An interventional study of Cord Blood Red Blood Cells and Standard Adult Donor Red Blood Cells in Extremely Premature Infant, Anemia Neonatal and Blood Transfusion, sponsored by Hospital Clinic of Barcelona. Not yet recruiting at 1 site in Spain. Open to participants aged 23 Weeks to 28 Weeks. Per ClinicalTrials.gov, last updated 2026-03-31.
Sponsored by Hospital Clinic of Barcelona · Not applicable, Interventional, and Prevention
Anemia is a condition in which there are not enough red blood cells to carry oxygen throughout the body. It is very common in extremely preterm infants (born before 28 weeks of pregnancy), and many of these babies require red blood cell transfusions during their hospital stay.
Currently, transfusions are given using red blood cells donated by adults. An alternative option is to use red blood cells collected from umbilical cord blood, which may be more similar to a newborn's own blood. This approach has been used in some neonatal units with encouraging results and no reported safety concerns.
This study aims to determine whether transfusion with umbilical cord blood improves clinical outcomes and reduces potential side effects compared to standard adult donor blood transfusion in extremely preterm infants. We hypothesize that umbilical cord blood transfusion will be at least as safe as adult donor blood and may provide clinical benefits.
About 115 extremely preterm infants admitted to neonatal units in Catalonia will participate. If parents agree, their baby will be randomly assigned to receive either compatible umbilical cord blood or compatible adult donor blood if a transfusion becomes necessary. Babies will only receive a transfusion if they clinically need one. If cord blood is not available at the time of transfusion, the baby will receive compatible adult donor blood regardless of the assigned group.
To evaluate the response to treatment, small blood samples will be collected at birth, at one month of life, and 24 hours after any transfusion. These samples are taken at the same times as routine blood tests, so participation does not require additional needle sticks. The amount of blood collected is minimal (about 0.2 mL per sample).
In addition, a painless and non-invasive sensor will be placed on the baby's head for 24 hours to measure oxygen delivery to the brain. Urine samples will also be collected before and after transfusion to help assess how oxygen reaches body tissues.
Participation will continue until the baby reaches 36 weeks of postmenstrual age or is discharged from the hospital, whichever comes first.
Neonatal anemia is a common condition in extremely preterm infants (born before 28 weeks of gestation) and is associated with significant health risks. Despite the implementation of evidence-based strategies to reduce anemia, such as delayed umbilical cord clamping and cord milking, many extremely preterm infants still require red blood cell transfusions during the first weeks of life due to a multifactorial decline in hemoglobin levels.
Currently, red blood cell transfusions for these infants use blood from adult donors. Transfusion of adult donor blood has been associated with complications linked to fluctuations in tissue oxygen levels, including retinopathy of prematurity and bronchopulmonary dysplasia. One key factor contributing to these complications is the lower proportion of fetal hemoglobin (HbF) in adult donor blood compared to the infant's natural blood. HbF has a higher affinity for oxygen and releases oxygen more slowly, whereas adult hemoglobin (HbA) delivers oxygen more rapidly to tissues, increasing the risk of oxygen toxicity. Additionally, adult donor blood may contain trace amounts of heavy metals, which could potentially affect extremely preterm infants, although this has not been formally studied.
Red blood cell concentrates derived from umbilical cord blood (CB-RBC) provide an alternative that is closer to the infant's own blood composition. CB-RBC transfusions contain higher levels of HbF, which may reduce tissue oxygen stress. Pilot studies in our center have shown that CB-RBC transfusions are feasible, safe, and effective. In one preliminary study, ten extremely preterm infants (\<28 weeks gestation) received a total of 23 CB-RBC transfusions without adverse reactions, indicating that this approach is safe in clinical practice. However, medium- and long-term benefits of CB-RBC transfusions remain unclear.
Recent research shows that higher HbF levels are inversely correlated with morbidities related to tissue hyperoxygenation, such as bronchopulmonary dysplasia and retinopathy of prematurity. Studies in Italy, including those by Teofili et al., have shown encouraging trends toward reducing severe retinopathy, although small sample sizes prevented statistical significance. These findings support the need for a larger randomized multicenter trial to evaluate clinical outcomes more conclusively.
This study is a randomized multicenter clinical trial coordinated among all major level 3A and 3B public neonatal units in the Barcelona area, with unanimous support from participating units. Approximately 115 extremely preterm infants will be enrolled. Eligible infants will be randomly assigned to receive either CB-RBC transfusions or standard adult donor red blood cell transfusions if a transfusion is clinically indicated. Transfusions will only be performed when medically necessary. If cord blood is not available at the time of transfusion, compatible adult donor blood will be used regardless of assigned group.
To assess the effects of transfusion, small blood samples will be collected at birth, at one month of age, and 24 hours after any transfusion. Blood collection follows routine clinical practice, and volumes are minimal (\~0.2 mL per sample). Non-invasive sensors will be placed on the infant's head for 24 hours to monitor cerebral oxygenation. Urine samples will also be collected before and after transfusion to evaluate tissue oxygen delivery. All procedures are designed to minimize risk and discomfort for participants.
Study Hypothesis: We hypothesize that transfusion with cord blood red blood cell concentrates will reduce the combined outcome of bronchopulmonary dysplasia, retinopathy of prematurity, and death before 36 weeks postmenstrual age or hospital discharge (whichever occurs first), compared to transfusions with standard adult donor red blood cells.
The results of this study aim to provide strong evidence regarding the clinical benefits of CB-RBC transfusions in extremely preterm infants, including the potential to reduce transfusion-related complications and improve outcomes. If successful, this approach could be implemented more widely to enhance neonatal care for this vulnerable population
305 studies on the registry are indexed under beta-Thalassemia; 70 are open to participants now.
This study's planned enrollment of 176 is above the median of 38 across 211 interventional studies indexed under beta-Thalassemia.
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Exclusion Criteria:
Extremely preterm infants randomized to this arm will receive red blood cell transfusions derived from umbilical cord blood (CB-RBC) when a transfusion is clinically indicated according to standard neonatal guidelines. If compatible cord blood units are not available at the time of transfusion, standard adult donor red blood cells may be used.
Biological: Cord Blood Red Blood Cells
Extremely preterm infants randomized to this arm will receive standard adult donor red blood cell transfusions when a transfusion is clinically indicated according to standard neonatal guidelines.
Biological: Standard Adult Donor Red Blood Cells
Neonates receive transfusions of red blood cells derived from allogeneic umbilical cord blood, ABO/RhD compatible. Dosage: 15-20 mL/kg per transfusion, administered according to clinical indication and availability. If cord blood is not available at the time of transfusion, adult donor red blood cells (CH-SA) are given instead. Monitoring: Vital signs, complete blood count, hematocrit, fetal hemoglobin (HbF), and tissue oxygenation (via NIRS) are recorded before and after transfusion.
Also known as: CH-SCU
Neonates receive transfusions of red blood cells derived from adult donors, ABO/RhD compatible. Dosage: 15-20 mL/kg per transfusion, administered according to clinical indication and the protocol of each neonatal unit. Transfusions are performed only when medically necessary. Monitoring: Vital signs, complete blood count, hematocrit, fetal hemoglobin (HbF), and tissue oxygenation (via NIRS) are recorded before and after transfusion.
Also known as: CH-SA
Composite outcome of bronchopulmonary dysplasia, retinopathy of prematurity, or death in extremely prematurs
The primary outcome is the occurrence of: * Bronchopulmonary dysplasia (BPD, any grade) defined as the need for oxygen therapy or any respiratory support at 36 weeks postmenstrual age (PMA). Classified according to Jensen et al. (2019), assessed at 36 weeks PMA. * Retinopathy of prematurity (ROP, any stage) diagnosed according to the International Classification of Retinopathy of Prematurity, assessed by ophthalmologists blinded to group allocation using ophthalmoscopy and the Catalonia Ophthalmic Telemedicine Network (RTOC). * Death before 36 weeks postmenstrual age or hospital discharge, whichever occurs first. This composite outcome is used to evaluate the clinical benefit of cord blood-derived red blood cell transfusions compared to standard adult donor transfusions in extremely preterm infants.
Time frame: From birth until 36 weeks postmenstrual age or hospital discharge (whichever occurs first).
Fetal hemoglobin (HbF) threshold at one month associated with clinical outcomes
To evaluate the fetal haemoglobin (HbF) percentage cutoff at one month of life that best correlates with a reduction in the composite outcome of retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), or death, as well as with each outcome individually. Due to limited availability of cord blood units (CB-RBC), some infants assigned to this group may receive adult donor red blood cells. This analysis aims to identify protective or critical HbF thresholds for the development of ROP and BPD.
Time frame: At one month of life.
Oxygen-free days within 90 days post-randomization
To evaluate the impact of cord blood-derived red blood cell transfusion (CB-RBC) versus standard adult donor red blood cell transfusion (AD-RBC) on intermediate outcomes, specifically the number of oxygen-free days during the 90 days following randomization.
Time frame: Up to 90 days after randomization.
Hematologic parameters post-transfusion (1)
Assessment of transfusion efficacy via changes in total hematocrit.An increment in hematocrit by 12 ± 5 points 24 hours after the transfusion will be considered effective. This analysis aims to demonstrate non-inferiority of CB-RBC vs AD-RBC.
Time frame: Pre-transfusion, 24 hours post-transfusion, and at 1 month of age
Hematologic parameters post-transfusion (2)
Assessment of transfusion efficacy via changes in total hemoglobin. An increment in total hemoglobin by 4 ± 2 g / dL 24 hours after the transfusion will be considered effective. Samples will be analysed by microhematocrit method. This analysis aims to demonstrate non-inferiority of CB-RBC vs AD-RBC.
Time frame: Pre-transfusion, 24 hours post-transfusion, and at 1 month of age
Fetal hemoglobin (HbF) percentage evolution
Measure changes in HbF percentage over time (at birth, pre- and post-transfusion, and at 1 month), evaluating its association with intermediate and clinical outcomes.
Time frame: At birth, 24 hours post-transfusion, and 1 month of age
Tissue oxygenation measured by NIRS
Evaluate cerebral oxygenation changes using near-infrared spectroscopy (NIRS ("INVOS 5100C Cerebral/somatic oximeter "(Medtronic Minneapolis, MM)) during and 24 hours after transfusion to assess tissue oxygen delivery.
Time frame: From transfusion initiation until 24 hours post-transfusion
Red blood cell transfusion requirements (1)
Total volume of transfusions (mililiters) received until 36 weeks PMA or hospital discharge, comparing CB-RBC vs AD-RBC.
Time frame: From birth until 36 weeks PMA or hospital discharge
Red blood cell transfusion requirements (2)
Total number of transfusions received until 36 weeks PMA or hospital discharge, comparing CB-RBC vs AD-RBC.
Time frame: From birth until 36 weeks PMA or hospital discharge
Markers of oxidative stress
Measure urinary isoprostanes as an oxidative stress marker at birth, post-transfusion and 1 month of age
Time frame: At birth, post-transfusion, and 1 month of age
Bone marrow regeneration parameters
Reticulocyte counts will be measured at 1 month of life as an indicator of marrow regeneration
Time frame: 1 month of life
Iron metabolism values
Ferritin levels at 1 month of life will be measured as an indicator of iron metabolism
Time frame: 1 month of life
Plan to share: No
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Anemia, Neonatal
Hospital Clinic of Barcelona