The Correlation Between Red Cell Transfusion and Complications of Prematurity

Premature infants are the group that receives the most red blood cell transfusions. Between 50% and 90% of very low birth weight (VLBW) infants (less than 1500 g) and up to 95% of extremely low birth weight (ELBW) infants (less than 1000 g) will receive at least one red blood cell transfusion during hospitalisation.

To date, there are no clear guidelines for transfusion in premature infants in clinical practice.

Premature infants are particularly susceptible to tissue injury caused by impaired oxygen delivery, and complications are associated with this imbalance in tissue oxygenation. The pathophysiology of complications in transfused premature infants involves several interconnected mechanisms arising from organ immaturity and the specific effects of transfusion.

Over the past twenty years, numerous scientific studies have investigated the adverse effects of packed red blood cell transfusions. Many of these studies have associated red blood cell transfusions with a higher risk of both early and late complications of prematurity, such as necrotising enterocolitis (NEC), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH), and issues in later neurodevelopment. Only a few studies have reported beneficial effects of transfusion.

Red blood cell transfusion, along with other comorbidities in preterm infants, may contribute to neurological and neurodevelopmental damage. Some studies have confirmed that a restrictive approach leads to better neurodevelopmental outcomes, while others have shown abnormal brain structures and volumes at school age.

Based on previous research and the varied results obtained, the investigators aim to investigate the relationship between packed red blood cell transfusion, the number of transfusions, and the age at the time of transfusion concerning the occurrence of early and late prematurity complications. The investigators also seek to determine whether the haemoglobin level at the time of transfusion influences the development of complications. Although the impact on neurodevelopmental outcomes is partly understood and studied in younger premature children (aged 2 to 5), there are few studies and limited research on the effects in older children.

The hypothesis of this study is that premature infants who received packed red blood cell transfusions during the neonatal period have a higher rate of early prematurity complications and poorer neurological and neurodevelopmental outcomes at six years of age compared to premature infants who did not receive transfusions.

Investigation plan In the first, retrospective part, the investigators will collect epidemiological data from premature newborns (less then 32 weeks of gestation) from the hospital information system (IBIS) and the medical histories of the participants between June 2018 and December 2021.

The participants will be split into those who received a transfusion of packed red blood cells and those who did not.

In the second phase of the study, the investigators will evaluate the neurological and neurodevelopmental outcomes of the same participants during preschool age (at 6 years old adjusted for chronological age), based on the transfusion treatment. This phase will take place from September 2025 to December 2028. Parents of each child meeting the inclusion criteria will receive a notice about the study, which will be delivered by a primary care paediatrician during the examination that all children should have before starting their first year of primary school. After reading the notice, parents will sign the inform consent form if they agree to participate. The primary paediatrician will inform the main investigator, after which the child and parent or guardian will be invited to the Paediatrics Clinic for a neurological and neurodevelopmental assessment. Once all data collection is complete, statistical analysis will be performed to explore whether there is a connection between transfused preterm infants, early prematurity complications, and neurological and neurodevelopmental outcomes.