This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Background Medical device development is an area facing multiple challenges, resulting in a high number of products not reaching the clinical setting. Neonatal hyperbilirubinemia, manifesting as neonatal jaundice (NNJ), is an important cause of newborn morbidity and mortality. It is important to identify infants with neonatal hyperbilirubinemia at an early stage, but currently there is a lack of tools that are both accurate and affordable. Objective This study aimed to develop a novel system to assess the presence of NNJ. The device should provide accurate results, be approved as a medical device, be easy to use, and be produced at a price that is affordable even in low-resource settings. Methods We used an iterative approach to develop a smartphone-based system to detect the presence of NNJ. We performed technical development, followed by clinical and usability testing in parallel, after which we initiated the regulatory processes for certification. We updated the system in each iteration, and the final version underwent a clinical validation study on healthy term newborns aged 1 to 15 days before all documentation was submitted for conformity assessment to obtain Conformité Européenne (CE) certification. We developed a system that incorporates a smartphone app, a color calibration card, and a server. Results Three iterations of the smartphone-based system were developed; the final version was approved as a medical device after complying with Medical Device Regulation guidelines. A total of 201 infants were included in the validation study. Bilirubin values using the system highly correlated with total serum or plasma bilirubin levels (r=0.84). The system had a high sensitivity (94%) to detect severe jaundice, defined as total serum or plasma bilirubin >250 µmol/L, and maintained a high specificity (71%). Conclusions Our smartphone-based system has a high potential as a tool for identifying NNJ. An iterative approach to product development, conducted by working on different tasks in parallel, resulted in a functional and successful product. By adhering to the requirements for regulatory approval from the beginning of the project, we were able to develop a market-ready mobile health solution.

Many recent medical developments rely on image analysis, however, it is not convenient nor cost-efficient to use professional image acquisition tools in every clinic or laboratory. Hence, a reliable color calibration is necessary; color calibration refers to adjusting the pixel colors to a standard color space. During a real-life project on neonatal jaundice disease detection, we faced a problem to perform skin color calibration on already taken images of neonatal babies. These images were captured with a smartphone (Samsung Galaxy S7, equipped with a 12 Mega Pixel camera to capture 4032x3024 resolution images) in the presence of a specific calibration pattern. This post-processing image analysis deprived us from calibrating the camera itself. There is currently no comprehensive study on color calibration methods applied to human skin images, particularly when using amateur cameras (e.g. smartphones). We made a comprehensive study and we proposed a novel approach for color calibration, Gaussian process regression (GPR), a machine learning model that adapts to environmental variables. The results show that the GPR achieves equal results to state-of-the-art color calibration techniques, while also creating more general models.

In recent years, smartphone-based colour imaging systems are being increasingly used for Neonatal jaundice detection applications. These systems are based on the estimation of bilirubin concentration levels that correlates with newborns’ skin colour images corresponding to total serum bilirubin (TSB) and transcutaneous bilirubinometry (TcB) measurements. However, the colour reproduction capacity of smartphone cameras are known to be influenced by various factors including the technological and acquisition process variabilities. To make an accurate bilirubin estimation, irrespective of the type of smartphone and illumination conditions used to capture the newborns’ skin images, an inclusive and complete model, or data set, which can represent all the possible real world acquisitions scenarios needs to be utilized. Due to various challenges in generating such a model or a data set, some solutions tend towards the application of reduced data set (designed for reference conditions and devices only) and colour correction systems (for the transformation of other smartphone skin images to the reference space). Such approaches will make the bilirubin estimation methods highly dependent on the accuracy of their employed colour correction systems, and the capability of reducing device-to-device colour reproduction variability. However, the state-of-the-art methods with similar methodologies were only evaluated and validated on a single smartphone camera. The vulnerability of the systems in making an incorrect jaundice diagnosis can only be shown with a thorough investigation of the colour reproduction variability for extended number of smartphones and illumination conditions. Accordingly, this work presents and discuss the results of such broad investigation, including the evaluation of seven smartphone cameras, ten light sources, and three different colour correction approaches. The overall results show statistically significant colour differences among devices, even after colour correction applications, and that further analysis on clinically significance of such differences is required for skin colour based jaundice diagnosis.

No abstract