A brighter future for preterm neonates

Fresenius Kabi actively supports the BORN cord blood transfusion study – in close collaboration with Fondazione Policlinico Universitario A. Gemelli IRCCS Università Cattolica del Sacro Cuore, Rome, Italy.

Premature newborn lying in an incubator in a neonatal intensive care unit, connected to various life-support and monitoring devices.

The birth of a child is an extremely special, emotional and significant moment in any new parent’s life. But when that child is born prematurely, this precious time can also become immensely stressful.

Extremely low gestational age neonates (ELGANs) are at a high risk of complications and morbidities, including severe retinopathy of prematurity (ROP) and lung injuries (bronchopulmonary dysplasia) – which can lead to lifelong disabilities. In recent years, Dr. Luciana Teofili has been at the forefront of research efforts in this area. As a hematologist with many years of clinical experience, Dr. Teofili began to focus on neonatal blood transfusions using umbilical cord-blood red blood cells.

“Neonatologists had begun to understand that the reduction of fetal hemoglobin in these infants may have clinical relevance,” Dr. Teofili explains. “But at the beginning of my life in transfusion, I learned that while there had already been some attempts to break up the umbilical cord units as a kind of laboratory exercise, a clinical trial had never been considered.”

Prof. Luciana Teofili smiling, dressed in a white lab coat and blue turtleneck sweater, standing in front of a glass partition with a visible clinical or laboratory environment in the background, where healthcare personnel are working at computer stations
Prof. Luciana Teofili Transfusion Medicine Department, Fondazione Policlinico Universitario A. Gemelli IRCCS Università Cattolica del Sacro Cuore

Opening up the research pathway for cord blood transfusions

Dr. Teofili and her colleagues at the Gemelli’s hospital, including neonatology expert Dr. Patrizia Papacci, were highly motivated to explore the potential value of cord blood for ELGAN transfusions. As Dr. Papacci explains:

“One of the main issues ELGAN infants can face is anemia – and transfusions can have a very heavy impact on this category of children, especially if the body rejects the blood.”

The researchers considered that the metabolisms and bodies of these extremely young infants operate based on fetal hemoglobin, which releases oxygen more slowly in the tissues. As Dr. Papacci states, “When these babies are born, they are exposed to several transfusions with adult blood that releases oxygen with high kinetic reactions to unprepared tissues.”

The research team was considering the possibility of creating a safe clinical method for storing and transfusing umbilical cord blood to ELGANs. As Dr. Teofili explains, “We published an initial feasibility study in 2015. Then, our goal was to translate these notions into a practice whereby these newborns could receive a product that could be just as safe and effective.”

Prof. Patrizia Papacci dressed in a white lab coat and blue scrubs, standing in front of a glass partition with a view into a clinical or laboratory setting, where medical staff are working at computer stations in the background.
Prof. Patrizia Papacci Neonatal Intensive Care Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS Università Cattolica del Sacro Cuore

Intensifying the research required a strong partner

Next, the team conducted a further study which aimed to demonstrate that by transfusing fetal hemoglobin into anemic ELGAN infants, the anemia could be corrected without depleting the patient’s own fetal hemoglobin reserves. As Dr. Teofili reflects, “After publishing our findings, we understood that moving forward would have required extensive trials, therefore more patients, analyses and, last but not least, new partners.”

For Dr. Teofili and her colleagues, the question of funding was about more than simply money – there were also numerous technical issues to consider regarding the preparation and storage of red cells from cord blood.

“So far, cord blood has never been used for transfusions, at least in our countries. It was generally collected as a source of stem cells, which would then be frozen while the red blood cells were largely disregarded. Not only that, but cord blood donations are around a third or a quarter of the volume of the blood donations you would receive from adult donors.” 

Technical solutions were needed to manage the small, precious cord blood volumes, including suitable bags and filters, as well as achieving safe and replicable methods to test, store and infuse these aliquots into the infants.

Support at every step from Fresenius Kabi – from study design to execution

As Dr. Teofili and her team were preparing to conduct this trial, known as the BORN study (umBilical blOod to tRansfuse preterm Neonates), Fresenius Kabi emerged as the partner of choice. As Dr. Teofili explains: 

“While we spoke to several companies, we chose Fresenius Kabi because they listened to us. They believed in our scientific rationale, and they also showed greater sensitivity when it came to neonatal transfusions, particularly with respect to the use of non-toxic materials.”

A total of eight neonatal intensive care centers were involved in the randomized trial, in locations throughout Italy. Fresenius Kabi worked together with the study teams to develop procedures for cord blood fractionation and exported the required method and equipment to the participating centers. Fresenius Kabi products such as the CompoMat G5 blood separator, non-DEHP blood bags and the standalone BioR flex filter were all incorporated into the process.

As Dr. Teofili notes, “This process allowed cord blood units to be obtained with consistent characteristics, produced in the same, automated way, fractionated in bags that are optimal for neonatal transfusion.” Furthermore, as the study continued, Fresenius Kabi played an active and constant role in helping the team to improve and optimize their procedures: 

“They were always supporting our partners in any location, ensuring that each center could rely upon the application specialist, who knew our study and the methodology we were using.”

Passionate clinicians, highly supportive parents

Dr. Teofili and her team worked with passion and relentless dedication throughout this long-term and emotionally demanding project. At the same time, she notes that parents of the small BORN patients have been universally supportive: “We have not seen any parents refusing to join this study, considering what a dramatic event it is for a family a child born months before the planned date. These parents gave their confidence and trust to us, as professionals and people, and to our research.”

Listening to Dr. Teofili and Dr. Papacci, it is easy to understand why their levels of motivation remain so high. As Dr. Papacci explains, “Neurological, visual and respiratory disabilities have an enormous social impact. These conditions can totally turn family lives upside down. I know several families with children with disabilities; I know their struggles for rights, in everyday life, and for acceptance in school and in social life. The goal of reducing or perhaps even eliminating disability in ELGAN newborns is a dream, but I think we can get there.”

Reflecting on a positive experience

Summing up the study’s progression to date, Dr. Teofili reflects, “This has been a wonderful experience, highlighting how it is more productive and fulfilling to work in a team – with experts and different skills, integrating knowledge. For those like me who perform transfusions, it is important to know that the service we provide can be delivered as part of a wider multidisciplinary network where we work together and develop our skills, yet always with the patient at the center.”

Dr. Papacci shares Dr. Teofili’s hopes for the future of ELGAN care – building on the strong foundations of this important research. “As long time neonatologists, we lived in times where the goal was improving outcomes in children born weighing 2 kilos at 33 or 34 weeks. Now the life clock can start ticking 10 weeks earlier, and we know we hold the knowledge and the technologies to deal with the frightening challenges that ELGANs face. One day, 23-week-old babies will be able to live their lives without ROP and other conditions – this is what we are aiming for.” Finally, Dr. Teofili returns to the strong partnership that the BORN study team has built with Fresenius Kabi:

Prof. Luciana Teofili and Prof. Patrizia Papacci in white lab coats standing in front of a glass wall with a clinical setting and staff visible in the background.
“I must say that Fresenius Kabi believed in us, not only to support a study of this type, but they really put themselves by our side to understand how to design and perform this study. Their experience and technical expertise have made this possible.”
The information shared in this story represents the personal opinions and experiences of the customer. These views are solely their own and do not necessarily reflect the opinions, positions, or policies of our company.

Related content