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Optimising Newborn Nutrition During Therapeutic Hypothermia.

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ClinicalTrials.gov Identifier: NCT03278847
Recruitment Status : Not yet recruiting
First Posted : September 12, 2017
Last Update Posted : September 12, 2017
Sponsor:
Collaborators:
University of Nottingham
Bliss the charity for babies born premature or sick
Information provided by (Responsible Party):
Imperial College London

Brief Summary:

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.


Condition or disease Intervention/treatment
Infant, Newborn Asphyxia Neonatorum Hypothermia, Induced Parenteral Nutrition Infant Nutrition Necrotizing Enterocolitis Neonatal Sepsis Dietary Supplement: Received enteral (milk) feeds during therapeutic hypothermia Dietary Supplement: Enteral (milk) feeds withheld during therapeutic hypothermia Dietary Supplement: Received parenteral nutrition during therapeutic hypothermia Dietary Supplement: Did not receive parenteral nutrition during therapeutic hypothermia

Detailed Description:

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.


Study Type : Observational
Estimated Enrollment : 7200 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Optimising Newborn Nutrition During Therapeutic Hypothermia: an Observational Study Using Routinely Collected Data
Estimated Study Start Date : September 2017
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : March 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hypothermia

Group/Cohort Intervention/treatment
Enteral nutrition comparison
This comparison refers to differences in enteral nutrition during therapeutic hypothermia
Dietary Supplement: Received enteral (milk) feeds during therapeutic hypothermia

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)

Dietary Supplement: Enteral (milk) feeds withheld during therapeutic hypothermia
Withholding enteral feeds (keeping a baby nil per os) for the duration of hypothermia.

Parenteral nutrition comparison
This comparison refers to differences in parenteral nutrition during therapeutic hypothermia
Dietary Supplement: Received parenteral nutrition during therapeutic hypothermia

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).

Dietary Supplement: Did not receive parenteral nutrition during therapeutic hypothermia
Received standard intravenous fluids (10% dextrose with additional electrolytes added where required) for the duration of hypothermia.




Primary Outcome Measures :
  1. 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 ]
    Defined according to the case definition of Battersby et al., 2017, JAMA Pediatrics

  2. 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 ]
    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


Secondary Outcome Measures :
  1. Survival [ Time Frame: From date of birth until date of final neonatal unit discharge, assessed up to 1 year ]
  2. Length of stay [ Time Frame: From date of birth until date of final neonatal unit discharge, assessed up to 1 year ]
    Number of days between first neonatal unit admission and final neonatal unit discharge for surviving infants

  3. Breastfeeding [ Time Frame: At the point of final discharge from neonatal care, assessed up to 1 year ]
    Any breastfeeding (suckling at the breast) at discharge

  4. Hypoglycaemia [ Time Frame: From date of birth until date of final neonatal unit discharge, assessed up to 1 year ]
    Any diagnosis of hypoglycaemia recorded after therapeutic hypothermia is commenced and before the final neonatal unit discharge

  5. Time to full feeds [ Time Frame: From date of birth until date of final neonatal unit discharge, assessed up to 1 year ]
    The number of days until an infant is recorded as not requiring any parenteral nutrition or fluid

  6. Growth [ Time Frame: From date of birth until date of final neonatal unit discharge, assessed up to 1 year ]
    Weight and head circumference for post-menstrual age standard deviation score at final neonatal unit discharge



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 4 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Infants born at 36 gestational weeks or later who received therapeutic hypothermia for Hypoxic Ischaemic Encephalopathy (HIE) for least 72 hours, or who died during therapeutic hypothermia.
Criteria

Inclusion Criteria:

  1. Received neonatal care at a unit that is part of the UK Neonatal Collaborative; this includes all NHS neonatal units in England, Scotland and Wales
  2. Recorded gestational age at birth ≥36 weeks
  3. Recorded as receiving therapeutic hypothermia for 72 hours or died during therapeutic hypothermia

Exclusion Criteria:

1. Infants with missing data for principal background and outcome variables.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03278847


Contacts
Contact: Richard Colquhoun 44(0)20 3315 5841 ndau@imperial.ac.uk

Locations
United Kingdom
Imperial College London, Chelsea and Westminster Hospital campus Active, not recruiting
London, United Kingdom, SW10 9NH
Sponsors and Collaborators
Imperial College London
University of Nottingham
Bliss the charity for babies born premature or sick
Investigators
Principal Investigator: Chris Gale, MBBS, PhD Imperial College London

Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT03278847     History of Changes
Other Study ID Numbers: 17IC4064
16/79/03 ( Other Grant/Funding Number: National Institute for Health Research (NIHR) HTA )
17/EM/0307 ( Other Identifier: United Kingdom Health Research Authority )
First Posted: September 12, 2017    Key Record Dates
Last Update Posted: September 12, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan 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.

Supporting Materials: Study Protocol
Clinical Study Report (CSR)
Time Frame: The NNRD holds data from 2007 to present.
Access Criteria: Access criteria and guidance is found at the URL below
URL: http://www.imperial.ac.uk/neonatal-data-analysis-unit/neonatal-data/utilising-the-nnrd/

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Imperial College London:
NNRD
matching
propensity score

Additional relevant MeSH terms:
Hypothermia
Enterocolitis
Enterocolitis, Necrotizing
Neonatal Sepsis
Asphyxia
Asphyxia Neonatorum
Body Temperature Changes
Signs and Symptoms
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Sepsis
Infection
Infant, Newborn, Diseases
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Death
Wounds and Injuries