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

NCT07109856 | Not Yet Recruiting DMC

• 2 other identifiers: POP-ScoreEthical board number 1010/2025
• Study Type: observational
• Target: 93
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

NIRS; near-infrared spectroscopy; POP-Score; neonates; preterm neonates

Outcome Measures

Primary Outcomes (1)

• Optimal Cut-Off Value of the POP-Score to Predict Elevated CRP (≥ 20 mg/L)

  Determine the optimal cut-off value of the non-invasive POP-Score (unitless score), measured within the first 6 hours after birth, to predict elevated C-reactive protein (CRP) levels (≥ 20 mg/L) within the first 48 hours after birth in neonates with respiratory distress.

  Within the first 6 hours after birth (parameters of the POP-Score) and CRP within 48 hours

Secondary Outcomes (4)

• Difference in Peripheral Muscle Tissue Oxygenation by NIRS Between Neonates With and Without Elevated CRP

  NIRS within 6 hours after birth; CRP within 48 hours

• Difference in Cerebral Tissue Oxygenation by NIRS Between Neonates With and Without Elevated CRP

  NIRS within 6 hours after birth; CRP within 48 hours

• Difference in Intestinal Tissue Oxygenation by NIRS Between Neonates With and Without Elevated CRP

  NIRS within 6 hours after birth; CRP within 48 hours

• Difference in Flank Tissue Oxygenation by NIRS Between Neonates With and Without Elevated CRP

  NIRS within 6 hours after birth; CRP within 48 hours

Other Outcomes (4)

• Difference in Cerebral Fractional Tissue Oxygen Extraction (cFTOE) Between Neonates With and Without Elevated CRP

  FTOE within 6 hours after birth; CRP within 48 hours

• Difference in Peripheral Muscle Fractional Tissue Oxygen Extraction (pFTOE) Between Neonates With and Without Elevated CRP

  FTOE within 6 hours after birth; CRP within 48 hours

• Difference in Intestinal Fractional Tissue Oxygen Extraction (sFTOE) Between Neonates With and Without Elevated CRP

  FTOE within 6 hours after birth; CRP within 48 hours

Study Arms (1)

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.

Diagnostic Test: POP-Score Assessment; Device: Near-Infrared Spectroscopy (NIRS)

Interventions

POP-Score Assessment 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.

Observational cohort

Near-Infrared Spectroscopy (NIRS) 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.

Observational cohort

Eligibility Criteria

• Age: 0 Hours - 6 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Term and moderate-to-late preterm neonates (birth weight ≥ 2000 grams) with signs of respiratory distress within the first 6 hours after birth, admitted to the neonatal intensive care unit at the Medical University of Graz. All participants must have a gestational age allowing for clinical stability and must meet inclusion criteria including full life support decision and informed consent obtained within 6 hours of birth.

You may qualify if:

• birth weight ≥ 2000 grams
• Decision to conduct full life support
• Age \< 6 hours

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of Graz: lead

Study Sites (1)

Medical University of Graz, Division of Neonatology

Graz, Styria, 8036, Austria

Location

Related Publications (18)

• Pichler G, Pocivalnik M, Riedl R, Pichler-Stachl E, Zotter H, Muller W, Urlesberger B. C reactive protein: impact on peripheral tissue oxygenation and perfusion in neonates. Arch Dis Child Fetal Neonatal Ed. 2012 Nov;97(6):F444-8. doi: 10.1136/archdischild-2011-300578. Epub 2012 Jan 31.

  PMID: 22294473 BACKGROUND

• Nanas S, Gerovasili V, Renieris P, Angelopoulos E, Poriazi M, Kritikos K, Siafaka A, Baraboutis I, Zervakis D, Markaki V, Routsi C, Roussos C. Non-invasive assessment of the microcirculation in critically ill patients. Anaesth Intensive Care. 2009 Sep;37(5):733-9. doi: 10.1177/0310057X0903700516.

  PMID: 19775036 BACKGROUND

• Chiesa C, Pellegrini G, Panero A, Osborn JF, Signore F, Assumma M, Pacifico L. C-reactive protein, interleukin-6, and procalcitonin in the immediate postnatal period: influence of illness severity, risk status, antenatal and perinatal complications, and infection. Clin Chem. 2003 Jan;49(1):60-8. doi: 10.1373/49.1.60.

  PMID: 12507961 BACKGROUND

• Pichler G, Holler N, Baik-Schneditz N, Schwaberger B, Mileder L, Stadler J, Avian A, Pansy J, Urlesberger B. Avoiding Arterial Hypotension in Preterm Neonates (AHIP)-A Single Center Randomised Controlled Study Investigating Simultaneous Near Infrared Spectroscopy Measurements of Cerebral and Peripheral Regional Tissue Oxygenation and Dedicated Interventions. Front Pediatr. 2018 Feb 1;6:15. doi: 10.3389/fped.2018.00015. eCollection 2018.

  PMID: 29450194 BACKGROUND

• 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.

  PMID: 19240298 BACKGROUND

• 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.

  PMID: 17185431 BACKGROUND

• Pichler G, Pocivalnik M, Riedl R, Pichler-Stachl E, Morris N, Zotter H, Muller W, Urlesberger B. 'Multi-associations': predisposed to misinterpretation of peripheral tissue oxygenation and circulation in neonates. Physiol Meas. 2011 Aug;32(8):1025-34. doi: 10.1088/0967-3334/32/8/003. Epub 2011 Jun 7.

  PMID: 21654025 BACKGROUND

• Pichler G, Wolf M, Roll C, Weindling MA, Greisen G, Wardle SP, Zaramella P, Naulaers G, Pellicer A, Austin T, Bartocci M, Urlesberger B. Recommendations to increase the validity and comparability of peripheral measurements by near infrared spectroscopy in neonates. 'Round table', section of haematology, oxygen transport and microcirculation, 48th annual meeting of ESPR, Prague 2007. Neonatology. 2008;94(4):320-2. doi: 10.1159/000151655. Epub 2008 Sep 11.

  PMID: 18784432 BACKGROUND

• Holler N, Urlesberger B, Mileder L, Baik N, Schwaberger B, Pichler G. Peripheral Muscle Near-Infrared Spectroscopy in Neonates: Ready for Clinical Use? A Systematic Qualitative Review of the Literature. Neonatology. 2015;108(4):233-45. doi: 10.1159/000433515. Epub 2015 Aug 25.

  PMID: 26338668 BACKGROUND

• Wolfsberger CH, Hoeller N, Baik-Schneditz N, Schwaberger B, Suppan E, Mileder LP, Avian A, Schlatzer C, Urlesberger B, Pichler G. Reference ranges of peripheral-muscle oxygenation in term neonates delivered by Caesarean section during immediate transition after birth. Acta Paediatr. 2024 Dec;113(12):2582-2589. doi: 10.1111/apa.17376. Epub 2024 Aug 8.

  PMID: 39115093 BACKGROUND

• Wolfsberger CH, Holler N, Baik-Schneditz N, Schwaberger B, Suppan E, Mileder L, Avian A, Urlesberger B, Pichler G. Peripheral muscle fractional tissue oxygen extraction in stable term and preterm neonates during the first 24 h after birth. Front Pediatr. 2023 Nov 15;11:1276769. doi: 10.3389/fped.2023.1276769. eCollection 2023.

  PMID: 38034828 BACKGROUND

• Pichler G, Binder C, Avian A, Beckenbach E, Schmolzer GM, Urlesberger B. Reference ranges for regional cerebral tissue oxygen saturation and fractional oxygen extraction in neonates during immediate transition after birth. J Pediatr. 2013 Dec;163(6):1558-63. doi: 10.1016/j.jpeds.2013.07.007. Epub 2013 Aug 22.

  PMID: 23972642 BACKGROUND

• Naulaers G, Morren G, Van Huffel S, Casaer P, Devlieger H. Cerebral tissue oxygenation index in very premature infants. Arch Dis Child Fetal Neonatal Ed. 2002 Nov;87(3):F189-92. doi: 10.1136/fn.87.3.f189.

  PMID: 12390989 BACKGROUND

• Bailey SM, Hendricks-Munoz KD, Mally P. Cerebral, renal, and splanchnic tissue oxygen saturation values in healthy term newborns. Am J Perinatol. 2014 Apr;31(4):339-44. doi: 10.1055/s-0033-1349894. Epub 2013 Jul 19.

  PMID: 23873114 BACKGROUND

• Alderliesten T, Dix L, Baerts W, Caicedo A, van Huffel S, Naulaers G, Groenendaal F, van Bel F, Lemmers P. Reference values of regional cerebral oxygen saturation during the first 3 days of life in preterm neonates. Pediatr Res. 2016 Jan;79(1-1):55-64. doi: 10.1038/pr.2015.186. Epub 2015 Sep 21.

  PMID: 26389823 BACKGROUND

• 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.

  PMID: 32498045 BACKGROUND

• 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.

  PMID: 36081622 BACKGROUND

• Jobsis FF. Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. Science. 1977 Dec 23;198(4323):1264-7. doi: 10.1126/science.929199.

  PMID: 929199 BACKGROUND

MeSH Terms

Conditions

Premature Birth; Infections; Neonatal Sepsis

Interventions

Spectroscopy, Near-Infrared

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Sepsis; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Central Study Contacts

Christina H. Wolfsberger, MD, PhD

CONTACT

+43 316 385 81135; christina.wolfsberger@medunigraz.at

Gerhard Pichler, Prof

CONTACT

gerhard.pichler@medunigraz.at

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 31, 2025
• First Posted: August 7, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: September 9, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)