The Peripheral(-Muscle) Oxygenation and Perfusion Score as a New Non-invasive Tool to Predict Elevations in C-reactive Protein Levels in Neonates

NCT ID: NCT07109856

Last Updated: 2025-09-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Total Enrollment

93 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-10-01

Study Completion Date

2028-05-01

Brief Summary

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This is a prospective, single-center Phase II observational study investigating the predictive value of the "Peripheral(-muscle) Oxygenation and Perfusion Score" (POP-Score), a novel non-invasive composite index, for early detection of infection/inflammation in neonates. The POP-Score combines peripheral muscle oxygenation measured via near-infrared spectroscopy (NIRS) with routinely monitored clinical parameters (heart rate, oxygen saturation, systolic blood pressure, and subcutaneous fat thickness). The study aims to determine the optimal cut-off value of the POP-Score measured within the first 6 hours after birth to predict elevated C-reactive protein (CRP ≥20 mg/L) within 48 hours. Additionally, multi-site NIRS measurements (cerebral, peripheral muscle, intestinal, and flank) will be evaluated to assess their association with inflammation. The study includes term and moderate-to-late preterm neonates (birth weight ≥2000g) with respiratory distress, admitted to the neonatal intensive care unit at the Medical University of Graz.

Detailed Description

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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.

Secondary aims include evaluating whether multi-site NIRS measurements (cerebral, peripheral muscle, intestinal, and flank) differ significantly between neonates with CRP ≥20 mg/L and those with CRP \<20 mg/L, potentially offering additional early indicators of infection or inflammation.

The target sample size is 93 neonates, assuming a 20% incidence of CRP ≥20 mg/L. This allows estimation of the AUC with a 95% confidence interval and acceptable precision. Data will be analyzed using appropriate statistical tests for categorical and continuous variables. Statistical analyses will be conducted in cooperation with the Institute for Medical Informatics, Statistics, and Documentation, Medical University of Graz.

The POP-Score and multi-site NIRS monitoring offer a potentially powerful, non-invasive approach for early identification of at-risk neonates, enabling earlier intervention and improved outcomes. If validated, this tool may support more accurate and timely clinical decision-making in neonatal intensive care settings.

Conditions

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Prematurity, Infections NIRS Near Infrared Spectroscopy Preterm Neonates Term Infant Infection Neonatal Sepsis, Early-Onset

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Observational cohort

This cohort includes term and moderate-to-late preterm neonates (birth weight ≥ 2000g) with respiratory distress within the first 6 hours after birth, admitted to the neonatal intensive care unit. All enrolled neonates undergo non-invasive monitoring to assess the predictive value of the POP-Score for identifying elevated CRP (≥20 mg/L) within the first 48 hours after birth. The cohort will also be analyzed to evaluate differences in multi-site NIRS measurements (peripheral muscle, cerebral, intestinal, and flank) between those with and without CRP elevation.

POP-Score Assessment

Intervention Type DIAGNOSTIC_TEST

A non-invasive score calculated within the first 6 hours after birth using peripheral muscle oxygenation (pTOI, measured via near-infrared spectroscopy), heart rate, arterial oxygen saturation (SpO2), systolic blood pressure (SABP), and subcutaneous fat layer thickness. The score is evaluated for its ability to predict C-reactive protein (CRP) levels ≥ 20 mg/L within 48 hours.

Near-Infrared Spectroscopy (NIRS)

Intervention Type DEVICE

NIRS measurements are performed within 6 hours after birth using the NIRO 200NX device at four anatomical sites (forearm, forehead, infraumbilical region, and left flank). Measurements assess peripheral muscle, cerebral, intestinal, and flank oxygenation to identify possible differences in tissue perfusion associated with early inflammation or infection.

Interventions

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POP-Score Assessment

A non-invasive score calculated within the first 6 hours after birth using peripheral muscle oxygenation (pTOI, measured via near-infrared spectroscopy), heart rate, arterial oxygen saturation (SpO2), systolic blood pressure (SABP), and subcutaneous fat layer thickness. The score is evaluated for its ability to predict C-reactive protein (CRP) levels ≥ 20 mg/L within 48 hours.

Intervention Type DIAGNOSTIC_TEST

Near-Infrared Spectroscopy (NIRS)

NIRS measurements are performed within 6 hours after birth using the NIRO 200NX device at four anatomical sites (forearm, forehead, infraumbilical region, and left flank). Measurements assess peripheral muscle, cerebral, intestinal, and flank oxygenation to identify possible differences in tissue perfusion associated with early inflammation or infection.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* birth weight ≥ 2000 grams
* Signs of respiratory distress at time-point of inclusion (tachypnoea \>60/min, grunting, intercostal/subcostal/jugular retractions, nasal flaring, supplemental oxygen or respiratory support)
* Decision to conduct full life support
* Written informed consent obtained within the first 6 hours after birth, before inclusion in the study
* Age \< 6 hours

Exclusion Criteria

* No decision to conduct full life support
* No written informed consent
* Birth weight \< 2000 grams
* Age \> 6 hours
* Severe congenital malformations,
* Umbilical cord artery pH \<7.20
Minimum Eligible Age

0 Hours

Maximum Eligible Age

6 Hours

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medical University of Graz

OTHER

Sponsor Role lead

Responsible Party

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Christina Wolfsberger, MD

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Medical University of Graz, Division of Neonatology

Graz, Styria, Austria

Site Status

Countries

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Austria

Central Contacts

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Christina H. Wolfsberger, MD, PhD

Role: CONTACT

+43 316 385 81135

Gerhard Pichler, Prof

Role: CONTACT

References

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Grossauer K, Pichler G, Schmolzer G, Zotter H, Mueller W, Urlesberger B. Comparison of peripheral and cerebral tissue oxygenation index in neonates. Arch Dis Child Fetal Neonatal Ed. 2009 Mar;94(2):F156. doi: 10.1136/adc.2008.146654. No abstract available.

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Pichler G, Grossauer K, Klaritsch P, Kutschera J, Zotter H, Muller W, Urlesberger B. Peripheral oxygenation in term neonates. Arch Dis Child Fetal Neonatal Ed. 2007 Jan;92(1):F51-2. doi: 10.1136/adc.2005.089037.

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Wolfsberger C, Baik-Schneditz N, Schwaberger B, Binder-Heschl C, Nina H, Mileder L, Bruckner M, Avian A, Urlesberger B, Pichler G. Changes in peripheral muscle oxygenation measured with near-infrared spectroscopy in preterm neonates within the first 24 h after birth. Physiol Meas. 2020 Aug 11;41(7):075003. doi: 10.1088/1361-6579/ab998b.

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Wolfsberger CH, Hoeller N, Suppan E, Schwaberger B, Urlesberger B, Nakstad B, Pichler G. Peripheral fractional oxygen extraction measured with near-infrared spectroscopy in neonates-A systematic qualitative review. Front Pediatr. 2022 Aug 23;10:940915. doi: 10.3389/fped.2022.940915. eCollection 2022.

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Other Identifiers

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Ethical board number 1010/2025

Identifier Type: OTHER

Identifier Source: secondary_id

POP-Score

Identifier Type: -

Identifier Source: org_study_id

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