Screening methods for neonatal hyperbilirubinemia:benefits, limitations, requirements, and novel developments

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. ImpactKey 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.Afdeling Klinische Chemie en Laboratoriumgeneeskunde (AKCL

Screening for neonatal jaundice with a smartphone

A method to screen for jaundice in neonates using a digital image of the sclera is proposed. The RGB pixel values from a raw format image are used to derive an estimate for the total serum bilirubin (TSB). A study at UCH Neonatal Unit found a correlation of r=0.71 (p<0.01) between measured TSB and TSB estimated by this method. The advantages of using a smartphone camera as a mobile screening device are discussed

Smartphone screening for neonatal jaundice via ambient-subtracted sclera chromaticity

Jaundice is a major cause of mortality and morbidity in the newborn. Globally, early identification and home monitoring are significant challenges in reducing the incidence of jaundice-related neurological damage. Smartphone cameras are promising as colour-based screening tools as they are low-cost, objective and ubiquitous. We propose a novel smartphone method to screen for neonatal jaundice by imaging the sclera. It does not rely on colour calibration cards or accessories, which may facilitate its adoption at scale and in less economically developed regions. Our approach is to explicitly address three confounding factors in relating colour to jaundice: (1) skin pigmentation, (2) ambient light, and (3) camera spectral response. (1) The variation in skin pigmentation is avoided by imaging the sclera. (2) With the smartphone screen acting as an illuminating flash, a flash/ no-flash image pair is captured using the front-facing camera. The contribution of ambient light is subtracted. (3) In principle, this permits a device- and ambient-independent measure of sclera chromaticity following a one-time calibration. We introduce the concept of Scleral-Conjunctival Bilirubin (SCB), in analogy with Transcutaneous Bilirubin (TcB). The scleral chromaticity is mapped to an SCB value. A pilot study was conducted in the UCL Hospital Neonatal Care Unit (n = 37). Neonates were imaged using a specially developed app concurrently with having a blood test for total serum bilirubin (TSB). The better of two models for SCB based on ambient-subtracted sclera chromaticity achieved r = 0.75 (p250μmol/L (area under receiver operating characteristic curve, AUROC, 0.86), and 92% (specificity 67%) in identifying newborns with TSB>205μmol/L (AUROC 0.85). These results are comparable to modern transcutaneous bilirubinometers

Screening for Neonatal Jaundice by Smartphone Sclera Imaging

Jaundice is observed in over 60% of neonates and must be carefully monitored. Ifsevere cases go unnoticed, death or permanent disability can result. Neonatal jaun-dice causes 100,000 deaths yearly, with low-income countries in Africa and SouthAsia particularly affected. There is an unmet need for an accessible and objectivescreening method. This thesis proposes a smartphone camera-based method forscreening based on quantification of yellow discolouration in the sclera.The primary aim is to develop and test an app to screen for neonatal jaundicethat requires only the smartphone itself. To this end, a novel ambient subtractionmethod is proposed and validated, with less dependence on external hardware orcolour cards than previous app-based methods. Another aim is to investigate thebenefits of screening via the sclera. An existing dataset of newborn sclera images(n=87) is used to show that sclera chromaticity can predict jaundice severity.The neoSCB app is developed to predict total serum bilirubin (TSB) fromambient-subtracted sclera chromaticity via a flash/ no-flash image pair. A studyis conducted in Accra, Ghana to evaluate the app. With 847 capture sessions, thisis the largest study on image-based jaundice detection to date. A model trained onsclera chromaticity is found to be more accurate than one based on skin. The modelis validated on an independent dataset collected at UCLH (n=38).The neoSCB app has a sensitivity of 100% and a specificity of 76% in iden-tifying neonates with TSB≥250μmol/L (n=179). This is equivalent to the TcB(JM-105) data collected concurrently, and as good as the best-performing app in theliterature (BiliCam). Following a one-time calibration, neoSCB works without spe-cialist equipment, which could help widen access to effective jaundice screening

Smartphone colorimetry using ambient subtraction: Application to neonatal jaundice screening in Ghana

A smartphone app to screen for neonatal jaundice has a large potential impact in reducing neonatal death and disability. Our app, neoSCB, uses a colour measurement of the sclera to make a screening decision. Although there are numerous benefits of a smartphone-based approach, smartphone colour measurement that is accurate and repeatable is a challenge. Using data from a clinical setting in Ghana, we compare sclera colour measurement using an ambient subtraction method to sclera colour measurement using a standard colour card method, and find they are comparable provided the subtracted signal-to-noise ratio (SSNR) is sufficient. Calculating a screening decision metric via the colour card method gave 100% sensitivity and 69% specificity (n=87), while applying the ambient subtraction method gave 100% sensitivity and 78% specificity (SSNR>3.5; n=50)

Smartphone-based photo analysis for the evaluation of anemia, jaundice and COVID-19

Anemia and jaundice are common health conditions that affect millions of children, adults, and the elderly worldwide. Recently, the pandemic caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the virus that leads to COVID-19, has generated an extreme worldwide concern and a huge impact on public health, education, and economy, reaching all spheres of society. The development of techniques for non-invasive diagnosis and the use of mobile health (mHealth) is reaching more and more space. The analysis of a simple photograph by smartphone can allow an assessment of a person's health status. Image analysis techniques have advanced a lot in a short time. Analyses that were previously done manually, can now be done automatically by methods involving artificial intelligence. The use of smartphones, combined with machine learning techniques for image analysis (preprocessing, extraction of characteristics, classification, or regression), capable of providing predictions with high sensitivity and specificity, seems to be a trend. We presented in this review some highlights of the evaluation of anemia, jaundice, and COVID-19 by photo analysis, emphasizing the importance of using the smartphone, machine learning algorithms, and applications that are emerging rapidly. Soon, this will certainly be a reality. Also, these innovative methods will encourage the incorporation of mHealth technologies in telemedicine and the expansion of people's access to health services and early diagnosis

Diagnosis and treatment of late jaundice in late preterm and term newborns: An integrative literature review / Diagnóstico e tratamento da icterícia tardia em recém-nascidos prematuros tardios e a termo: Uma revisão integrativa de literatura

Although it is a common clinical condition in neonatology, jaundice must have an adequate diagnosis and an on-time treatment since the excess of bilirubin can lead to the development of kernicterus – that, in rare cases, can lead to neonatal death. This study aimed to identify which diagnostic methods and treatment of late jaundice in late preterm and term show greater relevance, efficacy, and safety. An integrative review was performed through SciELO, Pubmed, and Bireme databases, of publications between 2015 and 2020, using the descriptors "neonatal jaundice", "neonatal hyperbilirubinemia", "neonatal jaundice" and "neonatal hyperbilirubinemia".  After the articles extraction, they were stratified in a dataset, from which 17 articles that deal with the diagnosis and / or treatment of late preterm newborns and / or suitable for gestational age were selected and arranged in narrative and charts. It was possible to establish that although serum bilirubin testing is widely used, extracorporeal methods are a good option in the diagnosis of jaundice, with good accuracy, for which phototherapy is the main treatment. There are effective, safe, and low-cost alternatives for the diagnosis and treatment of neonatal jaundice, that work by minimizing the risks of complications

Neonatal jaundice in Ghanaian children: Assessing maternal knowledge, attitude, and perceptions

Background: Neonatal jaundice (NNJ) is a major cause of preventable childhood mortality and long-term impairment especially in countries with significant prevalence of the inherited condition, glucose-6-phosphate dehydrogenase (G6PD) defect. In Ghana, routine screening of pregnant women for G6PD defect is standard care. Prevention of poor health outcomes from NNJ is contingent on population health literacy and early diagnosis. As part of a project to evaluate a screening tool for NNJ, we assessed the knowledge, attitude, and perceptions of Ghanaian mothers on NNJ at baseline. Methods: Using a cross-sectional design, mothers attending antenatal and postnatal clinics at 3 selected health facilities in 2 geographical regions of Ghana were interviewed. Data on mothers’ understanding, perceptions, beliefs, and actions towards NNJ were evaluated. Chi-square test was used to determine the association between selected maternal characteristics and knowledge, attitude, and perception to NNJ. Results: Of the 504 mothers interviewed, 428(85.4%) had heard about NNJ, 346 (68.7%) said the earliest signs are seen in the eyes, 384(76.2%) knew NNJ may be harmful and 467(92.7%) recommended seeking healthcare for the jaundiced newborn. None of the women knew about G6PD or their G6PD status following antenatal screening. Most did not know the signs/symptoms of severe NNJ. Of the 15 mothers who had had a jaundiced neonate, cost was the most perceived (8 out of 15) barrier to accessing health care. There were significant associations (p-value ≤ 0.05) between maternal age, educational level, and knowledge of NNJ. Conclusion: Despite the high level of awareness of NNJ, gaps still exit in the knowledge, attitudes and perceptions of mothers concerning NNJ. Improving education of women about the causes, symptoms/signs, and the role of G6PD in severe NNJ is recommended. Addressing barriers to accessing healthcare for the jaundiced infant may enhance timely management of NNJ and reduce the associated complications and mortality