ANZCTR - Registration

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

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]

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

Prematurity

Condition category

Condition code

Neurological

Other neurological disorders

Reproductive Health and Childbirth

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]

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]

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]

An MRI will be performed at 30 weeks and 40 weeks post menstrual ages (PMA).

Secondary outcome [1]

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]

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]

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]

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]

Neurological assessment
The Dubowitz neurological assessment assesses posture and tone, reflexes, movements and neurobehavioural responses.

Timepoint [3]

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]

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]

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]

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]

This assessment will be performed at term equivalent age in the preterm and term reference group.

Secondary outcome [6]

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]

The TIMP will be performed at term equivalent age and 3 months corrected age in the preterm group.

Secondary outcome [7]

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]

Infants in the preterm group and term reference group will undergo this medical assessment at 24 months corrected age.

Secondary outcome [8]

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]

Infants in the preterm group and term reference group will have these assessments at 24 months corrected age.

Secondary outcome [9]

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]

Infants in the preterm group and term reference group will have these assessments at 24 months corrected age.

Secondary outcome [10]

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]

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]

4029 - Royal Brisbane Hospital

Recruitment postcode(s) [2]

3168 - Clayton

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Health and Medical Research Council

Address [1]

1/16 Marcus Clarke Street, Canberra ACT 2601

Country [1]

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]

Individual

Name [1]

Professor Roslyn Boyd

Address [1]

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]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Children's Health Queensland HREC

Ethics committee address [1]

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]

Australia

Date submitted for ethics approval [1]

21/01/2015

Approval date [1]

18/02/2015

Ethics approval number [1]

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

Prof Paul Colditz

Address

Perinatal Research Centre
Level 4, UQCCR
Building 71/918
Royal Brisbane and Women's Hospital
Herston
Qld 4029

Country

Australia

Phone

+61 7 33466014

Fax

+61 7 33465594

[email protected]

Contact person for public queries

Name

Paul Colditz

Address

Perinatal Research Centre
Level 4, UQCCR
Building 71/918
Royal Brisbane and Women's Hospital
Herston
Qld 4029

Country

Australia

Phone

+61 7 33466014

Fax

+61 7 33465594

[email protected]

Contact person for scientific queries

Name

Paul Colditz

Address

Perinatal Research Centre
Level 4, UQCCR
Building 71/918
Royal Brisbane and Women's Hospital
Herston
Qld 4029

Country

Australia

Phone

+61 7 33466014

Fax

+61 7 33465594

[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

Source	Title	Year of Publication	DOI
Embase	Identifying Emergent Mesoscopic-Macroscopic Functional Brain Network Dynamics in Infants at Term-Equivalent Age with Electric Source Neuroimaging.	2021	https://dx.doi.org/10.1089/brain.2020.0965
Embase	Early Motor Repertoire of Very Preterm Infants and Relationships with 2-Year Neurodevelopment.	2022	https://dx.doi.org/10.3390/jcm11071833

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Registering a new trial?

Documents added manually

Documents added automatically