Transfusion-Related Changes in Oxidative Stress Biomarkers in Neonates

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.

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