Optimising newborn nutrition during therapeutic hypothermia
| ISRCTN | ISRCTN47404296 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN47404296 |
| Protocol serial number | 17IC4064 |
| Sponsor | Imperial College London |
| Funder | Health Technology Assessment Programme |
- Submission date
- 20/07/2017
- Registration date
- 24/07/2017
- Last edited
- 06/09/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English summary of protocol
Background and study aims
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 therefore 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). - 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 that causes inflammation of the digestive system) which might be more common with feeding. 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. It is not known how best to provide either milk or intravenous nutrition to cooled babies. This study compares these different ways of providing nutrition using 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. This has been developed closely with parents and charities. The aim of this study is to determine the best enteral and parenteral nutrition strategy for newborns with HIR during and after therapeutic hypothermia.
Who can participate?
Infants born at 36 gestational weeks or later who received therapeutic hypothermia for at least 72 hours
What does the study involve?
This study collects data in the NNRD about babies and their nutrition during therapeutic hypothermia. Babies who were fed milk while cooled are compared to those who were not fed any milk by collecting rates of necrotising enterocolitis. Babies who get intravenous nutrition are compared to those who get intravenous dextrose. The rate of infection, the amount of babies who died, how long they stayed in neonatal care, how soon they were able to breastfeed and how many who were breastfeed when they go home is collected from the NNRD. This is done to find the optimum nutrition strategy for newborns.
What are the possible benefits and risks of participating?
There are no direct benefits or risks with participating.
Where is the study run from?
This study is taking place at the Chelsea and Westminster Hospital (UK) and includes data from 200 NHS neonatal units in England, Scotland and Wales (UK).
When is the study starting and how long is it expected to run for?
September 2016 to January 2019
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
1. Mr Richard Colquhoun
ndau@imperial.ac.uk
2. Dr Chris Gale
christopher.gale@imperial.ac.uk
Contact information
Public
Neonatal Data Analysis Unit
Section of Neonatal Medicine
Imperial College London
Chelsea and Westminster Hospital Campus
369 Fulham Road
London
SW10 9NH
United Kingdom
| Phone | +44 203 315 5841 |
|---|---|
| ndau@imperial.ac.uk |
Scientific
Section of Neonatal Medicine
Imperial College London
Chelsea and Westminster Hospital Campus
369 Fulham Road
London
SW10 9NH
United Kingdom
 ORCID ID |
0000-0003-0707-876X |
|---|---|
| Phone | +44 203 315 3519 |
| christopher.gale@imperial.ac.uk |
Study information
| Primary study design | Observational |
|---|---|
| Study design | Retrospective cohort study |
| Secondary study design | Cohort study |
| Study type | Participant information sheet |
| Scientific title | Optimising newborn nutrition during therapeutic hypothermia: An observational study using routinely collected data |
| Study objectives | 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 we will perform two primary comparisons: 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. 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. |
| Ethics approval(s) | East Midlands-Leicester Central Research Ethics Commitee, ref: 17/EM/0307 |
| Health condition(s) or problem(s) studied | Hypoxic-ischaemic encephalopathy requiring therapeutic hypothermia |
| Intervention | This study collects existing data help in the National Neonatal Research Database (NNRD). The analysis will apply the potential outcomes framework using propensity score matching. The data was collected from January 2008 to December 2016. All analysis uses anonymised data held in an approved research database, the NNRD. No patient identifiable information is used in this study. The data is collected in order to compare the milk feeding and intravenous nutrition that babies receive during therapeutic hypothermia. Milk feeding: Data is collected about babies who are fed milk while cooled with those that are not fed any milk. This is to establish whether there is any difference in rates of necrotising enterocolitis. Intravenous Nutrition: Data is collected to compare babies who get intravenous nutrition with those that only get intravenous dextrose. The main data collected is the rate of infection. The amount of babies who die, how long they stay in neonatal care, how soon breastfeeding starts and many are breastfed when they go home is also collected. De-identified data held in the NNRD and the potential outcomes framework with application of propensity scoring is used to define matched subgroups for comparison. |
| Intervention type | Mixed |
| Primary outcome measure(s) |
1. Necrotising enterocolitis is defined using the case definition (Battersby et al 2017) between birth and final neonatal unit discharge, and is collected and analysed using the data from the NNRD |
| Key secondary outcome measure(s) |
1. Survival is measured using the NNRD data between birth and neonatal unit discharge |
| Completion date | 09/01/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Neonate |
| Sex | All |
| Target sample size at registration | 7200 |
| Total final enrolment | 6030 |
| Key inclusion criteria | 1. Infants born at 36 gestational weeks or later 3. Received therapeutic hypothermia for Hypoxic Ischaemic Encephalopathy (HIE) for at least 72 hours 3. Died during therapeutic hypothermia |
| Key exclusion criteria | Infants with missing data for principal background and outcome variables. Missing values for other variables will be dealt with using multiple imputation. |
| Date of first enrolment | 01/10/2017 |
| Date of final enrolment | 01/10/2018 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
London
SW10 9NH
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be stored in a non-publically available repository called the National Neonatal Research Database (NNRD) http://www.imperial.ac.uk/neonatal-data-analysis-unit/neonatal-data/utilising-the-nnrd/ The data stored here will be de-identified paraticipant level data that is updated quarterly. All parents are informed and have the opportunity to opt out of their baby's data from being included in the NNRD. To access the database, ethical as well as other approvals are required, which is outlined here: http://www.imperial.ac.uk/neonatal-data-analysis-unit/neonatal-data/utilising-the-nnrd/ |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 01/06/2021 | 08/06/2021 | Yes | No | |
| Results article | Feeding during therapeutic hypothermia | 30/06/2021 | 06/09/2023 | Yes | No |
| Results article | Parenteral nutrition during therapeutic hypothermia association with higher late-onset infection but lower mortality | 05/05/2021 | 06/09/2023 | Yes | No |
| Protocol article | protocol | 23/10/2018 | 26/11/2020 | Yes | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
06/09/2023: Two publication references added.
08/06/2021: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
26/11/2020: Publication reference added.
