Transfusion-Related Changes in Oxidative Stress Biomarkers in Neonates (NEO-REDOX)
Transfusion-Related Changes in Oxidative Stress Biomarkers in Neonates - a Three-Part Prospective Observational Pilot Study
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.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Undersøgelsestype
Tilmelding (Anslået)
Kontakter og lokationer
Studiekontakt
- Navn: Ena Suppan, MD
- Telefonnummer: +4331638581477; +436766459070
- E-mail: ena.suppan@medunigraz.at
Undersøgelse Kontakt Backup
- Navn: Gerhard Cvirn, Associate Professor, PhD
- Telefonnummer: +43-316-385-72122
- E-mail: gerhard.cvirn@medunigraz.at
Studiesteder
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Styria
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Graz, Styria, Østrig, 8036
- Rekruttering
- Divison of Neonatology, Department of Pediatrics, Medical University of Graz
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Kontakt:
- Ena Suppan, MD
- Telefonnummer: +43 676 645 90 70
- E-mail: ena.suppan@medunigraz.at
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Kontakt:
- Gerhard Pichler, University Professor, MD
- Telefonnummer: + 43-316-385-80520
- E-mail: gerhard.pichler@medunigraz.at
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Ledende efterforsker:
- Ena Suppan, MD
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Underforsker:
- Gerhard Cvirn, Associate Professor, PhD
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
- Barn
Tager imod sunde frivillige
Prøveudtagningsmetode
Studiebefolkning
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.
Beskrivelse
Inclusion Criteria:
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
Exclusion criteria (Part A, B, C)
- 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
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
Kohorter og interventioner
Gruppe / kohorte |
Intervention / Behandling |
|---|---|
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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.
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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.
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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.
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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.
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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.
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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.
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.
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Peroxide levels- Part A
Tidsramme: Part A: From enrollment to the end of blood sampling from the placental part of the umbilical cord, at latest 30 minutes after birth.
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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.
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Peroxide levels- Part B
Tidsramme: Part B: From enrollment until one week (7 days) after the admission to the neonatal intensive care unit.
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Peroxide levels at admission (<48h).
Peroxide levels 48-72 h after admission.
Peroxide levels 5-7 days after admission.
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Part B: From enrollment until one week (7 days) after the admission to the neonatal intensive care unit.
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Peroxide levels- Part C
Tidsramme: Part C: From enrollment to the postmenstrual age of 40+0 weeks.
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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:
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Part C: From enrollment to the postmenstrual age of 40+0 weeks.
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Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Ledende efterforsker: Ena Suppan, MD, Divison of Neonatology, Department of Pediatrics, Medical University of Graz, Auenbruggerplatz 32, 8036 Graz, Austria
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- 1319/2025
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
The following individual participant data will be shared:
De-identified individual participant data underlying the results reported in the primary and secondary outcome analyses, including baseline demographic characteristics (e.g., age, sex), eligibility variables, group assignment, outcome measures, and key covariates used in the statistical analyses.
The following data will not be shared:
Direct identifiers (e.g., names, addresses), free-text clinical notes, imaging files, genetic data, and any data that could reasonably lead to re-identification of participants.
IPD-delingstidsramme
IPD-delingsadgangskriterier
IPD-deling Understøttende informationstype
- STUDY_PROTOCOL
- SAP
- ICF
- ANALYTIC_CODE
- CSR
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