Assessing accuracy of BiliPredics algorithm in predicting individual bilirubin progression in neonates -results from a prospective multi-center study

Britta Steffens ^1,2* Gilbert Koch ^1,2 Axel Franz ³ Corinna Engel ³ Marc Pfister ^1,2 Sven Wellmann ^1,4

• ¹ NeoPrediX AG, Regensburg, Germany
• ² Pediatric Pharmacology and Pharmacometrics, University Children’s Hospital Basel, Basel, Switzerland
• ³ Center for Pediatric Clinical Studies (CPCS), University Children's Hospital Tübingen, Tuebingen, Germany
• ⁴ Department of Neonatology, Hospital St. Hedwig of the Order of St. John of God, University Children's Hospital Regensburg (KUNO), Regensburg, Germany

Background: Neonatal jaundice affects more than half of neonates. As bilirubin values usually peak few days after hospital discharge, jaundice remains a leading cause of rehospitalization. The recently developed BiliPredics algorithm, integrated in the first CE-approved bilirubin prediction tool, predicts individual bilirubin progression for up to 60 hours into the future. Goal of the prospective study was to assess accuracy of this algorithm in predicting individual bilirubin prior to hospital discharge in neonates.: A prospective multi-center study was conducted in 2021 at the University Children's Hospitals in Tübingen and Regensburg, Germany. Various scenarios differing in type and number of bilirubin measurements and in prediction horizon were tested. Primary objective was prediction accuracy of the BiliPredics algorithm based on total serum bilirubin (TSB) measurements or based on transcutaneous bilirubin (TcB) measurements alone. Secondary objective was prediction accuracy based on combinations of TSB and TcB measurements. For assessment of accuracy, two validation metrics, absolute prediction error (𝑎𝑃𝐸) and relative prediction error (𝑟𝑃𝐸), and two clinical acceptance conditions, margin of error of the 95%confidence interval (95%-CI) and percentage of clinically relevant mis-predictions defined as 𝑎𝑃𝐸 > 85 µmol/l, were investigated.Results: Out of 455 enrolled neonates, 276 neonates met bilirubin inclusion criteria and were included in the analyses. Irrespective from tested prediction horizons, median 𝑟𝑃𝐸 was small (8.5% to 9.5%) utilizing TSB measurements for up to 30 and 60 hours and slightly higher (13.8%) utilizing TcB measurements for up to 48 hours. The same applied for median 𝑎𝑃𝐸. Both clinical acceptance conditions were fulfilled across tested scenarios. Results for combined TSB-TcB scenarios up to a prediction horizon of 48 hours without adjustment for type of measurement were comparable to TSB and TcB scenarios fulfilling both clinical acceptance conditions.Results from this prospective study in neonates confirm that the BiliPredics algorithm accurately predicts bilirubin progression up to 60 hours with TSB measurements and up to 48 hours with TcB or combined TSB-TcB measurements. As such, prediction tools utilizing this algorithm are expected to facilitate and safely optimize jaundice risk assessment at hospital discharge with the potential to reduce jaundice-related rehospitalizations.