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Trial registered on ANZCTR


Registration number
ACTRN12615000591550
Ethics application status
Approved
Date submitted
21/05/2015
Date registered
5/06/2015
Date last updated
26/10/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Neurodevelopment of the preterm infant
Scientific title
Neurodevelopment of the preterm infant
Secondary ID [1] 286563 0
Nil
Universal Trial Number (UTN)
U1111-1169-4479
Trial acronym
PREBO - Preterm Brain Outcomes
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Brain development in preterm infants 294813 0
Prematurity 294814 0
Condition category
Condition code
Neurological 295088 295088 0 0
Other neurological disorders
Reproductive Health and Childbirth 295089 295089 0 0
Complications of newborn

Intervention/exposure
Study type
Observational
Patient registry
False
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 30-36 weeks gestational age, while the baby is still in the nursery we will carry out the following:
- clinical and medical information will be collected from the baby's chart
- a General Movements Assessment (GMs) which involves video of spontaneous movements in their incubator or cot (no handling of baby)
- a neurological/neurobehavioural assessment (involves a small amount of handling)
- a brain scan (MRI) using MRI compatible incubator. Infant is fed, wrapped and asleep during the scan, with no sedation used.
- a recording of the baby's brain electrical activity (EEG)

2. At term (40-42 weeks) gestational age; if the baby has returned home the family will be asked to visit the hospital. We will complete:
- a video of the baby's movements for a short period
- movement assessments and a neurological assessment. This assessment is videoed for scoring purposes
- assessment of the baby's visual functions
- a brain scan (MRI) using MRI compatible incubator
- a recording of the baby's brain electrical activity (EEG)

3. At 3 months corrected age we will visit the family at home and:
- GMs assessment (video the baby's spontaneous movements)
- perform a movement assessment. This assessment is videoed for scoring purposes.
- assessment of the baby's visual functions

4. At 12 months corrected age ( Brisbane site only) we will visit the family at home and:
-to perform neurodevelopment and movement assessments.These assessments are videoed for scoring purposes.
-a paediatrician assessment will be performed if required.

5. At 24 months corrected age we will ask the family to visit the hospital for:
- a paediatrician to assess the baby's general development
- to perform neurodevelopment and movement assessments. These assessments are videoed for scoring purposes.
Intervention code [1] 291669 0
Not applicable
Comparator / control treatment
Reference group of healthy, full term infants.
Assessed at > 1 week of age:
- a brain scan (MRI) using MRI compatible incubator. Infant is fed, wrapped and asleep during the scan, with no sedation used.
- movement assessments and a neurological assessment
- assessment of the baby's visual functions
- a recording of the baby's brain electrical activity (EEG)
Control group
Active

Outcomes
Primary outcome [1] 294850 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 24 months corrected age (CP/not CP)
Timepoint [1] 294850 0
An MRI will be performed at 30 weeks and 40 weeks post menstrual ages (PMA).
Secondary outcome [1] 314195 0
Prechtl's method on the qualitative assessment of general movements. The flow and spontaneity of movements from the infant will be correlated with neurological health scores from the EEG, MRI and Dubowitz neurological assessment.
Timepoint [1] 314195 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] 314196 0
Electrophysiology.
EEG recordings will be obtain from all infants. A quantitative assessment of the EEG will be performed, including coherence analysis and spectral analysis.
Timepoint [2] 314196 0
The EEG will be performed at 30 and 40 weeks PMA in the preterm group, and at term in the reference group.
Secondary outcome [3] 314197 0
Neurological assessment
The Dubowitz neurological assessment assesses posture and tone, reflexes, movements and neurobehavioural responses.
Timepoint [3] 314197 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] 314198 0
The NICU Network Neurobehavioural Scale (NNS) 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] 314198 0
The NNS will be performed at 30 and 40 weeks PMA in the preterm group, and at term in the reference group.
Secondary outcome [5] 314199 0
Visual assessment
The neonatal assessment of visual functions provides useful information on the various aspects of early neonatal visual function, including ocular motility, fixation, following, acuity and attention to distance. When the baby is alert they will be tested to see how they look at (fixes and follows) a series of cards designed to test their vision.
Timepoint [5] 314199 0
This assessment will be performed at term equivalent age in the preterm and term reference group.
Secondary outcome [6] 314200 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] 314200 0
The TIMP will be performed at term equivalent age and 3 months corrected age in the preterm group.
Secondary outcome [7] 314201 0
Medical assessment - single outcome
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 wil 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] 314201 0
Infants in the preterm group and term reference group will undergo this medical assessment at 24 months corrected age.
Secondary outcome [8] 314202 0
Assessment of Motor and neurodevelopmental outcome:
Bayley Scales of Infant and Toddler Development III (Bayley III - a discriminative tool designed to assess cognitive, language and motor development).
Timepoint [8] 314202 0
Infants in the preterm group and term reference group will have these assessments at 24 months corrected age.
Secondary outcome [9] 315031 0
Assessment of Motor and neurodevelopmental outcome:
Neurosensory Motor Developmental Assessment (NSMDA - examines gross and fine motor performance, neurological status, posture, balance and response to sensory input).
Timepoint [9] 315031 0
Infants in the preterm group and term reference group will have these assessments at 24 months corrected age.
Secondary outcome [10] 315032 0
Assessment of Motor and neurodevelopmental outcome:
Alberta Infant Motor Scale (AIMS - tests gross motor skills through the components of weight bearing, posture and anti-gravity movements).
Timepoint [10] 315032 0
Infants in the preterm group and term refernce group will have these assessments at 24 months corrected age.

Eligibility
Key inclusion criteria
PRETERM GROUP
Infants born at less than 31 weeks gestational age
English speaking family
Live within 200km of either the Royal Brisbane and Women's Hospital or Monash Medical Centre
Have no congenital or chromosomal abnormality that would impact their development

TERM REFERENCE GROUP
Infants born between 38 and 41 weeks postmenstrual age
English speaking family
Live within 200km of either the Royal Brisbane and Women's Hospital or Monash Medical Centre
Have no congenital or chromosomal abnormality that would impact their development
Minimum age
No limit
Maximum age
2 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
PRETERM GROUP
Infants born at greater than 31 weeks gestational age
Non English-speaking family
Live >200 km from the Royal Brisbane and Women's Hospital or Monash Medical Centre
Have a congenital or chromosomal abnormality that would impact their development

TERM REFERENCE GROUP
Infants born at less than 38 weeks gestational age
Non English-speaking family
Live >200 km from the Royal Brisbane and Women's Hospital or Monash Medical Centre
Have a congenital or chromosomal abnormality that would impact their development

Study design
Purpose
Duration
Selection
Timing
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/12/2015
Actual
9/03/2016
Date of last participant enrolment
Anticipated
1/02/2020
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
237
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment postcode(s) [1] 9539 0
4029 - Royal Brisbane Hospital
Recruitment postcode(s) [2] 9540 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 291125 0
Government body
Name [1] 291125 0
National Health and Medical Research Council
Country [1] 291125 0
Australia
Primary sponsor type
Individual
Name
Professor Paul Colditz
Address
Perinatal Research Center
The University of Queensland Centre for Clinical Research
Building 71/918
Royal Brisbane and Women's Hospital
Herston Rd
QLD 4029
Country
Australia
Secondary sponsor category [1] 289800 0
Individual
Name [1] 289800 0
Professor Roslyn Boyd
Address [1] 289800 0
Queensland Cerebral Palsy and Rehabilitation Research Centre, The University of Queensland, Level 6, Centre for Children's Health Research, 62 Graham Street, South Brisbane Qld 4101
Country [1] 289800 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292704 0
Children's Health Queensland HREC
Ethics committee address [1] 292704 0
Children’s Health Queensland, Human Research Ethics Committee Level 7, Centre for Children's Health Research, Lady Cilento Children's Hospital Precinct, 62 Graham Street, South Brisbane Qld 4101
Ethics committee country [1] 292704 0
Australia
Date submitted for ethics approval [1] 292704 0
21/01/2015
Approval date [1] 292704 0
18/02/2015
Ethics approval number [1] 292704 0
HREC/15/QRCH/7

Summary
Brief summary
The infant born very preterm (23-31 weeks gestation) is at high risk of an adverse neurodevelopmental outcome (10% cerebral palsy, 50% learning and behavioural difficulties at school age) which, if present, results in costs of billions of dollars annually in Australia.
Currently there is no accurate way to either predict the motor, cognitive and neurobehavioural outcomes in these high-risk infants or to adequately monitor structural and functional brain development. Cerebral palsy is often not diagnosed until the second year of life and cognitive and educational disability even later. As a result, early intervention to target those at most risk is not possible. However, in the several months after very preterm birth, the brain is at its maximal capacity for neuroplasticity and repair, which offers a window of opportunity for effective and safe interventions to be implemented to improve outcomes.
The purpose of this research is to learn which tests (clinical, MRI and EEG) can be used at 30 weeks and 40 weeks, to accurately identify which babies may have problems later in life, so that those babies and their families can be provided with the help they need as early as possible.
We aim to predict adverse neurodevelopment earlier and more accurately than currently possible in a cohort of 237 babies using:
(i) advanced brain MRI to determine the structural wiring diagram of the brain ('brain connectome'),
(ii) dense array EEG to establish the functional activity or electrical 'traffic' being carried on the main branches of the connectome and
(iii) structured clinical neurodevelopmental assessments to provide a cutting edge view of the state of brain development.
We aim to achieve this in a prospective longitudinal cohort study of 200 preterm infants born <31 weeks GA, and a reference group of 37 healthy term-born infants.
Infants will undergo a brain MRI at 30 and 40 weeks GA to develop our understanding of the brain structure and maturation that occurs between these time points. A combination of neurological, neuromotor and neurobehavioural assessments will be performed at 30 and 40 weeks GA to understand the relationship between brain structure and function. These data will be compared to clinical neurodevelopmental assessments at 3 months, 12 months and 24 months corrected age.
We will merge two research teams using Australia's only two MRI compatible incubators (RBWH and Monash Medical Centre) to establish the role of cutting edge approaches in clinical assessment, MRI and EEg methods to improve neurodevelopmental outcomes for preterm infants.
Trial website
Nil
Trial related presentations / publications
Nil
Public notes
Nil

Contacts
Principal investigator
Name 56654 0
Prof Paul Colditz
Address 56654 0
Perinatal Research Centre
Level 4, UQCCR
Building 71/918
Royal Brisbane and Women's Hospital
Herston
Qld 4029
Country 56654 0
Australia
Phone 56654 0
+61 7 33466014
Fax 56654 0
+61 7 33465594
Email 56654 0
[email protected]
Contact person for public queries
Name 56655 0
Paul Colditz
Address 56655 0
Perinatal Research Centre
Level 4, UQCCR
Building 71/918
Royal Brisbane and Women's Hospital
Herston
Qld 4029
Country 56655 0
Australia
Phone 56655 0
+61 7 33466014
Fax 56655 0
+61 7 33465594
Email 56655 0
[email protected]
Contact person for scientific queries
Name 56656 0
Paul Colditz
Address 56656 0
Perinatal Research Centre
Level 4, UQCCR
Building 71/918
Royal Brisbane and Women's Hospital
Herston
Qld 4029
Country 56656 0
Australia
Phone 56656 0
+61 7 33466014
Fax 56656 0
+61 7 33465594
Email 56656 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseIdentifying Emergent Mesoscopic-Macroscopic Functional Brain Network Dynamics in Infants at Term-Equivalent Age with Electric Source Neuroimaging.2021https://dx.doi.org/10.1089/brain.2020.0965
EmbaseEarly Motor Repertoire of Very Preterm Infants and Relationships with 2-Year Neurodevelopment.2022https://dx.doi.org/10.3390/jcm11071833
N.B. These documents automatically identified may not have been verified by the study sponsor.