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NCT Number: NCT03278847

Optimising Newborn Nutrition During Therapeutic Hypothermia.

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.

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Key information

Conditions

Infant, Newborn Asphyxia Neonatorum Body Temperature Changes Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Enterocolitis Enterocolitis, Necrotizing Gastroenteritis Gastrointestinal Diseases Hyperphagia Hypothermia Hypothermia, Induced Infant Nutrition Infant, Newborn, Diseases Infections Inflammation Intestinal Diseases Necrotizing Enterocolitis Neonatal SEPSIS Parenteral Nutrition Pathologic Processes Pathological Conditions, Signs and Symptoms Sepsis Signs and Symptoms Signs and Symptoms, Digestive Systemic Inflammatory Response Syndrome

Age range

Up to 4 day

Sex eligibility

All sexes

Study type

Observational

Primary location

Chelsea and Westminster Hospital and NHS Foundation Trust, London, United Kingdom

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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
  • Recorded gestational age at birth ≥36 weeks
  • Recorded as receiving therapeutic hypothermia for 72 hours or died during therapeutic hypothermia

Exclusion criteria

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

Treatment and study plan

Received enteral (milk) feeds during therapeutic hypothermia

Dietary Supplement

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)

Enteral (milk) feeds withheld during therapeutic hypothermia

Dietary Supplement

Withholding enteral feeds (keeping a baby nil per os) for the duration of hypothermia.

Received parenteral nutrition during therapeutic hypothermia

Dietary Supplement

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).

Did not receive parenteral nutrition during therapeutic hypothermia

Dietary Supplement

Received standard intravenous fluids (10% dextrose with additional electrolytes added where required) for the duration of hypothermia.

Primary outcomes

  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 outcomes

  1. Survival

    Time frame: From date of birth until date of final neonatal unit discharge, assessed up to 1 year

    Survival at neonatal unit discharge

  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. Duration of Central Venous Line

    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 having a central venous line

  6. Growth

    Time frame: 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)

Sponsors and collaborators

Lead sponsor

Imperial College London

Other

Collaborators

  • Bliss Charity
  • University of Nottingham

Registry information

Official study title

Optimising Newborn Nutrition During Therapeutic Hypothermia: an Observational Study Using Routinely Collected Data

Important dates

Study start
2010
Primary completion
2017
Study completion
2021
First posted
Sep 12, 2017
Registry last updated
Sep 14, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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