<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01702805</url>
  </required_header>
  <id_info>
    <org_study_id>NICHD-NRN-0050</org_study_id>
    <secondary_id>U01HL112776</secondary_id>
    <secondary_id>U01HL112748</secondary_id>
    <nct_id>NCT01702805</nct_id>
  </id_info>
  <brief_title>Transfusion of Prematures Trial</brief_title>
  <acronym>TOP</acronym>
  <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?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NICHD Neonatal Research Network</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>NICHD Neonatal Research Network</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of the TOP trial is to determine whether higher hemoglobin thresholds for&#xD;
      transfusing ELBW infants resulting in higher hemoglobin levels lead to improvement in the&#xD;
      primary outcome of survival and rates of neurodevelopmental impairment (NDI) at 22-26 months&#xD;
      of age, using standardized assessments by Bayley.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Long-term outcomes of extremely low birth weight (ELBW) preterm infants, those weighing less&#xD;
      than or equal to 1000 g at birth, are poor and pose a major health care burden. Virtually all&#xD;
      of these infants are transfused, but at inconsistent hemoglobin (Hgb) thresholds.&#xD;
&#xD;
      The investigators propose in TOP to randomize infants less than or equal to 1000 g BW and&#xD;
      gestational age at least 22 weeks but less than 29 weeks to receive red blood cell (RBC)&#xD;
      transfusions according to one of two strategies of Hgb thresholds, either a high Hgb (liberal&#xD;
      transfusion) or a low Hgb (restrictive transfusion) algorithm. It is currently unknown which&#xD;
      transfusion strategy is superior. TOP is powered to demonstrate which strategy reduces the&#xD;
      primary outcome of death or neurodisability in survivors at 22-26 months.&#xD;
&#xD;
      A secondary study entitled &quot;Effect of Blood Transfusion Practices on Cerebral and Somatic&#xD;
      Oximetry&quot;, also known as the NIRS study, will determine differences in cerebral oxygenation&#xD;
      and fractional tissue oxygen extraction with NIRS between high and low hemoglobin threshold&#xD;
      groups during red blood cell transfusions. The investigators also propose to determine&#xD;
      whether abnormal cerebral NIRS measures are a better predictor of NDI than hemoglobin alone&#xD;
      and whether abnormal mesenteric NIRS measures are associated with the development of NEC&#xD;
      within the 48 hours following a transfusion.&#xD;
&#xD;
      A secondary study entitled &quot;Economic Evaluation Ancillary to the Transfusion of Prematures&#xD;
      Randomized Controlled Trial&quot; will determine whether higher transfusion threshold will result&#xD;
      in lower total costs to society over the first 22 to 26 corrected months of life and estimate&#xD;
      the incremental cost-effectiveness ratio for survival without neurodevelopmental impairment,&#xD;
      from the perspective of society, the third-party payer, and the family.&#xD;
&#xD;
      Extended follow-up: Subjects will be seen for a follow-up visit at 5-6 years corrected age to&#xD;
      assess neurological and functional outcomes at early school age based on neonatal transfusion&#xD;
      threshold.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 2012</start_date>
  <completion_date type="Anticipated">August 2023</completion_date>
  <primary_completion_date type="Actual">January 2020</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Death or Neurodevelopmental Impairment</measure>
    <time_frame>Birth to 22-26 months corrected age</time_frame>
    <description>A composite outcome that measures the occurrence of death or neurodevelomental impairment between birth and 22-26 months corrected age.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Death</measure>
    <time_frame>Birth to 22-26 months corrected age</time_frame>
    <description>This is measured as Yes if an infant died between birth and 22-26 months corrected age; Otherwise, No.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Neurodevelopmental Impairment</measure>
    <time_frame>at 22-26 months corrected age</time_frame>
    <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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cognitive Delay</measure>
    <time_frame>at 22-26 months corrected age</time_frame>
    <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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Moderate or Severe Cerebral Palsy</measure>
    <time_frame>at 22-26 months corrected age</time_frame>
    <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 &quot;I&quot; denotes mild cerebral palsy (CP); level &quot;II&quot; or &quot;III&quot; moderate CP; level &quot;IV&quot; or &quot;V&quot; severe CP.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Severe Vision Impairment</measure>
    <time_frame>at 22-26 months corrected age</time_frame>
    <description>This is measured as Yes if the corrected visual acuity in the better eye of less than 20/200; Otherwise, No.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Severe Hearing Impairment</measure>
    <time_frame>at 22-26 months corrected age</time_frame>
    <description>This is measured as Yes if bilateral hearing loss occurred for which hearing aids or cochlear implants were warranted; Otherwise, No.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Survival to Discharge Without Severe Complications</measure>
    <time_frame>Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bronchopulmonary Dysplasia, Diagnosed on the Basis of the Need for Supplemental Oxygen After a Standardized Oxygen Reduction Test at 36 Weeks of Postmenstrual Age</measure>
    <time_frame>at 36 weeks postmenstrual age</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Retinopathy of Prematurity Stage &gt;=3 or Treatment for That Condition Received</measure>
    <time_frame>Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)</time_frame>
    <description>This is measured as Yes if experienced Retinopathy of Prematurity (ROP) Stage &gt;=3 or received treatment for that condition; Otherwise, No. Higher stages of ROP indicate a worse outcome; the stages range from 1 for &quot;mild&quot; disease, to 5 for &quot;severe&quot; disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Grade 3 or 4 Intraventricular Hemorrhage, Cystic Periventricular Leukomalacia, or Ventriculomegaly Diagnosed on Ultrasonographic Examination</measure>
    <time_frame>Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)</time_frame>
    <description>This is measured as Yes if experienced Grade 3 or 4 intraventricularhemorrhage, cystic periventricular leukomalacia, or ventriculomegaly diagnosed on ultrasonographic examination; Otherwise, No.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Necrotizing Enterocolitis, Bell's Stage &gt;=2</measure>
    <time_frame>Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)</time_frame>
    <description>This is measured as Yes if experienced necrotizing enterocolitis (NEC), Bell's stage &gt;=2; Otherwise, No. Higher scores of Bell's staging criteria denote a worse outcome, where &quot;1&quot; denotes suspect, &quot;2&quot; definite and &quot;3&quot; advanced NEC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Transfusions Per Infant</measure>
    <time_frame>Birth, up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age (PMA)</time_frame>
    <description>This is measured as the number of protocol compliant transfusions, clinically justified non-protocol transfusions and unjustified non-protocol transfusions (violations)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weight-for-age: Z-score</measure>
    <time_frame>at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length-for-age: Z-score</measure>
    <time_frame>at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Head Circumference-for-age: Z-score</measure>
    <time_frame>at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postmenstrual Age at Final Trachael Extubation</measure>
    <time_frame>at final trachael extubation, assessed from birth up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age</time_frame>
    <description>This is measured as the average postmenstrual age (in weeks) at final tracheal extubation in infants who were intubated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postmenstrual Age at Final Caffeine Dose in Infants Who Received Caffeine Treatment</measure>
    <time_frame>at final caffeine dose, assessed from birth up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age</time_frame>
    <description>This is measured as the average postmenstrual age (in weeks) at final caffeine dose in infants who received caffeine treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of Stay</measure>
    <time_frame>at initial hospital discharge or at death if it occurs earlier (a median of 97 days)</time_frame>
    <description>This is measured as the length of stay (in days) up to initial hospital discharge or death, whichever occurred first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Full Enteral Feeding</measure>
    <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)</time_frame>
    <description>This is measured as the amount of days it took for full enteral feeding to occur.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severe Cerebral Palsy</measure>
    <time_frame>at 22-26 months corrected age</time_frame>
    <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 &quot;I&quot; denotes mild cerebral palsy (CP); level &quot;II&quot; or &quot;III&quot; moderate CP; level &quot;IV&quot; or &quot;V&quot; severe CP.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hydrocephalus Shunt</measure>
    <time_frame>Initial hospital discharge to 22-26 months corrected age</time_frame>
    <description>This is measured as Yes if experienced Hydrocephalus shunt by follow-up; Otherwise, No.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Microcephaly</measure>
    <time_frame>at 22-26 months corrected age</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Seizure Disorder</measure>
    <time_frame>Initial hospital discharge to 22-26 months corrected age</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory Disease Necessitating Readmission Before Follow-up</measure>
    <time_frame>Initial hospital discharge to 22-26 months corrected age</time_frame>
    <description>This is measured as Yes if obtained Respiratory disease necessitating readmission before follow-up; Otherwise, No.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite Language Score Less Than 85</measure>
    <time_frame>at 22-26 months corrected age</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite Motor Score Less Than 85</measure>
    <time_frame>at 22-26 months corrected age</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite Cognitive Score Less Than 70</measure>
    <time_frame>at 22-26 months corrected age</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite Language Score Less Than 70</measure>
    <time_frame>at 22-26 months corrected age</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite Motor Score Less Than 70</measure>
    <time_frame>at 22-26 months corrected age</time_frame>
    <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.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1824</enrollment>
  <condition>Infant, Newborn, Diseases</condition>
  <condition>Infant, Extremely Low Birth Weight</condition>
  <condition>Infant, Small for Gestational Age</condition>
  <condition>Bronchopulmonary Dysplasia (BPD)</condition>
  <condition>Anemia</condition>
  <arm_group>
    <arm_group_label>Low Threshold Transfusion</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High Threshold Transfusion</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Transfusions will be administered using a higher threshold hemoglobin value.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Liberal Cell Transfusion</intervention_name>
    <arm_group_label>High Threshold Transfusion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Restricted red cell transfusion</intervention_name>
    <arm_group_label>Low Threshold Transfusion</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Birth weight less than or equal to 1000 grams.&#xD;
&#xD;
          -  Gestational age at least 22 weeks but less than 29 weeks&#xD;
&#xD;
          -  Admitted to the NICU within 48 hours of life&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Considered nonviable by the attending neonatologist&#xD;
&#xD;
          -  Cyanotic congenital heart disease&#xD;
&#xD;
          -  Parents opposed to the transfusion of blood&#xD;
&#xD;
          -  Parents with hemoglobinopathy or congenital anemia&#xD;
&#xD;
          -  In-utero fetal transfusion&#xD;
&#xD;
          -  Twin-to-twin transfusion syndrome&#xD;
&#xD;
          -  Isoimmune hemolytic disease&#xD;
&#xD;
          -  Lack of parental consent&#xD;
&#xD;
          -  Severe acute hemorrhage, acute shock, sepsis with coagulopathy, or need for&#xD;
             perioperative transfusion.&#xD;
&#xD;
          -  Prior blood transfusion on clinical grounds beyond the first 6 hours of life&#xD;
&#xD;
          -  Infant has received erythropoietin prior to randomization, or is intended to receive&#xD;
             erythropoietin through the neonatal course&#xD;
&#xD;
          -  Congenital condition, other than premature birth, that adversely affects life&#xD;
             expectancy or neurodevelopment.&#xD;
&#xD;
          -  High probability that the family is socially disorganized to the point of being unable&#xD;
             to attend follow-up at 22-26 months.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>48 Hours</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michele C Walsh, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Case Western Reserve University, Rainbow Babies and Children's Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Abhik Das, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>RTI International</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Beena Sood, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wayne State University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Abbot R Laptook, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brown University, Women &amp; Infants Hospital of Rhode Island</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Michael Cotten, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ravi Patel, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Greg Sokol, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Indiana University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Krisa P Van Meurs, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Brenda Poindexter, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital Medical Center, Cincinnati</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Waldemar A Carlo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Alabama at Birmingham</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kristi L Watterberg, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of New Mexico</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Myra Wyckoff, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Texas, Southwestern Medical Center at Dallas</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kathleen A Kennedy, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>The University of Texas Health Science Center, Houston</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Carl T D'Angio, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Rochester</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Pablo Sanchez, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Research Institute at Nationwide Children's Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>William Truog, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Mercy Hospital Kansas City</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Uday Devaskar, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, Los Angeles</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Haresh M Kirpalani, MD</last_name>
    <role>Study Director</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Bradley Yoder, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Utah</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama at Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California - Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wayne State University</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Mercy Hospital</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of New Mexico</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87131</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Rochester</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>RTI International</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati Children's Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Case Western Reserve University, Rainbow Babies and Children's Hospital</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Institute at Nationwide Children's Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Univeristy of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brown University, Women &amp; Infants Hospital of Rhode Island</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center at Dallas</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Health Science Center at Houston</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://neonatal.rti.org/</url>
    <description>NICHD NRN Website</description>
  </link>
  <link>
    <url>https://www.nichd.nih.gov/about/org/der/branches/ppb</url>
    <description>NICHD Pregnancy &amp; Perinatology Branch</description>
  </link>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>August 30, 2012</study_first_submitted>
  <study_first_submitted_qc>October 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 8, 2012</study_first_posted>
  <results_first_submitted>December 3, 2021</results_first_submitted>
  <results_first_submitted_qc>January 18, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">February 11, 2022</results_first_posted>
  <last_update_submitted>March 21, 2023</last_update_submitted>
  <last_update_submitted_qc>March 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>NICHD Neonatal Research Network</keyword>
  <keyword>Very Low Birth Weight (VLBW)</keyword>
  <keyword>Extremely Low Birth Weight (ELBW)</keyword>
  <keyword>Transfusions</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bronchopulmonary Dysplasia</mesh_term>
    <mesh_term>Infant, Newborn, Diseases</mesh_term>
    <mesh_term>Birth Weight</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>NIH has had a long-standing policy to share and make available to the public the results and accomplishments of the activities that it funds. The NRN plans to share de-identified data after final publication in an NIH supported data repository such as the NICHD Data and Specimen Hub (https://dash.nichd.nih.gov)</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 7, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/05/NCT01702805/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>High Tranfusion Threshold</title>
          <description>Transfusions were administered using a higher threshold hemoglobin value. AKA &quot;Liberal Cell Transfusion&quot; group.</description>
        </group>
        <group group_id="P2">
          <title>Low Transfusion Threshold</title>
          <description>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 &quot;Restricted Red Cell Transfusion&quot; group.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="911"/>
                <participants group_id="P2" count="913"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Completed Assessment for Neurodevelopmental Impairment</title>
              <participants_list>
                <participants group_id="P1" count="699"/>
                <participants group_id="P2" count="712"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Died After Discharge</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Died Before Discharge</title>
              <participants_list>
                <participants group_id="P1" count="127"/>
                <participants group_id="P2" count="125"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Survived to Discharge</title>
              <participants_list>
                <participants group_id="P1" count="781"/>
                <participants group_id="P2" count="781"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="845"/>
                <participants group_id="P2" count="847"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="66"/>
                <participants group_id="P2" count="66"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Data withdrawn prior to hospital discharge</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Incomplete Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Vital Status Assessment Only</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
                <participants group_id="P2" count="39"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>High Transfusion Threshold</title>
          <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
        </group>
        <group group_id="B2">
          <title>Low Transfusion Threshold</title>
          <description>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</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="911"/>
            <count group_id="B2" value="913"/>
            <count group_id="B3" value="1824"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <description>Age refers to the infant and is measured as gestational age in weeks</description>
          <units>weeks</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25.9" spread="1.5"/>
                    <measurement group_id="B2" value="25.9" spread="1.5"/>
                    <measurement group_id="B3" value="25.9" spread="1.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex/Gender, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="488"/>
                    <measurement group_id="B2" value="462"/>
                    <measurement group_id="B3" value="950"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="423"/>
                    <measurement group_id="B2" value="451"/>
                    <measurement group_id="B3" value="874"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="149"/>
                    <measurement group_id="B2" value="150"/>
                    <measurement group_id="B3" value="299"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="754"/>
                    <measurement group_id="B2" value="753"/>
                    <measurement group_id="B3" value="1507"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Maternal Race, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian, Native Hawaiian, or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="60"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="423"/>
                    <measurement group_id="B2" value="395"/>
                    <measurement group_id="B3" value="818"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More Than One Race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="35"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="41"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="419"/>
                    <measurement group_id="B2" value="437"/>
                    <measurement group_id="B3" value="856"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Death or Neurodevelopmental Impairment</title>
        <description>A composite outcome that measures the occurrence of death or neurodevelomental impairment between birth and 22-26 months corrected age.</description>
        <time_frame>Birth to 22-26 months corrected age</time_frame>
        <population>The analysis population includes all randomized infants with available data for death and/or neurodevelopmental impairment.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Death or Neurodevelopmental Impairment</title>
          <description>A composite outcome that measures the occurrence of death or neurodevelomental impairment between birth and 22-26 months corrected age.</description>
          <population>The analysis population includes all randomized infants with available data for death and/or neurodevelopmental impairment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="845"/>
                <count group_id="O2" value="847"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Death or Neurodevelopmental Impairment</title>
                  <measurement_list>
                    <measurement group_id="O1" value="423"/>
                    <measurement group_id="O2" value="422"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No Death nor Neurodevelopmental Impairment</title>
                  <measurement_list>
                    <measurement group_id="O1" value="422"/>
                    <measurement group_id="O2" value="425"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>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.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.93</p_value>
            <method>Robust Poisson Regression</method>
            <method_desc>The relative risk was adjusted for birth-weight and center stratum.</method_desc>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>1.00</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.92</ci_lower_limit>
            <ci_upper_limit>1.10</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Death</title>
        <description>This is measured as Yes if an infant died between birth and 22-26 months corrected age; Otherwise, No.</description>
        <time_frame>Birth to 22-26 months corrected age</time_frame>
        <population>The analysis population includes all randomized infants with available vital status.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Death</title>
          <description>This is measured as Yes if an infant died between birth and 22-26 months corrected age; Otherwise, No.</description>
          <population>The analysis population includes all randomized infants with available vital status.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="903"/>
                <count group_id="O2" value="901"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Death</title>
                  <measurement_list>
                    <measurement group_id="O1" value="146"/>
                    <measurement group_id="O2" value="135"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No Death</title>
                  <measurement_list>
                    <measurement group_id="O1" value="757"/>
                    <measurement group_id="O2" value="766"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Neurodevelopmental Impairment</title>
        <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.</description>
        <time_frame>at 22-26 months corrected age</time_frame>
        <population>The analysis population includes all randomized infants with available data for neurodevelopmental impairment.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Neurodevelopmental Impairment</title>
          <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.</description>
          <population>The analysis population includes all randomized infants with available data for neurodevelopmental impairment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="699"/>
                <count group_id="O2" value="712"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Neurodevelopmental Impairment</title>
                  <measurement_list>
                    <measurement group_id="O1" value="277"/>
                    <measurement group_id="O2" value="287"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No Neurodevelopmental Impairment</title>
                  <measurement_list>
                    <measurement group_id="O1" value="422"/>
                    <measurement group_id="O2" value="425"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Cognitive Delay</title>
        <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.</description>
        <time_frame>at 22-26 months corrected age</time_frame>
        <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Cognitive Delay</title>
          <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.</description>
          <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="695"/>
                <count group_id="O2" value="712"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Cognitive Delay</title>
                  <measurement_list>
                    <measurement group_id="O1" value="269"/>
                    <measurement group_id="O2" value="270"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No Cognitive Delay</title>
                  <measurement_list>
                    <measurement group_id="O1" value="426"/>
                    <measurement group_id="O2" value="442"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Moderate or Severe Cerebral Palsy</title>
        <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 &quot;I&quot; denotes mild cerebral palsy (CP); level &quot;II&quot; or &quot;III&quot; moderate CP; level &quot;IV&quot; or &quot;V&quot; severe CP.</description>
        <time_frame>at 22-26 months corrected age</time_frame>
        <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Moderate or Severe Cerebral Palsy</title>
          <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 &quot;I&quot; denotes mild cerebral palsy (CP); level &quot;II&quot; or &quot;III&quot; moderate CP; level &quot;IV&quot; or &quot;V&quot; severe CP.</description>
          <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="711"/>
                <count group_id="O2" value="720"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Moderate or Severe Cerebral Palsy</title>
                  <measurement_list>
                    <measurement group_id="O1" value="48"/>
                    <measurement group_id="O2" value="55"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild or No Cerebral Palsy</title>
                  <measurement_list>
                    <measurement group_id="O1" value="663"/>
                    <measurement group_id="O2" value="665"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Severe Vision Impairment</title>
        <description>This is measured as Yes if the corrected visual acuity in the better eye of less than 20/200; Otherwise, No.</description>
        <time_frame>at 22-26 months corrected age</time_frame>
        <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Severe Vision Impairment</title>
          <description>This is measured as Yes if the corrected visual acuity in the better eye of less than 20/200; Otherwise, No.</description>
          <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="713"/>
                <count group_id="O2" value="720"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>No Severe Vision Impairment</title>
                  <measurement_list>
                    <measurement group_id="O1" value="708"/>
                    <measurement group_id="O2" value="714"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe Vision Impairment</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Severe Hearing Impairment</title>
        <description>This is measured as Yes if bilateral hearing loss occurred for which hearing aids or cochlear implants were warranted; Otherwise, No.</description>
        <time_frame>at 22-26 months corrected age</time_frame>
        <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Severe Hearing Impairment</title>
          <description>This is measured as Yes if bilateral hearing loss occurred for which hearing aids or cochlear implants were warranted; Otherwise, No.</description>
          <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="710"/>
                <count group_id="O2" value="715"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>No Severe Hearing Impairment</title>
                  <measurement_list>
                    <measurement group_id="O1" value="696"/>
                    <measurement group_id="O2" value="690"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe Hearing Impairment</title>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Survival to Discharge Without Severe Complications</title>
        <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.</description>
        <time_frame>Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)</time_frame>
        <population>The analysis population includes all randomized infants with available data up to hospital discharge or death.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Survival to Discharge Without Severe Complications</title>
          <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.</description>
          <population>The analysis population includes all randomized infants with available data up to hospital discharge or death.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="901"/>
                <count group_id="O2" value="888"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>No Survival to Discharge Without Severe Complications</title>
                  <measurement_list>
                    <measurement group_id="O1" value="644"/>
                    <measurement group_id="O2" value="614"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Survival to Discharge Without Severe Complications</title>
                  <measurement_list>
                    <measurement group_id="O1" value="257"/>
                    <measurement group_id="O2" value="274"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <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</title>
        <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.</description>
        <time_frame>at 36 weeks postmenstrual age</time_frame>
        <population>The analysis population includes all randomized infants with available data at 36 weeks postmenstrual age.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <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</title>
          <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.</description>
          <population>The analysis population includes all randomized infants with available data at 36 weeks postmenstrual age.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="795"/>
                <count group_id="O2" value="805"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Bronchopulmonary Dysplasia at 36 Weeks Postmenstrual Age</title>
                  <measurement_list>
                    <measurement group_id="O1" value="469"/>
                    <measurement group_id="O2" value="453"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No Bronchopulmonary Dysplasia at 36 Weeks Postmenstrual Age</title>
                  <measurement_list>
                    <measurement group_id="O1" value="326"/>
                    <measurement group_id="O2" value="352"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Retinopathy of Prematurity Stage &gt;=3 or Treatment for That Condition Received</title>
        <description>This is measured as Yes if experienced Retinopathy of Prematurity (ROP) Stage &gt;=3 or received treatment for that condition; Otherwise, No. Higher stages of ROP indicate a worse outcome; the stages range from 1 for &quot;mild&quot; disease, to 5 for &quot;severe&quot; disease.</description>
        <time_frame>Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)</time_frame>
        <population>The analysis population includes all randomized infants with available data up to hospital discharge or death.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Retinopathy of Prematurity Stage &gt;=3 or Treatment for That Condition Received</title>
          <description>This is measured as Yes if experienced Retinopathy of Prematurity (ROP) Stage &gt;=3 or received treatment for that condition; Otherwise, No. Higher stages of ROP indicate a worse outcome; the stages range from 1 for &quot;mild&quot; disease, to 5 for &quot;severe&quot; disease.</description>
          <population>The analysis population includes all randomized infants with available data up to hospital discharge or death.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="797"/>
                <count group_id="O2" value="797"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>No Retinopathy of Prematurity at least Stage 3 and did not Receive Treatment for Such Condition</title>
                  <measurement_list>
                    <measurement group_id="O1" value="640"/>
                    <measurement group_id="O2" value="660"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Retinopathy of Prematurity at least Stage 3 or Received Treatment for Such Condition</title>
                  <measurement_list>
                    <measurement group_id="O1" value="157"/>
                    <measurement group_id="O2" value="137"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Grade 3 or 4 Intraventricular Hemorrhage, Cystic Periventricular Leukomalacia, or Ventriculomegaly Diagnosed on Ultrasonographic Examination</title>
        <description>This is measured as Yes if experienced Grade 3 or 4 intraventricularhemorrhage, cystic periventricular leukomalacia, or ventriculomegaly diagnosed on ultrasonographic examination; Otherwise, No.</description>
        <time_frame>Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)</time_frame>
        <population>The analysis population includes all randomized infants with available data up to hospital discharge or death.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Grade 3 or 4 Intraventricular Hemorrhage, Cystic Periventricular Leukomalacia, or Ventriculomegaly Diagnosed on Ultrasonographic Examination</title>
          <description>This is measured as Yes if experienced Grade 3 or 4 intraventricularhemorrhage, cystic periventricular leukomalacia, or ventriculomegaly diagnosed on ultrasonographic examination; Otherwise, No.</description>
          <population>The analysis population includes all randomized infants with available data up to hospital discharge or death.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="855"/>
                <count group_id="O2" value="859"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Grade 3 or 4 intraventricular hemorrhage, cystic periventricular leukomalacia, or ventriculomegaly</title>
                  <measurement_list>
                    <measurement group_id="O1" value="146"/>
                    <measurement group_id="O2" value="154"/>
                  </measurement_list>
                </category>
                <category>
                  <title>None of the stated head ultrasound diagnoses</title>
                  <measurement_list>
                    <measurement group_id="O1" value="709"/>
                    <measurement group_id="O2" value="705"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Necrotizing Enterocolitis, Bell's Stage &gt;=2</title>
        <description>This is measured as Yes if experienced necrotizing enterocolitis (NEC), Bell's stage &gt;=2; Otherwise, No. Higher scores of Bell's staging criteria denote a worse outcome, where &quot;1&quot; denotes suspect, &quot;2&quot; definite and &quot;3&quot; advanced NEC.</description>
        <time_frame>Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)</time_frame>
        <population>The analysis population includes all randomized infants with available data up to hospital discharge or death.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Necrotizing Enterocolitis, Bell's Stage &gt;=2</title>
          <description>This is measured as Yes if experienced necrotizing enterocolitis (NEC), Bell's stage &gt;=2; Otherwise, No. Higher scores of Bell's staging criteria denote a worse outcome, where &quot;1&quot; denotes suspect, &quot;2&quot; definite and &quot;3&quot; advanced NEC.</description>
          <population>The analysis population includes all randomized infants with available data up to hospital discharge or death.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="907"/>
                <count group_id="O2" value="906"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>NEC, Bell's Stage &gt;= 2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="91"/>
                    <measurement group_id="O2" value="95"/>
                  </measurement_list>
                </category>
                <category>
                  <title>NEC, Bell's Stage = 1 or no NEC</title>
                  <measurement_list>
                    <measurement group_id="O1" value="816"/>
                    <measurement group_id="O2" value="811"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Transfusions Per Infant</title>
        <description>This is measured as the number of protocol compliant transfusions, clinically justified non-protocol transfusions and unjustified non-protocol transfusions (violations)</description>
        <time_frame>Birth, up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age (PMA)</time_frame>
        <population>The analysis population includes all randomized infants with available data up to death, hospital discharge, or 36 weeks PMA, whichever occurs first</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Transfusions Per Infant</title>
          <description>This is measured as the number of protocol compliant transfusions, clinically justified non-protocol transfusions and unjustified non-protocol transfusions (violations)</description>
          <population>The analysis population includes all randomized infants with available data up to death, hospital discharge, or 36 weeks PMA, whichever occurs first</population>
          <units>Transfusions</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="911"/>
                <count group_id="O2" value="913"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.2" spread="4.3"/>
                    <measurement group_id="O2" value="4.4" spread="4.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Weight-for-age: Z-score</title>
        <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.</description>
        <time_frame>at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first</time_frame>
        <population>The analysis population includes all randomized infants with available data at 36 weeks postmenstrual age or at initial hospital discharge, whichever occurs first.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Weight-for-age: Z-score</title>
          <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.</description>
          <population>The analysis population includes all randomized infants with available data at 36 weeks postmenstrual age or at initial hospital discharge, whichever occurs first.</population>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="769"/>
                <count group_id="O2" value="774"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.2" spread="0.8"/>
                    <measurement group_id="O2" value="-1.3" spread="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Length-for-age: Z-score</title>
        <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.</description>
        <time_frame>at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first</time_frame>
        <population>The analysis population includes all randomized infants with available data at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Length-for-age: Z-score</title>
          <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.</description>
          <population>The analysis population includes all randomized infants with available data at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first.</population>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="715"/>
                <count group_id="O2" value="715"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.9" spread="1.0"/>
                    <measurement group_id="O2" value="-1.9" spread="0.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Head Circumference-for-age: Z-score</title>
        <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.</description>
        <time_frame>at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first</time_frame>
        <population>The analysis population includes all randomized infants with available data at 36 weeks postmenstrual age or at initial hospital discharge, whichever occurs first.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Head Circumference-for-age: Z-score</title>
          <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.</description>
          <population>The analysis population includes all randomized infants with available data at 36 weeks postmenstrual age or at initial hospital discharge, whichever occurs first.</population>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="754"/>
                <count group_id="O2" value="766"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.4" spread="1.0"/>
                    <measurement group_id="O2" value="-1.4" spread="1.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Postmenstrual Age at Final Trachael Extubation</title>
        <description>This is measured as the average postmenstrual age (in weeks) at final tracheal extubation in infants who were intubated.</description>
        <time_frame>at final trachael extubation, assessed from birth up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age</time_frame>
        <population>The analysis population includes all randomized infants with available data on trachael extubation.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Postmenstrual Age at Final Trachael Extubation</title>
          <description>This is measured as the average postmenstrual age (in weeks) at final tracheal extubation in infants who were intubated.</description>
          <population>The analysis population includes all randomized infants with available data on trachael extubation.</population>
          <units>Weeks</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="796"/>
                <count group_id="O2" value="804"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30" spread="3.4"/>
                    <measurement group_id="O2" value="30.2" spread="3.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Postmenstrual Age at Final Caffeine Dose in Infants Who Received Caffeine Treatment</title>
        <description>This is measured as the average postmenstrual age (in weeks) at final caffeine dose in infants who received caffeine treatment.</description>
        <time_frame>at final caffeine dose, assessed from birth up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age</time_frame>
        <population>The analysis population includes all randomized infants with available data on caffeine treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Postmenstrual Age at Final Caffeine Dose in Infants Who Received Caffeine Treatment</title>
          <description>This is measured as the average postmenstrual age (in weeks) at final caffeine dose in infants who received caffeine treatment.</description>
          <population>The analysis population includes all randomized infants with available data on caffeine treatment.</population>
          <units>Weeks</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="882"/>
                <count group_id="O2" value="887"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.8" spread="3.0"/>
                    <measurement group_id="O2" value="34.0" spread="2.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Length of Stay</title>
        <description>This is measured as the length of stay (in days) up to initial hospital discharge or death, whichever occurred first.</description>
        <time_frame>at initial hospital discharge or at death if it occurs earlier (a median of 97 days)</time_frame>
        <population>The analysis population includes all randomized infants with available data up to the initial hospital discharge or death, whichever occurs first.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Length of Stay</title>
          <description>This is measured as the length of stay (in days) up to initial hospital discharge or death, whichever occurred first.</description>
          <population>The analysis population includes all randomized infants with available data up to the initial hospital discharge or death, whichever occurs first.</population>
          <units>Days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="908"/>
                <count group_id="O2" value="906"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96" lower_limit="72" upper_limit="129"/>
                    <measurement group_id="O2" value="97" lower_limit="75" upper_limit="127"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Full Enteral Feeding</title>
        <description>This is measured as the amount of days it took for full enteral feeding to occur.</description>
        <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)</time_frame>
        <population>The analysis population includes all randomized infants with available data on enteral feeding.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Full Enteral Feeding</title>
          <description>This is measured as the amount of days it took for full enteral feeding to occur.</description>
          <population>The analysis population includes all randomized infants with available data on enteral feeding.</population>
          <units>Days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="808"/>
                <count group_id="O2" value="824"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.5" lower_limit="14" upper_limit="29"/>
                    <measurement group_id="O2" value="19.0" lower_limit="15" upper_limit="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Severe Cerebral Palsy</title>
        <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 &quot;I&quot; denotes mild cerebral palsy (CP); level &quot;II&quot; or &quot;III&quot; moderate CP; level &quot;IV&quot; or &quot;V&quot; severe CP.</description>
        <time_frame>at 22-26 months corrected age</time_frame>
        <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Severe Cerebral Palsy</title>
          <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 &quot;I&quot; denotes mild cerebral palsy (CP); level &quot;II&quot; or &quot;III&quot; moderate CP; level &quot;IV&quot; or &quot;V&quot; severe CP.</description>
          <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="710"/>
                <count group_id="O2" value="720"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>No Severe Cerebral Palsy</title>
                  <measurement_list>
                    <measurement group_id="O1" value="690"/>
                    <measurement group_id="O2" value="709"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe Cerebral Palsy</title>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Hydrocephalus Shunt</title>
        <description>This is measured as Yes if experienced Hydrocephalus shunt by follow-up; Otherwise, No.</description>
        <time_frame>Initial hospital discharge to 22-26 months corrected age</time_frame>
        <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Hydrocephalus Shunt</title>
          <description>This is measured as Yes if experienced Hydrocephalus shunt by follow-up; Otherwise, No.</description>
          <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="717"/>
                <count group_id="O2" value="728"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hydrocephalus Shunt</title>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No Hydrocephalus Shunt</title>
                  <measurement_list>
                    <measurement group_id="O1" value="697"/>
                    <measurement group_id="O2" value="706"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Microcephaly</title>
        <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.</description>
        <time_frame>at 22-26 months corrected age</time_frame>
        <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Microcephaly</title>
          <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.</description>
          <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="700"/>
                <count group_id="O2" value="710"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Microcephaly</title>
                  <measurement_list>
                    <measurement group_id="O1" value="61"/>
                    <measurement group_id="O2" value="52"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No Microcephaly</title>
                  <measurement_list>
                    <measurement group_id="O1" value="639"/>
                    <measurement group_id="O2" value="658"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Seizure Disorder</title>
        <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.</description>
        <time_frame>Initial hospital discharge to 22-26 months corrected age</time_frame>
        <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Seizure Disorder</title>
          <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.</description>
          <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="714"/>
                <count group_id="O2" value="726"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>No Seizure disorder</title>
                  <measurement_list>
                    <measurement group_id="O1" value="672"/>
                    <measurement group_id="O2" value="685"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Seizure disorder</title>
                  <measurement_list>
                    <measurement group_id="O1" value="42"/>
                    <measurement group_id="O2" value="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Respiratory Disease Necessitating Readmission Before Follow-up</title>
        <description>This is measured as Yes if obtained Respiratory disease necessitating readmission before follow-up; Otherwise, No.</description>
        <time_frame>Initial hospital discharge to 22-26 months corrected age</time_frame>
        <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Respiratory Disease Necessitating Readmission Before Follow-up</title>
          <description>This is measured as Yes if obtained Respiratory disease necessitating readmission before follow-up; Otherwise, No.</description>
          <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="715"/>
                <count group_id="O2" value="726"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>No Respiratory disease necessitating readmission before follow-up</title>
                  <measurement_list>
                    <measurement group_id="O1" value="467"/>
                    <measurement group_id="O2" value="496"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Respiratory disease necessitating readmission before follow-up</title>
                  <measurement_list>
                    <measurement group_id="O1" value="248"/>
                    <measurement group_id="O2" value="230"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Composite Language Score Less Than 85</title>
        <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.</description>
        <time_frame>at 22-26 months corrected age</time_frame>
        <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Composite Language Score Less Than 85</title>
          <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.</description>
          <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="671"/>
                <count group_id="O2" value="691"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Composite language score greater or equal to 85</title>
                  <measurement_list>
                    <measurement group_id="O1" value="316"/>
                    <measurement group_id="O2" value="323"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Composite language score less than 85</title>
                  <measurement_list>
                    <measurement group_id="O1" value="355"/>
                    <measurement group_id="O2" value="368"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Composite Motor Score Less Than 85</title>
        <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.</description>
        <time_frame>at 22-26 months corrected age</time_frame>
        <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Composite Motor Score Less Than 85</title>
          <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.</description>
          <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="678"/>
                <count group_id="O2" value="695"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Composite motor score greater or equal to 85</title>
                  <measurement_list>
                    <measurement group_id="O1" value="423"/>
                    <measurement group_id="O2" value="415"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Composite motor score less than 85</title>
                  <measurement_list>
                    <measurement group_id="O1" value="255"/>
                    <measurement group_id="O2" value="280"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Composite Cognitive Score Less Than 70</title>
        <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.</description>
        <time_frame>at 22-26 months corrected age</time_frame>
        <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Composite Cognitive Score Less Than 70</title>
          <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.</description>
          <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="695"/>
                <count group_id="O2" value="712"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Composite cognitive score greater or equal to 70</title>
                  <measurement_list>
                    <measurement group_id="O1" value="607"/>
                    <measurement group_id="O2" value="616"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Composite cognitive score less than 70</title>
                  <measurement_list>
                    <measurement group_id="O1" value="88"/>
                    <measurement group_id="O2" value="96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Composite Language Score Less Than 70</title>
        <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.</description>
        <time_frame>at 22-26 months corrected age</time_frame>
        <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Composite Language Score Less Than 70</title>
          <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.</description>
          <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="671"/>
                <count group_id="O2" value="691"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Composite language score greater or equal to 70</title>
                  <measurement_list>
                    <measurement group_id="O1" value="507"/>
                    <measurement group_id="O2" value="528"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Composite language score less than 70</title>
                  <measurement_list>
                    <measurement group_id="O1" value="164"/>
                    <measurement group_id="O2" value="163"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Composite Motor Score Less Than 70</title>
        <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.</description>
        <time_frame>at 22-26 months corrected age</time_frame>
        <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
        <group_list>
          <group group_id="O1">
            <title>High Transfusion Threshold</title>
            <description>Transfusions were administered using a higher threshold hemoglobin value. AKA 'Liberal Cell Transfusion' group.</description>
          </group>
          <group group_id="O2">
            <title>Low Transfusion Threshold</title>
            <description>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</description>
          </group>
        </group_list>
        <measure>
          <title>Composite Motor Score Less Than 70</title>
          <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.</description>
          <population>The analysis population includes all randomized infants with available data at the two-year followup.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="678"/>
                <count group_id="O2" value="695"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Composite motor score greater or equal to 70</title>
                  <measurement_list>
                    <measurement group_id="O1" value="591"/>
                    <measurement group_id="O2" value="596"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Composite motor score less than 70</title>
                  <measurement_list>
                    <measurement group_id="O1" value="87"/>
                    <measurement group_id="O2" value="99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Birth to 37 weeks PMA</time_frame>
      <group_list>
        <group group_id="E1">
          <title>High Tranfusion Threshold</title>
          <description>Transfusions were administered using a higher threshold hemoglobin value. AKA &quot;Liberal Cell Transfusion&quot; group.</description>
        </group>
        <group group_id="E2">
          <title>Low Transfusion Threshold</title>
          <description>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 &quot;Restricted Red Cell Transfusion&quot; group.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 17.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="146" subjects_at_risk="903"/>
                <counts group_id="E2" subjects_affected="135" subjects_at_risk="901"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="206" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="197" subjects_at_risk="906"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Hemolysis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="906"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Adrenal Insufficiency</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="906"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="906"/>
              </event>
              <event>
                <sub_title>Bell's stage &gt; 2 Necrotizing Enterocolitis (NEC)</sub_title>
                <counts group_id="E1" subjects_affected="58" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="62" subjects_at_risk="906"/>
              </event>
              <event>
                <sub_title>Bowel Obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="906"/>
              </event>
              <event>
                <sub_title>Esophageal Perforation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="906"/>
              </event>
              <event>
                <sub_title>Ischemic Bowel</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="906"/>
              </event>
              <event>
                <sub_title>Spontaneous Intestinal Perforation</sub_title>
                <counts group_id="E1" subjects_affected="29" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="38" subjects_at_risk="906"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Severe Hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="906"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nosocomial Sepsis up to 24 hours post-transfusion</sub_title>
                <counts group_id="E1" subjects_affected="31" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="906"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="906"/>
              </event>
              <event>
                <sub_title>Sepsis Bacterial</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="906"/>
              </event>
              <event>
                <sub_title>Sepsis Fungal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="906"/>
              </event>
              <event>
                <sub_title>Sepsis Viral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="906"/>
              </event>
              <event>
                <sub_title>Severe Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="906"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperkalemia -- non-hemolyzed specimen, up to 24 hours post-transfusion</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="906"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Seizures</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="906"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal Failure</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="906"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Persistent Pulmonary Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="906"/>
              </event>
              <event>
                <sub_title>Pulmonary Air Leaks</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="906"/>
              </event>
              <event>
                <sub_title>Pulmonary Hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="906"/>
              </event>
              <event>
                <sub_title>Respiratory Deterioration up to 24 hours post-transfusion</sub_title>
                <counts group_id="E1" subjects_affected="93" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="85" subjects_at_risk="906"/>
              </event>
              <event>
                <sub_title>Respiratory Failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="906"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Severe Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="906"/>
              </event>
              <event>
                <sub_title>Thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="906"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0.05</frequency_threshold>
        <default_vocab>MedDRA 17.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="184" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="164" subjects_at_risk="906"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperkalemia -- non-hemolyzed specimen, up to 24 hours post-transfusion</sub_title>
                <counts group_id="E1" subjects_affected="58" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="40" subjects_at_risk="906"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory Deterioration up to 24 hours post-transfusion</sub_title>
                <counts group_id="E1" subjects_affected="147" subjects_at_risk="908"/>
                <counts group_id="E2" subjects_affected="146" subjects_at_risk="906"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Investigators must adhere to the Neonatal Research Network Publication Policies</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Haresh Kirpalani</name_or_title>
      <organization>Emeritus Professor U Pennsylvania at CHOP and Emeritus Professor McMaster University, Dept Pediatrics</organization>
      <phone>267-844-3233</phone>
      <email>kirpalan@mcmaster.ca</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01702805
org study id: NICHD-NRN-0050
secondary id: U01HL112776
secondary id: U01HL112748
nct id: NCT01702805
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Death or Neurodevelopmental Impairment
time frame: Birth to 22-26 months corrected age
description: A composite outcome that measures the occurrence of death or neurodevelomental impairment between birth and 22-26 months corrected age.
measure: Death
time frame: Birth to 22-26 months corrected age
description: This is measured as Yes if an infant died between birth and 22-26 months corrected age; Otherwise, No.
measure: Neurodevelopmental Impairment
time frame: at 22-26 months corrected age
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.
measure: Cognitive Delay
time frame: at 22-26 months corrected age
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.
measure: Moderate or Severe Cerebral Palsy
time frame: at 22-26 months corrected age
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.
measure: Severe Vision Impairment
time frame: at 22-26 months corrected age
description: This is measured as Yes if the corrected visual acuity in the better eye of less than 20/200; Otherwise, No.
measure: Severe Hearing Impairment
time frame: at 22-26 months corrected age
description: This is measured as Yes if bilateral hearing loss occurred for which hearing aids or cochlear implants were warranted; Otherwise, No.
measure: Survival to Discharge Without Severe Complications
time frame: Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)
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.
measure: Bronchopulmonary Dysplasia, Diagnosed on the Basis of the Need for Supplemental Oxygen After a Standardized Oxygen Reduction Test at 36 Weeks of Postmenstrual Age
time frame: at 36 weeks 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.
measure: Retinopathy of Prematurity Stage >=3 or Treatment for That Condition Received
time frame: Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)
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.
measure: Grade 3 or 4 Intraventricular Hemorrhage, Cystic Periventricular Leukomalacia, or Ventriculomegaly Diagnosed on Ultrasonographic Examination
time frame: Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)
description: This is measured as Yes if experienced Grade 3 or 4 intraventricularhemorrhage, cystic periventricular leukomalacia, or ventriculomegaly diagnosed on ultrasonographic examination; Otherwise, No.
measure: Necrotizing Enterocolitis, Bell's Stage >=2
time frame: Birth to initial hospital discharge or to death if it occurs earlier (a median of 97 days)
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.
measure: Number of Transfusions Per Infant
time frame: Birth, up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age (PMA)
description: This is measured as the number of protocol compliant transfusions, clinically justified non-protocol transfusions and unjustified non-protocol transfusions (violations)
measure: Weight-for-age: Z-score
time frame: at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first
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.
measure: Length-for-age: Z-score
time frame: at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first
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.
measure: Head Circumference-for-age: Z-score
time frame: at 36 weeks postmenstrual age or initial hospital discharge, whichever occurs first
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.
measure: Postmenstrual Age at Final Trachael Extubation
time frame: at final trachael extubation, assessed from birth up to the earliest of: death, hospital discharge, or 36 weeks postmenstrual age
description: This is measured as the average postmenstrual age (in weeks) at final tracheal extubation in infants who were intubated.
measure: Postmenstrual Age 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
description: This is measured as the average postmenstrual age (in weeks) at final caffeine dose in infants who received caffeine treatment.
measure: Length of Stay
time frame: at initial hospital discharge or at death if it occurs earlier (a median of 97 days)
description: This is measured as the length of stay (in days) up to initial hospital discharge or death, whichever occurred first.
measure: Time to Full Enteral Feeding
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)
description: This is measured as the amount of days it took for full enteral feeding to occur.
measure: Severe Cerebral Palsy
time frame: at 22-26 months corrected age
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.
measure: Hydrocephalus Shunt
time frame: Initial hospital discharge to 22-26 months corrected age
description: This is measured as Yes if experienced Hydrocephalus shunt by follow-up; Otherwise, No.
measure: Microcephaly
time frame: at 22-26 months corrected age
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.
measure: Seizure Disorder
time frame: Initial hospital discharge to 22-26 months corrected age
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.
measure: Respiratory Disease Necessitating Readmission Before Follow-up
time frame: Initial hospital discharge to 22-26 months corrected age
description: This is measured as Yes if obtained Respiratory disease necessitating readmission before follow-up; Otherwise, No.
measure: Composite Language Score Less Than 85
time frame: at 22-26 months corrected age
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.
measure: Composite Motor Score Less Than 85
time frame: at 22-26 months corrected age
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.
measure: Composite Cognitive Score Less Than 70
time frame: at 22-26 months corrected age
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.
measure: Composite Language Score Less Than 70
time frame: at 22-26 months corrected age
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.
measure: Composite Motor Score Less Than 70
time frame: at 22-26 months corrected age
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.
arm group label: Low Threshold Transfusion
arm group type: Active Comparator
description: 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
arm group label: High Threshold Transfusion
arm group type: Active Comparator
description: Transfusions will be administered using a higher threshold hemoglobin value.
intervention type: Procedure
intervention name: Liberal Cell Transfusion
arm group label: High Threshold Transfusion
intervention type: Procedure
intervention name: Restricted red cell transfusion
arm group label: Low Threshold Transfusion
criteria: 
gender: All
minimum age: N/A
maximum age: 48 Hours
healthy volunteers: No
last name: Michele C Walsh, MD
role: Principal Investigator
affiliation: Case Western Reserve University, Rainbow Babies and Children's Hospital
last name: Abhik Das, PhD
role: Principal Investigator
affiliation: RTI International
last name: Beena Sood, MD
role: Principal Investigator
affiliation: Wayne State University
last name: Abbot R Laptook, MD
role: Principal Investigator
affiliation: Brown University, Women & Infants Hospital of Rhode Island
last name: Michael Cotten, MD
role: Principal Investigator
affiliation: Duke University
last name: Ravi Patel, MD
role: Principal Investigator
affiliation: Emory University
last name: Greg Sokol, MD
role: Principal Investigator
affiliation: Indiana University
last name: Krisa P Van Meurs, MD
role: Principal Investigator
affiliation: Stanford University
last name: Brenda Poindexter, MD
role: Principal Investigator
affiliation: Children's Hospital Medical Center, Cincinnati
last name: Waldemar A Carlo, MD
role: Principal Investigator
affiliation: University of Alabama at Birmingham
last name: Kristi L Watterberg, MD
role: Principal Investigator
affiliation: University of New Mexico
last name: Myra Wyckoff, MD
role: Principal Investigator
affiliation: University of Texas, Southwestern Medical Center at Dallas
last name: Kathleen A Kennedy, MD, MPH
role: Principal Investigator
affiliation: The University of Texas Health Science Center, Houston
last name: Carl T D'Angio, MD
role: Principal Investigator
affiliation: University of Rochester
last name: Pablo Sanchez, MD
role: Principal Investigator
affiliation: Research Institute at Nationwide Children's Hospital
last name: William Truog, MD
role: Principal Investigator
affiliation: Children's Mercy Hospital Kansas City
last name: Uday Devaskar, MD
role: Principal Investigator
affiliation: University of California, Los Angeles
last name: Haresh M Kirpalani, MD
role: Study Director
affiliation: University of Pennsylvania
last name: Bradley Yoder, MD
role: Principal Investigator
affiliation: University of Utah
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country: United States
url: http://neonatal.rti.org/
description: NICHD NRN Website
url: https://www.nichd.nih.gov/about/org/der/branches/ppb
description: NICHD Pregnancy & Perinatology Branch
responsible party type: Sponsor
mesh term: Bronchopulmonary Dysplasia
mesh term: Infant, Newborn, Diseases
mesh term: Birth Weight
sharing ipd: Yes
ipd description: NIH has had a long-standing policy to share and make available to the public the results and accomplishments of the activities that it funds. The NRN plans to share de-identified data after final publication in an NIH supported data repository such as the NICHD Data and Specimen Hub (https://dash.nichd.nih.gov)
provided document: 
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