Clinical trial NCT03767634: Outcomes Following Early Parenteral Nutrition Use in Preterm Neonates
Official title: Outcomes Following Early Parenteral Nutrition Use in Preterm Neonates
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Neonatal Death
Prematurity
Keywords: Preterm neonate
Parenteral nutrition
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2018-12-06
Enrollment: 97507
Sex: ALL
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Neonates born between 1st January 2012 and 31st December 2017 and admitted to a neonatal unit in England, Scotland and Wales).

Brief summary: BACKGROUND

An essential part of neonatal care is providing nutrition to ensure that babies grow and develop. Providing this can be difficult in premature babies because their intestines are underdeveloped. They often have difficulty digesting milk so feeds are introduced gradually. To help babies grow and develop during this period, additional nutrition may be provided as a fluid into a vein; this is called "parenteral nutrition" (PN). Unfortunately, PN increases the risk of serious complications like bloodstream infection (also known as "sepsis"). For babies who are moderately premature there is little evidence to guide decision making about which babies will benefit from PN. This group of babies have more reserves of fat and are less dependent on PN, but are still at risk of sepsis. As a consequence, some doctors use PN and others do not.

AIMS

Firstly, to describe which babies are given PN during the first postnatal week in neonatal units in England, Scotland and Wales.

Secondly, to determine whether in babies born 7-10 weeks preterm (moderately premature), providing PN in the first week after birth, compared to not to providing PN, improves survival to discharge from the neonatal unit.

Finally, to evaluate if the early use of PN in moderately preterm babies affects other important outcomes in the neonatal core outcomes set.

IMPORTANCE

This work will describe the extent of PN use in England, Scotland and Wales. This is currently unknown. This project will improve understanding of the balance of benefits and harms of PN use in premature babies and will help doctors and parents make informed treatment choices.

METHODS

The investigators will use the National Neonatal Research Database (NNRD) to study all babies born in England, Scotland and Wales; they will identify which babies were given PN during the first week, and which were not. The investigators will use the NNRD to identify babies born 7-10 weeks prematurely and compare outcomes in babies that were given and not given PN in the first week after birth. The investigators will use statistical techniques to identify two sets of babies in the NNRD who are very similar (in terms of how prematurely they were born, their birth weight, and so on), the only difference being whether they were given PN or not. As the two groups will be similar any difference in their outcomes (such as survival) is likely to be due to whether or not they received PN.

Detailed description: Premature birth abruptly ends the transplacental transmission of nutrients that allows normal foetal growth and development. Providing adequate nutrition is essential to allow premature babies to continue to grow and mature. Very preterm infants often have difficulty tolerating adequate volumes of milk feeds shortly after birth and so are given supplemental parenteral nutrition (PN). Preterm babies are among the highest PN users of all NHS patients. It has been estimated that PN is received by around 70% of neonatal unit admissions but it is not known exactly which babies receive PN. In addition, how PN affects outcomes has never been tested in a large scale, randomized, placebo controlled neonatal trial.

It is known that PN carries well established risks, of which the most serious and the most common is sepsis with estimates of risk ratios varying from 2.2 to 14.6. In addition there is a growing body of evidence that use of PN within the first seven days of admission to an intensive care unit is associated with worse outcomes in critically unwell adults and children. A subgroup analysis of the paediatric intensive care unit population focusing on neonates showed an increase in infections with early PN use. This suggests that uncertainty exists over the benefit of giving neonates PN in the early postnatal period. It is generally accepted that PN is beneficial to extremely preterm neonates, but in moderately preterm neonates the effect that PN use has on neonatal survival has never been conclusively demonstrated.

The uncertainty over how PN use affects neonatal outcomes is reflected by the wide variety in how PN is used in different units with large variation in use, timing and composition of PN. This is, in part, due to the lack of clear evidence of how PN affects neonatal outcomes like growth and survival. Neonates are also vulnerable to unanticipated treatment effects which can occur in different organ systems and so it is important to show that PN is not detrimental to important neonatal outcomes.

The postmenstrual age at which the nutritional benefits of PN outweigh the risks in moderately preterm babies (30-33 weeks postmenstrual age) is unknown. It is therefore unsurprising that their nutritional management is very variable. In moderately preterm neonates in 2012 and 2013 across England, Scotland and Wales PN was given to 45% of neonates, suggesting clinician equipoise around the balance of benefit to risk. Identifying whether moderately preterm neonates benefit from PN would have important implications for practice in the UK. This work will provide information to guide practice and inform future research.

In summary, PN is widely used in neonates but it is not known exactly how it is used in the UK. It is known to have risks and benefits but there is insufficient evidence to guide practice in moderately preterm neonates.

Study objectives:

* To describe the use of PN in neonatal units across England, Scotland and Wales.
* To identify if use of PN in the first seven postnatal days affects survival in neonates born between 30 and 33 weeks postmenstrual age.
* To explore how PN use in the first seven postnatal days affects other important neonatal outcomes in neonates born between 30 and 33 weeks postmenstrual age.

Study design:

Project A: an epidemiological survey of practice using the National Neonatal Research Database (NNRD).

Project B: a retrospective cohort study of matched groups of babies using data held in the NNRD.

Eligibility criteria: Inclusion Criteria:

Project A:

* Must be born between 1st January 2012 and 31st December 2017
* Must be admitted to a National Health Service (NHS) neonatal unit in England, Scotland or Wales

Project B:

* Must be born between 30 and 33 weeks postmenstrual age
* Must be born between 1st January 2012 and 31st December 2017
* Must be admitted to an NHS neonatal unit in England, Scotland or Wales

Exclusion Criteria:

Project A:

No exclusion criteria.

Project B:

* Major congenital gastrointestinal malformations
* Life limiting conditions
* Congenital conditions requiring surgery in the neonatal period
* Missing key background data (birthweight, sex or gestational age)
* Missing data for the primary outcome

Primary outcomes:
measure: Use of Parenteral Nutrition (Project A)
timeFrame: From birth until discharge home, assessed up to 1 year
measure: Survival to Discharge Home (Project B)
timeFrame: From birth until discharge home, assessed up to 1 year
Secondary outcomes:
measure: Late Onset Sepsis (Project B)
timeFrame: 72 hours of postnatal life to discharge home, assessed up to 1 year
measure: Necrotising Enterocolitis (Project B)
timeFrame: From birth until discharge home, assessed up to 1 year
measure: Brain Injury on Imaging (Project B)
timeFrame: From birth until discharge home, assessed up to 1 year
measure: Retinopathy of Prematurity (Project B)
timeFrame: From birth until discharge home, assessed up to 1 year
measure: Bronchopulmonary Dysplasia (Project B)
timeFrame: From birth until discharge home, assessed up to 1 year
measure: Need for Surgical Procedures (Project B)
timeFrame: From birth until discharge home, assessed up to 1 year
measure: Seizures (Project B)
timeFrame: From birth until discharge home, assessed up to 1 year
measure: Weight (Project B)
timeFrame: From birth until discharge home, assessed up to 1 year
measure: Head Circumference (Project B)
timeFrame: From birth until discharge home, assessed up to 1 year
measure: Blindness (Project B)
timeFrame: From birth until two years of age
measure: Deafness (Project B)
timeFrame: From birth until two years of age
measure: Ability to Walk (Project B)
timeFrame: From birth until two years of age
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Chelsea and Westminster Hospital
Study officials:
affiliation: Imperial College London
name: Chris RK Gale, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Webbe J, Battersby C, Longford N, Oughham K, Uthaya S, Modi N, Gale C. Use of parenteral nutrition in the first postnatal week in England and Wales: an observational study using real-world data. BMJ Paediatr Open. 2022 Aug;6(1):e001543. doi: 10.1136/bmjpo-2022-001543.
citation: Webbe JWH, Longford N, Battersby C, Oughham K, Uthaya SN, Modi N, Gale C. Outcomes in relation to early parenteral nutrition use in preterm neonates born between 30 and 33 weeks' gestation: a propensity score matched observational study. Arch Dis Child Fetal Neonatal Ed. 2022 Mar;107(2):131-136. doi: 10.1136/archdischild-2021-321643. Epub 2021 Sep 21.
citation: Webbe J, Longford N, Uthaya S, Modi N, Gale C. Outcomes following early parenteral nutrition use in preterm neonates: protocol for an observational study. BMJ Open. 2019 Jul 9;9(7):e029065. doi: 10.1136/bmjopen-2019-029065.