Alyssa Shapiro

BACKGROUND: Adverse consequences of neonatal hyperbilirubinemia disproportionately affect babies in low- and middle-income countries. Laboratory measurement of total serum bilirubin is limited in low-resource settings, necessitating simpler alternatives. Our study aimed to evaluate the diagnostic accuracy of visual inspection of jaundice via the World Health Organization Integrated Management of Childhood Illnesses algorithm compared to transcutaneous bilirubinometry for the identification of hyperbilirubinemia in community settings. METHODS: Hyperbilirubinemia was assessed by visual inspection for jaundice and transcutaneous bilirubinometry at 0-72 hours, 3-5 days, and 5-14 days postnatal in the PRISMA prospective cohort study in six sites in Asia and Africa. We assessed sensitivity, specificity, and positive and negative percent agreement. RESULTS: We analyzed data from 14,331 infants, including 1,852 preterm infants. 15% had hyperbilirubinemia, as defined by transcutaneous bilirubin values and the NICE nomograms, at 3-5 days postnatal. Visual inspection had a sensitivity of 16%, specificity of 96%, positive percent agreement of 56%, and negative percent agreement of 86% at 3-5 days postnatal age, pooled across all sites and gestational ages, versus transcutaneous bilirubin defined by NICE nomograms. CONCLUSION: The poor sensitivity of visual inspection underscores an urgent need for accurate, affordable screening tools to improve screening for hyperbilirubinemia. Impact Statement: We found poor sensitivity of visual inspection, identifying fewer than one in five neonatal jaundice cases, suggesting much worse diagnostic accuracy in this community-based context across five low- and middle-income countries (LMICs) as compared to the previous studies conducted in health facilities. Among preterm infants, sensitivity was modestly higher than in term infants but remained clinically inadequate, reinforcing that visual inspection alone is insufficient for this high-risk group. Despite standardized training and biannual refresher sessions, our study suggests that training for health care workers alone is unlikely to make visual inspection a reliable case-detection tool. Our findings suggest that the WHO should re-evaluate the IMCI recommendations to include tools with higher diagnostic accuracy to identify neonatal jaundice. Community-level jaundice screening should move beyond visual inspection alone towards validated, low-cost, objective tools; icterometers and smartphone apps with high diagnostic accuracy are promising alternatives.

Surface modification of polydimethylsiloxane (PDMS) for organ‐on‐a‐chip (OOC) systems is fundamental for the success of cell physiological assays. Although UV light is commonly used for this purpose, surface chemical modifications are only temporary. To overcome these limitations, an alternative approach is proposed: a physicochemical modification using ozone and the heterofunctional crosslinker sulfo‐SANPAH (SS). This simple one‐step approach is carried out on PDMS microchannels of OOC platforms. A broad physicochemical characterization based on spectroscopy and microscopy techniques confirms successful modification of the PDMS surface. The PDMS surface contact angle decreases after addition of SS (from 101.4° to 79.9°) but decreases as low as 20.8° after extracellular matrix deposition, demonstrating successful transition of the surface from hydrophobic to hydrophilic. For biological characterization, human liver sinusoidal endothelial cells (LSEC) and murine primary hepatocytes are cultured in OOC channels for up to 7 days. LSECs and hepatocytes establish strong cell adhesions under laminar flow and form a well‐established canaliculi network, respectively. This one‐step method of PDMS surface modification for OOC is simpler than others reported in the literature (e.g., based on 3‐aminopropyltriethoxysilane) and ideal for beginners interested in using microfluidic platforms for cell culture.

Neonatal jaundice is an important cause of morbidity and mortality worldwide, and neonates born in low and middle-income countries bear a disproportionate burden. We previously developed a low-cost, point-of-care system to measure total serum bilirubin (TSB) in neonates. This device was effective at detecting and monitoring jaundice; however, the disposable strips were difficult to produce at scale. Here, we report a new lateral flow cassette design, called BiliDx, that was produced at scale using traditional manufacturing techniques. We evaluated the performance of BiliDx at sites in Nigeria and Malawi. The lateral flow strip consists of plasma separation membranes, nitrocellulose, and a plastic cassette. We evaluated the performance of the strips and reader at two hospitals located in Nigeria and Malawi compared to reference standard TSB. We also assessed performance for samples with high direct bilirubin (DB) and high hematocrit (HCT). We collected 1,144 samples from 758 neonates (TSB ranged from 0.2 to 45.9 mg/dL). The mean bias of BiliDx measurements in the validation set was +0.75 mg/dL, and 95% limits of agreement were -2.57 to 4.07 mg/dL. The mean bias and limits of agreement were comparable for samples with HCT < 60% and HCT ≥ 60%, and for samples with low and intermediate DB levels; the samples with high DB levels had wider 95% limits of agreement (-4.50 to +3.03 mg/dL). Error grid analysis shows that 96.9% of samples measured with BiliDx would have resulted in the same clinical decision as the reference standard. This performance is comparable to previous results that used a handmade two-dimensional strip. Additionally, error grid analysis shows that all 20 samples with high DB levels would have resulted in the same clinical decision as the reference standard. This evaluation supports the use of BiliDx lateral flow cassettes to provide accurate point-of-care measurements in low-resource settings.