Trial Outcomes & Findings for Transfusion of Prematures Trial (NCT NCT01702805)

NCT ID: NCT01702805

Last Updated: 2025-11-14

Results Overview

A composite outcome that measures the occurrence of death or neurodevelomental impairment between birth and 22-26 months corrected age.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 1824 participants
• Primary outcome timeframe: Birth to 22-26 months corrected age
• Results posted on: 2025-11-14

Participant Flow

Participant milestones

Measure	High Tranfusion Threshold Transfusions were administered using a higher threshold hemoglobin value. AKA "Liberal Cell Transfusion" group.	Low Transfusion Threshold Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA "Restricted Red Cell Transfusion" group.
Overall Study STARTED	911	913
Overall Study Completed Assessment for Neurodevelopmental Impairment	699	712
Overall Study Died After Discharge	19	10
Overall Study Died Before Discharge	127	125
Overall Study Survived to Discharge	781	781
Overall Study COMPLETED	845	847
Overall Study NOT COMPLETED	66	66

Reasons for withdrawal

Measure	High Tranfusion Threshold Transfusions were administered using a higher threshold hemoglobin value. AKA "Liberal Cell Transfusion" group.	Low Transfusion Threshold Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA "Restricted Red Cell Transfusion" group.
Overall Study Data withdrawn prior to hospital discharge	3	7
Overall Study Incomplete Follow-up	18	15
Overall Study Vital Status Assessment Only	40	39
Overall Study Lost to Follow-up	5	5

Baseline Characteristics

Transfusion of Prematures Trial

Baseline characteristics by cohort

Measure	High Transfusion Threshold n=911 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	Low Transfusion Threshold n=913 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	Total n=1824 Participants Total of all reporting groups
Age, Continuous	25.9 weeks STANDARD_DEVIATION 1.5 • n=10 Participants	25.9 weeks STANDARD_DEVIATION 1.5 • n=10 Participants	25.9 weeks STANDARD_DEVIATION 1.5 • n=20 Participants
Sex/Gender, Customized Female	488 Participants n=10 Participants	462 Participants n=10 Participants	950 Participants n=20 Participants
Sex/Gender, Customized Male	423 Participants n=10 Participants	451 Participants n=10 Participants	874 Participants n=20 Participants
Race/Ethnicity, Customized Hispanic or Latino	149 Participants n=10 Participants	150 Participants n=10 Participants	299 Participants n=20 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	754 Participants n=10 Participants	753 Participants n=10 Participants	1507 Participants n=20 Participants
Race/Ethnicity, Customized Unknown or Not Reported	8 Participants n=10 Participants	10 Participants n=10 Participants	18 Participants n=20 Participants
Maternal Race, Customized American Indian or Alaska Native	8 Participants n=10 Participants	6 Participants n=10 Participants	14 Participants n=20 Participants
Maternal Race, Customized Asian, Native Hawaiian, or Other Pacific Islander	25 Participants n=10 Participants	35 Participants n=10 Participants	60 Participants n=20 Participants
Maternal Race, Customized Black or African American	423 Participants n=10 Participants	395 Participants n=10 Participants	818 Participants n=20 Participants
Maternal Race, Customized More Than One Race	20 Participants n=10 Participants	15 Participants n=10 Participants	35 Participants n=20 Participants
Maternal Race, Customized Unknown or Not Reported	16 Participants n=10 Participants	25 Participants n=10 Participants	41 Participants n=20 Participants
Maternal Race, Customized White	419 Participants n=10 Participants	437 Participants n=10 Participants	856 Participants n=20 Participants

PRIMARY outcome

Timeframe: Birth to 22-26 months corrected age

Population: The analysis population includes all randomized infants with available data for death and/or neurodevelopmental impairment.

A composite outcome that measures the occurrence of death or neurodevelomental impairment between birth and 22-26 months corrected age.

Outcome measures

Measure	Low Transfusion Threshold n=847 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=845 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Death or Neurodevelopmental Impairment Death or Neurodevelopmental Impairment	422 Participants	423 Participants
Death or Neurodevelopmental Impairment No Death nor Neurodevelopmental Impairment	425 Participants	422 Participants

PRIMARY outcome

Timeframe: Birth to 22-26 months corrected age

Population: The analysis population includes all randomized infants with available vital status.

This is measured as Yes if an infant died between birth and 22-26 months corrected age; Otherwise, No.

Outcome measures

Measure	Low Transfusion Threshold n=901 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=903 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Death Death	135 Participants	146 Participants
Death No Death	766 Participants	757 Participants

PRIMARY outcome

Timeframe: at 22-26 months corrected age

Population: The analysis population includes all randomized infants with available data for neurodevelopmental impairment.

This is measured as Yes if any hearing impairment or visual impairment is noted, if severe or moderate cerebral palsy is noted, or if the cognitive score of the Bayley III score is more than 1 standard deviation below the average; Otherwise, No.

Outcome measures

Measure	Low Transfusion Threshold n=712 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=699 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Neurodevelopmental Impairment Neurodevelopmental Impairment	287 Participants	277 Participants
Neurodevelopmental Impairment No Neurodevelopmental Impairment	425 Participants	422 Participants

PRIMARY outcome

Timeframe: at 22-26 months corrected age

Population: The analysis population includes all randomized infants with available data at the two-year followup.

This is measured as Yes if the Bayley Scale of Infant and Toddler Development (BSID)-III cognitive score is more than 1 standard deviation below the average; Otherwise, No.

Outcome measures

Measure	Low Transfusion Threshold n=712 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=695 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Cognitive Delay Cognitive Delay	270 Participants	269 Participants
Cognitive Delay No Cognitive Delay	442 Participants	426 Participants

PRIMARY outcome

Timeframe: at 22-26 months corrected age

Population: The analysis population includes all randomized infants with available data at the two-year followup.

This is measured as Yes if the Gross Motor Function Classification System (GMFCS) score is level II or higher; Otherwise, No. Higher values of the GMFCS are worse than lower values; a level of "I" denotes mild cerebral palsy (CP); level "II" or "III" moderate CP; level "IV" or "V" severe CP.

Outcome measures

Measure	Low Transfusion Threshold n=720 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=711 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Moderate or Severe Cerebral Palsy Moderate or Severe Cerebral Palsy	55 Participants	48 Participants
Moderate or Severe Cerebral Palsy Mild or No Cerebral Palsy	665 Participants	663 Participants

PRIMARY outcome

Timeframe: at 22-26 months corrected age

Population: The analysis population includes all randomized infants with available data at the two-year followup.

This is measured as Yes if the corrected visual acuity in the better eye of less than 20/200; Otherwise, No.

Outcome measures

Measure	Low Transfusion Threshold n=720 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=713 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Severe Vision Impairment No Severe Vision Impairment	714 Participants	708 Participants
Severe Vision Impairment Severe Vision Impairment	6 Participants	5 Participants

PRIMARY outcome

Timeframe: at 22-26 months corrected age

Population: The analysis population includes all randomized infants with available data at the two-year followup.

This is measured as Yes if bilateral hearing loss occurred for which hearing aids or cochlear implants were warranted; Otherwise, No.

Outcome measures

Measure	Low Transfusion Threshold n=715 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=710 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Severe Hearing Impairment No Severe Hearing Impairment	690 Participants	696 Participants
Severe Hearing Impairment Severe Hearing Impairment	25 Participants	14 Participants

SECONDARY outcome

Timeframe: Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)

Population: The analysis population includes all randomized infants with available data up to hospital discharge or death.

This is measured as Yes if survived to discharge without severe morbidity, defined as bronchopulmonary dysplasia, retinopathy of prematurity (stage 3 or higher or requiring treatment), or serious brain abnormality; Otherwise, No.

Outcome measures

Measure	Low Transfusion Threshold n=888 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=901 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Survival to Discharge Without Severe Complications No Survival to Discharge Without Severe Complications	614 Participants	644 Participants
Survival to Discharge Without Severe Complications Survival to Discharge Without Severe Complications	274 Participants	257 Participants

SECONDARY outcome

Timeframe: at 36 weeks postmenstrual age

Population: The analysis population includes all randomized infants with available data at 36 weeks postmenstrual age.

This is measured as Yes if experienced bronchopulmonary dysplasia, diagnosed on the basis of the need for supplemental oxygen after a standardized oxygen reduction test at 36 weeks of postmenstrual age; Otherwise, No.

Outcome measures

Measure	Low Transfusion Threshold n=805 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=795 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Bronchopulmonary Dysplasia, Diagnosed on the Basis of the Need for Supplemental Oxygen After a Standardized Oxygen Reduction Test at 36 Weeks of Postmenstrual Age No Bronchopulmonary Dysplasia at 36 Weeks Postmenstrual Age	352 Participants	326 Participants
Bronchopulmonary Dysplasia, Diagnosed on the Basis of the Need for Supplemental Oxygen After a Standardized Oxygen Reduction Test at 36 Weeks of Postmenstrual Age Bronchopulmonary Dysplasia at 36 Weeks Postmenstrual Age	453 Participants	469 Participants

SECONDARY outcome

Timeframe: Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)

Population: The analysis population includes all randomized infants with available data up to hospital discharge or death.

This is measured as Yes if experienced Retinopathy of Prematurity (ROP) Stage >=3 or received treatment for that condition; Otherwise, No. Higher stages of ROP indicate a worse outcome; the stages range from 1 for "mild" disease, to 5 for "severe" disease.

Outcome measures

Measure	Low Transfusion Threshold n=797 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=797 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Retinopathy of Prematurity Stage >=3 or Treatment for That Condition Received No Retinopathy of Prematurity at least Stage 3 and did not Receive Treatment for Such Condition	660 Participants	640 Participants
Retinopathy of Prematurity Stage >=3 or Treatment for That Condition Received Retinopathy of Prematurity at least Stage 3 or Received Treatment for Such Condition	137 Participants	157 Participants

SECONDARY outcome

Timeframe: Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)

Population: The analysis population includes all randomized infants with available data up to hospital discharge or death.

This is measured as Yes if experienced Grade 3 or 4 intraventricularhemorrhage, cystic periventricular leukomalacia, or ventriculomegaly diagnosed on ultrasonographic examination; Otherwise, No.

Outcome measures

Measure	Low Transfusion Threshold n=859 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=855 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Grade 3 or 4 Intraventricular Hemorrhage, Cystic Periventricular Leukomalacia, or Ventriculomegaly Diagnosed on Ultrasonographic Examination Grade 3 or 4 intraventricular hemorrhage, cystic periventricular leukomalacia, or ventriculomegaly	154 Participants	146 Participants
Grade 3 or 4 Intraventricular Hemorrhage, Cystic Periventricular Leukomalacia, or Ventriculomegaly Diagnosed on Ultrasonographic Examination None of the stated head ultrasound diagnoses	705 Participants	709 Participants

SECONDARY outcome

Timeframe: Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)

Population: The analysis population includes all randomized infants with available data up to hospital discharge or death.

This is measured as Yes if experienced necrotizing enterocolitis (NEC), Bell's stage >=2; Otherwise, No. Higher scores of Bell's staging criteria denote a worse outcome, where "1" denotes suspect, "2" definite and "3" advanced NEC.

Outcome measures

Measure	Low Transfusion Threshold n=906 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=907 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Necrotizing Enterocolitis, Bell's Stage >=2 NEC, Bell's Stage >= 2	95 Participants	91 Participants
Necrotizing Enterocolitis, Bell's Stage >=2 NEC, Bell's Stage = 1 or no NEC	811 Participants	816 Participants

SECONDARY outcome

Timeframe: Birth, up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age (PMA)

Population: The analysis population includes all randomized infants with available data up to death, hospital discharge, or 36 weeks PMA, whichever occurs first

This is measured as the number of protocol compliant transfusions, clinically justified non-protocol transfusions and unjustified non-protocol transfusions (violations)

Outcome measures

Measure	Low Transfusion Threshold n=913 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=911 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Number of Transfusions Per Infant	4.4 Transfusions Standard Deviation 4.0	6.2 Transfusions Standard Deviation 4.3

SECONDARY outcome

Timeframe: at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first

Population: The analysis population includes all randomized infants with available data at 36 weeks postmenstrual age or at initial hospital discharge, whichever occurs first.

This is measured as the weight-for-age Z-score at 36 weeks postmenstrual age or at initial hospital discharge, whichever occurs first. The Z-score is determined using Olsen percentile curves, and is derived from a normal distribution, where 0 designates average weight-for-age, and negative scores denote less than average weight-for-age.

Outcome measures

Measure	Low Transfusion Threshold n=774 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=769 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Weight-for-age: Z-score	-1.3 Z-score Standard Deviation 0.8	-1.2 Z-score Standard Deviation 0.8

SECONDARY outcome

Timeframe: at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first

Population: The analysis population includes all randomized infants with available data at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first.

This is measured as the length-for-age Z-score at 36 weeks postmenstrual age or at initial hospital discharge, whichever occurs first. The Z-score is determined using Olsen percentile curves, and is derived from a normal distribution, where 0 designates average length-for-age, and negative scores denote less than average length-for-age.

Outcome measures

Measure	Low Transfusion Threshold n=715 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=715 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Length-for-age: Z-score	-1.9 Z-score Standard Deviation 0.9	-1.9 Z-score Standard Deviation 1.0

SECONDARY outcome

Timeframe: at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first

Population: The analysis population includes all randomized infants with available data at 36 weeks postmenstrual age or at initial hospital discharge, whichever occurs first.

This is measured as the head circumference-for-age Z-score at 36 weeks postmenstrual age or at initial hospital discharge, whichever occurs first. The Z-score is determined using Olsen percentile curves, and is derived from a normal distribution, where 0 designates average head circumference-for-age, and negative scores denote less than average head circumference-for-age.

Outcome measures

Measure	Low Transfusion Threshold n=766 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=754 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Head Circumference-for-age: Z-score	-1.4 Z-score Standard Deviation 1.0	-1.4 Z-score Standard Deviation 1.0

SECONDARY outcome

Timeframe: at final trachael extubation, assessed from birth up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age

Population: The analysis population includes all randomized infants with available data on trachael extubation.

This is measured as the average postmenstrual age (in weeks) at final tracheal extubation in infants who were intubated.

Outcome measures

Measure	Low Transfusion Threshold n=804 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=796 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Postmenstrual Age at Final Trachael Extubation	30.2 Weeks Standard Deviation 3.3	30 Weeks Standard Deviation 3.4

SECONDARY outcome

Timeframe: at final caffeine dose, assessed from birth up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age

Population: The analysis population includes all randomized infants with available data on caffeine treatment.

This is measured as the average postmenstrual age (in weeks) at final caffeine dose in infants who received caffeine treatment.

Outcome measures

Measure	Low Transfusion Threshold n=887 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=882 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Postmenstrual Age at Final Caffeine Dose in Infants Who Received Caffeine Treatment	34.0 Weeks Standard Deviation 2.8	33.8 Weeks Standard Deviation 3.0

SECONDARY outcome

Timeframe: at initial hospital discharge or at death if it occurs earlier (a median of 97 days)

Population: The analysis population includes all randomized infants with available data up to the initial hospital discharge or death, whichever occurs first.

This is measured as the length of stay (in days) up to initial hospital discharge or death, whichever occurred first.

Outcome measures

Measure	Low Transfusion Threshold n=906 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=908 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Length of Stay	97 Days Interval 75.0 to 127.0	96 Days Interval 72.0 to 129.0

SECONDARY outcome

Timeframe: at first full enteral feeding, assessed from birth up to initial hospital discharge or to death if it occurs earlier (a median of 97 days)

Population: The analysis population includes all randomized infants with available data on enteral feeding.

This is measured as the amount of days it took for full enteral feeding to occur.

Outcome measures

Measure	Low Transfusion Threshold n=824 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=808 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Time to Full Enteral Feeding	19.0 Days Interval 15.0 to 30.0	19.5 Days Interval 14.0 to 29.0

SECONDARY outcome

Timeframe: at 22-26 months corrected age

Population: The analysis population includes all randomized infants with available data at the two-year followup.

This is measured as Yes if Gross Motor Function Classification System (GMFCS) is levels IV or V; Otherwise, No. Higher values of the GMFCS are worse than lower values; a level of "I" denotes mild cerebral palsy (CP); level "II" or "III" moderate CP; level "IV" or "V" severe CP.

Outcome measures

Measure	Low Transfusion Threshold n=720 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=710 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Severe Cerebral Palsy No Severe Cerebral Palsy	709 Participants	690 Participants
Severe Cerebral Palsy Severe Cerebral Palsy	11 Participants	20 Participants

SECONDARY outcome

Timeframe: Initial hospital discharge to 22-26 months corrected age

Population: The analysis population includes all randomized infants with available data at the two-year followup.

This is measured as Yes if experienced Hydrocephalus shunt by follow-up; Otherwise, No.

Outcome measures

Measure	Low Transfusion Threshold n=728 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=717 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Hydrocephalus Shunt Hydrocephalus Shunt	22 Participants	20 Participants
Hydrocephalus Shunt No Hydrocephalus Shunt	706 Participants	697 Participants

SECONDARY outcome

Timeframe: at 22-26 months corrected age

Population: The analysis population includes all randomized infants with available data at the two-year followup.

This is measured as a head circumference-for-age Z-score of less than -2; Otherwise, No. The Z-score is determined using WHO percentile curves, and is derived from a normal distribution, where 0 designates average head circumference-for-age, and negative scores denote less than average head circumference-for-age.

Outcome measures

Measure	Low Transfusion Threshold n=710 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=700 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Microcephaly Microcephaly	52 Participants	61 Participants
Microcephaly No Microcephaly	658 Participants	639 Participants

SECONDARY outcome

Timeframe: Initial hospital discharge to 22-26 months corrected age

Population: The analysis population includes all randomized infants with available data at the two-year followup.

This is measured as Yes if experienced one or more seizures since discharge or of regular use of anticonvulsants or seizure medications; Otherwise, No.

Outcome measures

Measure	Low Transfusion Threshold n=726 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=714 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Seizure Disorder No Seizure disorder	685 Participants	672 Participants
Seizure Disorder Seizure disorder	41 Participants	42 Participants

SECONDARY outcome

Timeframe: Initial hospital discharge to 22-26 months corrected age

Population: The analysis population includes all randomized infants with available data at the two-year followup.

This is measured as Yes if obtained Respiratory disease necessitating readmission before follow-up; Otherwise, No.

Outcome measures

Measure	Low Transfusion Threshold n=726 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=715 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Respiratory Disease Necessitating Readmission Before Follow-up No Respiratory disease necessitating readmission before follow-up	496 Participants	467 Participants
Respiratory Disease Necessitating Readmission Before Follow-up Respiratory disease necessitating readmission before follow-up	230 Participants	248 Participants

SECONDARY outcome

Timeframe: at 22-26 months corrected age

Population: The analysis population includes all randomized infants with available data at the two-year followup.

This is measured as Yes if scored less than 85 on the Bayley Scale of Infant and Toddler Development (BSID)-III composite language score; Otherwise, No. Higher scores indicate better performance. Composite BSID-III scores of less than 85 are less than 1 standard deviation below the mean of 100.

Outcome measures

Measure	Low Transfusion Threshold n=691 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=671 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Composite Language Score Less Than 85 Composite language score greater or equal to 85	323 Participants	316 Participants
Composite Language Score Less Than 85 Composite language score less than 85	368 Participants	355 Participants

SECONDARY outcome

Timeframe: at 22-26 months corrected age

Population: The analysis population includes all randomized infants with available data at the two-year followup.

This is measured as Yes if scored less than 85 on the Bayley Scale of Infant and Toddler Development (BSID)-III composite motor score; Otherwise, No. Higher scores indicate better performance. Composite BSID-III scores of less than 85 are less than 1 standard deviation below the mean of 100.

Outcome measures

Measure	Low Transfusion Threshold n=695 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=678 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Composite Motor Score Less Than 85 Composite motor score greater or equal to 85	415 Participants	423 Participants
Composite Motor Score Less Than 85 Composite motor score less than 85	280 Participants	255 Participants

SECONDARY outcome

Timeframe: at 22-26 months corrected age

Population: The analysis population includes all randomized infants with available data at the two-year followup.

This is measured as Yes if scored less than 85 on the Bayley Scale of Infant and Toddler Development (BSID)-III composite cognitive score; Otherwise, No. Higher scores indicate better performance. Composite BSID-III scores of less than 70 are less than 2 standard deviations below the mean of 100.

Outcome measures

Measure	Low Transfusion Threshold n=712 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=695 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Composite Cognitive Score Less Than 70 Composite cognitive score greater or equal to 70	616 Participants	607 Participants
Composite Cognitive Score Less Than 70 Composite cognitive score less than 70	96 Participants	88 Participants

SECONDARY outcome

Timeframe: at 22-26 months corrected age

Population: The analysis population includes all randomized infants with available data at the two-year followup.

This is measured as Yes if scored less than 85 on the Bayley Scale of Infant and Toddler Development (BSID)-III composite language score; Otherwise, No. Higher scores indicate better performance. Composite BSID-III scores of less than 70 are less than 2 standard deviations below the mean of 100.

Outcome measures

Measure	Low Transfusion Threshold n=691 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=671 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Composite Language Score Less Than 70 Composite language score greater or equal to 70	528 Participants	507 Participants
Composite Language Score Less Than 70 Composite language score less than 70	163 Participants	164 Participants

SECONDARY outcome

Timeframe: at 22-26 months corrected age

Population: The analysis population includes all randomized infants with available data at the two-year followup.

This is measured as Yes if scored less than 85 on the Bayley Scale of Infant and Toddler Development (BSID)-III composite motor score; Otherwise, No. Higher scores indicate better performance. Composite BSID-III scores of less than 70 are less than 2 standard deviations below the mean of 100.

Outcome measures

Measure	Low Transfusion Threshold n=695 Participants Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA 'Restricted Red C	High Transfusion Threshold n=678 Participants Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.
Composite Motor Score Less Than 70 Composite motor score greater or equal to 70	596 Participants	591 Participants
Composite Motor Score Less Than 70 Composite motor score less than 70	99 Participants	87 Participants

Adverse Events

High Tranfusion Threshold

Serious events: 206 serious events

Other events: 184 other events

Deaths: 146 deaths

Low Transfusion Threshold

Serious events: 197 serious events

Other events: 164 other events

Deaths: 135 deaths

Serious adverse events

Measure	High Tranfusion Threshold n=908 participants at risk Transfusions were administered using a higher threshold hemoglobin value. AKA "Liberal Cell Transfusion" group.	Low Transfusion Threshold n=906 participants at risk Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA "Restricted Red Cell Transfusion" group.
Blood and lymphatic system disorders Hemolysis	0.11% 1/908 • Birth to 37 weeks PMA	0.00% 0/906 • Birth to 37 weeks PMA
Endocrine disorders Adrenal Insufficiency	0.22% 2/908 • Birth to 37 weeks PMA	0.00% 0/906 • Birth to 37 weeks PMA
Gastrointestinal disorders Ascites	0.11% 1/908 • Birth to 37 weeks PMA	0.00% 0/906 • Birth to 37 weeks PMA
Gastrointestinal disorders Bell's stage > 2 Necrotizing Enterocolitis (NEC)	6.4% 58/908 • Birth to 37 weeks PMA	6.8% 62/906 • Birth to 37 weeks PMA
Gastrointestinal disorders Bowel Obstruction	0.11% 1/908 • Birth to 37 weeks PMA	0.22% 2/906 • Birth to 37 weeks PMA
Gastrointestinal disorders Esophageal Perforation	0.00% 0/908 • Birth to 37 weeks PMA	0.22% 2/906 • Birth to 37 weeks PMA
Gastrointestinal disorders Ischemic Bowel	0.00% 0/908 • Birth to 37 weeks PMA	0.11% 1/906 • Birth to 37 weeks PMA
Gastrointestinal disorders Spontaneous Intestinal Perforation	3.2% 29/908 • Birth to 37 weeks PMA	4.2% 38/906 • Birth to 37 weeks PMA
General disorders Severe Hemorrhage	0.55% 5/908 • Birth to 37 weeks PMA	0.22% 2/906 • Birth to 37 weeks PMA
Infections and infestations Nosocomial Sepsis up to 24 hours post-transfusion	3.4% 31/908 • Birth to 37 weeks PMA	2.4% 22/906 • Birth to 37 weeks PMA
Infections and infestations Pneumonia	0.11% 1/908 • Birth to 37 weeks PMA	0.11% 1/906 • Birth to 37 weeks PMA
Infections and infestations Sepsis Bacterial	0.33% 3/908 • Birth to 37 weeks PMA	0.00% 0/906 • Birth to 37 weeks PMA
Infections and infestations Sepsis Fungal	0.00% 0/908 • Birth to 37 weeks PMA	0.33% 3/906 • Birth to 37 weeks PMA
Infections and infestations Sepsis Viral	0.00% 0/908 • Birth to 37 weeks PMA	0.22% 2/906 • Birth to 37 weeks PMA
Infections and infestations Severe Cellulitis	0.11% 1/908 • Birth to 37 weeks PMA	0.00% 0/906 • Birth to 37 weeks PMA
Metabolism and nutrition disorders Hyperkalemia -- non-hemolyzed specimen, up to 24 hours post-transfusion	1.1% 10/908 • Birth to 37 weeks PMA	1.8% 16/906 • Birth to 37 weeks PMA
Nervous system disorders Seizures	0.22% 2/908 • Birth to 37 weeks PMA	0.11% 1/906 • Birth to 37 weeks PMA
Renal and urinary disorders Renal Failure	0.44% 4/908 • Birth to 37 weeks PMA	0.22% 2/906 • Birth to 37 weeks PMA
Respiratory, thoracic and mediastinal disorders Persistent Pulmonary Hypertension	0.11% 1/908 • Birth to 37 weeks PMA	0.22% 2/906 • Birth to 37 weeks PMA
Respiratory, thoracic and mediastinal disorders Pulmonary Air Leaks	0.11% 1/908 • Birth to 37 weeks PMA	0.33% 3/906 • Birth to 37 weeks PMA
Respiratory, thoracic and mediastinal disorders Pulmonary Hemorrhage	1.4% 13/908 • Birth to 37 weeks PMA	0.99% 9/906 • Birth to 37 weeks PMA
Respiratory, thoracic and mediastinal disorders Respiratory Deterioration up to 24 hours post-transfusion	10.2% 93/908 • Birth to 37 weeks PMA	9.4% 85/906 • Birth to 37 weeks PMA
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.00% 0/908 • Birth to 37 weeks PMA	0.44% 4/906 • Birth to 37 weeks PMA
Vascular disorders Severe Hypotension	0.11% 1/908 • Birth to 37 weeks PMA	0.11% 1/906 • Birth to 37 weeks PMA
Vascular disorders Thrombosis	0.11% 1/908 • Birth to 37 weeks PMA	0.11% 1/906 • Birth to 37 weeks PMA

Other adverse events

Measure	High Tranfusion Threshold n=908 participants at risk Transfusions were administered using a higher threshold hemoglobin value. AKA "Liberal Cell Transfusion" group.	Low Transfusion Threshold n=906 participants at risk Transfusions were administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group. AKA "Restricted Red Cell Transfusion" group.
Respiratory, thoracic and mediastinal disorders Respiratory Deterioration up to 24 hours post-transfusion	16.2% 147/908 • Birth to 37 weeks PMA	16.1% 146/906 • Birth to 37 weeks PMA
Metabolism and nutrition disorders Hyperkalemia -- non-hemolyzed specimen, up to 24 hours post-transfusion	6.4% 58/908 • Birth to 37 weeks PMA	4.4% 40/906 • Birth to 37 weeks PMA

Additional Information

Haresh Kirpalani

Emeritus Professor U Pennsylvania at CHOP and Emeritus Professor McMaster University, Dept Pediatrics

Phone: 267-844-3233

Email: kirpalan@mcmaster.ca

Results disclosure agreements

• Principal investigator is a sponsor employee Investigators must adhere to the Neonatal Research Network Publication Policies
• Publication restrictions are in place

Restriction type: OTHER