Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000280707
Ethics application status
Approved
Date submitted
7/03/2013
Date registered
8/03/2013
Date last updated
15/02/2019
Date data sharing statement initially provided
15/02/2019
Date results information initially provided
15/02/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Relationship between brain structure and function of very preterm infants to predict neurodevelopmental outcome
Scientific title
Prospective longitudinal study of the relationship between brain structure and function in infants born at less than 30 weeks gestation to predict neurodevelopmental outcome.
Secondary ID [1] 281471 0
Nil
Universal Trial Number (UTN)
U1111-1140-3567
Trial acronym
PPREMO - Prediction of PREterm Motor Outcomes
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Brain development in preterm infants 287729 0
Prematurity 287730 0
Prediction of Cerebral Palsy
Motor outcomes 288560 0
Condition category
Condition code
Neurological 288071 288071 0 0
Other neurological disorders
Reproductive Health and Childbirth 288072 288072 0 0
Complications of newborn

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Preterm Group
Infants will be assessed at 4 time-points:
1. At 30 weeks of age, while the infant is still in the nursery we will carry out the following:
-clinical and medical information will be collected from the infant's chart
-A General Movements Assessment (GMs) which involves video of spontaneous movements in their incubator or cot (up to 1 hour of video; no handling of the baby)
-A neurological/neurobehavioural assessment (15-20 minutes; involves a small amount of handling)
-A brain scan (MRI) using MRI compatible incubator which takes about an hour (20 minutes preparation and 40 minutes in the scanner). Infant is fed, wrapped and asleep during the scan, with no sedation used.

2. At 40 weeks which is term equivalent age; if the infant has returned home the family will be asked to visit the hospital. We will complete:
- A General Movements Assessment (GMs) which involves video of spontaneous movements (up to 1 hour of video; no handling of the baby)
-Movement assessments and a neurological assessment (30-40 minutes)
-Assessment of their visual functions (5 minutes)
-A brain scan (MRI) using MRI compatible incubator which takes about an hour (20 minutes preparation and 40 minutes in the scanner). Infant is fed, wrapped and asleep during the scan, with no sedation used.
-A recording of their brain’s electrical activity (EEG; 30 minutes preparation and 30 minutes recording).

3. At 12 weeks corrected age (3 months after term); the research team will visit the family at home and:
- GMs assessment (video the baby’s spontaneous movements for 5-15 minutes)
- Perform a movement assessment (40 minutes)
- Assess their visual function (5 minutes)

4. At 12 months corrected age; we will ask the family to visit the hospital:
- A paediatrician will assess the baby’s general development (30 minutes)
- We will perform movement assessments (1 1/2 hours)
Intervention code [1] 285975 0
Not applicable
Intervention code [2] 286696 0
Early detection / Screening
Intervention code [3] 286697 0
Diagnosis / Prognosis
Comparator / control treatment
Reference group of healthy, full term infants.
Assessed at 1 week of age:
-A brain scan (MRI) using MRI compatible incubator which takes about an hour (20 minutes preparation and 40 minutes in the scanner). Infant is fed, wrapped and asleep during the scan, with no sedation used.
-Movement assessments and a neurological assessment (30-40 minutes)
-Assessment of their visual functions (5 minutes)
-A recording of their brain’s electrical activity (EEG; 30 minutes preparation and 30 minutes recording).
Control group
Active

Outcomes
Primary outcome [1] 288276 0
Brain neuroimaging
Structural and diffusion imaging analyses will be performed, including high angular resolution diffusion imaging (HARDI). This will examine both the structural integrity, and structural connectivity of the brain. These data will be related to outcome at 12 months corrected age (CP/not CP)
Timepoint [1] 288276 0
An MRI will be performed at 30 weeks and 40 weeks post menstrual ages (PMA).
Secondary outcome [1] 299740 0
Prechtl's method on the qualitative assessment of general movements.
The flow and spontaneity of movement from the infant will be correlated with neurological health scores from the EEG, MRI and Dubowitz neurological assessment.
Timepoint [1] 299740 0
The General Movement's Assessment will be performed by scoring video recordings of the infant's spontaneous movements at 30 weeks PMA, 40 weeks PMA, and 3 months CA.
Secondary outcome [2] 299741 0
Electrophysiology.
EEG recordings will be obtained from all infants. A quantitative assessment of the EEG will be performed, including coherence analysis and spectral analysis.
Timepoint [2] 299741 0
The EEG will be performed at term equivalent age (40 weeks post menstrual age) in both the preterm and term reference groups.
Secondary outcome [3] 301624 0
Neurological assessment
The Dubowitz neurological assessment assesses posture and tone, reflexes, movements and neurobehavioural responses.
Timepoint [3] 301624 0
The Dubowitz assessment will be performed at 30 and 40 weeks PMA in the preterm group, and at term in the reference group.
Secondary outcome [4] 301625 0
The NICU Network Neurobehavioural Scale (NNNS) is designed to provide information relating to an infant’s development, behavioural maturation, central nervous system integrity and stress responses (Lester and Tronick 2004).
Timepoint [4] 301625 0
The NNNS will be performed at 30 and 40 weeks PMA in the preterm group, and at term in the reference group.
Secondary outcome [5] 301626 0
Visual assessment
The neonatal assessment of visual functions provides useful information on various aspects of early neonatal visual function, including ocular motility, fixation, following, acuity and attention at distance.
Timepoint [5] 301626 0
This assessment will be performed at term equivalent age in the preterm and term reference group.
Secondary outcome [6] 301627 0
Test of Infant Motor Performance (TIMP)
The test assesses the postural and selective control of movement needed for functional motor performance in early infancy.
Timepoint [6] 301627 0
The TIMP will be performed at term equivalent age and 3 months corrected age in the preterm group.
Secondary outcome [7] 301628 0
Medical Assessment
Infants in this study will be independently assessed by a paediatrician experienced in infant development. The purpose of this assessment is to discriminate which infants are developing typically from those who are not, and to confirm diagnoses of CP or not CP (Badawi 1998). In cases of CP, motor type and distribution will be recorded, and severity established through classification with the Gross Motor Function Classification System (GMFCS). Any additional medical diagnoses that have been made by this stage will be recorded.
Timepoint [7] 301628 0
Infants in the preterm group will undergo this medical assessment at 12 months corrected age.
Secondary outcome [8] 301629 0
Assessment of Motor and neurodevelopmental outcome:
1. Bayley Scales of Infant and Toddler Development III (Bayley III- a discriminative tool designed to assess cognitive, language and motor development).
2. Neurosensory Motor Developmental Assessment (NSMDA- examines gross and fine motor performance, neurological status, posture, balance and response to sensory input).
3. Alberta Infant Motor Scale (AIMS- tests gross motor skills through the components of weight bearing, posture and anti-gravity movements).
Timepoint [8] 301629 0
Infants in the preterm group will have these assessments at 12 months corrected age.

Eligibility
Key inclusion criteria
Infants born at less than 30 weeks gestational age
English speaking family
Live within 200km of the Royal Brisbane and Women's Hospital
Have no congenital or chromosomal abnormality that would impact their development
Minimum age
No limit
Maximum age
30 Weeks
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Infants born at greater than 30 weeks gestational age
Non English-speaking family
Live >200km from the Royal Brisbane and Women's Hospital
Have a congenital or chromosomal abnormality that would impact their development

Study design
Purpose
Duration
Selection
Timing
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
11/03/2013
Actual
11/02/2013
Date of last participant enrolment
Anticipated
31/12/2014
Actual
21/04/2016
Date of last data collection
Anticipated
Actual
21/04/2016
Sample size
Target
80
Accrual to date
Final
119
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 712 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 5928 0
4029

Funding & Sponsors
Funding source category [1] 286235 0
Charities/Societies/Foundations
Name [1] 286235 0
Cerebral Palsy Alliance
Country [1] 286235 0
Australia
Funding source category [2] 286236 0
University
Name [2] 286236 0
Perinatal Research Centre
Country [2] 286236 0
Australia
Primary sponsor type
University
Name
Professor Paul Colditz
Address
Perinatal Research Centre
Royal Brisbane & Women's Hospital
Cnr Butterfield St and Bowen Bridge Rd
Herston
QLD
4029
Country
Australia
Secondary sponsor category [1] 285638 0
University
Name [1] 285638 0
Professor Roslyn Boyd
Address [1] 285638 0
Queensland Cerebral Palsy and Rehabilitation Research Centre.
School of Medicine, The University of Queensland,
Rm 722A, Level 7, Block 6,
Royal Brisbane and Women's Hospital
Herston
QLD
4029
Country [1] 285638 0
Australia
Other collaborator category [1] 277146 0
Individual
Name [1] 277146 0
Joanne George
Address [1] 277146 0
Queensland Cerebral Palsy and Rehabilitation Research Centre (QCPRRC)
Level 7, Block 6
Department of Paediatrics and Child Health
The University of Queensland
Royal Brisbane and Women's Hospital
Herston Rd.
HERSTON
QLD 4029
Country [1] 277146 0
Australia
Other collaborator category [2] 277317 0
Individual
Name [2] 277317 0
Associate Professor Stephen Rose
Address [2] 277317 0
ICT, The Australian eHealth Research Centre
CSIRO
Royal Brisbane and Women's Hospital
Herston
4029
QLD
Country [2] 277317 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288315 0
Royal Brisbane and Women's Hospital Human Research Ethics Committee
Ethics committee address [1] 288315 0
Royal Brisbane and Women's Hospital
Butterfield Street
Herston
QLD
4029
Ethics committee country [1] 288315 0
Australia
Date submitted for ethics approval [1] 288315 0
27/07/2012
Approval date [1] 288315 0
10/09/2012
Ethics approval number [1] 288315 0
HREC/12/QRBW/245
Ethics committee name [2] 288316 0
The University of Queensland Medical Research Ethics Committee
Ethics committee address [2] 288316 0
The University of Queensland
Brisbane QLD 4072 Australia
Ethics committee country [2] 288316 0
Australia
Date submitted for ethics approval [2] 288316 0
18/09/2012
Approval date [2] 288316 0
20/09/2012
Ethics approval number [2] 288316 0
2012001060

Summary
Brief summary
Infants born prematurely (< 30 weeks gestational age) have a higher risk of developing cerebral palsy than infants born at term, due to immaturity of the developing brain at birth, and potential brain injuries that can occur in the neonatal period. Cerebral palsy is frequently not diagnosed till the second year of life, delaying the start of early intervention treatments which may be of benefit in minimising functional limitations and providing key family supports. To date magnetic resonance imaging (MRI) at term equivalent age and general movement assessment provide the most accurate prediction of neurodevelopmental outcome at 12 months corrected age.

This project aims to investigate the relationship between earlier brain MRI and neuromotor/neurobehavioural assessments at 30 weeks gestational age, and their ability to predict outcomes of cerebral palsy and motor difficulties at 3 and 12 months corrected age.

We aim to achieve this in a longitudinal prospective cohort study of 80 infants born at less than 30 weeks gestational age, at the Royal Brisbane and Women’s Hospital. Infants will undergo a brain MRI scan at 30 and 40 weeks gestational age to develop our understanding of very early brain structure at 30 weeks; and maturation that occurs between 30 and 40 weeks gestational age. A combination of neurological (Dubowitz neurological assessment), neuromotor (General Movements, Test of Infant Motor Performance, visual functions) and neurobehavioural assessments (the NICU Network Neurobehavioural Scale) will be performed at 30 and 40 weeks GA to understand the relationship between brain structure and function. These data will be compared to motor assessments at 12 weeks post term and 12 months corrected age. These data will be compared to outcomes at 12 months CA including a developmental assessment by a paediatrician (Bayley scales of Infant and Toddler Development), motor assessments (Alberta Infant Motor Scale, Neurosensory Motor Developmental Assessment) to differentiate atypical development (including cerebral palsy and/or motor delay).

At a time of increasing demand on health care resources, reliable ways of predicting neurodevelopmental outcome in premature infants is desirable to determine those that may benefit most from early intervention.
Trial website
No specific trial website, however details and contact information are available on the website of the Queensland Cerebral Palsy and Rehabilitation Research Centre (QCPRRC) www.som.uq.edu.au/cerebralpalsy
Trial related presentations / publications
Nil
Public notes
Nil

Contacts
Principal investigator
Name 34894 0
Prof Roslyn Boyd
Address 34894 0
Queensland Cerebral Palsy and Rehabilitation Research Centre

Child Health Research Centre
The University of Queensland
Centre for Children’s Health Research
Level 6, 62 Graham Street
South Brisbane QLD 4101 Australia
Country 34894 0
Australia
Phone 34894 0
+61 7 30697372
Fax 34894 0
+61 7 30697109
Email 34894 0
[email protected]
Contact person for public queries
Name 18141 0
Mrs Joanne George
Address 18141 0
Queensland Cerebral Palsy and Rehabilitation Research Centre (QCPRRC)
Level 7, Block 6,
Royal Brisbane and Women's Hospital
Herston
QLD
4029
Country 18141 0
Australia
Phone 18141 0
+423968680
Fax 18141 0
Email 18141 0
[email protected]
Contact person for scientific queries
Name 9069 0
Prof Roslyn Boyd
Address 9069 0
Queensland Cerebral Palsy and Rehabilitation Research Centre

Child Health Research Centre
The University of Queensland
Centre for Children’s Health Research
Level 6, 62 Graham Street
South Brisbane QLD 4101 Australia
Country 9069 0
Australia
Phone 9069 0
+61 7 30697372
Fax 9069 0
+61 7 30697109
Email 9069 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
1362Study protocol    363216-(Uploaded-14-02-2019-14-34-55)-Study-related document.pdf
1363Informed consent form    363216-(Uploaded-14-02-2019-14-35-21)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually

Documents added automatically
SourceTitleYear of PublicationDOI
EmbasePPREMO: A prospective cohort study of preterm infant brain structure and function to predict neurodevelopmental outcome.2015https://dx.doi.org/10.1186/s12887-015-0439-z
EmbasePredicting motor outcome in preterm infants from very early brain diffusion MRI using a deep learning convolutional neural network (CNN) model.2020https://dx.doi.org/10.1016/j.neuroimage.2020.116807
EmbaseAutomating quantitative measures of an established conventional MRI scoring system for preterm-born infants scanned between 29 and 47 weeks' postmenstrual age.2021https://dx.doi.org/10.3174/ajnr.A7230
EmbaseEarly clinical and MRI biomarkers of cognitive and motor outcomes in very preterm born infants.2021https://dx.doi.org/10.1038/s41390-021-01399-5
EmbaseNeurological examination at 32-weeks postmenstrual age predicts 12-month cognitive outcomes in very preterm-born infants.2023https://dx.doi.org/10.1038/s41390-022-02310-6
N.B. These documents automatically identified may not have been verified by the study sponsor.