Clinical trial NCT03278847: Optimising Newborn Nutrition During Therapeutic Hypothermia.
Official title: Optimising Newborn Nutrition During Therapeutic Hypothermia: an Observational Study Using Routinely Collected Data
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Infant, Newborn
Asphyxia Neonatorum
Hypothermia, Induced
Parenteral Nutrition
Infant Nutrition
Necrotizing Enterocolitis
Neonatal Sepsis
Keywords: NNRD
matching
propensity score
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: University of Nottingham
name: Bliss Charity
First posted: 2017-09-12
Enrollment: 6030
Sex: ALL
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

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.

Eligibility 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.

Primary outcomes:
measure: Necrotising Enterocolitis - for the Enteral Nutrition Comparison
timeFrame: From date of birth until date of final neonatal unit discharge, assessed up to 1 year
measure: Blood Stream Infection - for the Parenteral Nutrition Comparison
timeFrame: From date of birth until date of final neonatal unit discharge, assessed up to 1 year
Secondary outcomes:
measure: Survival
timeFrame: From date of birth until date of final neonatal unit discharge, assessed up to 1 year
measure: Length of Stay
timeFrame: From date of birth until date of final neonatal unit discharge, assessed up to 1 year
measure: Breastfeeding
timeFrame: At the point of final discharge from neonatal care, assessed up to 1 year
measure: Hypoglycaemia
timeFrame: From date of birth until date of final neonatal unit discharge, assessed up to 1 year
measure: Duration of Central Venous Line
timeFrame: From date of birth until date of final neonatal unit discharge, assessed up to 1 year
measure: Growth
timeFrame: From date of birth until date of final neonatal unit discharge, assessed up to 1 year
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Chelsea and Westminster Hospital and NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College London, Chelsea and Westminster Hospital campus
Study officials:
affiliation: Imperial College London
name: Chris Gale, MBBS, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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: 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: 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: 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.