Fetal Hemoglobin, Premature Infant Disease, Transfusion Related Complication
Conditions
Brief summary
Repeated transfusions have been associated with very poor outcome of preterm infants. Fetal hemoglobin (HbF) and adult Hb (HbA) have different affinity for oxygen. The high level of adult Hb may contribute to exacerbating the oxidative damage responsible for prematurity diseases. The investigators hypothesized that transfusing red blood cells (RBC) obtained from allogeneic cord blood (CB) of healthy full-term babies (which contains almost exclusively HbF) may prevent the non-physiological decrease of HbF in premature neonates, likewise protecting them from oxygen radical diseases. Cord blood transfusion in preterms - CB TRIP - is a monocentric prospective nonrandomized study aimed to monitor HbF levels in preterm neonates receiving RBC transfusions from either umbilical blood of full-term healthy babies (CB-RBC) and/or from adult donors (A-RBC).
Detailed description
Preterm neonates enrolled in this study are monitored for the level of HbF on capillary blood samples, from birth to the week 32 of postmenstrual age (PMA). To fulfill the RBC transfusion requirements, RBC concentrates obtained from umbilical blood of full-term healthy babies are utilized, if available; otherwise, RBC concentrates from adult donors are assigned. For every week of PMA, neonates undergo a minimum of three HbF determinations, and the median values are considered.
Interventions
None listed
Sponsors
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
preterm neonates born at PMA ≤30 weeks and/or with birth weight ≤1000 g born at the delivery room of Fondazione Policlinico Universitario A. Gemelli candidate to receive one or more RBC unit transfusion.
Exclusion criteria
One or more of the following criteria Maternal-fetal immunization Hydrops fetalis Major congenital malformations associated or not with genetic syndromes Previous transfusions Hemorrhage at birth Congenital infections (such as infections from TORCH complex) Out-born infants The health care team deems it inappropriate to approach the infant's family for informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Percentage of HbF at 32 Weeks of Post Menstrual Age | From study entry to the completion of postmenstrual age of 32 weeks | The HbF level was determined by high-performance liquid chromatography and was expressed as percentage of total Hb, calculated as the sum of fetal and adult Hb, according to the formula: HbF= \[HbF/ (FHbA1 + HbA2 + HbF)\]. HbF. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post-transfusion Hematocrit (Htc) Change | From enrollment to last HbF assessment occurring at 36 weeks, discharge or death | Change from baseline of Htc observed after either adult-RBC or cord-RBC transfusions. To this purpose, analysis was carried out between the two groups of RBC transfusions and patients were accordingly redistributed. |
| Intervals Between Transfusions | From enrollment to the last HbF assessment occurring at 36 weeks, discharge or death | Number of days between two consecutive transfusions.To this purpose, analysis was carried out between the two groups of RBC transfusions and patients were accordingly redistributed. |
| Median Percentage of HbF at Last Assessment | From enrollment to the last HbF assessment occurring at 36 weeks, discharge or death | Median percentage of HbF at last HbF assessment. The last HbF measure was obtained at the completion of the 36 week of age, discharge or death. |
Countries
Italy
Participant flow
Recruitment details
Parents of neonates with birth weight \< 1000 gr and/or postmenstrual age \< 30 weeks consecutively admitted to the intensive neonatal unit of Fondazione Poiliclinico Gemelli IRCCS were informed about the study and asked to paricipate.
Pre-assignment details
Among 29 couples, 25 accepted to participate and overall 25 patients were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Non-Transfused 13 patients not receiving transfusions. | 13 |
| Non-Transfused 13 patients not receiving transfusions. | 224 |
| Only Cord-RBC 3 patients receiving exclusively cord-RBC transfusions | 3 |
| Only Cord-RBC 3 patients receiving exclusively cord-RBC transfusions | 46 |
| Only Adult-RBC 4 patients receiving exclusively adult-RBC transfusions | 4 |
| Only Adult-RBC 4 patients receiving exclusively adult-RBC transfusions | 68 |
| Cord- and Adult-RBC 5 patients receiving both adult-RBC and cord-RBC transfusions | 5 |
| Cord- and Adult-RBC 5 patients receiving both adult-RBC and cord-RBC transfusions | 140 |
| Total | 503 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| From Enrollment to the Age of 32 Weeks | Death before the age of 32 weeks | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Non-Transfused | Only Cord-RBC | Only Adult-RBC | Cord- and Adult-RBC | Total |
|---|---|---|---|---|---|
| Age, Continuous | 30.0 weeks | 29.3 weeks | 28.5 weeks | 26.4 weeks | 29.4 weeks |
| Birth weight | 1285 grams | 710 grams | 1070 grams | 930 grams | 1030 grams |
| Hb at birth | 17.3 g/dL | 16.3 g/dL | 14.9 g/dL | 14.2 g/dL | 15.4 g/dL |
| Race and Ethnicity Not Collected | — | — | — | — | 0 Participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 2 Participants | 3 Participants | 12 Participants |
| Sex: Female, Male Male | 8 Participants | 1 Participants | 2 Participants | 2 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 1 / 3 | 1 / 4 | 0 / 5 |
| other Total, other adverse events | 0 / 13 | 0 / 3 | 0 / 4 | 0 / 5 |
| serious Total, serious adverse events | 1 / 13 | 3 / 3 | 3 / 4 | 5 / 5 |
Outcome results
Primary
Median Percentage of HbF at 32 Weeks of Post Menstrual Age
The HbF level was determined by high-performance liquid chromatography and was expressed as percentage of total Hb, calculated as the sum of fetal and adult Hb, according to the formula: HbF= \[HbF/ (FHbA1 + HbA2 + HbF)\]. HbF.
Time frame: From study entry to the completion of postmenstrual age of 32 weeks
Population: The overall amount of 264 HbF results were included in the analysis. HbF was expressed as percentage of total Hb (i.e. HbF+HbA1+HbA2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Non-transfused | Median Percentage of HbF at 32 Weeks of Post Menstrual Age | 93.2 percentage of total Hb |
| Only Cord-RBC | Median Percentage of HbF at 32 Weeks of Post Menstrual Age | 90.8 percentage of total Hb |
| Only adult_RBC | Median Percentage of HbF at 32 Weeks of Post Menstrual Age | 58.0 percentage of total Hb |
| Both Cord-RBC and adult_RBC | Median Percentage of HbF at 32 Weeks of Post Menstrual Age | 69.0 percentage of total Hb |
Comparison: Group comparison is carried out among HbF values grouped according to the transfusion regimen (only cord blood transfusions, only adult transfusions, both cord and adult transfusions).p-value: <0.0001Kruskal-Wallis
Secondary
Intervals Between Transfusions
Number of days between two consecutive transfusions.To this purpose, analysis was carried out between the two groups of RBC transfusions and patients were accordingly redistributed.
Time frame: From enrollment to the last HbF assessment occurring at 36 weeks, discharge or death
Population: Eight patients received a total number of 13 cord-RBC trasfusions and 9 patients received a total number of 18 adult -RBC transfusions. The intervals between two consecutive transfusions was recorded for each type of RBC unit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Non-transfused | Intervals Between Transfusions | 8.0 days |
| Only Cord-RBC | Intervals Between Transfusions | 7.0 days |
p-value: <0.05Wilcoxon (Mann-Whitney)
Secondary
Median Percentage of HbF at Last Assessment
Median percentage of HbF at last HbF assessment. The last HbF measure was obtained at the completion of the 36 week of age, discharge or death.
Time frame: From enrollment to the last HbF assessment occurring at 36 weeks, discharge or death
Population: Data recorded in all patient enetering the study were included in the analysis. Patients were grouped according to the type of RBC receved.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Non-transfused | Median Percentage of HbF at Last Assessment | 92.3 % HbF |
| Only Cord-RBC | Median Percentage of HbF at Last Assessment | 90.6 % HbF |
| Only adult_RBC | Median Percentage of HbF at Last Assessment | 53.6 % HbF |
| Both Cord-RBC and adult_RBC | Median Percentage of HbF at Last Assessment | 62.0 % HbF |
Comparison: Group comparison is carried out among HbF values grouped according to the transfusion regimen (only cord blood transfusions, only adult transfusions, both cord and adult transfusions).p-value: <0.0001Kruskal-Wallis
Secondary
Post-transfusion Hematocrit (Htc) Change
Change from baseline of Htc observed after either adult-RBC or cord-RBC transfusions. To this purpose, analysis was carried out between the two groups of RBC transfusions and patients were accordingly redistributed.
Time frame: From enrollment to last HbF assessment occurring at 36 weeks, discharge or death
Population: Eight patients received 13 cord-RBC units and 9 patients received 18 adult-RBC units. Change of hematocrit value after each transfusion was recorded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Non-transfused | Post-transfusion Hematocrit (Htc) Change | 9.0 percentage of total volume |
| Only Cord-RBC | Post-transfusion Hematocrit (Htc) Change | 11.5 percentage of total volume |
p-value: <0.05Wilcoxon (Mann-Whitney)