Condition category
Digestive System
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status

Plain English Summary

Background and study aims
About 11% of all babies born worldwide are preterm (premature), meaning that they are born more than three weeks before their due date. The earlier babies are born, the more likely they are to die or develop long-term complications, particularly those born before 32 weeks. Over the last 20 years, breathing support has improved significantly, meaning that more babies now service. Currently, the most common cause of serious illness after the first week are due to complications or infections in the gut (digestive system). About 20-25% of very preterm infants (born before 32 weeks) develop a serious infection (sepsis) or a bowel complication called necrotising enterocolitis (NEC). Infants who get sepsis or NEC have a much higher risk of dying or being disabled. Better methods of preventing these complications in very preterm infants are needed. The ELFIN study started recruiting infants in 2015, and will test whether giving them supplemental lactoferrin (a natural antibiotic protein from cow's milk) reduces the number of serious infections, and also whether it affects rates of gut complications. Regardless of the results of the ELFIN study, the way that the extract lactoferrin works on the gut will still be unknown. It is thought that lactoferrin will work by changing the pattern of bacteria in the gut, and that in turn this will reduce the number of harmful bacteria that might cause sepsis. Increasing the number of healthy bacteria in the gut may allow the infant to better tolerate milk feeds, and less likely to develop gut complications such as NEC. The aim of this study is to find out how lactoferrin supplements work by looking at changes to the gut bacteria.

Who can participate?
Premature babies who are taking part in the ELFIN study of lactoferrin.

What does the study involve?
Details about the ELFIN trial are available at:
For all participants, a sample of stool is collected from the nappy, and a urine sample (collected using cotton wool balls) each day the baby is in the hospital until they are close to going home. These samples are then stored at the local hospital before being transferred to central laboratories in Newcastle. The samples are analysed for the overall patterns of gut bacteria, as well as the presence of specific species that may be harmful or associated with improved recovery.

What are the possible benefits and risks of participating?
There are no direct benefits or risks involved for participants taking part in this study.

Where is the study run from?
The Neonatal Unit at Royal Victoria Infirmary (lead centre) and ten other neonatal units in NHS hospitals in the north of England (UK)

When is the study starting and how long is it expected to run for?
February 2016 to June 2019

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Dr Nicholas Embleton

Trial website

Contact information



Primary contact

Dr Nicholas Embleton


Contact details

The Royal Victoria Infirmary
Ward 35 RVI
Newcastle Hospitals NHS Foundation Trust
Newcastle Upon Tyne
United Kingdom

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

Mechanisms Affecting the Gut of Preterm Infants in Enteral feeding trials (MAGPIE)



Study hypothesis

The aim of this study is to determine, in preterm infants, whether the mechanism of action of enteral lactoferrin supplementation in reducing infections or gut complications involves changes in the pattern of gut bacteria.

This study is linked to the ELFIN – Enteral Lactoferrin in Neonates study (available via

Ethics approval

East Midlands - Nottingham 2 Research Ethics Committee, 16/03/2016, ref: 16/EM/0042

Study design

Observational cohort study

Primary study design


Secondary study design

Cohort study

Trial setting

Not specified

Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Specialty: Children, Primary sub-specialty: Neonatal; UKCRC code/ Disease: Oral & Gastro/ Other diseases of the digestive system


Infants who join the trial will all have been enrolled in the ELFIN study, and are anticipated to be recruited to MAGPIE at the same time in most cases i.e. within the first few days after delivery. We will collect a daily stool and urine sample from the infants from recruitment until hospital discharge (average 6 weeks, range 3-12 weeks in total duration). These samples will be collected at the cot-side and then placed in a freezer on the neonatal intensive care unit (NICU). Samples will be transferred to central laboratories and the most informative samples chosen for analysis of gut microbiota (16s next generation sequencing) and metabolomic analysis (stool and urine).

Intervention type



Drug names

Primary outcome measures

Gut microbial diversity (Shannon Diversity Index) and differences in the proportions of key bacterial taxa measured using 16s next generation sequencing in stool samples collected after enrolment on days 1-3, 7, 10-14, and 21 (+/- 1) days.

Secondary outcome measures

1. The association between the pattern of gut microbiota and the stool metabolome using mixed effect models, structural equation modelling and ordination analyses. Stool metabolome is measured using Gas Chromatography and/or Liquid Chromatography in samples collected on days 1-3, 7, 10-14, and 21 (+/- 1) days.
2. Pattern of gut microbiota prior to the onset of NEC or sepsis (diagnosed according to criteria used in the ELFIN trial) is measured using up to 7 daily stool samples in the period immediately prior to disease compared to samples from control cases who do not develop disease
3. The gut tissue inflammatory response in surgically resected gut tissue affected by NEC and in control tissue (either non-affected tissue from the same infant, or tissue from an infant requiring gut resection who does not have disease), is determined by immune-histochemistry using paraffin blocks cut into small sections for staining, a digital slide scanner and white cell infiltrates identified using antibodies. This is measured after trial completion by retrieving samples from hospital pathology archives.

Overall trial start date


Overall trial end date


Reason abandoned


Participant inclusion criteria

Preterm infants < 32 weeks gestation who have been enrolled into the ELFIN study of lactoferrin.

Participant type


Age group




Target number of participants

Planned Sample Size: 480; UK Sample Size: 480

Participant exclusion criteria

Lack of informed consent

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Royal Victoria Infirmary
Neonatal Unit Richardson Road
Newcastle upon Tyne
United Kingdom

Trial participating centre

Sunderland Royal Hospital
Neonatal Unit Kayll Road
United Kingdom

Trial participating centre

University Hospital of North Tees
Neonatal Unit Hardwick Road
TS19 8PE
United Kingdom

Trial participating centre

James Cook University Hospital
Marton Road
United Kingdom

Trial participating centre

Leeds General Infirmary
Neonatal Unit Great George Street
United Kingdom

Trial participating centre

Bradford Royal Infirmary
Duckworth Lane
United Kingdom

Trial participating centre

Birmingham Women's Hospital
Neonatal Unit Queen Elizabeth Medical Centre Mindelsohn Way
B15 2TG
United Kingdom

Trial participating centre

Nottingham City Hospital
Neonatal Unit Hucknall Road
United Kingdom

Trial participating centre

Nottingham University Hospital
Neonatal Unit Queen's Medical Centre Campus Derby Road
United Kingdom

Trial participating centre

Sheffield Teaching Hospital
Neonatal Unit Jessop Wing Tree Root Walk
S10 2SF

Sponsor information


The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Sponsor details

Newcastle Joint Research Office
1st Floor Regent Point
Regent Farm Road
United Kingdom

Sponsor type

Hospital/treatment centre



Funder type


Funder name

National Institute for Health Research

Alternative name(s)


Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government


United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication of a protocol in 2017 and the first stage analysis (effects on gut microbiota) in 2019 in a relevant peer reviewed journal. Metabolomic and integrative analysis, and tissue analysis publication will be in 2019-2020. It is anticipated that the preliminary results will be presented at international conferences. However, because this is an embedded mechanistic study, no key (un-blinded) data collected as part of MAGPIE will be presented or published until the primary results of the ELFIN trial have been accepted for publication.

Intention to publish date


Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes