Optimising Newborn Nutrition During Therapeutic Hypothermia.

Completed

• Conditions: Infant, Newborn; Asphyxia Neonatorum; Hypothermia, Induced; Necrotizing Enterocolitis; Neonatal Sepsis; Infant Nutrition; Parenteral Nutrition
• Interventions: Dietary Supplement: Received parenteral nutrition during therapeutic hypothermia; Dietary Supplement: Received enteral (milk) feeds during therapeutic hypothermia; Dietary Supplement: Enteral (milk) feeds withheld during therapeutic hypothermia; Dietary Supplement: Did not receive parenteral nutrition during therapeutic hypothermia

• Registration Number: NCT03278847
• Lead Sponsor: 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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2010-01-01
• Study First Submitted: 2017-08-23
• Study First Submitted QC: 2017-09-07
• Study First Posted: 2017-09-12
• Primary Completion: 2017-12-31
• Study Completion: 2021-01-01
• Results First Submitted: 2021-09-20
• Status Verified: 2022-11
• Results First Submitted QC: 2022-11-07
• Last Update Submitted: 2022-11-07
• Results First Posted: 2023-09-14
• Last Update Posted: 2023-09-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 6030

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

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Exclusion Criteria

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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Enteral nutrition comparison	Enteral (milk) feeds withheld during therapeutic hypothermia	This comparison refers to differences in enteral nutrition during therapeutic hypothermia
Parenteral nutrition comparison	Received parenteral nutrition during therapeutic hypothermia	This comparison refers to differences in parenteral nutrition during therapeutic hypothermia
Parenteral nutrition comparison	Did not receive parenteral nutrition during therapeutic hypothermia	This comparison refers to differences in parenteral nutrition during therapeutic hypothermia
Enteral nutrition comparison	Received enteral (milk) feeds during therapeutic hypothermia	This comparison refers to differences in enteral nutrition during therapeutic hypothermia

Primary Outcome Measures

Name	Time	Method
Necrotising Enterocolitis - for the Enteral Nutrition Comparison	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
Blood Stream Infection - for the Parenteral Nutrition Comparison	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

Name	Time	Method
Survival	From date of birth until date of final neonatal unit discharge, assessed up to 1 year	Survival at neonatal unit discharge
Length of Stay	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
Breastfeeding	At the point of final discharge from neonatal care, assessed up to 1 year	Any breastfeeding (suckling at the breast) at discharge
Growth	From date of birth until date of final neonatal unit discharge, assessed up to 1 year	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)
Duration of Central Venous Line	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 having a central venous line
Hypoglycaemia	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

Trial Locations

Locations (2)

Chelsea and Westminster Hospital and NHS Foundation Trust; 🇬🇧 London, United Kingdom

Imperial College London, Chelsea and Westminster Hospital campus; 🇬🇧 London, United Kingdom