Retinopathy of Prematurity (ROP)NCT07123948
The Correlation Between Red Cell Transfusion and Complications of Prematurity
An observational study of Retinopathy of Prematurity (ROP) and Bronchopulmonary Dysplasia (BPD), run by Clinical Hospital Center Rijeka at 1 site in Croatia.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 7 years
- Conditions the study is for
- Retinopathy of Prematurity (ROP), Bronchopulmonary Dysplasia (BPD), Enterocolitis, Necrotizing
- What is being tested?
- Wechsler Intelligence Test, performed by educated psychologists
- How many people
- 128 participants
- Where
- 1 siteCroatia
- Study dates
- 1 Sep 2025to 1 Mar 2029
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 7 years
- All sexes
- No healthy volunteers
- Child
Study population: The participants will be identified and selected by the primary care paediatricians in Primorsko-Goranska, Istarska, and Ličko-Senjska County (western part of Croatia)
Who may be able to join
- 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
Who cannot join
- genetic syndromes, severe congenital anomalies
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
senada šerifi contact
Croatia1 site, 1 recruiting
- Recruiting
Clinical Hospital Centre Rijeka, Department of Paediatrics
Rijeka, Primorje-Gorski Kotar County, 51000
Kristina Lah Tomulić, +385992015885, kristina.lah.tomulic@medri.uniri.hr
Senada Šerifi, MD, senada.serifi@medri.uniri.hr
About this study
Official title: The Correlation Between Packed Red Blood Cell Transfusion and Early and Late Complications of Prematurity
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.
Read the 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
- Being tested
- Wechsler Intelligence Test, performed by educated psychologists
- Keywords
- Infant, Premature;, Erythrocyte Transfusion, Neurodevelopmental Disorder
- Medical subject headings
- Retinopathy of Prematurity, Bronchopulmonary Dysplasia, Enterocolitis, Necrotizing, Premature Birth, Neurodevelopmental Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Wechsler Intelligence Test, performed by educated psychologistsDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Diagnostic Test: Wechsler Intelligence Test, performed by educated psychologists |
What is being measured
The primary outcome is the main question the study is designed to answer.
Motor function at the age of 6 years in premature infants who received erythrocyte transfusion compared to those who did not
The outcome measure is the motor function of premature infants (less than 32 weeks of gestation) at the age of 6 years who received erythrocyte transfusion in the neonatal period.
The aim is to identify the proportion of participants with normal, mildly impaired, moderately impaired, or severely impaired motor function.
The Gross Motor Function Classification System (GMFCS) will be used to assess motor function.
GMFCS is a standardized classification tool used to evaluate and describe motor function levels in children with cerebral palsy. It was created to offer a dependable framework for understanding restrictions in gross motor skills in children of different age groups.
If The GMFCS score is 0, motor function is normal. Cerebral palsy will be classified as mild if the GMFCS score is 1, moderate if the GMFCS score is 2, and severe if the GMFCS score is 3 or higher.
On the GMFCS scale, the minimum value is 0, and the maximum value is 5. The higher score means a worse outcome.
Measured: From enrollment to the end of the neurologic assessment at 4 weeks.
Hearing assessment at the age of 6 years in premature infants who received erythrocyte transfusion compared to those who did not
The aim is to identify the proportion of participants with normal and impaired hearing function.
Hearing assessment depends on whether the child requires hearing aids. If the child needs hearing aids, the score will be 1; if not, the score will be 0.
The minimum value is 0, and the maximum value is 1. A higher score means a worse outcome.
Measured: From enrollment to the end of the hearing assessment at 4 weeks.
Visual assessment at the age of 6 years in premature infants who received erythrocyte transfusion compared to those who did not
The aim is to identify the proportion of participants with normal and impaired visual function.
Visual assessment depends on whether the child requires visual aids. If the child needs visual aids, the score will be 1; if not, the score will be 0.
The minimum value is 0, and the maximum value is 1. A higher score means a worse outcome.
Measured: From enrollment to the end of the hearing assessment at 4 weeks.
Neurodevelopmental outcome of premature infants who received erythrocyte transfusion compared to those who did not
Neurodevelopmental assessment will be conducted using the Wechsler Intelligence Scale for Children (WISC-IV). It is a clinical tool for evaluating the intelligence of children aged 6 to 16 years and 11 months.
The test includes 15 subtests - 10 core and 5 supplementary. Intellectual functioning in specific cognitive areas is also represented by four composite scores: the Verbal Comprehension Index (VCI), the Perceptual Reasoning Index (PRI), the Working Memory Index (WMI), and the Information Processing Speed Index (PSI). The total test score (UIQ) is calculated based on the sum of scaled scores across the 10 core subtests. The resulting IQ scores are categorized as follows: 69 and below is extremely low; 70 to 79 is borderline; 80 to 89 is low average; 90 to 109 is average; 110 to 119 is high average; 120 to 129 is superior; and 130 and above is very superior.
Minimum value is 40, and the maximum value is 200. The higher score means a better outcome.
Measured: From enrollment to the end of the neurologic assessment at 4 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2025
- Study start1 Sep 2025
- Primary completion31 Dec 2028 (estimated)
- Study completion1 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Retinopathy of Prematurity (ROP)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 128 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Clinical Hospital Center Rijeka
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kristina Lah Tomulić, Clinical Hospital Center Rijeka
- Investigators
- senada šerifi, Principal investigator, Clinical Hospital Centre Rijeka, Croatia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07123948
- Sponsor's protocol ID
- 003-05/24-01/150
- Status last verified
- Oct 2026
- First submitted
- 15 Jul 2025
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The ethics committee's initial decision was that the IPD would not be shared. However, the investigators may share the summarised and statistically processed data of the participants.