The Correlation Between Red Cell Transfusion and Complications of Prematurity

NCT ID: NCT07123948

Last Updated: 2025-08-14

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 128 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-09-01
• Study Completion Date: 2029-03-01

Brief Summary

The aim of this clinical trial is to learn if there is a correlation between the erythrocyte transfusion in the early neonatal period in premature infants and early and late complications of prematurity. The main questions it aims to answer are:

• Do premature infants who receive blood transfusions within their first month of life have a higher risk of early prematurity complications, such as retinopathy of prematurity, necrotising enterocolitis, bronchopulmonary dysplasia, and intraventricular haemorrhage?
• Do premature infants who receive blood transfusions during their first month of life have worse neurological and neurodevelopmental outcomes than those who do not? The first part of the study is retrospective, using data collected from participants' histories. The second part is prospective, evaluating neurological and neurodevelopmental outcomes at the age of six years.

Detailed Description

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.

Conditions

Retinopathy of Prematurity (ROP); Bronchopulmonary Dysplasia (BPD); Enterocolitis, Necrotizing; Intraventricular Hemorrhage Neonatal

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Assesment of the neurological and neurodevelopmental outcome at the age of six

All premature infants (less than 32 weeks of gestation) will be neurologically assessed at the age of six. Also, their neurodevelopmental outcome will be assessed at the age of six using the Wechsler Intelligence Test.

Wechsler Intelligence Test, performed by educated psychologists

Intervention Type: DIAGNOSTIC_TEST

At the age of six, parents of children who meet the inclusion criteria will receive a notification about the study from the responsible paediatrician. If they agree to participate, they will sign an informed consent form. They will then be invited to the clinic for a neurological and neurodevelopmental assessment. The neurological examination will be conducted by the principal investigator or collaborators who are paediatric specialists. The neurodevelopmental evaluation will be performed by a qualified psychologist using the Wechsler Intelligence Test.

The Wechsler Intelligence Test for Children - Fourth Edition is a clinical tool for measuring the intelligence of children aged 6 to 16 years and 11 months. It assists in identifying specific learning difficulties, hyperactivity disorder, speech and language challenges, and intellectual impairments. The test comprises 15 subtests.

Interventions

Wechsler Intelligence Test, performed by educated psychologists

At the age of six, parents of children who meet the inclusion criteria will receive a notification about the study from the responsible paediatrician. If they agree to participate, they will sign an informed consent form. They will then be invited to the clinic for a neurological and neurodevelopmental assessment. The neurological examination will be conducted by the principal investigator or collaborators who are paediatric specialists. The neurodevelopmental evaluation will be performed by a qualified psychologist using the Wechsler Intelligence Test.

The Wechsler Intelligence Test for Children - Fourth Edition is a clinical tool for measuring the intelligence of children aged 6 to 16 years and 11 months. It assists in identifying specific learning difficulties, hyperactivity disorder, speech and language challenges, and intellectual impairments. The test comprises 15 subtests.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• all children born as premature infants <32. weeks of gestation in Clinical Hospital Centre Rijeka from June 2018. to December 2021. (and who will be on September 2025. six years old)
• signed informed consent

Exclusion Criteria

• genetic syndromes, severe congenital anomalies

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 7 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clinical Hospital Center Rijeka

OTHER

Sponsor Role: lead

Responsible Party

Kristina Lah Tomulić

assoc. professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

senada šerifi

Role: PRINCIPAL_INVESTIGATOR

Clinical Hospital Centre Rijeka, Croatia

Locations

Clinical Hospital Centre Rijeka, Department of Paediatrics

Rijeka, Primorje-Gorski Kotar County, Croatia

Countries

Croatia

Central Contacts

Kristina Lah Tomulić

Role: CONTACT

kristina.lah.tomulic@medri.uniri.hr

+385992015885

senada šerifi

Role: CONTACT

senada.serifi@medri.uniri.hr

Facility Contacts

Kristina Lah Tomulić

Role: primary

kristina.lah.tomulic@medri.uniri.hr

+385992015885

Senada Šerifi, MD

Role: backup

senada.serifi@medri.uniri.hr

Other Identifiers

003-05/24-01/150

Identifier Type: -

Identifier Source: org_study_id