Severe neonatal hyperbilirubinemia (SNH) is a serious condition that occurs worldwide. Timely recognition with bilirubin determination is key in the management of SNH. Visual assessment of jaundice is unreliable. Fortunately, transcutaneous bilirubin measurement for screening newborn infants is routinely available in many hospitals and outpatient settings. Despite a few limitations, the use of transcutaneous devices facilitates early recognition and appropriate management of neonatal jaundice. Unfortunately, however, advanced and often costly screening modalities are not accessible to everyone, while there is an urgent need for inexpensive yet accurate instruments to assess total serum bilirubin (TSB). In the near future, novel icterometers, and in particular optical bilirubin estimates obtained with a smartphone camera and processed with a smartphone application (app), seem promising methods for screening for SNH. If proven reliable, these methods may empower outpatient health workers as well as parents at home to detect jaundice using a simple portable device. Successful implementation of ubiquitous bilirubin screening may contribute substantially to the reduction of the worldwide burden of SNH. The benefits of non-invasive bilirubin screening notwithstanding, any bilirubin determination obtained through non-invasive screening must be confirmed by a diagnostic method before treatment. IMPACT: Key message: Screening methods for neonatal hyperbilirubinemia facilitate early recognition and timely treatment of severe neonatal hyperbilirubinemia (SNH). Any bilirubin screening result obtained must be confirmed by a diagnostic method. What does this article add to the existing literature? Data on optical bilirubin estimation are summarized. Niche research strategies for prevention of SNH are presented. Impact: Transcutaneous screening for neonatal hyperbilirubinemia contributes to the prevention of SNH. A smartphone application with optical bilirubin estimation seems a promising low-cost screening method, especially in low-resource settings or at home.

Beatrix Children's Hospital University Medical Center Groningen Groningen The Netherlands

Bilimetrix s r l Trieste Italy

Clinical Chemistry and Laboratory Medicine Leiden University Medical Center Leiden The Netherlands

Dutch Foundation for Quality Assessment in Medical Laboratories Nijmegen The Netherlands

Institute of Medical Biochemistry and Laboratory Diagnostics and 4th Department of Internal Medicine 1st Faculty of Medicine Charles University Prague Czech Republic

Italian Liver Foundation Trieste Italy

MCA Laboratory Queen Beatrix Hospital Winterswijk The Netherlands

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Bhutani, V. K. et al. Predischarge screening for severe neonatal hyperbilirubinemia identifies infants who need phototherapy. J. Pediatr. 162, 477–82.e1 (2013). PubMed DOI PMC

Bhutani, V. K. et al. Neonatal hyperbilirubinemia and Rhesus disease of the newborn: incidence and impairment estimates for 2010 at regional and global levels. Pediatr. Res. 74, 86–100 (2013). PubMed DOI PMC

Donneborg, M.L., Hansen, B.M., Vandborg, P.K., Rodrigo-Domingo, M., Ebbesen, F. Extreme neonatal hyperbilirubinemia and kernicterus spectrum disorder in Denmark during the years 2000–2015. J Perinatol. 40, 194–202 (2020).

Greco, C. et al. Neonatal jaundice in low- and middle-income countries: lessons and future directions from the 2015 Don Ostrow trieste yellow retreat. Neonatology 110, 172–80 (2016). PubMed DOI PMC

Bang, A. T., Bang, R. A., Baitule, S., Deshmukh, M. & Reddy, M. H. Burden of morbidities and the unmet need for health care in rural neonates – a prospective observational study in Gadchiroli, India. Indian Pediatr. 38, 952–65 (2001). PubMed PMC

Ngashangva, L., Bachu, V. & Goswami, P. Development of new methods for determination of bilirubin. J. Pharm. Biomed. Anal. 162, 272–85 (2019). PubMed DOI PMC

Hansen, T. W. R. Pioneers in the scientific study of neonatal jaundice and kernicterus. Pediatrics 106, e15 (2000). PubMed DOI PMC

Kramer, L. I. Advancement of dermal Icterus in the jaundiced newborn. Am. J. Dis. Child 118, 454–8 (1969). PubMed PMC

Davidson, L. T., Merritt, K. K. & Weech, A. A. Hyperbilirubinemia in the newborn. Am. J. Dis. Child 61, 958–80 (1941).

Moyer, V. A., Ahn, C. & Sneed, S. Accuracy of clinical judgment in neonatal jaundice. Arch. Pediatr. Adolesc. Med 154, 391–4 (2000). PubMed DOI PMC

Riskin, A., Tamir, A., Kugelman, A., Hemo, M. & Bader, D. Is visual assessment of jaundice reliable as a screening tool to detect SNH? J. Pediatr. 152, 782–7, e1–2 (2008). PubMed DOI PMC

Keren, R., Tremont, K., Luan, X. & Cnaan, A. Visual assessment of jaundice in term and late preterm infants. Arch. Dis. Child Fetal Neonatal Ed. 94, F317–22 (2009). PubMed DOI PMC

Allen, F. H. Jr Early jaundice in the newborn; aids to detection. N. Engl. J. Med 258, 1302–3 (1958). PubMed DOI PMC

Gosset, I. H. A perspex icterometer for neonates. Lancet 1, 87–88 (1960). PubMed DOI PMC

Schumacher, R. E., Thornbery, J. M. & Gutcher, G. R. Transcutaneous bilirubinometry: a comparison of old and new methods. Pediatrics 76, 10–4 (1985). PubMed PMC

Bilgen, H., Ince, Z., Ozek, E., Bekiroglu, N. & Ors, R. Transcutaneous measurement of hyperbilirubinaemia: comparison of the Minolta jaundice meter and the Ingram icterometer. Ann. Trop. Paediatr. 18, 325–8 (1998). PubMed DOI PMC

NICE National Institute for Health and Care Excellence. Neonatal jaundice 2010. https://www.nice.org.uk/guidance/cg98/evidence/full-guideline-245411821 .

Olusanya, B. O., Slusher, T. M., Imosemi, D. O. & Emokpae, A. A. Maternal detection of neonatal jaundice during birth hospitalization using a novel two-color icterometer. PLoS ONE 12, e0183882 (2017). PubMed DOI PMC

Lee, A. C. et al. A novel icterometer for hyperbilirubinemia screening in low-resource settings. Pediatrics 143, e20182039 (2019). PubMed DOI PMC

Hannemann, R. E., DeWitt, D. P. & Wiechel, J. F. Neonatal serum bilirubin from skin reflectance. Pediatr. Res 12, 207–10 (1978). PubMed DOI PMC

Peevy, K. H. et al. Estimation of serum bilirubin by spectral reflectance of the skin, Duke University Medical Center. Pediatr. Res 12, 532 (1978). DOI

Yamanouchi, I., Yamauchi, Y. & Igarashi, I. Transcutaneous bilirubinometry: preliminary studies of noninvasive transcutaneous bilirubin meter in the Okayama National Hospital. Pediatrics 65, 195–202 (1980). PubMed DOI PMC

https://www.draeger.com/en_me/Hospital/Products/Thermoregulation-and-Jaundice-Management/Jaundice-Management-and-Phototherapy/Jaundice-Screening/Jaundice-Meter-JM-105#instructions_for_use Last accessed at May 23

https://philipsproductcontent.blob.core.windows.net/assets/20170616/f722df04b6ce4e7dad79a7940147347a.pdf Last accessed on May 23

Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 114, 297–316 (2004). DOI

Van den Esker-Jonker, B., Den Boer, L., Pepping, R. M. C. & Bekhof, J. Transcutaneous bilirubinometry in jaundiced neonates: a randomized controlled trial. Pediatrics 138, e20162414 (2016). PubMed DOI PMC

Chokemungmeepisarn, P., Tantiprabha, W., Kosarat, S. & Manopunya, S. Accuracy of the BilicareTM transcutaneous bilirubinometer as the predischarge screening tool for significant hyperbilirubinemia in healthy term and late preterm neonates. J. Matern Fetal Neonatal Med 33, 57–61 (2020). PubMed DOI PMC

Cucuy, M., Juster-Reicher, A., Flidel, O. & Shinwell, E. Correlation between transcutaneous and serum bilirubin in preterm infants before, during, and after phototherapy. J. Matern. Fetal Neonatal. Med. 31, 1323–6 (2018). PubMed DOI PMC

Arman, D., Topcuoğlu, S., Gürsoy, T., Ovalı, F. & Karatekin, G. The accuracy of transcutaneous bilirubinometry in preterm infants. J. Perinatol. 40, 212–8 (2020). PubMed DOI PMC

Nahar, N. et al. Comparison of Serum Bilirubin with Transcutaneous Bilirubinometry in Late Preterm and Term Newborn. Mymensingh Med. J. 26, 621–7 (2017). PubMed PMC

Johnson, S. M. et al. Validation of transcutaneous bilirubinometry during phototherapy for detection and monitoring of neonatal jaundice in a low-income setting. Paediatr. Int. Child Health 40, 25–29 (2020). PubMed DOI PMC

Aranda Cazón, C., Torrubia Doredo, B., Álvarez López, C., De Gracia Hils, Y. & Cuadrado Cenzual, M. C. Determining the correlation and accuracy of three methods of measuring neonatal bilirubin concentration: serum, capillary and transcutaneous bilirubin. Biomed. J. Sci. Tech. Res. 1, 722–6 (2017).

Grohmann, K. et al. Bilirubin measurement for neonates: comparison of 9 frequently used methods. Pediatrics 117, 1174–83 (2006). PubMed DOI PMC

Hemmati, F. & Rad, N. A. K. The value of Bilicheck® as a screening tool for neonatal jaundice in the South of Iran. Iran. J. Med Sci. 38, 122–8 (2013). PubMed PMC

Mussavi, M., Niknafs, P. & Bijari, B. Determining the correlation and accuracy of three methods of measuring neonatal bilirubin concentration. Iran. J. Pediatr. 23, 333–9 (2013). PubMed PMC

Ozkan, H., Oren, H., Duman, N. & Duman, M. Dermal bilirubin kinetics during phototherapy in term neonates. Acta Paediatr. 92, 577–81 (2003). PubMed DOI PMC

Starowicz, O., Edwards, P., Schmidt, P. & Birch, P. Evaluation of the Kejian KJ-8000 bilirubinometer in an Australian setting. J. Paediatr. Child Health 56, 283–8 (2020). PubMed DOI

Hulzebos, C. V., Vader-van Imhoff, D. E., Bos, A. F. & Dijk, P. H. Should transcutaneous bilirubin be measured in preterm infants receiving phototherapy? The relationship between transcutaneous and total serum bilirubin in preterm infants with and without phototherapy. PLoS ONE 14, e0218131 (2019). PubMed DOI PMC

Neocleous, C. et al. A comparison between transcutaneous and total serum bilirubin in healthy-term Greek neonates with clinical jaundice. Prague Med. Rep. 115, 33–42 (2014). PubMed DOI

Taylor, J. A. et al. Discrepancies between transcutaneous and serum bilirubin measurements. Pediatrics 135, 224–31 (2015). PubMed DOI PMC

Olusanya, B. O. & Emokpae, A. A. Use of transcutaneous bilirubin to determine the need for phototherapy in resource-limited settings. Neonatology 111, 324–30 (2017). PubMed DOI PMC

Maisels, M. J. Transcutaneous bilirubin measurement: does it work in the real world? Pediatrics 135, 364–6 (2015). PubMed DOI PMC

Rodríguez-Capote, K., Kim, K., Paes, B., Turner, D. & Grey, V. Clinical implication of the difference between transcutaneous bilirubinometry and total serum bilirubin for the classification of newborns at risk of hyperbilirubinemia. Clin. Biochem. 42, 176–9 (2009). PubMed DOI PMC

Maisels, M. J., Bhutani, V. K., Bogen, D., Newman, T. B., Stark, A. R. & Watchko, J. F. Hyperbilirubinemia in the newborn infant > or = 35 weeks’ gestation: an update with clarifications. Pediatrics 124, 1193–8 (2009). PubMed DOI PMC

Maisels, M. J., Coffey, M. P. & Kring, E. Transcutaneous bilirubin levels in newborns <35 weeks’ gestation. J. Perinatol. 35, 739–44 (2015). PubMed DOI PMC

Nagar, G., Vandermeer, B., Campbell, S. & Kumar, M. Reliability of transcutaneous bilirubin devices in preterm infants: a systematic review. Pediatrics 132, 871–81 (2013). PubMed DOI PMC

Briscoe, L., Clark, S. & Yoxall, C. W. Can transcutaneous bilirubinometry reduce the need for blood tests in jaundiced full term babies? Arch. Dis. Child Fetal Neonatal Ed. 86, F190–2 (2002). PubMed DOI PMC

De Luca, D., Jackson, G. L., Tridente, A., Carnielli, V. P. & Engle, W. D. Transcutaneous bilirubin nomograms: a systematic review of population differences and analysis of bilirubin kinetics. Arch. Pediatr. Adolesc. Med 163, 1054–9 (2009). PubMed PMC

Yu, Z. B., Han, S. P. & Chen, C. Bilirubin nomograms for identification of neonatal hyperbilirubinemia in healthy term and late-preterm infants: a systematic review and meta-analysis. World J. Pediatr. 10, 211–8 (2014). PubMed DOI PMC

Bosschaart, N. et al. Limitations and opportunities of transcutaneous bilirubin measurements. Pediatrics 129, 689–94 (2012). PubMed DOI PMC

Baker, C., et al. BME 272 NCIIA Project Proposal Neonatal Jaundice. (2012).

Patel, P. ClikJaundice: using mobile technology to detect yellow in newborns. http://thealternative.in/social-business/clickjaundiceusing-the-phone-to-prevent-jaundice-in-newborns/ . (2013).

De Greef, L., et al. BiliCam: using mobile phones to monitor newborn jaundice. In: Proceedings of the 2014 ACM International Joint Conference on Pervasive and Ubiquitous Computing (UbiComp ’14); 331–342 (Seattle, WA, 2014).

Leung, T. S. et al. Screening neonatal jaundice based on the sclera color of the eye using digital photography. Biomed. Opt. Express 6, 4529–38 (2015). PubMed DOI PMC

Rong, Z. H. et al. Evaluation of an automatic image-based screening technique for neonatal hyperbilirubinemia. Zhonghua Er Ke Za Zhi 54, 597–600 (2016). PubMed PMC

Aydin, M., Hardalac, F., Ural, B. & Karap, S. Neonatal jaundice detection system. J. Med. Syst. 40, 166 (2016). PubMed DOI PMC

Swarna, S., Pasupathy, S., Chinnasami, B., Manasa, D. N. & Ramraj, B. The smart phone study: assessing the reliability and accuracy of neonatal jaundice measurement using smart phone application. Int. J. Contemp. Pediatr. 5, 285–9 (2017). DOI

Taylor, J. A. et al. Use of a smartphone app to assess neonatal jaundice. Pediatrics 140, e20170312 (2017). PubMed DOI PMC

Munkholm, S. B., Krøgholt, T., Ebbesen, F., Szecsi, P. B. & Kristensen, S. R. The smartphone camera as a potential method for transcutaneous bilirubin measurement. PLoS ONE 13, e0197938 (2018). PubMed DOI PMC

Leartveravat, S. Transcutaneous bilirubin measurement in full term neonate by digital camera. Med J Srisaket Surin Buriram Hospit. 24, 108–18 (2009).

Sufian, A. T., Jones, G. R., Shabeer, H. M., Elzagzoug, E. Y. & Spencer, J. W. Chromatic techniques for in vivo monitoring jaundice in neonate tissues. Physiol. Meas. 39, 095004 (2018). PubMed DOI PMC

Rizvi, M. R., Alaskar, F. M., Albaradie, R. S., Rizvi, N. F. & Al-Abdulwahab, K. A novel non-invasive technique of measuring bilirubin levels using BiliCapture. Oman Med J. 34, 26–33 (2019). PubMed DOI PMC

Leung, T. S., Outlaw, F., MacDonald, L. W. & Meek, J. Jaundice Eye Color Index (JECI): quantifying the yellowness of the sclera in jaundiced neonates with digital photography. Biomed. Opt. Express 10, 1250–6 (2019). PubMed DOI PMC

Padidar, P. et al. Detection of neonatal jaundice by using an android OS-based smartphone application. Iran. J. Pediatr. 29, e84397 (2019).

Outlaw, F. et al. Smartphone screening for neonatal jaundice via ambient-subtracted sclera chromaticity. PLoS ONE 15, e0216970 (2020). PubMed DOI PMC

Aune, A., Vartdal, G., Bergseng, H., Randeberg, L. L. & Darj, E. Bilirubin estimates from smartphone images of newborn infants’ skin correlated highly to serum bilirubin levels. Acta Paediatr. 1–7 (2020).

Watchko, J. F. Maternal instruction on neonatal jaundice: what can we learn from the Stop Kernicterus in Nigeria (SKIN) experience? J. Pediatr. 221, 7–8 (2020). PubMed DOI PMC

Wennberg, R. P. et al. Maternal instruction about jaundice and the incidence of acute bilirubin encephalopathy in Nigeria. J. Pediatr. 221, 47–54 (2020). PubMed DOI PMC

Inamori, G. et al. Neonatal wearable device for colorimetry-based real-time detection of jaundice with simultaneous sensing of vitals. Sci. Adv. 7, eabe3793 (2021). PubMed DOI PMC