Outcomes Following Early Parenteral Nutrition Use in Preterm Neonates

Prematurity Clinical Trial

Official title:

Outcomes Following Early Parenteral Nutrition Use in Preterm Neonates

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03767634
• Other study ID #: 18IC4724
• Status: Completed
• Start date: January 1, 2019
• Est. completion date: August 1, 2021

Study information

• Verified date: January 2022
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 97507
• Est. completion date: August 1, 2021
• Est. primary completion date: September 1, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 2 Years

Eligibility

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

Related Conditions & MeSH terms

• Neonatal Death
• Perinatal Death
• Prematurity

Intervention

Other:
• Parenteral nutrition
Parenteral nutrition is the administration of an intravenous solution containing amino acids (with or without lipids) to provide nutritional support.

Locations

Country	Name	City	State
United Kingdom	Chelsea and Westminster Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Imperial College London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Use of Parenteral Nutrition (Project A)	Any use of parenteral nutrition in the first seven days of postnatal life (assessed using daily data extracted from the National Neonatal Research Database as described in the project protocol); This outcome formed part of Project A ONLY, and in keeping with the research protocol is only analysed and reported for the babies in this research arm.	From birth until discharge home, assessed up to 1 year
Primary	Survival to Discharge Home (Project B)	Defined as recorded alive at final neonatal unit discharge; This outcome formed part of Project B ONLY, and in keeping with the research protocol is only analysed and reported for the babies in this research arm.	From birth until discharge home, assessed up to 1 year
Secondary	Late Onset Sepsis (Project B)	Number of participants with diagnosed Later Onset Sepsis: defined in line with the Royal College of Paediatrics and Child Health National Neonatal Audit Programme (NNAP) definition "pure growth of a pathogen from blood" or "pure growth of a skin commensal" or a "mixed growth" after the first 72 hours of life	72 hours of postnatal life to discharge home, assessed up to 1 year
Secondary	Necrotising Enterocolitis (Project B)	Number of participants with diagnosed necrotising enterocolitis: defined using the NNAP definition: NEC may be diagnosed at surgery, post-mortem or on the basis of the following clinical and radiographic signs: At least one clinical feature from: (i) Bilious gastric aspirate or emesis (ii) Abdominal distension (iii) Occult or gross blood in stool (no fissure); And at least one radiographic feature from: (i) Pneumatosis (ii) Hepato-biliary gas (iii) Pneumoperitoneum	From birth until discharge home, assessed up to 1 year
Secondary	Brain Injury on Imaging (Project B)	Number of participants with diagnosed brain injury on imaging: defined as documented diagnosis of intraventricular haemorrhage (grade 3-4) or cystic periventricular leucomalacia	From birth until discharge home, assessed up to 1 year
Secondary	Retinopathy of Prematurity (Project B)	Number of participants with diagnosed retinopathy of prematurity: defined as a record of any retinopathy of prematurity on routine screening in the National Neonatal Dataset "retinopathy of prematurity ad-hoc form"	From birth until discharge home, assessed up to 1 year
Secondary	Bronchopulmonary Dysplasia (Project B)	Number of participants with diagnosed bronchopulmonary dysplasia: defined using the NNAP definition of significant bronchopulmonary dysplasia: Receiving respiratory support at 36 weeks corrected gestational age.	From birth until discharge home, assessed up to 1 year
Secondary	Need for Surgical Procedures (Project B)	Defined as any record of surgical procedure during the neonatal admission	From birth until discharge home, assessed up to 1 year
Secondary	Seizures (Project B)	Number of participants diagnosed as having a seizure: defined as any recorded diagnosis of seizures or seizure disorder	From birth until discharge home, assessed up to 1 year
Secondary	Weight (Project B)	Weight z-score at discharge home. Weights at discharge home were converted to a z-score: a z-score of 0 represents the population mean, while score higher scores indicate a greater weight.	From birth until discharge home, assessed up to 1 year
Secondary	Head Circumference (Project B)	Head circumference in centimetres at discharge; head circumference velocity (measured as increase in head circumference in centimetres/day) from birth until discharge	From birth until discharge home, assessed up to 1 year
Secondary	Blindness (Project B)	Defined as an answer of Yes to the question "Does this child have a visual impairment?" on the NNAP follow up form	From birth until two years of age
Secondary	Deafness (Project B)	Defined as an answer of Yes to the question "Does this child have a hearing impairment?" on the NNAP follow up form	From birth until two years of age
Secondary	Ability to Walk (Project B)	Defined as an answer of Yes to the question "Is this child unable to walk without assistance?" on the NNAP follow up form	From birth until two years of age