Trial Outcomes & Findings for Outcomes Following Early Parenteral Nutrition Use in Preterm Neonates (NCT NCT03767634)

Results Overview

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.

Recruitment status

COMPLETED

Target enrollment

97507 participants

Primary outcome timeframe

From birth until discharge home, assessed up to 1 year

Results posted on

2022-03-17

Participant Flow

Project A: 4,196,314 neonates were born in England and Wales. 347,959 neonates were admitted to NHS neonatal units . 62,147 neonates received PN during the first postnatal week. Project B: 37,302 neonates were born over the study period. 36,644 were admitted to an NHS neonatal unit. Prior to the propensity score analysis 843 neonates were excluded due to congenital conditions and 439 were excluded due to missing key data. This left 35,362 included in the propensity score analysis

Participant milestones

Participant milestones
Measure	Neonatal Population (Project A) Neonates born between 1st January 2012 and 31st December 2017 and admitted to a neonatal unit in England and Wales).	No PN Use (Project B) All neonates born between 30 and 33 weeks postmenstrual age in England and Wales and admitted to a NHS neonatal unit between 1st January 2012 and 31st December 2017 who did not receive any parenteral nutrition (for any duration, by any intravenous route) in the first seven postnatal days.	PN Use (Project B) All neonates born between 30 and 33 weeks postmenstrual age in England and Wales and admitted to a NHS neonatal unit between 1st January 2012 and 31st December 2017 who received any parenteral nutrition (for any duration, by any intravenous route) in the first seven postnatal days. Parenteral nutrition: Parenteral nutrition is the administration of an intravenous solution containing amino acids (with or without lipids) to provide nutritional support.
Overall Study STARTED	62145	19080	16282
Overall Study COMPLETED	62145	19080	16282
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Neonatal Population (Project A) n=62145 Participants Neonates born between 1st January 2012 and 31st December 2017 and admitted to a neonatal unit in England and Wales).	No PN Use (Project B) n=8146 Participants All neonates born between 30 and 33 weeks postmenstrual age in England and Wales and admitted to a NHS neonatal unit between 1st January 2012 and 31st December 2017 who did not receive any parenteral nutrition (for any duration, by any intravenous route) in the first seven postnatal days.	PN Use (Project B) n=8146 Participants All neonates born between 30 and 33 weeks postmenstrual age in England and Wales and admitted to a NHS neonatal unit between 1st January 2012 and 31st December 2017 who received any parenteral nutrition (for any duration, by any intravenous route) in the first seven postnatal days. Parenteral nutrition: Parenteral nutrition is the administration of an intravenous solution containing amino acids (with or without lipids) to provide nutritional support.	Total n=78437 Participants Total of all reporting groups
Age, Categorical <=18 years	62145 Participants n=62145 Participants	8146 Participants n=8146 Participants	8146 Participants n=8146 Participants	78437 Participants n=78437 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=62145 Participants	0 Participants n=8146 Participants	0 Participants n=8146 Participants	0 Participants n=78437 Participants
Age, Categorical >=65 years	0 Participants n=62145 Participants	0 Participants n=8146 Participants	0 Participants n=8146 Participants	0 Participants n=78437 Participants
Sex: Female, Male Female	27965 Participants n=62145 Participants	3664 Participants n=8146 Participants	3733 Participants n=8146 Participants	35362 Participants n=78437 Participants
Sex: Female, Male Male	34180 Participants n=62145 Participants	4482 Participants n=8146 Participants	4413 Participants n=8146 Participants	43075 Participants n=78437 Participants
Race and Ethnicity Not Collected	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: From birth until discharge home, assessed up to 1 year

Population: This outcome formed part of Project A ONLY, and in keeping with the research protocol has only been collected, analysed and reported for the neonates in this research arm. In Project B 'use of parenteral nutrition' formed a key background characteristic, and so this outcome is not reported for the two arms of Project B.

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.

Outcome measures

Outcome measures
Measure	Neonatal Population (Project A) n=347959 Participants Neonates born between 1st January 2012 and 31st December 2017 and admitted to a neonatal unit in England, Scotland and Wales).	PN Use (Project B) All neonates born between 30 and 33 weeks postmenstrual age in England and Wales and admitted to a NHS neonatal unit between 1st January 2012 and 31st December 2017 who received any parenteral nutrition (for any duration, by any intravenous route) in the first seven postnatal days. Parenteral nutrition: Parenteral nutrition is the administration of an intravenous solution containing amino acids (with or without lipids) to provide nutritional support.
Use of Parenteral Nutrition (Project A)	62145 Participants	—

PRIMARY outcome

Timeframe: From birth until discharge home, assessed up to 1 year

Population: Analysis of propensity score matched cohorts as per the pre-specified analysis plan 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.

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.

Outcome measures

Outcome measures
Measure	Neonatal Population (Project A) n=8146 Participants Neonates born between 1st January 2012 and 31st December 2017 and admitted to a neonatal unit in England, Scotland and Wales).	PN Use (Project B) n=8146 Participants All neonates born between 30 and 33 weeks postmenstrual age in England and Wales and admitted to a NHS neonatal unit between 1st January 2012 and 31st December 2017 who received any parenteral nutrition (for any duration, by any intravenous route) in the first seven postnatal days. Parenteral nutrition: Parenteral nutrition is the administration of an intravenous solution containing amino acids (with or without lipids) to provide nutritional support.
Survival to Discharge Home (Project B)	7987 Participants	8057 Participants

SECONDARY outcome

Timeframe: 72 hours of postnatal life to discharge home, assessed up to 1 year

Population: Analysis of propensity score matched cohorts as per the pre-specified analysis plan

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

Outcome measures

Outcome measures
Measure	Neonatal Population (Project A) n=8146 Participants Neonates born between 1st January 2012 and 31st December 2017 and admitted to a neonatal unit in England, Scotland and Wales).	PN Use (Project B) n=8146 Participants All neonates born between 30 and 33 weeks postmenstrual age in England and Wales and admitted to a NHS neonatal unit between 1st January 2012 and 31st December 2017 who received any parenteral nutrition (for any duration, by any intravenous route) in the first seven postnatal days. Parenteral nutrition: Parenteral nutrition is the administration of an intravenous solution containing amino acids (with or without lipids) to provide nutritional support.
Late Onset Sepsis (Project B)	59 Participants	179 Participants

SECONDARY outcome

Timeframe: From birth until discharge home, assessed up to 1 year

Population: Analysis of propensity score matched cohorts as per the pre-specified analysis plan

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

Outcome measures

Outcome measures
Measure	Neonatal Population (Project A) n=8146 Participants Neonates born between 1st January 2012 and 31st December 2017 and admitted to a neonatal unit in England, Scotland and Wales).	PN Use (Project B) n=8146 Participants All neonates born between 30 and 33 weeks postmenstrual age in England and Wales and admitted to a NHS neonatal unit between 1st January 2012 and 31st December 2017 who received any parenteral nutrition (for any duration, by any intravenous route) in the first seven postnatal days. Parenteral nutrition: Parenteral nutrition is the administration of an intravenous solution containing amino acids (with or without lipids) to provide nutritional support.
Necrotising Enterocolitis (Project B)	285 Participants	660 Participants

SECONDARY outcome

Timeframe: From birth until discharge home, assessed up to 1 year

Population: Analysis of propensity score matched cohorts as per the pre-specified analysis plan

Number of participants with diagnosed brain injury on imaging: defined as documented diagnosis of intraventricular haemorrhage (grade 3-4) or cystic periventricular leucomalacia

Outcome measures

Outcome measures
Measure	Neonatal Population (Project A) n=8146 Participants Neonates born between 1st January 2012 and 31st December 2017 and admitted to a neonatal unit in England, Scotland and Wales).	PN Use (Project B) n=8146 Participants All neonates born between 30 and 33 weeks postmenstrual age in England and Wales and admitted to a NHS neonatal unit between 1st January 2012 and 31st December 2017 who received any parenteral nutrition (for any duration, by any intravenous route) in the first seven postnatal days. Parenteral nutrition: Parenteral nutrition is the administration of an intravenous solution containing amino acids (with or without lipids) to provide nutritional support.
Brain Injury on Imaging (Project B)	48 Participants	73 Participants

SECONDARY outcome

Timeframe: From birth until discharge home, assessed up to 1 year

Population: Analysis of propensity score matched cohorts as per the pre-specified analysis plan

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"

Outcome measures

Outcome measures
Measure	Neonatal Population (Project A) n=8146 Participants Neonates born between 1st January 2012 and 31st December 2017 and admitted to a neonatal unit in England, Scotland and Wales).	PN Use (Project B) n=8146 Participants All neonates born between 30 and 33 weeks postmenstrual age in England and Wales and admitted to a NHS neonatal unit between 1st January 2012 and 31st December 2017 who received any parenteral nutrition (for any duration, by any intravenous route) in the first seven postnatal days. Parenteral nutrition: Parenteral nutrition is the administration of an intravenous solution containing amino acids (with or without lipids) to provide nutritional support.
Retinopathy of Prematurity (Project B)	272 Participants	297 Participants

SECONDARY outcome

Timeframe: From birth until discharge home, assessed up to 1 year

Population: Analysis of propensity score matched cohorts as per the pre-specified analysis plan

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.

Outcome measures

Outcome measures
Measure	Neonatal Population (Project A) n=8146 Participants Neonates born between 1st January 2012 and 31st December 2017 and admitted to a neonatal unit in England, Scotland and Wales).	PN Use (Project B) n=8146 Participants All neonates born between 30 and 33 weeks postmenstrual age in England and Wales and admitted to a NHS neonatal unit between 1st January 2012 and 31st December 2017 who received any parenteral nutrition (for any duration, by any intravenous route) in the first seven postnatal days. Parenteral nutrition: Parenteral nutrition is the administration of an intravenous solution containing amino acids (with or without lipids) to provide nutritional support.
Bronchopulmonary Dysplasia (Project B)	302 Participants	619 Participants

SECONDARY outcome

Timeframe: From birth until discharge home, assessed up to 1 year

Population: Analysis of propensity score matched cohorts as per the pre-specified analysis plan

Defined as any record of surgical procedure during the neonatal admission

Outcome measures

Outcome measures
Measure	Neonatal Population (Project A) n=8146 Participants Neonates born between 1st January 2012 and 31st December 2017 and admitted to a neonatal unit in England, Scotland and Wales).	PN Use (Project B) n=8146 Participants All neonates born between 30 and 33 weeks postmenstrual age in England and Wales and admitted to a NHS neonatal unit between 1st January 2012 and 31st December 2017 who received any parenteral nutrition (for any duration, by any intravenous route) in the first seven postnatal days. Parenteral nutrition: Parenteral nutrition is the administration of an intravenous solution containing amino acids (with or without lipids) to provide nutritional support.
Need for Surgical Procedures (Project B)	69 Participants	147 Participants

SECONDARY outcome

Timeframe: From birth until discharge home, assessed up to 1 year

Population: Analysis of propensity score matched cohorts as per the pre-specified analysis plan

Number of participants diagnosed as having a seizure: defined as any recorded diagnosis of seizures or seizure disorder

Outcome measures

Outcome measures
Measure	Neonatal Population (Project A) n=8146 Participants Neonates born between 1st January 2012 and 31st December 2017 and admitted to a neonatal unit in England, Scotland and Wales).	PN Use (Project B) n=8146 Participants All neonates born between 30 and 33 weeks postmenstrual age in England and Wales and admitted to a NHS neonatal unit between 1st January 2012 and 31st December 2017 who received any parenteral nutrition (for any duration, by any intravenous route) in the first seven postnatal days. Parenteral nutrition: Parenteral nutrition is the administration of an intravenous solution containing amino acids (with or without lipids) to provide nutritional support.
Seizures (Project B)	81 Participants	114 Participants

SECONDARY outcome

Timeframe: From birth until discharge home, assessed up to 1 year

Population: Analysis of propensity score matched cohorts as per the pre-specified analysis plan

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.

Outcome measures

Outcome measures
Measure	Neonatal Population (Project A) n=8146 Participants Neonates born between 1st January 2012 and 31st December 2017 and admitted to a neonatal unit in England, Scotland and Wales).	PN Use (Project B) n=8146 Participants All neonates born between 30 and 33 weeks postmenstrual age in England and Wales and admitted to a NHS neonatal unit between 1st January 2012 and 31st December 2017 who received any parenteral nutrition (for any duration, by any intravenous route) in the first seven postnatal days. Parenteral nutrition: Parenteral nutrition is the administration of an intravenous solution containing amino acids (with or without lipids) to provide nutritional support.
Weight (Project B)	0.073 Z-score Standard Deviation 0.98	-0.024 Z-score Standard Deviation 0.96

SECONDARY outcome

Timeframe: From birth until discharge home, assessed up to 1 year

Population: Initial analyses revealed considerable amounts of missing data (\>90% missing): as the data represented under 10% of the true population it would not be possible to meaningfully summarise this data and it was highly unreliable (due to the high risk of systematic bias in this unrepresentative sample). For this reason full data relating to this outcome was not extracted from the National Neonatal Research Database as it was not in any way informative, and any further analysis was unjustified.

Head circumference in centimetres at discharge; head circumference velocity (measured as increase in head circumference in centimetres/day) from birth until discharge

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From birth until two years of age

Population: Initial analyses revealed considerable amounts of missing data (\>90% missing): as the data represented under 10% of the true population it would not be possible to meaningfully summarise this data and it was highly unreliable (due to the high risk of systematic bias in this unrepresentative sample). For this reason full data relating to this outcome was not extracted from the National Neonatal Research Database as it was not in any way informative, and any further analysis was unjustified.

Defined as an answer of Yes to the question "Does this child have a visual impairment?" on the NNAP follow up form

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From birth until two years of age

Population: Initial analyses revealed considerable amounts of missing data (\>90% missing): as the data represented under 10% of the true population it would not be possible to meaningfully summarise this data and it was highly unreliable (due to the high risk of systematic bias in this unrepresentative sample). For this reason full data relating to this outcome was not extracted from the National Neonatal Research Database as it was not in any way informative, and any further analysis was unjustified.

Defined as an answer of Yes to the question "Does this child have a hearing impairment?" on the NNAP follow up form

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From birth until two years of age

Population: Initial analyses revealed considerable amounts of missing data (\>90% missing): as the data represented under 10% of the true population it would not be possible to meaningfully summarise this data and it was highly unreliable (due to the high risk of systematic bias in this unrepresentative sample). For this reason full data relating to this outcome was not extracted from the National Neonatal Research Database as it was not in any way informative, and any further analysis was unjustified.

Defined as an answer of Yes to the question "Is this child unable to walk without assistance?" on the NNAP follow up form

Outcome measures

Outcome data not reported

Adverse Events

Neonatal Population (Project A)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 5725 deaths

No PN Use (Project B)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 163 deaths

PN Use (Project B)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 90 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr Chris Gale

Imperial College London

Phone: +44 (0)20 3315 3519

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place