotometric or high pressure liquid chromatography (HPLC) determination of TSB. The first generation of bilirubinometers showed an accuracy * Corresponding author. Francesco Raimondi MD PhD. Assistant Professor of Pediatrics, Division of Neonatology, Department of Pediatrics, Universita` “Federico II” di Napoli, 80131 Naples, Italy. Tel.: +39 0817462908. E-mail address: [email protected] (F. Raimondi). 0378-3782/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved.
© 2012 Elsevier Ireland Ltd. All rights reserved.
strongly limited by skin pigmentation. More recently, a new generation of bilirubinometers has overcome the problem. At present, the most widely used devices are BiliCheck and JM-103, which use different algorithms but somewhat similar principles of operation. BiliCheck (SpectRX, Norcross, GA) scans the whole spectrum of visible light and automatically subtracts the beam reflected by confounding factors like haemoglobin, dermal thickness or melanin; it isolates the absorption of light due to bilirubin in the capillary bed and subcutaneous tissue, therefore calculating the concentration of bilirubin; it needs to be calibrated using a disposable “BiliCal” before each measurement. JM-103 (Draeger Medical Systems, Inc., Telford, PA) uses two wavelengths and a dual optical path system. The principle of operation includes the formation of two beams, one of which reaches only the shallow areas of the subcutaneous tissue, while the other penetrates the deeper layers. The differences between the optical densities are detected by blue and green photocells. Measurement of bilirubin primarily accumulated in the deeper subcutaneous tissue should decrease the influence of other pigments in the skin, such as melanin and haemoglobin. JM-103 does not need to be calibrated with a disposable item before each determination [3]. Whatever the device, transcutaneous bilirubinometry measures the bilirubin in the subcutaneous tissue and therefore TcB is related to serum bilirubin but it is NOT the same value. The available literature demonstrated excellent linear correlation between TSB and TcB for these two devices in term and late preterm neonates. In particular JM-103 and BiliCheck reach almost a 100% sensitivity to predict hyperbilirubinaemia up to a TcB value of 11 mg/dl [4,5]. It is therefore often recommended to perform a TSB when TcB is higher than 11 mg/dl. In the past few years, specific nomograms for transcutaneous bilirubin have been published. Maisels et al. published a nomogram based on 3984 healthy North American neonates (GA ≥35 weeks) from 6 to 96 h of age using the JM-103; they found that infants requiring additional monitoring were
S26
L. Capasso et al. / Early Human Development 88S2 (2012) S25–S26
those whose TcB concentrations were ≥95th percentile, i.e., those whose TcB is increasing at a rate >0.22 mg/dl/h in the first 24 hours, >0.15 mg/dl/h between 24 and 48 h, or >0.06 mg/dl/h after 48 h [6]. Furthermore, combining pre-discharge TcB levels with two clinical risk factors such as gestational age and exclusive breastfeeding, significantly improved the prediction of subsequent hyperbilirubinaemia [7]. Recently, an hour-specific nomogram for the Italian population was developed; the 75th percentile of this TcB nomogram used as a cut off value efficiently excludes any subsequent severe hyperbilirubinaemia from 48 h of life ahead [8]. Definitely, transcutaneous bilirubinometry in term and late preterm infants, as reassumed by Schumacher, seems “to have useful diagnostic accuracy when used as a mass-screening device. It can help establish a risk estimate and answer the question: – Should I worry about this infant? –. If this is the way one practices, then this might be the right job for the tool” [9]. 3. Transcutaneous bilirubinometers and ethnicity As already mentioned, accuracy of the first generation of bilirubinometers was influenced by skin pigmentation, an issue that had to be solved for practical use in most multi-racial societies. Furthermore, De Luca et al., in a systematic review of population differences and analysis of bilirubin kinetics, confirmed that hyperbilirubinaemia trends and kinetics are different among ethnic groups [10]. Though the majority of published studies validated TcB meters on Caucasian neonates, some authors investigated these technologies also on mostly homogeneous populations of Asian, African and Hispanic infants. Sanpavat et al. [11] compared BiliCheck vs JM-103 on Thai neonates and found similar correlation of the two devices with TSB but a better accuracy for JM-103. Engle et al. [12] showed a lower sensitivity of BiliCheck on Hispanic compared with nonHispanic neonates; in order to have an almost 100% sensitivity in predicting a TSB >10 mg/dl and >15 mg/dl, a TcB cut off of 8 and 9 mg/dl had to be chosen. This was probably due to the higher incidence of hyperbilirubinaemia in the Hispanic population and to the tendency of TcB to underestimate TSB. In African-American infants, the correlation between BiliChek TcB and HPLC measurements of the TSB was as good as in Caucasian infants [13]. To provide useful clinical information, our group (Raimondi et al., submitted) compared the performance of three transcutaneous bilirubinometers – BiliCheck, JM-103 and BiliMed – on a Caucasian and African population of term and late preterm neonates. We also provided the first direct comparison of Bilicheck and JM-103 in a mixed African and Caucasian population, as previous authors investigated these technologies on Asian or Caucasian infants. We showed that BiliCheck and JM-103 but not BiliMed are reliable screening tools for moderate neonatal hyperbilirubinaemia. Considering the whole population we demonstrated the poor accuracy of BiliMed compared to BiliCheck and JM-103, which had a similar performance; within the African subgroup, BiliMed lost further ground to JM-103 and BiliCheck. 4. Transcutaneous bilirubinometer and preterm infants Few data are available on very preterm neonates. Schmidt et al. [14] demonstrated a sensitivity >90% using a cut off of
6 mg/dl of TcB to predict a TSB >8 mg/dl in preterm >29 wk of GA but the sensitivity decreased for preterm <29 wk of GA. A study on 340 Italian preterm infants between 30 and 36 weeks showed that BiliCheck has a good reliability although not as good as in healthy term babies, and its tendency to overestimate suggests its use only for screening purposes. The authors, considering the whole time for serum bilirubin measurement, showed that transcutaneous bilirubinometry is a faster but more expensive technique with a cost of about 5 euro/ measurement. Nevertheless, using BiliCheck as a screening device they could safely avoid 58–79% of blood samples and this would allow a cost reduction of 1555–2120 euro/year [15]. 5. Conclusions There is today considerable evidence to recommend transcutaneous bilirubin measurement as a non-invasive technology that spares working time to nurses and blood and pain to neonates. Transcutaneous bilirubin measurement results should not be confused with bilirubin concentration in the serum. The former can (and perhaps should) be used as a safe surrogate in term and late preterm neonates older than 48 h for moderate hyperbilirubinaemia. Conflict of interest statement The authors have no conflicts of interest to declare. References 1. Raimondi F, Maffucci R, Milite P, Ferrara T, Borrelli AC, Sodano A, et al. Why should we care about neonatal hyperbilirubinemia in 2011? J Matern Fetal Neonatal Med 2011;24(Suppl 1):83–84. 2. AAP. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004;114;297–316. 3. Maisels MJ. Historical perspectives: transcutaneous bilirubinometry. Neoreviews 2006;7;e217–25. 4. Maisels MJ, Ostrea EM Jr, Touch S, Clune SE, Cepeda E, Kring E, et al. Evaluation of a new transcutaneous bilirubinometer. Pediatrics 2004;113;1628. 5. Rubaltelli F, Gourley GR, Loskamp N, Modi N, Roth-Kleiner M, Sender A, et al. Transcutaneous bilirubin measurement: a multicenter evaluation of a new device. Pediatrics 2001;107;1264. 6. Maisels MJ, Kring E. Transcutaneous bilirubin level in the first 96 hours in a normal newborn population of ≥35 weeks’ gestation. Pediatrics 2006;117: 1169–73. 7. Maisels MJ, Deridder JM, Kring EA, Balasubramaniam M. Routine transcutaneous bilirubin measurements combined with clinical risk factors improve the prediction of subsequent hyperbilirubinemia. J Perinatol 2009;29(9):612–7 8. Romagnoli C, Tiberi E, Barone G, De Curtis M, Regoli D, Paolillo P, et al. Validation of transcutaneous bilirubin nomogram in identifying neonates not at risk of hyperbilirubinaemia: a prospective, observational, multicenter study. Early Hum Dev 2012;88(1):51–5. 9. Schumacher RE. Transcutaneous bilirubinometry and diagnostic tests: “the right job for the tool”. Pediatrics 2002;110;407. 10. De Luca D, Jackson GL, Tridente A, Carnielli VP, Engle WD. Transcutaneous bilirubin nomograms. Arch Pediatr Adolesc Med 2009;163(11):1054–9. 11. Sanpavat S, Nuchprayoon I. Comparison of two transcutaneous bilirubinometers – Minolta AirShields Jaundice Meter JM103 and Spectrx Bilicheck – in Thai neonates. Southeast Asian J Trop Med Public Health 2005;36(6):1533–7. 12. Engle WD, Jackson GL, Sendelbach D, Manning D, Frawley WH. Assessment of transcutaneous device in the evaluation of neonatal hyperbilirubinemia in a primarily Hispanic population. Pediatrics 2002;110(1 Pt 1):61–7. 13. Bhutani V, Gourley GR, Adler S, Kreamer B, Dalman C, Johnson LH. Noninvasive measurement of total serum bilirubin in a multiracial predischarge newborn population to assess the risk of severe hyperbilirubinemia. Pediatrics 2000;106: e17. 14. Schmidt ET, Wheeler CA, Jackson GL, Engle WD. Evaluation of transcutaneous bilirubinometry in preterm neonates. J Perinatol 2009;29:564–9. 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;83:313–7.