TOP: Transfusion of Prematures Trial

• Sponsor: NICHD Neonatal Research Network (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01702805
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 1,824
• Locations: 20
• Arms: 2
• Anticipated Duration (Months): 128
• Patients Per Site: 91.2
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The objective of the TOP trial is to determine whether higher hemoglobin thresholds for transfusing ELBW infants resulting in higher hemoglobin levels lead to improvement in the primary outcome of survival and rates of neurodevelopmental impairment (NDI) at 22-26 months of age, using standardized assessments by Bayley.

Condition or Disease	Intervention/Treatment	Phase
Infant, Newborn, Diseases; Infant, Extremely Low Birth Weight; Infant, Small for Gestational Age; Bronchopulmonary Dysplasia (BPD); Anemia	Procedure: Liberal Cell Transfusion; Procedure: Restricted red cell transfusion	Phase 3

Detailed Description

Long-term outcomes of extremely low birth weight (ELBW) preterm infants, those weighing less than or equal to 1000 g at birth, are poor and pose a major health care burden. Virtually all of these infants are transfused, but at inconsistent hemoglobin (Hgb) thresholds.

The investigators propose in TOP to randomize infants less than or equal to 1000 g BW and gestational age at least 22 weeks but less than 29 weeks to receive red blood cell (RBC) transfusions according to one of two strategies of Hgb thresholds, either a high Hgb (liberal transfusion) or a low Hgb (restrictive transfusion) algorithm. It is currently unknown which transfusion strategy is superior. TOP is powered to demonstrate which strategy reduces the primary outcome of death or neurodisability in survivors at 22-26 months.

A secondary study entitled "Effect of Blood Transfusion Practices on Cerebral and Somatic Oximetry", also known as the NIRS study, will determine differences in cerebral oxygenation and fractional tissue oxygen extraction with NIRS between high and low hemoglobin threshold groups during red blood cell transfusions. The investigators also propose to determine whether abnormal cerebral NIRS measures are a better predictor of NDI than hemoglobin alone and whether abnormal mesenteric NIRS measures are associated with the development of NEC within the 48 hours following a transfusion.

A secondary study entitled "Economic Evaluation Ancillary to the Transfusion of Prematures Randomized Controlled Trial" will determine whether higher transfusion threshold will result in lower total costs to society over the first 22 to 26 corrected months of life and estimate the incremental cost-effectiveness ratio for survival without neurodevelopmental impairment, from the perspective of society, the third-party payer, and the family.

Extended follow-up: Subjects will be seen for a follow-up visit at 5-6 years corrected age to assess neurological and functional outcomes at early school age based on neonatal transfusion threshold.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1824 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Transfusion of Prematures (TOP) Trial: Does a Liberal Red Blood Cell Transfusion Strategy Improve Neurologically-Intact Survival of Extremely-Low-Birth-Weight Infants as Compared to a Restrictive Strategy?
• Actual Study Start Date: Dec 1, 2012
• Actual Primary Completion Date: Jan 1, 2020
• Anticipated Study Completion Date: Aug 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Low Threshold Transfusion Transfusions will be administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group	Procedure: Restricted red cell transfusion
Active Comparator: High Threshold Transfusion Transfusions will be administered using a higher threshold hemoglobin value.	Procedure: Liberal Cell Transfusion

Outcome Measures

Primary Outcome Measures

1. Death or Neurodevelopmental Impairment [Birth to 22-26 months corrected age]

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

2. Death [Birth to 22-26 months corrected age]

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

3. Neurodevelopmental Impairment [at 22-26 months corrected age]

   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.

4. Cognitive Delay [at 22-26 months corrected age]

   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.

5. Moderate or Severe Cerebral Palsy [at 22-26 months corrected age]

   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.

6. Severe Vision Impairment [at 22-26 months corrected age]

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

7. Severe Hearing Impairment [at 22-26 months corrected age]

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

Secondary Outcome Measures

1. Survival to Discharge Without Severe Complications [Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)]

   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.

2. Bronchopulmonary Dysplasia, Diagnosed on the Basis of the Need for Supplemental Oxygen After a Standardized Oxygen Reduction Test at 36 Weeks of Postmenstrual Age [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.

3. Retinopathy of Prematurity Stage >=3 or Treatment for That Condition Received [Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)]

   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.

4. Grade 3 or 4 Intraventricular Hemorrhage, Cystic Periventricular Leukomalacia, or Ventriculomegaly Diagnosed on Ultrasonographic Examination [Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)]

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

5. Necrotizing Enterocolitis, Bell's Stage >=2 [Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)]

   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.

6. Number of Transfusions Per Infant [Birth, up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age (PMA)]

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

7. Weight-for-age: Z-score [at 36 weeks postmenstrual age or 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.

8. Length-for-age: Z-score [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.

9. Head Circumference-for-age: Z-score [at 36 weeks postmenstrual age or 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.

10. Postmenstrual Age at Final Trachael Extubation [at final trachael extubation, assessed from birth up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age]

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

11. Postmenstrual Age at Final Caffeine Dose in Infants Who Received Caffeine Treatment [at final caffeine dose, assessed from birth up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age]

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

12. Length of Stay [at initial hospital discharge or at death if it occurs earlier (a median of 97 days)]

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

13. Time to Full Enteral Feeding [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)]

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

14. Severe Cerebral Palsy [at 22-26 months corrected age]

    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.

15. Hydrocephalus Shunt [Initial hospital discharge to 22-26 months corrected age]

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

16. Microcephaly [at 22-26 months corrected age]

    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.

17. Seizure Disorder [Initial hospital discharge to 22-26 months corrected age]

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

18. Respiratory Disease Necessitating Readmission Before Follow-up [Initial hospital discharge to 22-26 months corrected age]

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

19. Composite Language Score Less Than 85 [at 22-26 months corrected age]

    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.

20. Composite Motor Score Less Than 85 [at 22-26 months corrected age]

    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.

21. Composite Cognitive Score Less Than 70 [at 22-26 months corrected age]

    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.

22. Composite Language Score Less Than 70 [at 22-26 months corrected age]

    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.

23. Composite Motor Score Less Than 70 [at 22-26 months corrected age]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 48 Hours
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Birth weight less than or equal to 1000 grams.

• Gestational age at least 22 weeks but less than 29 weeks

• Admitted to the NICU within 48 hours of life

Exclusion Criteria:

• Considered nonviable by the attending neonatologist

• Cyanotic congenital heart disease

• Parents opposed to the transfusion of blood

• Parents with hemoglobinopathy or congenital anemia

• In-utero fetal transfusion

• Twin-to-twin transfusion syndrome

• Isoimmune hemolytic disease

• Lack of parental consent

• Severe acute hemorrhage, acute shock, sepsis with coagulopathy, or need for perioperative transfusion.

• Prior blood transfusion on clinical grounds beyond the first 6 hours of life

• Infant has received erythropoietin prior to randomization, or is intended to receive erythropoietin through the neonatal course

• Congenital condition, other than premature birth, that adversely affects life expectancy or neurodevelopment.

• High probability that the family is socially disorganized to the point of being unable to attend follow-up at 22-26 months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	University of California - Los Angeles	Los Angeles	California	United States	90025
3	Stanford University	Palo Alto	California	United States	94304
4	Emory University	Atlanta	Georgia	United States	30303
5	Indiana University	Indianapolis	Indiana	United States	46202
6	University of Iowa	Iowa City	Iowa	United States	52242
7	Wayne State University	Detroit	Michigan	United States	48201
8	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
9	University of New Mexico	Albuquerque	New Mexico	United States	87131
10	University of Rochester	Rochester	New York	United States	14642
11	RTI International	Durham	North Carolina	United States	27705
12	Duke University	Durham	North Carolina	United States	27710
13	Cincinnati Children's Medical Center	Cincinnati	Ohio	United States	45267
14	Case Western Reserve University, Rainbow Babies and Children's Hospital	Cleveland	Ohio	United States	44106
15	Research Institute at Nationwide Children's Hospital	Columbus	Ohio	United States	43205
16	Univeristy of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
17	Brown University, Women & Infants Hospital of Rhode Island	Providence	Rhode Island	United States	02905
18	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas	United States	75235
19	University of Texas Health Science Center at Houston	Houston	Texas	United States	77030
20	University of Utah	Salt Lake City	Utah	United States	84108

Sponsors and Collaborators

• NICHD Neonatal Research Network
• National Heart, Lung, and Blood Institute (NHLBI)
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: Michele C Walsh, MD, Case Western Reserve University, Rainbow Babies and Children's Hospital
• Principal Investigator: Abhik Das, PhD, RTI International
• Principal Investigator: Beena Sood, MD, Wayne State University
• Principal Investigator: Abbot R Laptook, MD, Brown University, Women & Infants Hospital of Rhode Island
• Principal Investigator: Michael Cotten, MD, Duke University
• Principal Investigator: Ravi Patel, MD, Emory University
• Principal Investigator: Greg Sokol, MD, Indiana University
• Principal Investigator: Krisa P Van Meurs, MD, Stanford University
• Principal Investigator: Brenda Poindexter, MD, Children's Hospital Medical Center, Cincinnati
• Principal Investigator: Waldemar A Carlo, MD, University of Alabama at Birmingham
• Principal Investigator: Kristi L Watterberg, MD, University of New Mexico
• Principal Investigator: Myra Wyckoff, MD, University of Texas, Southwestern Medical Center at Dallas
• Principal Investigator: Kathleen A Kennedy, MD, MPH, The University of Texas Health Science Center, Houston
• Principal Investigator: Carl T D'Angio, MD, University of Rochester
• Principal Investigator: Pablo Sanchez, MD, Research Institute at Nationwide Children's Hospital
• Principal Investigator: William Truog, MD, Children's Mercy Hospital Kansas City
• Principal Investigator: Uday Devaskar, MD, University of California, Los Angeles
• Study Director: Haresh M Kirpalani, MD, University of Pennsylvania
• Principal Investigator: Bradley Yoder, MD, University of Utah

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 7, 2016

More Information

Additional Information:

• NICHD NRN Website
• NICHD Pregnancy & Perinatology Branch

Publications

None provided.

• Responsible Party: NICHD Neonatal Research Network
• ClinicalTrials.gov Identifier: NCT01702805
• Other Study ID Numbers: NICHD-NRN-0050; U01HL112776; U01HL112748
• First Posted: Oct 8, 2012
• Last Update Posted: Feb 11, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by NICHD Neonatal Research Network: NICHD Neonatal Research Network; Very Low Birth Weight (VLBW); Extremely Low Birth Weight (ELBW); Transfusions
• Additional relevant MeSH terms: Bronchopulmonary Dysplasia; Infant, Newborn, Diseases; Birth Weight

Study Results

Participant Flow

Arm/Group Title	High Tranfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA "Liberal Cell Transfusion" group.	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.
Period Title: Overall Study
STARTED	911	913
Completed Assessment for Neurodevelopmental Impairment	699	712
Died After Discharge	19	10
Died Before Discharge	127	125
Survived to Discharge	781	781
COMPLETED	845	847
NOT COMPLETED	66	66

Baseline Characteristics

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold	Total
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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 of all reporting groups
Overall Participants	911	913	1824
Age (weeks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [weeks]	25.9 (1.5)	25.9 (1.5)	25.9 (1.5)
Sex/Gender, Customized (Count of Participants)
Female	488 53.6%	462 50.6%	950 52.1%
Male	423 46.4%	451 49.4%	874 47.9%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	149 16.4%	150 16.4%	299 16.4%
Not Hispanic or Latino	754 82.8%	753 82.5%	1507 82.6%
Unknown or Not Reported	8 0.9%	10 1.1%	18 1%
Maternal Race, Customized (Count of Participants)
American Indian or Alaska Native	8 0.9%	6 0.7%	14 0.8%
Asian, Native Hawaiian, or Other Pacific Islander	25 2.7%	35 3.8%	60 3.3%
Black or African American	423 46.4%	395 43.3%	818 44.8%
More Than One Race	20 2.2%	15 1.6%	35 1.9%
Unknown or Not Reported	16 1.8%	25 2.7%	41 2.2%
White	419 46%	437 47.9%	856 46.9%

Outcome Measures

1. Primary Outcome

Title	Death or Neurodevelopmental Impairment
Description	A composite outcome that measures the occurrence of death or neurodevelomental impairment between birth and 22-26 months corrected age.
Time Frame	Birth to 22-26 months corrected age

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	845	847
Death or Neurodevelopmental Impairment	423 46.4%	422 46.2%
No Death nor Neurodevelopmental Impairment	422 46.3%	425 46.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Low Transfusion Threshold
	Comments	Null hypothesis: A higher hemoglobin threshold for red-cell transfusions, as compared with a lower threshold, will not reduce nor increase the incidence of death or neurodevelopmental impairment in infants at 22 to 26 months of age corrected for prematurity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.93
	Comments
	Method	Robust Poisson Regression
	Comments	The relative risk was adjusted for birth-weight and center stratum.
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.92 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Death
Description	This is measured as Yes if an infant died between birth and 22-26 months corrected age; Otherwise, No.
Time Frame	Birth to 22-26 months corrected age

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	903	901
Death	146 16%	135 14.8%
No Death	757 83.1%	766 83.9%

3. Primary Outcome

Title	Neurodevelopmental Impairment
Description	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.
Time Frame	at 22-26 months corrected age

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	699	712
Neurodevelopmental Impairment	277 30.4%	287 31.4%
No Neurodevelopmental Impairment	422 46.3%	425 46.5%

4. Primary Outcome

Title	Cognitive Delay
Description	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.
Time Frame	at 22-26 months corrected age

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	695	712
Cognitive Delay	269 29.5%	270 29.6%
No Cognitive Delay	426 46.8%	442 48.4%

5. Primary Outcome

Title	Moderate or Severe Cerebral Palsy
Description	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.
Time Frame	at 22-26 months corrected age

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	711	720
Moderate or Severe Cerebral Palsy	48 5.3%	55 6%
Mild or No Cerebral Palsy	663 72.8%	665 72.8%

6. Primary Outcome

Title	Severe Vision Impairment
Description	This is measured as Yes if the corrected visual acuity in the better eye of less than 20/200; Otherwise, No.
Time Frame	at 22-26 months corrected age

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	713	720
No Severe Vision Impairment	708 77.7%	714 78.2%
Severe Vision Impairment	5 0.5%	6 0.7%

7. Primary Outcome

Title	Severe Hearing Impairment
Description	This is measured as Yes if bilateral hearing loss occurred for which hearing aids or cochlear implants were warranted; Otherwise, No.
Time Frame	at 22-26 months corrected age

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	710	715
No Severe Hearing Impairment	696 76.4%	690 75.6%
Severe Hearing Impairment	14 1.5%	25 2.7%

8. Secondary Outcome

Title	Survival to Discharge Without Severe Complications
Description	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.
Time Frame	Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	901	888
No Survival to Discharge Without Severe Complications	644 70.7%	614 67.3%
Survival to Discharge Without Severe Complications	257 28.2%	274 30%

9. Secondary Outcome

Title	Bronchopulmonary Dysplasia, Diagnosed on the Basis of the Need for Supplemental Oxygen After a Standardized Oxygen Reduction Test at 36 Weeks of Postmenstrual Age
Description	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.
Time Frame	at 36 weeks postmenstrual age

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	795	805
Bronchopulmonary Dysplasia at 36 Weeks Postmenstrual Age	469 51.5%	453 49.6%
No Bronchopulmonary Dysplasia at 36 Weeks Postmenstrual Age	326 35.8%	352 38.6%

10. Secondary Outcome

Title	Retinopathy of Prematurity Stage >=3 or Treatment for That Condition Received
Description	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.
Time Frame	Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	797	797
No Retinopathy of Prematurity at least Stage 3 and did not Receive Treatment for Such Condition	640 70.3%	660 72.3%
Retinopathy of Prematurity at least Stage 3 or Received Treatment for Such Condition	157 17.2%	137 15%

11. Secondary Outcome

Title	Grade 3 or 4 Intraventricular Hemorrhage, Cystic Periventricular Leukomalacia, or Ventriculomegaly Diagnosed on Ultrasonographic Examination
Description	This is measured as Yes if experienced Grade 3 or 4 intraventricularhemorrhage, cystic periventricular leukomalacia, or ventriculomegaly diagnosed on ultrasonographic examination; Otherwise, No.
Time Frame	Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	855	859
Grade 3 or 4 intraventricular hemorrhage, cystic periventricular leukomalacia, or ventriculomegaly	146 16%	154 16.9%
None of the stated head ultrasound diagnoses	709 77.8%	705 77.2%

12. Secondary Outcome

Title	Necrotizing Enterocolitis, Bell's Stage >=2
Description	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.
Time Frame	Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	907	906
NEC, Bell's Stage >= 2	91 10%	95 10.4%
NEC, Bell's Stage = 1 or no NEC	816 89.6%	811 88.8%

13. Secondary Outcome

Title	Number of Transfusions Per Infant
Description	This is measured as the number of protocol compliant transfusions, clinically justified non-protocol transfusions and unjustified non-protocol transfusions (violations)
Time Frame	Birth, up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age (PMA)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	911	913
Mean (Standard Deviation) [Transfusions]	6.2 (4.3)	4.4 (4.0)

14. Secondary Outcome

Title	Weight-for-age: Z-score
Description	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.
Time Frame	at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	769	774
Mean (Standard Deviation) [Z-score]	-1.2 (0.8)	-1.3 (0.8)

15. Secondary Outcome

Title	Length-for-age: Z-score
Description	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.
Time Frame	at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	715	715
Mean (Standard Deviation) [Z-score]	-1.9 (1.0)	-1.9 (0.9)

16. Secondary Outcome

Title	Head Circumference-for-age: Z-score
Description	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.
Time Frame	at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	754	766
Mean (Standard Deviation) [Z-score]	-1.4 (1.0)	-1.4 (1.0)

17. Secondary Outcome

Title	Postmenstrual Age at Final Trachael Extubation
Description	This is measured as the average postmenstrual age (in weeks) at final tracheal extubation in infants who were intubated.
Time Frame	at final trachael extubation, assessed from birth up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	796	804
Mean (Standard Deviation) [Weeks]	30 (3.4)	30.2 (3.3)

18. Secondary Outcome

Title	Postmenstrual Age at Final Caffeine Dose in Infants Who Received Caffeine Treatment
Description	This is measured as the average postmenstrual age (in weeks) at final caffeine dose in infants who received caffeine treatment.
Time Frame	at final caffeine dose, assessed from birth up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	882	887
Mean (Standard Deviation) [Weeks]	33.8 (3.0)	34.0 (2.8)

19. Secondary Outcome

Title	Length of Stay
Description	This is measured as the length of stay (in days) up to initial hospital discharge or death, whichever occurred first.
Time Frame	at initial hospital discharge or at death if it occurs earlier (a median of 97 days)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	908	906
Median (Inter-Quartile Range) [Days]	96	97

20. Secondary Outcome

Title	Time to Full Enteral Feeding
Description	This is measured as the amount of days it took for full enteral feeding to occur.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	808	824
Median (Inter-Quartile Range) [Days]	19.5	19.0

21. Secondary Outcome

Title	Severe Cerebral Palsy
Description	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.
Time Frame	at 22-26 months corrected age

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	710	720
No Severe Cerebral Palsy	690 75.7%	709 77.7%
Severe Cerebral Palsy	20 2.2%	11 1.2%

22. Secondary Outcome

Title	Hydrocephalus Shunt
Description	This is measured as Yes if experienced Hydrocephalus shunt by follow-up; Otherwise, No.
Time Frame	Initial hospital discharge to 22-26 months corrected age

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	717	728
Hydrocephalus Shunt	20 2.2%	22 2.4%
No Hydrocephalus Shunt	697 76.5%	706 77.3%

23. Secondary Outcome

Title	Microcephaly
Description	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.
Time Frame	at 22-26 months corrected age

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	700	710
Microcephaly	61 6.7%	52 5.7%
No Microcephaly	639 70.1%	658 72.1%

24. Secondary Outcome

Title	Seizure Disorder
Description	This is measured as Yes if experienced one or more seizures since discharge or of regular use of anticonvulsants or seizure medications; Otherwise, No.
Time Frame	Initial hospital discharge to 22-26 months corrected age

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	714	726
No Seizure disorder	672 73.8%	685 75%
Seizure disorder	42 4.6%	41 4.5%

25. Secondary Outcome

Title	Respiratory Disease Necessitating Readmission Before Follow-up
Description	This is measured as Yes if obtained Respiratory disease necessitating readmission before follow-up; Otherwise, No.
Time Frame	Initial hospital discharge to 22-26 months corrected age

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	715	726
No Respiratory disease necessitating readmission before follow-up	467 51.3%	496 54.3%
Respiratory disease necessitating readmission before follow-up	248 27.2%	230 25.2%

26. Secondary Outcome

Title	Composite Language Score Less Than 85
Description	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.
Time Frame	at 22-26 months corrected age

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	671	691
Composite language score greater or equal to 85	316 34.7%	323 35.4%
Composite language score less than 85	355 39%	368 40.3%

27. Secondary Outcome

Title	Composite Motor Score Less Than 85
Description	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.
Time Frame	at 22-26 months corrected age

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	678	695
Composite motor score greater or equal to 85	423 46.4%	415 45.5%
Composite motor score less than 85	255 28%	280 30.7%

28. Secondary Outcome

Title	Composite Cognitive Score Less Than 70
Description	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.
Time Frame	at 22-26 months corrected age

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	695	712
Composite cognitive score greater or equal to 70	607 66.6%	616 67.5%
Composite cognitive score less than 70	88 9.7%	96 10.5%

29. Secondary Outcome

Title	Composite Language Score Less Than 70
Description	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.
Time Frame	at 22-26 months corrected age

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	671	691
Composite language score greater or equal to 70	507 55.7%	528 57.8%
Composite language score less than 70	164 18%	163 17.9%

30. Secondary Outcome

Title	Composite Motor Score Less Than 70
Description	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.
Time Frame	at 22-26 months corrected age

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	High Transfusion Threshold	Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.	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
Measure Participants	678	695
Composite motor score greater or equal to 70	591 64.9%	596 65.3%
Composite motor score less than 70	87 9.5%	99 10.8%

Adverse Events

Time Frame	Birth to 37 weeks PMA
Arm/Group Title	High Tranfusion Threshold		Low Transfusion Threshold
Arm/Group Description	Transfusions were administered using a higher threshold hemoglobin value. AKA "Liberal Cell Transfusion" group.		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.
All Cause Mortality
	High Tranfusion Threshold		Low Transfusion Threshold
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	146/903 (16.2%)		135/901 (15%)
Serious Adverse Events
	High Tranfusion Threshold		Low Transfusion Threshold
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	206/908 (22.7%)		197/906 (21.7%)
Blood and lymphatic system disorders
Hemolysis	1/908 (0.1%)		0/906 (0%)
Endocrine disorders
Adrenal Insufficiency	2/908 (0.2%)		0/906 (0%)
Gastrointestinal disorders
Ascites	1/908 (0.1%)		0/906 (0%)
Bell's stage > 2 Necrotizing Enterocolitis (NEC)	58/908 (6.4%)		62/906 (6.8%)
Bowel Obstruction	1/908 (0.1%)		2/906 (0.2%)
Esophageal Perforation	0/908 (0%)		2/906 (0.2%)
Ischemic Bowel	0/908 (0%)		1/906 (0.1%)
Spontaneous Intestinal Perforation	29/908 (3.2%)		38/906 (4.2%)
General disorders
Severe Hemorrhage	5/908 (0.6%)		2/906 (0.2%)
Infections and infestations
Nosocomial Sepsis up to 24 hours post-transfusion	31/908 (3.4%)		22/906 (2.4%)
Pneumonia	1/908 (0.1%)		1/906 (0.1%)
Sepsis Bacterial	3/908 (0.3%)		0/906 (0%)
Sepsis Fungal	0/908 (0%)		3/906 (0.3%)
Sepsis Viral	0/908 (0%)		2/906 (0.2%)
Severe Cellulitis	1/908 (0.1%)		0/906 (0%)
Metabolism and nutrition disorders
Hyperkalemia -- non-hemolyzed specimen, up to 24 hours post-transfusion	10/908 (1.1%)		16/906 (1.8%)
Nervous system disorders
Seizures	2/908 (0.2%)		1/906 (0.1%)
Renal and urinary disorders
Renal Failure	4/908 (0.4%)		2/906 (0.2%)
Respiratory, thoracic and mediastinal disorders
Persistent Pulmonary Hypertension	1/908 (0.1%)		2/906 (0.2%)
Pulmonary Air Leaks	1/908 (0.1%)		3/906 (0.3%)
Pulmonary Hemorrhage	13/908 (1.4%)		9/906 (1%)
Respiratory Deterioration up to 24 hours post-transfusion	93/908 (10.2%)		85/906 (9.4%)
Respiratory Failure	0/908 (0%)		4/906 (0.4%)
Vascular disorders
Severe Hypotension	1/908 (0.1%)		1/906 (0.1%)
Thrombosis	1/908 (0.1%)		1/906 (0.1%)
Other (Not Including Serious) Adverse Events
	High Tranfusion Threshold		Low Transfusion Threshold
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	184/908 (20.3%)		164/906 (18.1%)
Metabolism and nutrition disorders
Hyperkalemia -- non-hemolyzed specimen, up to 24 hours post-transfusion	58/908 (6.4%)		40/906 (4.4%)
Respiratory, thoracic and mediastinal disorders
Respiratory Deterioration up to 24 hours post-transfusion	147/908 (16.2%)		146/906 (16.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Investigators must adhere to the Neonatal Research Network Publication Policies