The lifesaving role of blood transfusion in preterm infants

Mahsa Yazdanbakhsh is a PhD candidate training in the laboratory of Canadian Blood Services’ Senior Research Scientist, Dr. Jason Acker and recipient of Canadian Blood Services’ Graduate Fellowship Program award. Mahsa was the lead author on a basic science article published in the peer reviewed journal Pediatric Research in October 2024. Following publication, this research was also featured in an editorial written by international transfusion experts in the same journal. In this blog post, Mahsa summarizes the work which earned this editorial feature.

Preterm infants (babies born before 32 weeks of gestation) often require red blood cell (RBC) transfusions. While much focus has been placed on determining the right timing and volumes for transfusions, further investigation will help us understand more about other critical aspects, such as the ideal blood product and the impact of donor factors on transfusion outcomes.

Our research team, led by Canadian Blood Services’ senior research scientist, Dr. Jason Acker at the University of Alberta, has been investigating the effects of transfused adult RBCs on preterm infants with the goal of understanding better-matched alternatives for these vulnerable recipients. Working closely with neonatologists and colleagues at the Royal Alexandra Hospital, Alberta Children’s Hospital Research Institute and the University of Calgary, our studies aimed to optimize transfusion practices and improve overall outcomes.

How adult blood affects preterm infants

To donate blood in Canada, the minimum age for donors must be 17 years of age or older. However, this can present a developmental mismatch for preterm infants who are the recipients of RBC transfusions from these adult donors. Preterm infants primarily have a fetal version of the hemoglobin (HbF) protein which carries oxygen molecules within the red blood cell. Fetal hemoglobin has a higher affinity (how well hemoglobin binds to and releases oxygen molecules) for oxygen to support oxygen transfer from the mother to the fetus. Following birth, when preterm infants receive adult RBC transfusions, their HbF is replaced by RBCs containing adult hemoglobin (HbA), which has a lower oxygen affinity.

In our study, we explored the impact of adult RBC transfusions on fetal RBC oxygen affinity. By mixing together adult RBCs and umbilical cord blood (UCB) from preterm infants, we measured the concentration-dependent changes in a metric known as “p50”, which is the amount of oxygen required in blood to saturate 50% of hemoglobin. The p50 measurement can indicate how well hemoglobin can bind to and carry oxygen molecules. The better hemoglobin is at binding to oxygen, the lower the p50 value will be.

We found that as the proportion of adult RBCs in the cell mixture increased, the p50 decreased, indicating that the addition of adult RBCs increases the amount of oxygen bound to hemoglobin in the cord blood. While this shift could improve oxygen delivery to tissues, it may also lead to hyperoxia, where there is too much oxygen at the cellular level. This can cause overproduction of molecules called reactive oxygen species (ROS) which have been linked to prematurity-related conditions such as retinopathy of prematurity (blindness), necrotizing enterocolitis, and bronchopulmonary dysplasia.

Alternative blood sources for premature infants

To minimize these risks, our research is investigating alternative blood sources that may better meet the needs of preterm infants. Two promising options include using young red blood cells (Y-RBCs) isolated from adult red blood cell products, and cryopreserved red blood cells from umbilical cord blood (UCB). RBCs from UCB contains a higher proportion of fetal hemoglobin, which is better suited for oxygen delivery in infants and produces fewer ROS. RBCs derived from UCB are being explored in international clinical trials as a potential alternative to adult RBCs, and early clinical studies are evaluating their safety and efficacy. 

Despite the progress made, much remains unknown about how transfused adult RBCs impact neonatal oxygen affinity and what the optimal oxygen affinity for transfused RBCs should be. Y-RBCs, isolated from red cell concentrates (packed RBCs from whole blood), may provide improved oxygen affinity and lower ROS production compared to RBC units from adult donors. Our current research focuses on isolating and cryopreserving Y-RBCs for infant transfusions. Preliminary findings suggest that the addition of Y-RBCs to fetal blood may improve the oxygen affinity of fetal RBCs, potentially enhancing oxygen delivery and reducing ROS-related risks.

Our results suggest that both UCB and Y-RBCs could offer significant benefits over conventional adult blood transfusions. These alternatives may help create more tailored transfusion strategies for infants, improving long-term health outcomes.

Optimizing transfusions for premature neonates

As part of our ongoing research, we are exploring factors such as RBC storage duration, donor age, sex, and potential RBC modifications to better mimic neonatal blood characteristics. Understanding how these factors influence neonatal outcomes is crucial to refining transfusion protocols and donor selection criteria, with the ultimate goal of improving oxygen delivery and health outcomes in premature neonates. Every drop of blood has the potential to save a life, and by informing the optimization of transfusion practices, our research aims to enhance the survival and well-being of the most vulnerable blood recipients. 

Canadian Blood Services – Driving world-class innovation

Through discovery, development and applied research, Canadian Blood Services drives world-class innovation in blood transfusion, cellular therapy and transplantation—bringing clarity and insight to an increasingly complex healthcare future. Our dedicated research team and extended network of partners engage in exploratory and applied research to create new knowledge, inform and enhance best practices, contribute to the development of new services and technologies, and build capacity through training and collaboration. Find out more about our research impact.   

The opinions reflected in this post are those of the author and do not necessarily reflect the opinions of Canadian Blood Services nor do they reflect the views of Health Canada or any other funding agency.