<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/NCT03278847</url>
  </required_header>
  <id_info>
    <org_study_id>17IC4064</org_study_id>
    <secondary_id>16/79/03</secondary_id>
    <secondary_id>17/EM/0307</secondary_id>
    <nct_id>NCT03278847</nct_id>
  </id_info>
  <brief_title>Optimising Newborn Nutrition During Therapeutic Hypothermia.</brief_title>
  <official_title>Optimising Newborn Nutrition During Therapeutic Hypothermia: an Observational Study Using Routinely Collected Data</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Imperial College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Nottingham</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bliss the charity for babies born premature or sick</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Imperial College London</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overarching aim of this project is to determine the optimum enteral and parenteral&#xD;
      nutrition strategy for newborns with Hypoxic Ischaemic Encephalopathy (HIE) during and after&#xD;
      therapeutic hypothermia. To do this the investigators will perform two primary comparisons:&#xD;
&#xD;
        1. ENTERAL: to determine whether any enteral (milk) feeding, when compared to withholding&#xD;
           enteral feeding (no milk), during therapeutic hypothermia, is associated with a&#xD;
           difference in the incidence of necrotising enterocolitis.&#xD;
&#xD;
        2. PARENTERAL: to determine whether provision of intravenous dextrose, when compared to&#xD;
           provision of parenteral nutrition, during therapeutic hypothermia, is associated with a&#xD;
           difference in the incidence of blood stream infection.&#xD;
&#xD;
      The investigators will use de-identified data held in an established research database called&#xD;
      the National Neonatal Research Database (NNRD) and we will use the potential outcomes&#xD;
      framework with application of propensity scoring to define matched subgroups for comparison.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Every year about 1200 babies in England, Wales and Scotland suffer from a lack of oxygen&#xD;
      around birth which can lead to long-term brain injury or death. This is called Hypoxic&#xD;
      Ischaemic Encephalopathy (HIE). Research has shown that cooling babies with HIE by a few&#xD;
      degrees for the first 3 days protects the brain; all babies with moderate or severe HIE in&#xD;
      the UK are treated with therapeutic hypothermia (cooling).&#xD;
&#xD;
      Doctors do not know how best to care for babies while they are cooled. A key question is &quot;how&#xD;
      to provide nutrition to babies during cooling&quot;. There are two main parts to this question,&#xD;
      milk feeds (&quot;enteral&quot; nutrition) and intravenous nutrition (&quot;parenteral&quot; nutrition). Doctors&#xD;
      don't know how best to provide either milk or intravenous nutrition to cooled babies.&#xD;
&#xD;
        -  MILK FEEDS: Some neonatal units in the UK carefully feed babies (usually with maternal&#xD;
           breast milk) while they are cooled. This avoids intravenous lines and is believed to&#xD;
           help them feed and go home earlier. Other neonatal units do not feed cooled babies&#xD;
           because they worry about a condition called necrotising enterocolitis (a devastating and&#xD;
           often fatal disease) which might be more common with feeding.&#xD;
&#xD;
        -  INTRAVENOUS NUTRITION: All cooled babies need intravenous fluid (even when milk feeds&#xD;
           are given it takes several days before enough fluid can be given this way). Some&#xD;
           neonatal units give babies intravenous nutrition (which contains fat, protein,&#xD;
           carbohydrate, vitamins and minerals) as this may improve growth and recovery. Other&#xD;
           neonatal units only give intravenous dextrose with simple salts because of concerns that&#xD;
           intravenous nutrition leads to more infections. This study will compare these different&#xD;
           ways of providing nutrition. It will use a research database called the National&#xD;
           Neonatal Research Database (NNRD). In England, Scotland and Wales doctors and nurses&#xD;
           looking after babies in neonatal care (including all cooled babies) use an Electronic&#xD;
           Health Record system. Data from this system are anonymised (no baby can be identified)&#xD;
           and form the NNRD, so the NNRD holds data from all babies who have been looked after on&#xD;
           NHS neonatal units.&#xD;
&#xD;
      The investigators have worked closely with parents and charities in developing the NNRD. The&#xD;
      investigators will use the NNRD to study all term babies who received cooling in England,&#xD;
      Scotland and Wales since 2008. The investigators will compare the milk feeding and&#xD;
      intravenous nutrition they receive.&#xD;
&#xD;
        -  MILK FEEDING: The investigators will compare babies who are fed milk while cooled with&#xD;
           those that are not fed any milk. The investigator's main goal is to establish whether&#xD;
           there is any difference in rates of necrotising enterocolitis.&#xD;
&#xD;
        -  INTRAVENOUS NUTRITION: The investigators will compare babies who get intravenous&#xD;
           nutrition with those that only get intravenous dextrose. The main difference we are&#xD;
           looking for is in the rate of infection. The investigators will also study how many&#xD;
           babies die, how long they stay in neonatal care, how soon breastfeeding starts and many&#xD;
           are breastfed when they go home.&#xD;
&#xD;
      The investigators will apply a statistical approach called &quot;potential outcomes framework&quot; in&#xD;
      which babies are matched in each group (e.g. babies who are fed and those who are not fed) as&#xD;
      closely as possible. This will ensure that any difference in outcomes is due to the different&#xD;
      nutritional treatments and not due to background differences or other confounders (like how&#xD;
      sick a baby is).&#xD;
&#xD;
      The results from this study will help to ensure that babies who need to be cooled for HIE&#xD;
      receive the best and safest nutrition in the future.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2010</start_date>
  <completion_date type="Actual">January 1, 2021</completion_date>
  <primary_completion_date type="Actual">December 31, 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Necrotising Enterocolitis - for the Enteral Nutrition Comparison</measure>
    <time_frame>From date of birth until date of final neonatal unit discharge, assessed up to 1 year</time_frame>
    <description>Defined according to the case definition of Battersby et al., 2017, JAMA Pediatrics</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood Stream Infection - for the Parenteral Nutrition Comparison</measure>
    <time_frame>From date of birth until date of final neonatal unit discharge, assessed up to 1 year</time_frame>
    <description>defined according to the Healthcare Quality Improvement Partnership (HQIP) National Neonatal Audit Programme (NNAP) case definition: pure growth of a recognised pathogen from a normally sterile site</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Survival</measure>
    <time_frame>From date of birth until date of final neonatal unit discharge, assessed up to 1 year</time_frame>
    <description>Survival at neonatal unit discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of Stay</measure>
    <time_frame>From date of birth until date of final neonatal unit discharge, assessed up to 1 year</time_frame>
    <description>Number of days between first neonatal unit admission and final neonatal unit discharge for surviving infants</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Breastfeeding</measure>
    <time_frame>At the point of final discharge from neonatal care, assessed up to 1 year</time_frame>
    <description>Any breastfeeding (suckling at the breast) at discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hypoglycaemia</measure>
    <time_frame>From date of birth until date of final neonatal unit discharge, assessed up to 1 year</time_frame>
    <description>Any diagnosis of hypoglycaemia recorded after therapeutic hypothermia is commenced and before the final neonatal unit discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Central Venous Line</measure>
    <time_frame>From date of birth until date of final neonatal unit discharge, assessed up to 1 year</time_frame>
    <description>The number of days until an infant is recorded as not having a central venous line</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Growth</measure>
    <time_frame>From date of birth until date of final neonatal unit discharge, assessed up to 1 year</time_frame>
    <description>Weight for post-menstrual age standard deviation score at final neonatal unit discharge.&#xD;
Standard deviation score, higher score means higher growth (higher weight for gestational age)</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">6030</enrollment>
  <condition>Infant, Newborn</condition>
  <condition>Asphyxia Neonatorum</condition>
  <condition>Hypothermia, Induced</condition>
  <condition>Parenteral Nutrition</condition>
  <condition>Infant Nutrition</condition>
  <condition>Necrotizing Enterocolitis</condition>
  <condition>Neonatal Sepsis</condition>
  <arm_group>
    <arm_group_label>Enteral nutrition comparison</arm_group_label>
    <description>This comparison refers to differences in enteral nutrition during therapeutic hypothermia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Parenteral nutrition comparison</arm_group_label>
    <description>This comparison refers to differences in parenteral nutrition during therapeutic hypothermia</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Received enteral (milk) feeds during therapeutic hypothermia</intervention_name>
    <description>In the enteral component of nutrition, the health technology to be assessed is the gradual introduction of enteral (milk) feeds during therapeutic hypothermia:&#xD;
Included in this is any type of milk (e.g. expressed maternal breast milk, expressed donor breast milk and artificial formula)&#xD;
This health technology includes different routes of administering enteral feeds such as nasogastric tube (gavage feeding) and bottle&#xD;
This health technology also includes different rates of increasing enteral feeds (for example by 15ml/kg/day, by 30ml/kg/day or faster)</description>
    <arm_group_label>Enteral nutrition comparison</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Enteral (milk) feeds withheld during therapeutic hypothermia</intervention_name>
    <description>Withholding enteral feeds (keeping a baby nil per os) for the duration of hypothermia.</description>
    <arm_group_label>Enteral nutrition comparison</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Received parenteral nutrition during therapeutic hypothermia</intervention_name>
    <description>In the parenteral component, the health technology being assessed is administration of parenteral nutrition during therapeutic hypothermia:&#xD;
Included in this are different compositions of parenteral nutrition (for example standard, pre-prepared bags of nutrition and individually tailored parenteral nutrition)&#xD;
This health technology includes different routes of administration of parenteral nutrition such as via a peripheral intravenous cannula, percutaneous central venous catheter ('long line') or umbilical venous catheter.&#xD;
This health technology also includes different volumes of parenteral nutrition (e.g. 40ml/kg/day, 60ml/kg/day or greater).</description>
    <arm_group_label>Parenteral nutrition comparison</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Did not receive parenteral nutrition during therapeutic hypothermia</intervention_name>
    <description>Received standard intravenous fluids (10% dextrose with additional electrolytes added where required) for the duration of hypothermia.</description>
    <arm_group_label>Parenteral nutrition comparison</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Infants born at 36 gestational weeks or later who received therapeutic hypothermia for&#xD;
        Hypoxic Ischaemic Encephalopathy (HIE) for least 72 hours, or who died during therapeutic&#xD;
        hypothermia.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Received neonatal care at a unit that is part of the UK Neonatal Collaborative; this&#xD;
             includes all NHS neonatal units in England, Scotland and Wales&#xD;
&#xD;
          2. Recorded gestational age at birth ≥36 weeks&#xD;
&#xD;
          3. Recorded as receiving therapeutic hypothermia for 72 hours or died during therapeutic&#xD;
             hypothermia&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        1. Infants with missing data for principal background and outcome variables.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>4 Days</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chris Gale, MBBS, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Imperial College London</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Chelsea and Westminster Hospital and NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <zip>SW10 9NH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Imperial College London, Chelsea and Westminster Hospital campus</name>
      <address>
        <city>London</city>
        <zip>SW10 9NH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Battersby C, Longford N, Patel M, Selby E, Ojha S, Dorling J, Gale C. Study protocol: optimising newborn nutrition during and after neonatal therapeutic hypothermia in the United Kingdom: observational study of routinely collected data using propensity matching. BMJ Open. 2018 Oct 23;8(10):e026739. doi: 10.1136/bmjopen-2018-026739.</citation>
    <PMID>30355795</PMID>
  </reference>
  <reference>
    <citation>Gale C, Jeyakumaran D, Longford N, Battersby C, Ojha S, Oughham K, Dorling J. Administration of parenteral nutrition during therapeutic hypothermia: a population level observational study using routinely collected data held in the National Neonatal Research Database. Arch Dis Child Fetal Neonatal Ed. 2021 Nov;106(6):608-613. doi: 10.1136/archdischild-2020-321299. Epub 2021 May 5.</citation>
    <PMID>33952628</PMID>
  </reference>
  <results_reference>
    <citation>Gale C, Longford NT, Jeyakumaran D, Ougham K, Battersby C, Ojha S, Dorling J. Feeding during neonatal therapeutic hypothermia, assessed using routinely collected National Neonatal Research Database data: a retrospective, UK population-based cohort study. Lancet Child Adolesc Health. 2021 Jun;5(6):408-416. doi: 10.1016/S2352-4642(21)00026-2. Epub 2021 Apr 21.</citation>
    <PMID>33891879</PMID>
  </results_reference>
  <results_reference>
    <citation>Gale C, Jeyakumaran D, Battersby C, Ougham K, Ojha S, Culshaw L, Selby E, Dorling J, Longford N. Nutritional management in newborn babies receiving therapeutic hypothermia: two retrospective observational studies using propensity score matching. Health Technol Assess. 2021 Jun;25(36):1-106. doi: 10.3310/hta25360.</citation>
    <PMID>34096500</PMID>
  </results_reference>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>August 23, 2017</study_first_submitted>
  <study_first_submitted_qc>September 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <results_first_submitted>September 20, 2021</results_first_submitted>
  <results_first_submitted_qc>November 7, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">September 14, 2023</results_first_posted>
  <last_update_submitted>November 7, 2022</last_update_submitted>
  <last_update_submitted_qc>November 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>NNRD</keyword>
  <keyword>matching</keyword>
  <keyword>propensity score</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neonatal Sepsis</mesh_term>
    <mesh_term>Enterocolitis</mesh_term>
    <mesh_term>Enterocolitis, Necrotizing</mesh_term>
    <mesh_term>Asphyxia Neonatorum</mesh_term>
    <mesh_term>Hypothermia</mesh_term>
    <mesh_term>Asphyxia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All study data will be extracted from the National Neonatal Research Database (NNRD). The NNRD has been created through the collaborative efforts of neonatal services across the country to be a national resource. The NNRD is maintained and managed at the Neonatal Data Analysis Unit (NDAU) at Imperial College London and Chelsea and Westminster NHS Foundation Trust.&#xD;
Researchers, clinicians, managers, commissioners, and others are welcome and encouraged to utilise the NNRD.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>The NNRD holds data from 2007 to present.</ipd_time_frame>
    <ipd_access_criteria>Access criteria and guidance is found at the URL below</ipd_access_criteria>
    <ipd_url>https://www.imperial.ac.uk/neonatal-data-analysis-unit/neonatal-data-analysis-unit/utilising-the-national-neonatal-research-database/</ipd_url>
  </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>December 15, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/47/NCT03278847/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>This was an observational study. 6030 babies were included in the overall study cohort and from this two pairs of matched groups were formed to examine the impact of enteral feeding during therapeutic hypothermia (two matched groups of 1618) and of parenteral nutrition during therapeutic hypothermia (two matched groups of 1240).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Received Enteral (Milk) Feeds During Therapeutic Hypothermia</title>
          <description>The gradual introduction of enteral (milk) feeds during therapeutic hypothermia:&#xD;
Included in this is any type of milk (e.g. expressed maternal breast milk, expressed donor breast milk and artificial formula)&#xD;
This health technology includes different routes of administering enteral feeds such as nasogastric tube (gavage feeding) and bottle&#xD;
This health technology also includes different rates of increasing enteral feeds (for example by 15ml/kg/day, by 30ml/kg/day or faster)</description>
        </group>
        <group group_id="P2">
          <title>Enteral (Milk) Feeds Withheld During Therapeutic Hypothermia</title>
          <description>Withholding enteral feeds (keeping a baby nil per os) for the duration of hypothermia.</description>
        </group>
        <group group_id="P3">
          <title>Received Parenteral Nutrition During Therapeutic Hypothermia:</title>
          <description>Administration of parenteral nutrition during therapeutic hypothermia:&#xD;
Included in this are different compositions of parenteral nutrition (for example standard, pre-prepared bags of nutrition and individually tailored parenteral nutrition)&#xD;
This health technology includes different routes of administration of parenteral nutrition such as via a peripheral intravenous cannula, percutaneous central venous catheter ('long line') or umbilical venous catheter.&#xD;
This health technology also includes different volumes of parenteral nutrition (e.g. 40ml/kg/day, 60ml/kg/day or greater).</description>
        </group>
        <group group_id="P4">
          <title>Did Not Receive Parenteral Nutrition During Therapeutic Hypothermia</title>
          <description>Received standard intravenous fluids (10% dextrose with additional electrolytes added where required) for the duration of hypothermia.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1618"/>
                <participants group_id="P2" count="1618"/>
                <participants group_id="P3" count="1240"/>
                <participants group_id="P4" count="1240"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1618"/>
                <participants group_id="P2" count="1618"/>
                <participants group_id="P3" count="1240"/>
                <participants group_id="P4" count="1240"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Received Enteral (Milk) Feeds During Therapeutic Hypothermia</title>
          <description>The gradual introduction of enteral (milk) feeds during therapeutic hypothermia:&#xD;
Included in this is any type of milk (e.g. expressed maternal breast milk, expressed donor breast milk and artificial formula)&#xD;
This health technology includes different routes of administering enteral feeds such as nasogastric tube (gavage feeding) and bottle&#xD;
This health technology also includes different rates of increasing enteral feeds (for example by 15ml/kg/day, by 30ml/kg/day or faster)</description>
        </group>
        <group group_id="B2">
          <title>Enteral (Milk) Feeds Withheld During Therapeutic Hypothermia</title>
          <description>Withholding enteral feeds (keeping a baby nil per os) for the duration of hypothermia.</description>
        </group>
        <group group_id="B3">
          <title>Received Parenteral Nutrition During Therapeutic Hypothermia:</title>
          <description>Administration of parenteral nutrition during therapeutic hypothermia:&#xD;
Included in this are different compositions of parenteral nutrition (for example standard, pre-prepared bags of nutrition and individually tailored parenteral nutrition)&#xD;
This health technology includes different routes of administration of parenteral nutrition such as via a peripheral intravenous cannula, percutaneous central venous catheter ('long line') or umbilical venous catheter.&#xD;
This health technology also includes different volumes of parenteral nutrition (e.g. 40ml/kg/day, 60ml/kg/day or greater).</description>
        </group>
        <group group_id="B4">
          <title>Did Not Receive Parenteral Nutrition During Therapeutic Hypothermia</title>
          <description>Received standard intravenous fluids (10% dextrose with additional electrolytes added where required) for the duration of hypothermia.</description>
        </group>
        <group group_id="B5">
          <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="1618"/>
            <count group_id="B2" value="1618"/>
            <count group_id="B3" value="1240"/>
            <count group_id="B4" value="1240"/>
            <count group_id="B5" value="5716"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <description>Gestation at birth in weeks</description>
          <population>This is a factorial study where the same group of babies were included in enteral and parenteral nutrition analyses</population>
          <units>Weeks</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>Enteral feeding</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="1618"/>
                    <count group_id="B2" value="1618"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="0"/>
                    <count group_id="B5" value="3236"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="39.5" spread="1.5"/>
                    <measurement group_id="B2" value="39.5" spread="1.5"/>
                    <measurement group_id="B5" value="39.5" spread="1.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Parenteral feeding</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="1240"/>
                    <count group_id="B4" value="1240"/>
                    <count group_id="B5" value="2480"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="39.4" spread="1.6"/>
                    <measurement group_id="B4" value="39.4" spread="1.6"/>
                    <measurement group_id="B5" value="39.4" spread="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <population>This is a factorial study where the same group of babies were included in enteral and parenteral nutrition analyses</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Enteral feeding</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="1618"/>
                    <count group_id="B2" value="1618"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="0"/>
                    <count group_id="B5" value="3236"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="715"/>
                    <measurement group_id="B2" value="715"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1430"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="903"/>
                    <measurement group_id="B2" value="903"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1806"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Parenteral nutrition</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="1240"/>
                    <count group_id="B4" value="1240"/>
                    <count group_id="B5" value="2480"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="576"/>
                    <measurement group_id="B4" value="588"/>
                    <measurement group_id="B5" value="1164"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="664"/>
                    <measurement group_id="B4" value="652"/>
                    <measurement group_id="B5" value="1316"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <population>This is a factorial study where the same group of babies were included in enteral and parenteral nutrition analyses</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Enteral feeding - White</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="1618"/>
                    <count group_id="B2" value="1618"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="0"/>
                    <count group_id="B5" value="3236"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1040"/>
                    <measurement group_id="B2" value="1041"/>
                    <measurement group_id="B5" value="2081"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Enteral feeding - Asian or mixed Asian</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="1618"/>
                    <count group_id="B2" value="1618"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="0"/>
                    <count group_id="B5" value="3236"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="169"/>
                    <measurement group_id="B2" value="174"/>
                    <measurement group_id="B5" value="343"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Enteral feeding - Black or mixed black African</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="1618"/>
                    <count group_id="B2" value="1618"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="0"/>
                    <count group_id="B5" value="3236"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="103"/>
                    <measurement group_id="B2" value="99"/>
                    <measurement group_id="B5" value="202"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Enteral feeding - Other and missing</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="1618"/>
                    <count group_id="B2" value="1618"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="0"/>
                    <count group_id="B5" value="3236"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="306"/>
                    <measurement group_id="B2" value="304"/>
                    <measurement group_id="B5" value="610"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Parenteral nutrition - White</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="1240"/>
                    <count group_id="B4" value="1240"/>
                    <count group_id="B5" value="2480"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="991"/>
                    <measurement group_id="B4" value="1002"/>
                    <measurement group_id="B5" value="1993"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Parenteral nutrition - Asian or Mixed Asian</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="1240"/>
                    <count group_id="B4" value="1240"/>
                    <count group_id="B5" value="2480"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="93"/>
                    <measurement group_id="B4" value="98"/>
                    <measurement group_id="B5" value="191"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Parenteral nutrition - Black or mixed black African</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="1240"/>
                    <count group_id="B4" value="1240"/>
                    <count group_id="B5" value="2480"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="62"/>
                    <measurement group_id="B4" value="53"/>
                    <measurement group_id="B5" value="115"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Parenteral nutrition - Other and missing</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="1240"/>
                    <count group_id="B4" value="1240"/>
                    <count group_id="B5" value="2480"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="94"/>
                    <measurement group_id="B4" value="86"/>
                    <measurement group_id="B5" value="180"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <population>This is a factorial study where the same group of babies were included in enteral and parenteral nutrition analyses</population>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United Kingdom</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="1618"/>
                    <count group_id="B2" value="1618"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="0"/>
                    <count group_id="B5" value="3236"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1618"/>
                    <measurement group_id="B2" value="1618"/>
                    <measurement group_id="B5" value="3236"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United Kingdom</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="1618"/>
                    <count group_id="B2" value="1618"/>
                    <count group_id="B3" value="1240"/>
                    <count group_id="B4" value="1240"/>
                    <count group_id="B5" value="5716"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1240"/>
                    <measurement group_id="B4" value="1240"/>
                    <measurement group_id="B5" value="2480"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Cord pH &lt;6.9</title>
          <population>This is a factorial study where the same babies are included in both enteral and parenteral analyses</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Enteral feeding</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="1618"/>
                    <count group_id="B2" value="1618"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="0"/>
                    <count group_id="B5" value="3236"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="368"/>
                    <measurement group_id="B2" value="368"/>
                    <measurement group_id="B5" value="736"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Parenteral nutrition</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="1240"/>
                    <count group_id="B4" value="1240"/>
                    <count group_id="B5" value="2480"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="280"/>
                    <measurement group_id="B4" value="280"/>
                    <measurement group_id="B5" value="560"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Apgar score 0 or 1 at 5 minutes</title>
          <population>This is a factorial study where the same babies are included in both enteral and parenteral analyses</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Enteral feeding</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="1618"/>
                    <count group_id="B2" value="1618"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="0"/>
                    <count group_id="B5" value="3236"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="678"/>
                    <measurement group_id="B2" value="720"/>
                    <measurement group_id="B5" value="1398"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Parenteral nutrition</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="1240"/>
                    <count group_id="B4" value="1240"/>
                    <count group_id="B5" value="2480"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="562"/>
                    <measurement group_id="B4" value="553"/>
                    <measurement group_id="B5" value="1115"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Treatment with inotropes on day of admission</title>
          <population>This is a factorial study and the same babies are included in both enteral and parenteral analyses</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Enteral feeding</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="1618"/>
                    <count group_id="B2" value="1618"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="0"/>
                    <count group_id="B5" value="3236"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="288"/>
                    <measurement group_id="B2" value="295"/>
                    <measurement group_id="B5" value="583"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Parenteral nutrition</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="1240"/>
                    <count group_id="B4" value="1240"/>
                    <count group_id="B5" value="2480"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="287"/>
                    <measurement group_id="B4" value="295"/>
                    <measurement group_id="B5" value="582"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Necrotising Enterocolitis - for the Enteral Nutrition Comparison</title>
        <description>Defined according to the case definition of Battersby et al., 2017, JAMA Pediatrics</description>
        <time_frame>From date of birth until date of final neonatal unit discharge, assessed up to 1 year</time_frame>
        <population>NA indicates &lt;5 where the cell value is withheld to avoid identifying participants</population>
        <group_list>
          <group group_id="O1">
            <title>Received Enteral (Milk) Feeds During Therapeutic Hypothermia</title>
            <description>The gradual introduction of enteral (milk) feeds during therapeutic hypothermia:&#xD;
Included in this is any type of milk (e.g. expressed maternal breast milk, expressed donor breast milk and artificial formula)&#xD;
This health technology includes different routes of administering enteral feeds such as nasogastric tube (gavage feeding) and bottle&#xD;
This health technology also includes different rates of increasing enteral feeds (for example by 15ml/kg/day, by 30ml/kg/day or faster)</description>
          </group>
          <group group_id="O2">
            <title>Enteral (Milk) Feeds Withheld During Therapeutic Hypothermia</title>
            <description>Withholding enteral feeds (keeping a baby nil per os) for the duration of hypothermia.</description>
          </group>
          <group group_id="O3">
            <title>Received Parenteral Nutrition During Therapeutic Hypothermia:</title>
            <description>Administration of parenteral nutrition during therapeutic hypothermia:&#xD;
Included in this are different compositions of parenteral nutrition (for example standard, pre-prepared bags of nutrition and individually tailored parenteral nutrition)&#xD;
This health technology includes different routes of administration of parenteral nutrition such as via a peripheral intravenous cannula, percutaneous central venous catheter ('long line') or umbilical venous catheter.&#xD;
This health technology also includes different volumes of parenteral nutrition (e.g. 40ml/kg/day, 60ml/kg/day or greater).</description>
          </group>
          <group group_id="O4">
            <title>Did Not Receive Parenteral Nutrition During Therapeutic Hypothermia</title>
            <description>Received standard intravenous fluids (10% dextrose with additional electrolytes added where required) for the duration of hypothermia.</description>
          </group>
        </group_list>
        <measure>
          <title>Necrotising Enterocolitis - for the Enteral Nutrition Comparison</title>
          <description>Defined according to the case definition of Battersby et al., 2017, JAMA Pediatrics</description>
          <population>NA indicates &lt;5 where the cell value is withheld to avoid identifying participants</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="1618"/>
                <count group_id="O2" value="1618"/>
                <count group_id="O3" value="1240"/>
                <count group_id="O4" value="1240"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA">NA indicates &lt;5 where the cell value is withheld to avoid identifying participants</measurement>
                    <measurement group_id="O2" value="NA">NA indicates &lt;5 where the cell value is withheld to avoid identifying participants</measurement>
                    <measurement group_id="O3" value="NA">NA indicates &lt;5 where the cell value is withheld to avoid identifying participants</measurement>
                    <measurement group_id="O4" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Blood Stream Infection - for the Parenteral Nutrition Comparison</title>
        <description>defined according to the Healthcare Quality Improvement Partnership (HQIP) National Neonatal Audit Programme (NNAP) case definition: pure growth of a recognised pathogen from a normally sterile site</description>
        <time_frame>From date of birth until date of final neonatal unit discharge, assessed up to 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Received Enteral (Milk) Feeds During Therapeutic Hypothermia</title>
            <description>The gradual introduction of enteral (milk) feeds during therapeutic hypothermia:&#xD;
Included in this is any type of milk (e.g. expressed maternal breast milk, expressed donor breast milk and artificial formula)&#xD;
This health technology includes different routes of administering enteral feeds such as nasogastric tube (gavage feeding) and bottle&#xD;
This health technology also includes different rates of increasing enteral feeds (for example by 15ml/kg/day, by 30ml/kg/day or faster)</description>
          </group>
          <group group_id="O2">
            <title>Enteral (Milk) Feeds Withheld During Therapeutic Hypothermia</title>
            <description>Withholding enteral feeds (keeping a baby nil per os) for the duration of hypothermia.</description>
          </group>
          <group group_id="O3">
            <title>Received Parenteral Nutrition During Therapeutic Hypothermia:</title>
            <description>Administration of parenteral nutrition during therapeutic hypothermia:&#xD;
Included in this are different compositions of parenteral nutrition (for example standard, pre-prepared bags of nutrition and individually tailored parenteral nutrition)&#xD;
This health technology includes different routes of administration of parenteral nutrition such as via a peripheral intravenous cannula, percutaneous central venous catheter ('long line') or umbilical venous catheter.&#xD;
This health technology also includes different volumes of parenteral nutrition (e.g. 40ml/kg/day, 60ml/kg/day or greater).</description>
          </group>
          <group group_id="O4">
            <title>Did Not Receive Parenteral Nutrition During Therapeutic Hypothermia</title>
            <description>Received standard intravenous fluids (10% dextrose with additional electrolytes added where required) for the duration of hypothermia.</description>
          </group>
        </group_list>
        <measure>
          <title>Blood Stream Infection - for the Parenteral Nutrition Comparison</title>
          <description>defined according to the Healthcare Quality Improvement Partnership (HQIP) National Neonatal Audit Programme (NNAP) case definition: pure growth of a recognised pathogen from a normally sterile site</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1618"/>
                <count group_id="O2" value="1618"/>
                <count group_id="O3" value="1240"/>
                <count group_id="O4" value="1240"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA">NA indicates &lt;5 where the cell value is withheld to avoid identifying participants</measurement>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="11"/>
                    <measurement group_id="O4" value="NA">NA indicates &lt;5 where the cell value is withheld to avoid identifying participants</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Survival</title>
        <description>Survival at neonatal unit discharge</description>
        <time_frame>From date of birth until date of final neonatal unit discharge, assessed up to 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Received Enteral (Milk) Feeds During Therapeutic Hypothermia</title>
            <description>The gradual introduction of enteral (milk) feeds during therapeutic hypothermia:&#xD;
Included in this is any type of milk (e.g. expressed maternal breast milk, expressed donor breast milk and artificial formula)&#xD;
This health technology includes different routes of administering enteral feeds such as nasogastric tube (gavage feeding) and bottle&#xD;
This health technology also includes different rates of increasing enteral feeds (for example by 15ml/kg/day, by 30ml/kg/day or faster)</description>
          </group>
          <group group_id="O2">
            <title>Enteral (Milk) Feeds Withheld During Therapeutic Hypothermia</title>
            <description>Withholding enteral feeds (keeping a baby nil per os) for the duration of hypothermia.</description>
          </group>
          <group group_id="O3">
            <title>Received Parenteral Nutrition During Therapeutic Hypothermia:</title>
            <description>Administration of parenteral nutrition during therapeutic hypothermia:&#xD;
Included in this are different compositions of parenteral nutrition (for example standard, pre-prepared bags of nutrition and individually tailored parenteral nutrition)&#xD;
This health technology includes different routes of administration of parenteral nutrition such as via a peripheral intravenous cannula, percutaneous central venous catheter ('long line') or umbilical venous catheter.&#xD;
This health technology also includes different volumes of parenteral nutrition (e.g. 40ml/kg/day, 60ml/kg/day or greater).</description>
          </group>
          <group group_id="O4">
            <title>Did Not Receive Parenteral Nutrition During Therapeutic Hypothermia</title>
            <description>Received standard intravenous fluids (10% dextrose with additional electrolytes added where required) for the duration of hypothermia.</description>
          </group>
        </group_list>
        <measure>
          <title>Survival</title>
          <description>Survival at neonatal unit discharge</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1618"/>
                <count group_id="O2" value="1618"/>
                <count group_id="O3" value="1240"/>
                <count group_id="O4" value="1240"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1552"/>
                    <measurement group_id="O2" value="1465"/>
                    <measurement group_id="O3" value="1154"/>
                    <measurement group_id="O4" value="1116"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Length of Stay</title>
        <description>Number of days between first neonatal unit admission and final neonatal unit discharge for surviving infants</description>
        <time_frame>From date of birth until date of final neonatal unit discharge, assessed up to 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Received Enteral (Milk) Feeds During Therapeutic Hypothermia</title>
            <description>The gradual introduction of enteral (milk) feeds during therapeutic hypothermia:&#xD;
Included in this is any type of milk (e.g. expressed maternal breast milk, expressed donor breast milk and artificial formula)&#xD;
This health technology includes different routes of administering enteral feeds such as nasogastric tube (gavage feeding) and bottle&#xD;
This health technology also includes different rates of increasing enteral feeds (for example by 15ml/kg/day, by 30ml/kg/day or faster)</description>
          </group>
          <group group_id="O2">
            <title>Enteral (Milk) Feeds Withheld During Therapeutic Hypothermia</title>
            <description>Withholding enteral feeds (keeping a baby nil per os) for the duration of hypothermia.</description>
          </group>
          <group group_id="O3">
            <title>Received Parenteral Nutrition During Therapeutic Hypothermia:</title>
            <description>Administration of parenteral nutrition during therapeutic hypothermia:&#xD;
Included in this are different compositions of parenteral nutrition (for example standard, pre-prepared bags of nutrition and individually tailored parenteral nutrition)&#xD;
This health technology includes different routes of administration of parenteral nutrition such as via a peripheral intravenous cannula, percutaneous central venous catheter ('long line') or umbilical venous catheter.&#xD;
This health technology also includes different volumes of parenteral nutrition (e.g. 40ml/kg/day, 60ml/kg/day or greater).</description>
          </group>
          <group group_id="O4">
            <title>Did Not Receive Parenteral Nutrition During Therapeutic Hypothermia</title>
            <description>Received standard intravenous fluids (10% dextrose with additional electrolytes added where required) for the duration of hypothermia.</description>
          </group>
        </group_list>
        <measure>
          <title>Length of Stay</title>
          <description>Number of days between first neonatal unit admission and final neonatal unit discharge for surviving infants</description>
          <units>Days</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1618"/>
                <count group_id="O2" value="1618"/>
                <count group_id="O3" value="1240"/>
                <count group_id="O4" value="1240"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.7" lower_limit="12.0" upper_limit="13.3"/>
                    <measurement group_id="O2" value="14.8" lower_limit="14.2" upper_limit="15.5"/>
                    <measurement group_id="O3" value="15.0" lower_limit="14.1" upper_limit="15.8"/>
                    <measurement group_id="O4" value="14.1" lower_limit="13.6" upper_limit="14.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Breastfeeding</title>
        <description>Any breastfeeding (suckling at the breast) at discharge</description>
        <time_frame>At the point of final discharge from neonatal care, assessed up to 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Received Enteral (Milk) Feeds During Therapeutic Hypothermia</title>
            <description>The gradual introduction of enteral (milk) feeds during therapeutic hypothermia:&#xD;
Included in this is any type of milk (e.g. expressed maternal breast milk, expressed donor breast milk and artificial formula)&#xD;
This health technology includes different routes of administering enteral feeds such as nasogastric tube (gavage feeding) and bottle&#xD;
This health technology also includes different rates of increasing enteral feeds (for example by 15ml/kg/day, by 30ml/kg/day or faster)</description>
          </group>
          <group group_id="O2">
            <title>Enteral (Milk) Feeds Withheld During Therapeutic Hypothermia</title>
            <description>Withholding enteral feeds (keeping a baby nil per os) for the duration of hypothermia.</description>
          </group>
          <group group_id="O3">
            <title>Received Parenteral Nutrition During Therapeutic Hypothermia:</title>
            <description>Administration of parenteral nutrition during therapeutic hypothermia:&#xD;
Included in this are different compositions of parenteral nutrition (for example standard, pre-prepared bags of nutrition and individually tailored parenteral nutrition)&#xD;
This health technology includes different routes of administration of parenteral nutrition such as via a peripheral intravenous cannula, percutaneous central venous catheter ('long line') or umbilical venous catheter.&#xD;
This health technology also includes different volumes of parenteral nutrition (e.g. 40ml/kg/day, 60ml/kg/day or greater).</description>
          </group>
          <group group_id="O4">
            <title>Did Not Receive Parenteral Nutrition During Therapeutic Hypothermia</title>
            <description>Received standard intravenous fluids (10% dextrose with additional electrolytes added where required) for the duration of hypothermia.</description>
          </group>
        </group_list>
        <measure>
          <title>Breastfeeding</title>
          <description>Any breastfeeding (suckling at the breast) at discharge</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1618"/>
                <count group_id="O2" value="1618"/>
                <count group_id="O3" value="1240"/>
                <count group_id="O4" value="1240"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="883"/>
                    <measurement group_id="O2" value="752"/>
                    <measurement group_id="O3" value="575"/>
                    <measurement group_id="O4" value="582"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Hypoglycaemia</title>
        <description>Any diagnosis of hypoglycaemia recorded after therapeutic hypothermia is commenced and before the final neonatal unit discharge</description>
        <time_frame>From date of birth until date of final neonatal unit discharge, assessed up to 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Received Enteral (Milk) Feeds During Therapeutic Hypothermia</title>
            <description>The gradual introduction of enteral (milk) feeds during therapeutic hypothermia:&#xD;
Included in this is any type of milk (e.g. expressed maternal breast milk, expressed donor breast milk and artificial formula)&#xD;
This health technology includes different routes of administering enteral feeds such as nasogastric tube (gavage feeding) and bottle&#xD;
This health technology also includes different rates of increasing enteral feeds (for example by 15ml/kg/day, by 30ml/kg/day or faster)</description>
          </group>
          <group group_id="O2">
            <title>Enteral (Milk) Feeds Withheld During Therapeutic Hypothermia</title>
            <description>Withholding enteral feeds (keeping a baby nil per os) for the duration of hypothermia.</description>
          </group>
          <group group_id="O3">
            <title>Received Parenteral Nutrition During Therapeutic Hypothermia:</title>
            <description>Administration of parenteral nutrition during therapeutic hypothermia:&#xD;
Included in this are different compositions of parenteral nutrition (for example standard, pre-prepared bags of nutrition and individually tailored parenteral nutrition)&#xD;
This health technology includes different routes of administration of parenteral nutrition such as via a peripheral intravenous cannula, percutaneous central venous catheter ('long line') or umbilical venous catheter.&#xD;
This health technology also includes different volumes of parenteral nutrition (e.g. 40ml/kg/day, 60ml/kg/day or greater).</description>
          </group>
          <group group_id="O4">
            <title>Did Not Receive Parenteral Nutrition During Therapeutic Hypothermia</title>
            <description>Received standard intravenous fluids (10% dextrose with additional electrolytes added where required) for the duration of hypothermia.</description>
          </group>
        </group_list>
        <measure>
          <title>Hypoglycaemia</title>
          <description>Any diagnosis of hypoglycaemia recorded after therapeutic hypothermia is commenced and before the final neonatal unit discharge</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1618"/>
                <count group_id="O2" value="1618"/>
                <count group_id="O3" value="1240"/>
                <count group_id="O4" value="1240"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="293"/>
                    <measurement group_id="O2" value="269"/>
                    <measurement group_id="O3" value="212"/>
                    <measurement group_id="O4" value="235"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Central Venous Line</title>
        <description>The number of days until an infant is recorded as not having a central venous line</description>
        <time_frame>From date of birth until date of final neonatal unit discharge, assessed up to 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Received Enteral (Milk) Feeds During Therapeutic Hypothermia</title>
            <description>The gradual introduction of enteral (milk) feeds during therapeutic hypothermia:&#xD;
Included in this is any type of milk (e.g. expressed maternal breast milk, expressed donor breast milk and artificial formula)&#xD;
This health technology includes different routes of administering enteral feeds such as nasogastric tube (gavage feeding) and bottle&#xD;
This health technology also includes different rates of increasing enteral feeds (for example by 15ml/kg/day, by 30ml/kg/day or faster)</description>
          </group>
          <group group_id="O2">
            <title>Enteral (Milk) Feeds Withheld During Therapeutic Hypothermia</title>
            <description>Withholding enteral feeds (keeping a baby nil per os) for the duration of hypothermia.</description>
          </group>
          <group group_id="O3">
            <title>Received Parenteral Nutrition During Therapeutic Hypothermia:</title>
            <description>Administration of parenteral nutrition during therapeutic hypothermia:&#xD;
Included in this are different compositions of parenteral nutrition (for example standard, pre-prepared bags of nutrition and individually tailored parenteral nutrition)&#xD;
This health technology includes different routes of administration of parenteral nutrition such as via a peripheral intravenous cannula, percutaneous central venous catheter ('long line') or umbilical venous catheter.&#xD;
This health technology also includes different volumes of parenteral nutrition (e.g. 40ml/kg/day, 60ml/kg/day or greater).</description>
          </group>
          <group group_id="O4">
            <title>Did Not Receive Parenteral Nutrition During Therapeutic Hypothermia</title>
            <description>Received standard intravenous fluids (10% dextrose with additional electrolytes added where required) for the duration of hypothermia.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Central Venous Line</title>
          <description>The number of days until an infant is recorded as not having a central venous line</description>
          <units>Days</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1618"/>
                <count group_id="O2" value="1618"/>
                <count group_id="O3" value="1240"/>
                <count group_id="O4" value="1240"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.3" lower_limit="4.1" upper_limit="4.5"/>
                    <measurement group_id="O2" value="5.5" lower_limit="5.3" upper_limit="5.7"/>
                    <measurement group_id="O3" value="6" lower_limit="5.7" upper_limit="6.3"/>
                    <measurement group_id="O4" value="5.1" lower_limit="5" upper_limit="5.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Growth</title>
        <description>Weight for post-menstrual age standard deviation score at final neonatal unit discharge.&#xD;
Standard deviation score, higher score means higher growth (higher weight for gestational age)</description>
        <time_frame>From date of birth until date of final neonatal unit discharge, assessed up to 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Received Enteral (Milk) Feeds During Therapeutic Hypothermia</title>
            <description>The gradual introduction of enteral (milk) feeds during therapeutic hypothermia:&#xD;
Included in this is any type of milk (e.g. expressed maternal breast milk, expressed donor breast milk and artificial formula)&#xD;
This health technology includes different routes of administering enteral feeds such as nasogastric tube (gavage feeding) and bottle&#xD;
This health technology also includes different rates of increasing enteral feeds (for example by 15ml/kg/day, by 30ml/kg/day or faster)</description>
          </group>
          <group group_id="O2">
            <title>Enteral (Milk) Feeds Withheld During Therapeutic Hypothermia</title>
            <description>Withholding enteral feeds (keeping a baby nil per os) for the duration of hypothermia.</description>
          </group>
          <group group_id="O3">
            <title>Received Parenteral Nutrition During Therapeutic Hypothermia:</title>
            <description>Administration of parenteral nutrition during therapeutic hypothermia:&#xD;
Included in this are different compositions of parenteral nutrition (for example standard, pre-prepared bags of nutrition and individually tailored parenteral nutrition)&#xD;
This health technology includes different routes of administration of parenteral nutrition such as via a peripheral intravenous cannula, percutaneous central venous catheter ('long line') or umbilical venous catheter.&#xD;
This health technology also includes different volumes of parenteral nutrition (e.g. 40ml/kg/day, 60ml/kg/day or greater).</description>
          </group>
          <group group_id="O4">
            <title>Did Not Receive Parenteral Nutrition During Therapeutic Hypothermia</title>
            <description>Received standard intravenous fluids (10% dextrose with additional electrolytes added where required) for the duration of hypothermia.</description>
          </group>
        </group_list>
        <measure>
          <title>Growth</title>
          <description>Weight for post-menstrual age standard deviation score at final neonatal unit discharge.&#xD;
Standard deviation score, higher score means higher growth (higher weight for gestational age)</description>
          <units>Standard deviation score</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1618"/>
                <count group_id="O2" value="1618"/>
                <count group_id="O3" value="1240"/>
                <count group_id="O4" value="1240"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.54" lower_limit="-0.59" upper_limit="-0.48"/>
                    <measurement group_id="O2" value="-0.6" lower_limit="-0.65" upper_limit="-0.55"/>
                    <measurement group_id="O3" value="-0.65" lower_limit="-0.71" upper_limit="-0.58"/>
                    <measurement group_id="O4" value="-0.66" lower_limit="-0.71" upper_limit="-0.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Until end of neonatal unit stay</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Received Enteral (Milk) Feeds During Therapeutic Hypothermia</title>
          <description>The gradual introduction of enteral (milk) feeds during therapeutic hypothermia:&#xD;
Included in this is any type of milk (e.g. expressed maternal breast milk, expressed donor breast milk and artificial formula)&#xD;
This health technology includes different routes of administering enteral feeds such as nasogastric tube (gavage feeding) and bottle&#xD;
This health technology also includes different rates of increasing enteral feeds (for example by 15ml/kg/day, by 30ml/kg/day or faster)</description>
        </group>
        <group group_id="E2">
          <title>Enteral (Milk) Feeds Withheld During Therapeutic Hypothermia</title>
          <description>Withholding enteral feeds (keeping a baby nil per os) for the duration of hypothermia.</description>
        </group>
        <group group_id="E3">
          <title>Received Parenteral Nutrition During Therapeutic Hypothermia:</title>
          <description>Administration of parenteral nutrition during therapeutic hypothermia:&#xD;
Included in this are different compositions of parenteral nutrition (for example standard, pre-prepared bags of nutrition and individually tailored parenteral nutrition)&#xD;
This health technology includes different routes of administration of parenteral nutrition such as via a peripheral intravenous cannula, percutaneous central venous catheter ('long line') or umbilical venous catheter.&#xD;
This health technology also includes different volumes of parenteral nutrition (e.g. 40ml/kg/day, 60ml/kg/day or greater).</description>
        </group>
        <group group_id="E4">
          <title>Did Not Receive Parenteral Nutrition During Therapeutic Hypothermia</title>
          <description>Received standard intravenous fluids (10% dextrose with additional electrolytes added where required) for the duration of hypothermia.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="66" subjects_at_risk="1618"/>
                <counts group_id="E2" subjects_affected="153" subjects_at_risk="1618"/>
                <counts group_id="E3" subjects_affected="86" subjects_at_risk="1240"/>
                <counts group_id="E4" subjects_affected="124" subjects_at_risk="1240"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1618"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1618"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1240"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1240"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1618"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1618"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1240"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="1240"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr Chris Gale, Reader in Neonatal Medicine</name_or_title>
      <organization>Imperial College London</organization>
      <phone>+44 203 3153519</phone>
      <email>christopher.gale@imperial.ac.uk</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/NCT03278847
org study id: 17IC4064
secondary id: 16/79/03
secondary id: 17/EM/0307
nct id: NCT03278847
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The overarching aim of this project is to determine the optimum enteral and parenteral
      nutrition strategy for newborns with Hypoxic Ischaemic Encephalopathy (HIE) during and after
      therapeutic hypothermia. To do this the investigators will perform two primary comparisons:

        1. ENTERAL: to determine whether any enteral (milk) feeding, when compared to withholding
           enteral feeding (no milk), during therapeutic hypothermia, is associated with a
           difference in the incidence of necrotising enterocolitis.

        2. PARENTERAL: to determine whether provision of intravenous dextrose, when compared to
           provision of parenteral nutrition, during therapeutic hypothermia, is associated with a
           difference in the incidence of blood stream infection.

      The investigators will use de-identified data held in an established research database called
      the National Neonatal Research Database (NNRD) and we will use the potential outcomes
      framework with application of propensity scoring to define matched subgroups for comparison.
Every year about 1200 babies in England, Wales and Scotland suffer from a lack of oxygen
      around birth which can lead to long-term brain injury or death. This is called Hypoxic
      Ischaemic Encephalopathy (HIE). Research has shown that cooling babies with HIE by a few
      degrees for the first 3 days protects the brain; all babies with moderate or severe HIE in
      the UK are treated with therapeutic hypothermia (cooling).

      Doctors do not know how best to care for babies while they are cooled. A key question is "how
      to provide nutrition to babies during cooling". There are two main parts to this question,
      milk feeds ("enteral" nutrition) and intravenous nutrition ("parenteral" nutrition). Doctors
      don't know how best to provide either milk or intravenous nutrition to cooled babies.

        -  MILK FEEDS: Some neonatal units in the UK carefully feed babies (usually with maternal
           breast milk) while they are cooled. This avoids intravenous lines and is believed to
           help them feed and go home earlier. Other neonatal units do not feed cooled babies
           because they worry about a condition called necrotising enterocolitis (a devastating and
           often fatal disease) which might be more common with feeding.

        -  INTRAVENOUS NUTRITION: All cooled babies need intravenous fluid (even when milk feeds
           are given it takes several days before enough fluid can be given this way). Some
           neonatal units give babies intravenous nutrition (which contains fat, protein,
           carbohydrate, vitamins and minerals) as this may improve growth and recovery. Other
           neonatal units only give intravenous dextrose with simple salts because of concerns that
           intravenous nutrition leads to more infections. This study will compare these different
           ways of providing nutrition. It will use a research database called the National
           Neonatal Research Database (NNRD). In England, Scotland and Wales doctors and nurses
           looking after babies in neonatal care (including all cooled babies) use an Electronic
           Health Record system. Data from this system are anonymised (no baby can be identified)
           and form the NNRD, so the NNRD holds data from all babies who have been looked after on
           NHS neonatal units.

      The investigators have worked closely with parents and charities in developing the NNRD. The
      investigators will use the NNRD to study all term babies who received cooling in England,
      Scotland and Wales since 2008. The investigators will compare the milk feeding and
      intravenous nutrition they receive.

        -  MILK FEEDING: The investigators will compare babies who are fed milk while cooled with
           those that are not fed any milk. The investigator's main goal is to establish whether
           there is any difference in rates of necrotising enterocolitis.

        -  INTRAVENOUS NUTRITION: The investigators will compare babies who get intravenous
           nutrition with those that only get intravenous dextrose. The main difference we are
           looking for is in the rate of infection. The investigators will also study how many
           babies die, how long they stay in neonatal care, how soon breastfeeding starts and many
           are breastfed when they go home.

      The investigators will apply a statistical approach called "potential outcomes framework" in
      which babies are matched in each group (e.g. babies who are fed and those who are not fed) as
      closely as possible. This will ensure that any difference in outcomes is due to the different
      nutritional treatments and not due to background differences or other confounders (like how
      sick a baby is).

      The results from this study will help to ensure that babies who need to be cooled for HIE
      receive the best and safest nutrition in the future.
observational model: Cohort
time perspective: Retrospective
measure: Necrotising Enterocolitis - for the Enteral Nutrition Comparison
time frame: From date of birth until date of final neonatal unit discharge, assessed up to 1 year
description: Defined according to the case definition of Battersby et al., 2017, JAMA Pediatrics
measure: Blood Stream Infection - for the Parenteral Nutrition Comparison
time frame: From date of birth until date of final neonatal unit discharge, assessed up to 1 year
description: defined according to the Healthcare Quality Improvement Partnership (HQIP) National Neonatal Audit Programme (NNAP) case definition: pure growth of a recognised pathogen from a normally sterile site
measure: Survival
time frame: From date of birth until date of final neonatal unit discharge, assessed up to 1 year
description: Survival at neonatal unit discharge
measure: Length of Stay
time frame: From date of birth until date of final neonatal unit discharge, assessed up to 1 year
description: Number of days between first neonatal unit admission and final neonatal unit discharge for surviving infants
measure: Breastfeeding
time frame: At the point of final discharge from neonatal care, assessed up to 1 year
description: Any breastfeeding (suckling at the breast) at discharge
measure: Hypoglycaemia
time frame: From date of birth until date of final neonatal unit discharge, assessed up to 1 year
description: Any diagnosis of hypoglycaemia recorded after therapeutic hypothermia is commenced and before the final neonatal unit discharge
measure: Duration of Central Venous Line
time frame: From date of birth until date of final neonatal unit discharge, assessed up to 1 year
description: The number of days until an infant is recorded as not having a central venous line
measure: Growth
time frame: From date of birth until date of final neonatal unit discharge, assessed up to 1 year
description: Weight for post-menstrual age standard deviation score at final neonatal unit discharge.
Standard deviation score, higher score means higher growth (higher weight for gestational age)
arm group label: Enteral nutrition comparison
description: This comparison refers to differences in enteral nutrition during therapeutic hypothermia
arm group label: Parenteral nutrition comparison
description: This comparison refers to differences in parenteral nutrition during therapeutic hypothermia
intervention type: Dietary Supplement
intervention name: Received enteral (milk) feeds during therapeutic hypothermia
description: In the enteral component of nutrition, the health technology to be assessed is the gradual introduction of enteral (milk) feeds during therapeutic hypothermia:
Included in this is any type of milk (e.g. expressed maternal breast milk, expressed donor breast milk and artificial formula)
This health technology includes different routes of administering enteral feeds such as nasogastric tube (gavage feeding) and bottle
This health technology also includes different rates of increasing enteral feeds (for example by 15ml/kg/day, by 30ml/kg/day or faster)
arm group label: Enteral nutrition comparison
intervention type: Dietary Supplement
intervention name: Enteral (milk) feeds withheld during therapeutic hypothermia
description: Withholding enteral feeds (keeping a baby nil per os) for the duration of hypothermia.
arm group label: Enteral nutrition comparison
intervention type: Dietary Supplement
intervention name: Received parenteral nutrition during therapeutic hypothermia
description: In the parenteral component, the health technology being assessed is administration of parenteral nutrition during therapeutic hypothermia:
Included in this are different compositions of parenteral nutrition (for example standard, pre-prepared bags of nutrition and individually tailored parenteral nutrition)
This health technology includes different routes of administration of parenteral nutrition such as via a peripheral intravenous cannula, percutaneous central venous catheter ('long line') or umbilical venous catheter.
This health technology also includes different volumes of parenteral nutrition (e.g. 40ml/kg/day, 60ml/kg/day or greater).
arm group label: Parenteral nutrition comparison
intervention type: Dietary Supplement
intervention name: Did not receive parenteral nutrition during therapeutic hypothermia
description: Received standard intravenous fluids (10% dextrose with additional electrolytes added where required) for the duration of hypothermia.
arm group label: Parenteral nutrition comparison
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: 4 Days
healthy volunteers: No
last name: Chris Gale, MBBS, PhD
role: Principal Investigator
affiliation: Imperial College London
facility: 
facility: 
country: United Kingdom
citation: Battersby C, Longford N, Patel M, Selby E, Ojha S, Dorling J, Gale C. Study protocol: optimising newborn nutrition during and after neonatal therapeutic hypothermia in the United Kingdom: observational study of routinely collected data using propensity matching. BMJ Open. 2018 Oct 23;8(10):e026739. doi: 10.1136/bmjopen-2018-026739.
PMID: 30355795
citation: Gale C, Jeyakumaran D, Longford N, Battersby C, Ojha S, Oughham K, Dorling J. Administration of parenteral nutrition during therapeutic hypothermia: a population level observational study using routinely collected data held in the National Neonatal Research Database. Arch Dis Child Fetal Neonatal Ed. 2021 Nov;106(6):608-613. doi: 10.1136/archdischild-2020-321299. Epub 2021 May 5.
PMID: 33952628
citation: Gale C, Longford NT, Jeyakumaran D, Ougham K, Battersby C, Ojha S, Dorling J. Feeding during neonatal therapeutic hypothermia, assessed using routinely collected National Neonatal Research Database data: a retrospective, UK population-based cohort study. Lancet Child Adolesc Health. 2021 Jun;5(6):408-416. doi: 10.1016/S2352-4642(21)00026-2. Epub 2021 Apr 21.
PMID: 33891879
citation: Gale C, Jeyakumaran D, Battersby C, Ougham K, Ojha S, Culshaw L, Selby E, Dorling J, Longford N. Nutritional management in newborn babies receiving therapeutic hypothermia: two retrospective observational studies using propensity score matching. Health Technol Assess. 2021 Jun;25(36):1-106. doi: 10.3310/hta25360.
PMID: 34096500
responsible party type: Sponsor
mesh term: Neonatal Sepsis
mesh term: Enterocolitis
mesh term: Enterocolitis, Necrotizing
mesh term: Asphyxia Neonatorum
mesh term: Hypothermia
mesh term: Asphyxia
sharing ipd: Yes
ipd description: All study data will be extracted from the National Neonatal Research Database (NNRD). The NNRD has been created through the collaborative efforts of neonatal services across the country to be a national resource. The NNRD is maintained and managed at the Neonatal Data Analysis Unit (NDAU) at Imperial College London and Chelsea and Westminster NHS Foundation Trust.
Researchers, clinicians, managers, commissioners, and others are welcome and encouraged to utilise the NNRD.
ipd info type: Study Protocol
ipd info type: Clinical Study Report (CSR)
ipd time frame: The NNRD holds data from 2007 to present.
ipd access criteria: Access criteria and guidance is found at the URL below
ipd url: https://www.imperial.ac.uk/neonatal-data-analysis-unit/neonatal-data-analysis-unit/utilising-the-national-neonatal-research-database/
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 