Transfusion-Related Changes in Oxidative Stress Biomarkers in Neonates

NCT07672275 | Recruiting

• 1 other identifier: 1319/2025
• Study Type: observational
• Target: 170
• Locations: 1 country
• Sites: 1

Brief Summary

Reactive oxygen species (ROS), which include peroxides, are generated in the human body as by-products of cellular metabolism. In small amounts, they fulfill important physiological functions. However, when produced in excess, they can damage cells and tissues. Extremely low gestation age neonates (ELGANs) are particularly vulnerable to such harmful effects because their antioxidant defense systems are immature, and they are exposed to increased ROS levels due to the oxygen therapy required after birth. Fetal hemoglobin (HbF), the primary oxygen carrier in the blood of newborns, plays a crucial role in this context. Compared with adult hemoglobin (HbA), it has a higher oxygen affinity and a more pronounced pseudoperoxidase activity, which helps protect organs during early development from peroxides. In addition to oxygen administration, blood transfusions can also contribute to increased ROS formation. Due to the immature hematopoietic system and the diagnostic blood sampling required, ELGANs frequently receive transfusions with adult red blood cell (A-RBC) concentrates. These lead to a rapid shift from HbF to HbA, further promoting the generation of ROS. Measuring ROS in blood is particularly challenging because these molecules are extremely short-lived. Consequently, reference values for newborns are lacking. Therefore, the investigators aim to establish reference ranges for one ROS, the peroxide in both term and preterm healty neonates from birth event onward and to assess the effects of A-RBC transfusions on this parameter in ELGANs. Furthermore, combining near-infrared spectroscopy-derived measurements of cerebral regional tissue oxygenation with peroxide assessments requiring only minimal blood volumes (0.5 mL per sample) will provide a more comprehensive and quantitatively robust understanding of the physiological changes induced by A-RBC transfusions in ELGANs. Excessive ROS exposure is considered a key risk factor for severe complications of prematurity, including brain injury, retinopathy, and chronic lung disease. With this project, investigators aim to improve the understanding of these risks and promote new evidence-based strategies in transfusion medicine. In the long term, transfusions with HbF-rich red blood cells derived from cord blood could help reduce ROS formation and provide effective protection for particularly vulnerable preterm infants.

Conditions

Oxidative Stress in Neonates; Near Infrared Spectroscopy; Fetal Hemoglobin; Erythrocyte Transfusion

Keywords

fetal hemoglobin; erythrocyte transfusion; preterm neonates; peroxide; oxidative stress

Outcome Measures

Primary Outcomes (3)

• Peroxide levels- Part A

  Baseline peroxide levels in umbilical artery Baseline peroxide levels in umbilical vein

  Part A: From enrollment to the end of blood sampling from the placental part of the umbilical cord, at latest 30 minutes after birth.

• Peroxide levels- Part B

  Peroxide levels at admission (\<48h). Peroxide levels 48-72 h after admission. Peroxide levels 5-7 days after admission.

  Part B: From enrollment until one week (7 days) after the admission to the neonatal intensive care unit.

• Peroxide levels- Part C

  FHbF and HbFc in pre-transfusional and post-transfusional routinely sampled blood samples in ELGANs undergoing A-RBC transfusions up to 8 days after each transfusion. Peroxide levels in pre-transfusional and post-transfusional blood samples, synchronized with routine blood draws in ELGANs undergoing A-RBC transfusions up to 8 days after each transfusion. Cerebral NIRS measurement of the regional tissue oxygenation: 1. Around an A-RBC transfusion: 1h before, 6h during and 1h after 2. 12-24 hours after an A-RBC transfusion: over 1h 3. 6-8 days following an A-RBC transfusion: over 1h

  Part C: From enrollment to the postmenstrual age of 40+0 weeks.

Study Arms (3)

Part A: healthy preterm and term neonates

All neonates routinely monitored immediately after birth at the Division of Neonatology, Department of Pediatrics, Medical University of Graz, will be eligible for peroxide measurements from umbilical cord blood to establish baseline values.

Diagnostic Test: Peroxide analysis-TOC Omnignostica Forschungs GmbH

Part B: Preterm and term neonates admitted to the NICU

Preterm and term neonates admitted to the NICU for medical treatment without exposure to RBC transfusions, will be eligible for the measurement of time-dependent changes in peroxide levels.

Diagnostic Test: Peroxide analysis-TOC Omnignostica Forschungs GmbH

Part C: Extremely low gestational age neonates <28+0 weeks gestation

ELGANs (22+5-27+6 weeks´gestation) will be included in the study on the effects of RBC transfusions on changes in peroxide levels alongside a NIRS measurement of changes in regional cerebral oxygenation before, during and after the transfusion.

Diagnostic Test: Peroxide analysis-TOC Omnignostica Forschungs GmbH; Device: Near Infrared Imaging

Interventions

Peroxide analysis-TOC Omnignostica Forschungs GmbH DIAGNOSTIC_TEST

1\. Freshly prepared serum or EDTA plasma samples (total volume 0.5 ml) stored at room temperature for no longer than 30 minutes will be used for the peroxide analysis (TOC Omnignostica Forschungs GmbH, Höflein/Danube, Austria). If an immediate testing is not possible, samples will be stored at -20 °C for a maximum of two weeks.

Part A: healthy preterm and term neonates; Part B: Preterm and term neonates admitted to the NICU; Part C: Extremely low gestational age neonates <28+0 weeks gestation

Near Infrared Imaging DEVICE

For NIRS measurements the t-NIRS 1 (Hamamatsu, Japan) will be used. This monitor uses a "continuous wave spatially resolved" technique and measures cerebral regional oxygen saturation (crSO2) non-invasively. A cerebral sensor will be placed and fixed with a CPAP cap on the left forehead. Duration of the transfusional measurement will be 8 hours (1h before, 6h during and 1h after the transfusion). Duration of post-transfusional measurement will be 1 hour and performed 12-24h and 6-8 days after the transfusion.

Also known as: t-NIRS

Part C: Extremely low gestational age neonates <28+0 weeks gestation

Eligibility Criteria

• Age: 5 Minutes - 5 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Part A: All neonates routinely monitored immediately after birth at the Division of Neonatology, Department of Pediatrics, Medical University of Graz, will be eligible for peroxide measurements from umbilical cord blood to establish baseline values. Part B: Preterm and term neonates (\>=37+0 weeks ́gestation) admitted to the NICU for medical treatment without RBC transfusions, will be included in the study of time-dependent changes in peroxide levels. Part C: ELGANs (22+5-27+6 weeks ́gestation) will be included in the study on the effects of RBC transfusions on changes in peroxide levels.

You may qualify if:

• Part A:
• Neonates who are monitored on the NICU immediately after birth
• Written parental informed consent
• Part B:
• Term and preterm neonates admitted to the NICU for medical treatment
• Age ad admission \<48 hours
• Written parental informed consent
• Part C:
• ELGANs 22(+5)-27(+6) weeks (days) gestation admitted to the NICU
• Decision to conduct full life support
• Written parental informed consent

You may not qualify if:

• No decision to conduct full life support
• No parental written informed consent
• Congenital malformations
• Family history of hemoglobinopathies (e.g. sickle cell anemia, thalassemia)
• Fetal anemia requiring in-utero A-RBC transfusions

Sponsors & Collaborators

• Medical University of Graz: lead

Study Sites (1)

Divison of Neonatology, Department of Pediatrics, Medical University of Graz

Graz, Styria, 8036, Austria

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Whole blood will be extracted. After centrifugation, plasma will be used for peroxide measurements.

MeSH Terms

Conditions

beta-Thalassemia

Condition Hierarchy (Ancestors)

Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Ena Suppan, MD

  Divison of Neonatology, Department of Pediatrics, Medical University of Graz, Auenbruggerplatz 32, 8036 Graz, Austria

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ena Suppan, MD

CONTACT

+4331638581477; +436766459070; ena.suppan@medunigraz.at

Gerhard Cvirn, Associate Professor, PhD

CONTACT

+43-316-385-72122; gerhard.cvirn@medunigraz.at

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2025
• First Posted: June 26, 2026
• Study Start: December 12, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: June 26, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: IPD and supporting information will be available beginning 6 months after publication of the primary results and ending 5 years after publication.
• Access Criteria: De-identified individual participant data underlying the published results may be shared with qualified researchers upon reasonable request, subject to approval by the study investigators and execution of a data-sharing agreement.

Locations

AU (1)