Skin color influences transcutaneous bilirubin measurements: a systematic in vitro evaluation.

OBJECTIVE: Concerns have been raised about the effect of skin color on the accuracy of transcutaneous bilirubin (TcB) measurements, a widely used method for hyperbilirubinemia diagnosis in newborns. Literature is inconclusive, with both reported under- and overestimations of the TcB with increasing skin pigmentation. Therefore, the influence of skin color on TcB measurements was systematically evaluated in a controlled, in vitro setting. METHODS: A bilirubin meter (JM-105) was evaluated on layered phantoms that mimic neonatal skin with varying dermal bilirubin concentrations (0-250 µmol/L) and varying epidermal melanosome volume fractions (0-40%; light-dark skin color). RESULTS: TcB measurements were influenced by skin pigmentation. Larger mimicked melanosome volume fractions and higher bilirubin levels led to larger underestimations of the measured TcB, compared to an unpigmented epidermis. In the in vitro setting of this study, these underestimations amounted to 26-132 µmol/L at a TcB level of 250 µmol/L. CONCLUSION: This in vitro study provides insight into the effect of skin color on TcB measurements: the TcB is underestimated as skin pigmentation increases and this effect becomes more pronounced at higher bilirubin levels. Our results highlight the need for improved TcB meter design and cautious interpretation of TcB readings on newborns with dark skin. IMPACT: Key message: Skin color influences transcutaneous bilirubin measurements: the darker the skin, the larger the underestimation. What this study adds to existing literature: Existing literature is inconclusive regarding the influence of skin color on transcutaneous bilirubin measurements. This study systematically evaluates and clarifies the influence of skin color on transcutaneous bilirubin measurements in a controlled, in vitro setting. IMPACT: This study aids to better interpret the measured TcB level in patients with varying skin colors, and is particularly important when using TcB meters on patients with dark skin colors.

Quantification of cephalocaudal progression of jaundice in preterm infants.

BACKGROUND: The cephalocaudal progression (CCP) of neonatal jaundice is a well-known phenomenon, but quantitative information on CCP in preterm infants is absent. In this study, CCP was quantified in preterm infants as a function of postnatal age and body location. METHODS: 5.693 transcutaneous bilirubin (TcB) measurements were performed in 101 preterm infants from birth until postnatal day seven at five body locations (forehead, sternum, hipbone, tibia, ankle). Multi-level linear regression analysis was performed to evaluate the CCP as a function of body location and postnatal age. TcB measurements at all body locations and postnatal days were compared to total serum bilirubin (TSB) levels (N = 1.113). RESULTS: The overall average change in ratio of TcB compared to forehead was for sternum +0.04 [95% CI -0.02;0.09]; hipbone +0.05 [0.00;0.01]; tibia -0.33 [-0.38;-0.27] and ankle -0.62 [-0.68;-0.57]. No effect modification of CCP by sex, gestational age, birthweight, phototherapy, and TSB was found. The TcB maximally underestimated the TSB at the ankle -79.5 µmol [-0.1;159.2]. CONCLUSIONS: CCP is present in preterm infants and is relatively stable over time. Since TcB measurements on the tibia and ankle underestimate TSB significantly, we advise to use only measurement locations cephalic from the tibia; i.e., hipbone, sternum, and forehead. IMPACT: Cephalocaudal progression (CCP) of jaundice in preterm infants, assessed by transcutaneous bilirubin (TcB) measurements, is substantial and rather stable over postnatal day 0 to 7. To the best of our knowledge, this study is the first to investigate CCP of jaundice in preterm infants as a function of postnatal age in preterm infants. Our results demonstrate that TcB measurements at the tibia and ankle differ from the TSB beyond the clinically used TcB safety margins. We advise to perform TcB measurements only at locations cephalic from the tibia; i.e., hipbone, forehead, and sternum.

Irradiance footprint of phototherapy devices: a comparative study.

BACKGROUND: Phototherapy (PT) is the standard treatment of neonatal unconjugated hyperbilirubinemia. The irradiance footprint, i.e., the illuminated area by the PT device with sufficient spectral irradiance, is essential for PT to be effective. Irradiance footprint measurements are not performed in current clinical practice. We describe a user-friendly method to systematically evaluate the high spectral irradiance (HSI) footprint (illuminated area with spectral irradiance of ≥30 µW cm-2 nm-1) of PT devices in clinical practice. MATERIALS AND METHODS: Six commercially available LED-based overhead PT devices were evaluated in overhead configuration with an incubator. Spectral irradiance (µW cm-2 nm-1) and HSI footprint were measured with a radiospectrometer (BiliBlanket Meter II). RESULTS: The average measured spectral irradiance ranged between 27 and 52 µW cm-2 nm-1 and HSI footprint ranged between 67 and 1465 cm2, respectively. Three, two, and one PT devices out of six covered the average BSA of an infant born at 22, 26-32, and 40 weeks of gestation, respectively. CONCLUSION: Spectral irradiance of LED-based overhead PT devices is often lower than manufacturer's specifications, and HSI footprints not always cover the average BSA of a newborn infant. The proposed measurement method will contribute to awareness of the importance of irradiance level as well as footprint measurements in the management of neonatal jaundice. IMPACT: While a sufficient spectral irradiance footprint is essential for PT to be effective, some PT devices have spectral irradiance footprints that are too small to cover the entire body surface area (BSA) of a newborn infant. This study introduces a user-friendly, accessible method to systematically evaluate the spectral irradiance level and footprint of PT devices. This study supports awareness on the role of the spectral irradiance footprint in the efficacy of PT devices. Irradiance footprint can be easily measured during phototherapy with the proposed method.

Inter-device reproducibility of transcutaneous bilirubin meters.

BACKGROUND: Transcutaneous bilirubinometry is a widely used screening method for neonatal hyperbilirubinemia. Deviation of the transcutaneous bilirubin concentration (TcB) from the total serum bilirubin concentration (TSB) is often ascribed to biological variation between patients, but variations between TcB meters may also have a role. This study aims to provide a systematic evaluation of the inter-device reproducibility of TcB meters. MATERIALS AND METHODS: Thirteen commercially available TcB meters (JM-105 and JM-103) were evaluated in vitro on phantoms that optically mimic neonatal skin. The mimicked TcB was varied within the clinical range (0.5-181.3 µmol/L). RESULTS: Absolute differences between TcB meter outcomes increased with the measured TcB, from a difference of 5.0 µmol/L (TcB = 0.5 µmol/L phantom) up to 65.0 µmol/L (TcB = 181.3 µmol/L phantom). CONCLUSION: The inter-device reproducibility of the examined TcB meters is substantial and exceeds the specified accuracy of the device (±25.5 µmol/L), as well as the clinically used TcB safety margins (>50 µmol/L below phototherapy threshold). Healthcare providers should be well aware of this additional uncertainty in the TcB determination, especially when multiple TcB meters are employed in the same clinic. We strongly advise using a single TcB meter per patient to evaluate the TcB over time. IMPACT: Key message: The inter-device reproducibility of TcB meters is substantial and exceeds the clinically used TcB safety margins. What this study adds to existing literature: The inter-device reproducibility of transcutaneous bilirubin (TcB) meters has not been reported in the existing literature. This in vitro study systematically evaluates this inter-device reproducibility. IMPACT: This study aids in a better interpretation of the measured TcB value from a patient and is of particular importance during patient monitoring when using multiple TcB meters within the same clinical department. We strongly advise using a single TcB meter per patient to evaluate the TcB over time.

How skin anatomy influences transcutaneous bilirubin determinations: an in vitro evaluation.

BACKGROUND: Transcutaneous bilirubinometry is an effective screening method for neonatal hyperbilirubinemia. Current transcutaneous bilirubin (TcB) meters are designed for the "standard" situation of TcB determinations on the forehead or sternum of term newborns. We hypothesize that skin anatomy can considerably influence TcB determinations in non-standard situations-e.g., on preterm newborns or alternative body locations. METHODS: A commercially available TcB meter (JM-105) was evaluated in vitro on phantoms that accurately mimic neonatal skin. We varied the mimicked cutaneous hemoglobin content (0-2.5 g/L), bone depth (0.26-5.26 mm), and skin maturity-related light scattering (1.36-2.27 mm-1) within the clinical range and investigated their influence on the TcB determination. To obtain a reference frame for bone depth at the forehead, magnetic resonance head scans of 46 newborns were evaluated. RESULTS: The TcB meter adequately corrected for mimicked hemoglobin content. However, TcB determinations were influenced considerably by clinically realistic variations in mimicked bone depth and light scattering (deviations up to 72 µmol/L). This greatly exceeds the specified accuracy of the device (±25.5 µmol/L). CONCLUSION: As bone depth and light scattering vary with gestational maturity and body location, caretakers should be cautious when interpreting TcB measurements on premature newborns and non-standard body locations.

Image-guided point-shear-wave elastography: a valid and reliable technique for liver fibrotic staging.

PURPOSE: Despite progressive implementation of image-guided point-shear wave elastography (pSWE) in guidelines as an alternative to transient elastography for the staging of fibrotic liver disease, pSWE is not widely adopted in clinical workflow. More information on reliability and validity of pSWE systems is needed. Therefore, we performed a phantom study to evaluate the validity and reliability of pSWE with ultrasound systems. METHODS: Validity and reliability of pSWE measurements from three ultrasound systems were evaluated. Measurements were performed on an elasticity phantom with reference elasticities of 7 ± 1 (low) (median ± interquartile range (IQR)), 14 ± 2 (medium) and 26 ± 3 (high) kPa. Measurements were repeated in tenfold for each reference at 2, 3 and 4 cm depth. Results were considered valid when median elasticity ± IQR was between the uncertainty limits (IQR) for each reference elasticity value and reliable when IQR/median < 0.30. RESULTS: pSWE with the systems provided valid results for all reference elasticities and focal depths, except for overestimation of high reference elasticity at 2 and 4 cm depth for one system (41.5 ± 4.3 and 39.0 ± 1.2 kPa, respectively). Measurements were reliable with a maximum IQR/median of 0.13, well below the guideline of IQR/median < 0.30. DISCUSSION: The results support the use of pSWE as an alternative to invasive or non-image guided noninvasive techniques for liver fibrotic staging. CONCLUSIONS: pSWE with ultrasound systems from different vendors is valid and reliable and can therefore be implemented to optimize clinical workflow by performing imaging and elastography simultaneously.

Design and characterization of color printed polyurethane films as biomedical phantom layers.

We propose a new, user-friendly and accessible approach for fabricating thin phantoms with controllable absorption properties in magnitude, spectral shape, and spatial distribution. We utilize a standard office laser color printer to print on polyurethane thin films (40 - 60 µm), commonly available as medical film dressings and ultrasound probe covers. We demonstrate that the optical attenuation and absorption of the printed films correlate linearly with the printer input settings (opacity), which facilitates a systematic phantom design. The optical and acoustic properties of these polyurethane films are similar to biological tissue. We argue that these thin phantoms are applicable to a wide range of biomedical applications. Here, we introduce two potential applications: (1) homogeneous epidermal melanin phantoms and (2) spatially resolved absorbers for photoacoustic imaging. We characterize the thin phantoms in terms of optical properties, thickness, microscopic structure, and reproducibility of the printing process.