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.
Neonates who are monitored on the NICU immediately after birth
Written parental informed consent
Term and preterm neonates admitted to the NICU for medical treatment
Age ad admission <48 hours
No decision to conduct full life support
No parental written informed consent
Congenital malformations
Family history of hemoglobinopathies (e.g. sickle cell anemia, thalassemia)
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.
Cohort
Prospective
Peroxide analysis-TOC Omnignostica Forschungs GmbH
Diagnostic test1\. 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.
Near Infrared Imaging
DeviceFor 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.
Peroxide levels- Part A
Baseline peroxide levels in umbilical artery Baseline peroxide levels in umbilical vein
Peroxide levels- Part B
Peroxide levels at admission (\<48h). Peroxide levels 48-72 h after admission. Peroxide levels 5-7 days after admission.
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
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