The Peripheral(-Muscle) Oxygenation and Perfusion Score (POPScore) a New Non-invasive Tool to Predict Elevations in C-reactive Protein Levels in Neonates - a Prospective Phase II Observational Study

Early identification of neonatal infection and inflammation remains a major challenge in neonatal intensive care, particularly in term and moderate-to-late preterm infants with respiratory distress. Current diagnostic approaches rely heavily on clinical symptoms and laboratory markers, which may be subtle or delayed. This study evaluates the diagnostic potential of a novel, non-invasive scoring system-the Peripheral(-muscle) Oxygenation and Perfusion Score (POP-Score)-in predicting elevated C-reactive protein (CRP) levels (≥20 mg/L) within 48 hours after birth.

The POP-Score integrates near-infrared spectroscopy (NIRS)-based peripheral muscle tissue oxygenation measurements (pTOI) with standard clinical monitoring parameters: arterial oxygen saturation (SpO2), heart rate (HR), systolic arterial blood pressure (SABP), and subcutaneous fat layer thickness (measured by ultrasound). A pilot study demonstrated that a POP-Score >1.00 within 6 hours after birth had high sensitivity (100%) and specificity (87%) in predicting elevated CRP values, suggesting potential for early infection screening.

This is a prospective, single-center, observational Phase II study conducted at the Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Austria. Term and moderate-to-late preterm neonates (birth weight ≥2000g) with respiratory distress and risk factors for infection are eligible. Exclusion criteria include severe congenital anomalies, birth weight <2000g, age >6 hours at time of consent, or umbilical artery pH <7.20.

NIRS measurements will be performed within the first 6 hours after birth at four anatomical sites: peripheral muscle (right forearm), cerebral (left forehead), intestinal (infraumbilical), and flank (left posterior flank at T12-L2). Each site will be measured five times using short-duration sensor reapplications to improve data precision. Concurrently, SpO2 and HR (via pulse oximetry), blood pressure, temperature, and subcutaneous fat thickness (via ultrasound) will be recorded. CRP and other laboratory parameters (including leukocyte count, IT-ratio) will be obtained as part of routine care on the first and second day after birth.

The primary aim is to identify the optimal cut-off level of the POP-Score, calculated within the first 6 hours, to predict CRP ≥20 mg/L within 48 hours. Receiver Operating Characteristic (ROC) analysis will be used, with the area under the curve (AUC) estimated and the optimal cut-off determined via the Youden Index.