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| Name | Class |
|---|---|
| Hospital Sant Joan de Deu | OTHER |
| Hospital de la Santa creu i Sant Pau - Barcelona | OTHER |
| Hospital Vall d'Hebron | OTHER |
| Germans Trias i Pujol Hospital |
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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cord Blood-Derived Red Blood Cell Transfusion | Experimental | 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. |
|
| Adult Donor Red Blood Cell Transfusion | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cord Blood Red Blood Cells | Biological | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Composite outcome of bronchopulmonary dysplasia, retinopathy of prematurity, or death in extremely prematurs | The primary outcome is the occurrence of:
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. | From birth until 36 weeks postmenstrual age or hospital discharge (whichever occurs first). |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Pre-transfusion, 24 hours post-transfusion, and at 1 month of age |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Miguel Maria Alsina Casanova, MD | Contact | +34932275600 | 7503 | mmalsina@clinic.cat |
| Dinara Smarkanova, MD | Contact | +34935573500 | 6563 | dsamarkanova@bst.cat |
| Name | Affiliation | Role |
|---|---|---|
| Miguel Maria Alsina Casanova, MD | Hospital Clinic of Barcelona | Principal Investigator |
| Dinara Smarkanova, MD | Banc de Sang i Teixits | Study Director |
| Miguel Ramón Jiménez, MD |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Clínic de Barcelona - Maternitat | Barcelona | 08028 | Spain |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37900679 | Background | Torrejon-Rodriguez L, Pinilla-Gonzalez A, Lara Canton I, Albiach-Delgado A, Cascant-Vilaplana MM, Cernada M, Kuligowski J, Solves Alcaina MP, Gomez I, Vento M, Aguar Carrascosa M. Effect of autologous umbilical cord blood transfusion in the development of retinopathy of prematurity: randomized clinical trial - study protocol. Front Pediatr. 2023 Oct 12;11:1269797. doi: 10.3389/fped.2023.1269797. eCollection 2023. | |
| 39113069 |
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| OTHER |
| Parc Taulí Hospital Universitari | OTHER |
Extremely preterm infants who require a red blood cell transfusion will be randomly assigned in a 1:1 ratio to receive either cord blood-derived red blood cell concentrates (CB-RBC) or standard adult donor red blood cell transfusions. Transfusions will only be administered when clinically indicated according to standard neonatal transfusion guidelines. If cord blood units are not available at the time of transfusion, compatible adult donor blood will be used.
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|
|
| Standard Adult Donor Red Blood Cells | Biological | 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. |
|
|
| 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. | Up to 90 days after randomization. |
| 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. | 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. | 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. | 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. | 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. | 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 | 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 | 1 month of life |
| Iron metabolism values | Ferritin levels at 1 month of life will be measured as an indicator of iron metabolism | 1 month of life |
| Hospital Sant Joan de Deu |
| Principal Investigator |
| Fátima Camba Longueira, MD | Hospital Vall d'Hebron | Principal Investigator |
| María José García Borau, MD | Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau | Principal Investigator |
| Marta Ocaña Rico, MD | Germans Trias i Pujol Hospital | Principal Investigator |
| Mònica Domingo Puiggròs, MD | Hospital Parc Taulí | Principal Investigator |
| Background |
| Teofili L, Papacci P, Dani C, Cresi F, Remaschi G, Pellegrino C, Bianchi M, Ansaldi G, Campagnoli MF, Vania B, Lepore D, Franco FGS, Fabbri M, de Vera d' Aragona RP, Molisso A, Beccastrini E, Dragonetti A, Orazi L, Pasciuto T, Mozzetta I, Baldascino A, Locatelli E, Valentini CG, Giannantonio C, Carducci B, Gabbriellini S, Albiani R, Ciabatti E, Nicolotti N, Baroni S, Mazzoni A, Besso FG, Serrao F, Purcaro V, Coscia A, Pizzolo R, Raffaeli G, Villa S, Mondello I, Trimarchi A, Beccia F, Ghirardello S, Vento G. Cord blood transfusions in extremely low gestational age neonates to reduce severe retinopathy of prematurity: results of a prespecified interim analysis of the randomized BORN trial. Ital J Pediatr. 2024 Aug 7;50(1):142. doi: 10.1186/s13052-024-01714-w. |
| 32510635 | Background | Teofili L, Papacci P, Orlando N, Bianchi M, Molisso A, Purcaro V, Valentini CG, Giannantonio C, Serrao F, Chiusolo P, Nicolotti N, Pellegrino C, Carducci B, Vento G, De Stefano V. Allogeneic cord blood transfusions prevent fetal haemoglobin depletion in preterm neonates. Results of the CB-TrIP study. Br J Haematol. 2020 Oct;191(2):263-268. doi: 10.1111/bjh.16851. Epub 2020 Jun 8. |
| 33370228 | Background | Gonzalez EG, Casanova MA, Samarkanova D, Aldecoa-Bilbao V, Teresa-Palacio M, Busquets EF, Figueras-Aloy J, Salvia-Roiges M, Querol S. Feasibility of umbilical cord blood as a source of red blood cell transfusion in preterm infants. Blood Transfus. 2021 Nov;19(6):510-517. doi: 10.2450/2020.0169-20. Epub 2020 Dec 18. |
| ID | Term |
|---|---|
| D000751 | Anemia, Neonatal |
| D017086 | beta-Thalassemia |
| D001997 | Bronchopulmonary Dysplasia |
| D012178 | Retinopathy of Prematurity |
| D066087 | Perinatal Death |
| ID | Term |
|---|---|
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007232 | Infant, Newborn, Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D013789 | Thalassemia |
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D055397 | Ventilator-Induced Lung Injury |
| D055370 | Lung Injury |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D007235 | Infant, Premature, Diseases |
| D012164 | Retinal Diseases |
| D005128 | Eye Diseases |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D003643 | Death |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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