ANZCTR - Registration

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

ACTRN12620000019909

Ethics application status

Approved

Date submitted

16/12/2019

Date registered

14/01/2020

Date last updated

28/04/2024

Date data sharing statement initially provided

14/01/2020

Date results information initially provided

19/05/2023

Type of registration

Prospectively registered

Titles & IDs

Public title

Supporting communication between parents and babies from birth: The Communicating and Understanding your Baby (CUB) study

Scientific title

A randomised-controlled trial of a parent-mediated intervention for optimising social and communication development of newborns at increased familial risk of autism spectrum disorders

Secondary ID [1]

Nil

Universal Trial Number (UTN)

U1111-1244-6011

Trial acronym

CUB Study

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Autism Spectrum Disorder

Condition category

Condition code

Mental Health

Autistic spectrum disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

The Communicating and Understanding your Baby (CUB) intervention was developed by the study team using existing knowledge of typical and atypical social communication development, human and non-human primate studies of early life predictors of later social communication skills, and evidence based strategies for promoting early social engagement in the infant. The theoretical premise of the CUB program is that a responsive communication partner who is sensitive to a baby’s developmental stage and abilities provides the optimal environment to nurture the social and communication development of the baby. Similar to the iBASIS-VIPP therapy framework, CUB employs a ‘carer-mediated’ delivery mechanism and the use of video feedback to coach parents to understand the social and communication cues of their baby, and to respond in ways that have been shown to promote further communication.

The therapy program involves one antenatal session in the third pregnancy trimester, and 10 postnatal sessions from when the infant is 4 weeks to 8 months of age. The antenatal session is a single psychoeducation group seminar (3 hours in length), hosted in a community clinic, with an ideal group size of 4 - 6 sets of parents. The group is led by a facilitator, who introduces the therapy rationale and requirements, demonstrates the range of a newborn’s skills and capacities, illustrates how influential parents are to babies’ social and communication development; and prepares parents to learn their baby’s communication behaviours from birth. A range of videos are used to highlight these key points.

The postnatal sessions commence when the infant is 4 weeks of age, and there are 7 core sessions up to when the baby is 5 months of age. Each session is approximately 1 hour in length, and will be delivered by either child health nurses or speech pathologists. The sessions commence at fortnightly intervals (4 weeks to 10 weeks) but then progress to monthly intervals (3 months to 5 months). Each core session focuses on a single theme, based on the developmental stage of the baby. The first core session involves the delivery of the Newborn Behavioural Observation (NBO) system, a structured set of activities designed to help the clinician and parent to observe the baby’s unique behavioural capacities. The NBO consists of 18 activities designed to direct the caregiver’s attention toward the infant’s behaviours. The items include observations of the infant's capacity to habituate to light and sound, the quality of motor tone and activity level, the capacity for self regulation, and the infant's visual, auditory, and social-interactive capacities. There is currently low-quality evidence that the NBO improves sensitive and contingent responding of parents during infant interactions. Core sessions 2 to 7 all follow a similar structure, consisting of an initial review of the baby’s development since the previous session, the filming of a video of the parent and baby interacting, review of the video with the parent, and a summary discussion of the session.

The video recordings of parent-baby interactions are built around everyday activities for newborns (e.g., feeding, settling, nappy changes and dressing) and infants (singing nursery rhymes, playing with toys, and sharing books). The program allows a high degree of flexibility when identifying filming contexts, particularly in the early postnatal sessions. The filming context is jointly agreed by the parent and clinician, and appropriate to the baby’s state of alertness and the baby’s needs at the time. The clinician video records the parent interacting with their baby. During filming, the clinician observes the dyad and, being mindful of the session theme, identifies key messages to be communicated during the video review. The clinician then watches the video through themself, prior to reviewing the video with parents, while the parent attends to the baby. The parent and clinician then review the video in its entirety, with the clinician pausing the video to highlight key moments of the interaction. A range of video feedback techniques are used by the clinician to help the parent reflect on his/her interactions with the baby, the responses of the baby to the interaction, and how they might tailor their own behaviours to optimise the interactions.

Following the completion of the core sessions when the baby is 5 months of age, there are three focused sessions at monthly intervals which serve to reinforce key interaction strategies important for the individual dyad, as well as target any areas of infant social communication development where there may be an identified concern or difficulty. The sessions are structured similarly to the core sessions.

Trial therapists will complete a four-day training course, delivered by the developers of the intervention, which will include theoretical background, clinical observations, and practical opportunities. Trial therapists will receive fortnightly supervision by the lead clinician for the trial (MR), who will also coordinate across-site therapist meetings. All interventions sessions will be videotaped, and a random selection of 5% of videotapes will be independently rated for fidelity using a scale developed for this trial. Compliance in the ‘treatment’ condition will be monitored via a case report form completed by the clinician at each therapy session.

Intervention code [1]

Behaviour

Intervention code [2]

Treatment: Other

Comparator / control treatment

Participants in the control group will not receive any intervention by the trial therapists. Given that developmental interventions for newborns is not current standard practice in the locations of the two study sites (Perth and Melbourne, Australia), we anticipate that the majority of clinical contact for this group will be the standard developmental monitoring carried out by community nursing services in these areas. All contact with clinical services will be recorded.

Control group

Active

Outcomes

Primary outcome [1]

Manchester-Assessment of Caregiver-infant Interaction (MACI) - Caregiver Non-directiveness subscale

Method of assessment: Parent-Infant free play interaction sample. Scored from video by researcher with demonstrated high level reliability, who is blind to treatment group.

Timepoint [1]

Immediate treatment endpoint (when infant is 9 months of age)

Primary outcome [2]

Autism Diagnostic Observation Scale (2nd edition) - Total score, and Social Affect and Restricted and Repetitive Behaviours subscale

Method of assessment: Researcher-administered semi-structured play assessment with infant. Scored by a researcher with demonstrated high level reliability, who is blind to treatment group.

Timepoint [2]

Follow-up assessment (when infant is 24 months of age)

Secondary outcome [1]

Manchester-Assessment of Caregiver-infant Interaction (MACI) - Caregiver sensitive responsiveness, Infant Attentiveness, and Infant Positive Affect subscales

Method of assessment: Parent-Infant free play interaction sample. Scored from video by researcher with demonstrated high level reliability, who is blind to treatment group.

Timepoint [1]

Immediate treatment endpoint (when infant is 9 months of age)

Secondary outcome [2]

Mullen Scales of Early Learning - Visual Reception, Fine Motor, and Gross motor subscales.

Method of Assessment: Researcher-administered standardised developmental assessment. Scored live by researcher administering the assessment.

Timepoint [2]

Immediate treatment endpoint (when infant is 9 months of age)

Secondary outcome [3]

Preschool Language Scale – 5th edition - Auditory Comprehension and Expressive Communication subscales.

Method of assessment: A standardised, play-based assessment of language skills, which is administered by researchers and scored live.

Timepoint [3]

Immediate treatment endpoint (when infant is 9 months of age)

Secondary outcome [4]

Infant Behavior Questionnaire-Revised - Surgency, Negative Affect, and Effortful Control subscales

Method of assessment: Informant-report questionnaires measuring broad features of infant behaviour across various dimensions of temperament. Scored by researcher.

Timepoint [4]

Immediate treatment endpoint (when infant is 9 months of age)

Secondary outcome [5]

Ages and Stages Questionnaire: Social Emotional (2nd edition), 12 month version - Total score

Method of assessment: Parent-report questionnaire of infant social and emotional development, scored by researcher.

Timepoint [5]

Immediate treatment endpoint (when infant is 9 months of age)

Secondary outcome [6]

Ages and Stages Questionnaire (3rd edition), 9 month version - Total Score, and the Communication, Gross Motor, Fine Motor, Problem Solving and Personal Social subscales.

Method of assessment: Parent-report questionnaire of infant development, scored by researcher.

Timepoint [6]

Immediate treatment endpoint (when infant is 9 months of age)

Secondary outcome [7]

MacArthur-Bates Communicative Development Inventory: Words and Gestures Form - Expressive Vocabulary Count, Receptive Vocabulary Count, and a Total Gestures score.

Method of assessment: Parent-report questionnaire, scored by researcher.

Timepoint [7]

Immediate treatment endpoint (when infant is 9 months of age)

Secondary outcome [8]

Communication and Symbolic Behaviour Scales Developmental Profile (Infant Toddler Checklist) - Total Score, and Social, Speech and Symbolic composites.

Method of assessment: Parent-report questionnaire of early social and communication skills, scored by researcher

Timepoint [8]

Immediate treatment endpoint (when infant is 9 months of age)

Secondary outcome [9]

Vineland Adaptive Behavior Scales (3rd edition) - Communication and Socialization subscales.

Method of assessment: Parent-report questionnaire of infant adaptive functioning, scored by researcher.

Timepoint [9]

Immediate treatment endpoint (when infant is 9 months of age)

Secondary outcome [10]

Diamond Maternal Reflective Functioning Scale - Total score

Method of assessment: Parent-report questionnaire of maternal reflective functioning, scored by researcher.

Timepoint [10]

Immediate treatment endpoint (when infant is 9 months of age)

Secondary outcome [11]

Parenting Sense of Competence (PSOC) - Satisfaction, Efficacy and Interest subscales

Method of assessment: Parent-report questionnaire, of parental self efficacy, scored by researcher.

Timepoint [11]

Immediate treatment endpoint (when infant is 9 months of age)

Secondary outcome [12]

Perceived Maternal Parental Self-Efficacy (PMP S-E)

Method of assessment: Parent-report questionnaire, of parental self efficacy, scored by researcher.

Timepoint [12]

Immediate treatment endpoint (when infant is 9 months of age)

Secondary outcome [13]

Manchester-Assessment of Caregiver-infant Interaction (MACI) - Caregiver non-directiveness, Caregiver sensitive responsiveness, Infant Attentiveness, and Infant Positive Affect subscales

Method of assessment: Parent-Infant free play interaction sample. Scored from video by researcher with demonstrated high level reliability, who is blind to treatment group.

Timepoint [13]

Follow-up assessment (when infant is 24 months of age)

Secondary outcome [14]

Mullen Scales of Early Learning - Visual Reception, Fine Motor, and Gross motor subscales.

Method of assessment: Researcher-administered standardised developmental assessment. Scored live by researcher administering the assessment.

Timepoint [14]

Follow-up assessment (when infant is 24 months of age)

Secondary outcome [15]

Timepoint [15]

Follow-up assessment (when infant is 24 months of age)

Secondary outcome [16]

Early Childhood Behavior Questionnaire (Revised)- Surgency, Negative Affect, and Effortful Control subscales

Method of assessment: Informant-report questionnaires measuring broad features of infant behaviour across various dimensions of temperament. Scored by researcher.

Timepoint [16]

Follow-up assessment (when infant is 24 months of age)

Secondary outcome [17]

Ages and Stages Questionnaire: Social Emotional (2nd edition), 24 month version - Total score

Method of Assessment: Parent-report questionnaire of infant social and emotional development, scored by researcher.

Timepoint [17]

Follow-up assessment (when infant is 24 months of age)

Secondary outcome [18]

Ages and Stages Questionnaire (3rd edition), 24 month version - Total Score, and the Communication, Gross Motor, Fine Motor, Problem Solving and Personal Social subscales.

Method of Assessment: Parent-report questionnaire of infant development, scored by researcher.

Timepoint [18]

Follow-up assessment (when infant is 24 months of age)

Secondary outcome [19]

MacArthur-Bates Communicative Development Inventory: Words and Gestures Form - Expressive Vocabulary Count, Receptive Vocabulary Count, and a Total Gestures score.

Method of Assessment: Parent-report questionnaire, scored by researcher.

Timepoint [19]

Follow-up assessment (when infant is 24 months of age)

Secondary outcome [20]

Communication and Symbolic Behaviour Scales Developmental Profile (Infant Toddler Checklist) - Total Score, and Social, Speech and Symbolic composites.

Method of Assessment: Parent-report questionnaire of early social and communication skills, scored by researcher

Timepoint [20]

Follow-up assessment (when infant is 24 months of age)

Secondary outcome [21]

Vineland Adaptive Behavior Scales (3rd edition) - Communication and Socialization subscales.

Method of assessment: Parent-report questionnaire of infant adaptive functioning, scored by researcher.

Timepoint [21]

Follow-up assessment (when infant is 24 months of age)

Secondary outcome [22]

Diamond Maternal Reflective Functioning Scale - Total score

Method of Assessment: Parent-report questionnaire of maternal reflective functioning, scored by researcher.

Timepoint [22]

Follow-up assessment (when infant is 24 months of age)

Secondary outcome [23]

Parenting Sense of Competence (PSOC) - Satisfaction, Efficacy and Interest subscales

Method of assessment: Parent-report questionnaire, of parental self efficacy, scored by researcher.

Timepoint [23]

Follow-up assessment (when infant is 24 months of age)

Secondary outcome [24]

Perceived Maternal Parental Self-Efficacy (PMP S-E)

Method of assessment: Parent-report questionnaire, of parental self efficacy, scored by researcher.

Timepoint [24]

Follow-up assessment (when infant is 24 months of age)

Secondary outcome [25]

Autism Observation Scale for Infants

Method of assessment: Researcher-administered semi-structured play assessment with infant. Scored by a researcher with demonstrated high level reliability, who is blind to treatment group.

Timepoint [25]

Immediate treatment endpoint assessment (when infant is 24 months of age)

Eligibility

Key inclusion criteria

Inclusion criteria for the trial are:
(a) Pregnant woman (eligible inclusion answer = Yes)
(b) Carrying a singleton pregnancy (eligible inclusion answer = Yes);
(c) Carrying a foetus with a relatively ‘high’ or ‘moderate’ likelihood of developing ASD based on the following criteria (eligible answer = Yes):
• High likelihood: The foetus has a biological mother, biological father, or full sibling with a clinical diagnosis of ASD. The diagnosis of the ‘proband’ (index case with the autism diagnosis) is confirmed by a copy of the diagnostic report.
• Moderate likelihood: The foetus has a biological mother, biological father or full sibling with ADHD or intellectual disability (with no known cause), OR a biological grandparent, biological uncle/aunt, half sibling with autism. The diagnosis of the ‘proband’ (index case with the autism, ADHD or intellectual disability diagnosis) is confirmed by a copy of the diagnostic report.
(d) To the best of their knowledge, the primary carer and offspring are intending to remain in the Perth or Melbourne metropolitan area for the next two and a half years (eligible inclusion answer = Yes); and
(e) English is the main language spoken at home (eligible inclusion answer = Yes).

Minimum age

No limit

Maximum age

No limit

Sex

Females

Can healthy volunteers participate?

Key exclusion criteria

Exclusion criteria for the trial are:
(a) The foetus/offspring has been diagnosed with a serious medical condition requiring ongoing care, as determined by the study team (exclusion answer = yes).
(b) The proband has a known genetic mutation associated with their clinical diagnosis (e.g., tuberous sclerosis complex, PTEN mutation etc.) that isn’t typically inherited (exclusion answer = yes).
(c) The primary carer has a serious mental or physical health condition requiring ongoing care, as determined by the study team (exclusion answer = yes).

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Eligibility interviews will be conducted by a research staff member, prior to treatment allocation. Once an individual is deemed eligible to take part, and have provided consent to do so, the participant's details will be forwarded to the project manager, who will randomise the family into treatment or control groups (based on computer algorithm).

The trial therapists will be housed separately to study investigators and research assistants conducting the assessments sessions, and will also attend separate meetings. The assessment sessions will be conducted by blinded assessors, and be structured so as to avoid inadvertent unblinding of the treatment group to the assessors. The assessments will take place in a different setting, and using different materials to the therapy sessions, which will minimise the risk of a familiarity effect for those children in the treatment group.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Randomisation, via minimisation, will be conducted separately for the Perth and Melbourne sites. Randomisation of individual mothers will be completed in batches every 4 to 6 weeks; the number of mothers attending the antenatal (intervention) session will be dependent on the number of mothers enrolled within the batch and the outcome of the minimisation allocation (groups will likely range from n = 2 to n = 6). Allocation of participants to the Treatment or Control group will be by minimisation, stratified by the number of the mother’s previous children (0 vs 1 or more), family ‘liability’ level (’high liability’ vs ‘moderate liability’), and social disadvantage (greater than or equal to the 40th percentile vs less than the 40th percentile of the Index of Relative Socio-economic Disadvantage, based on postcode).

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

The primary outcome variable at immediate treatment endpoint (9-month) assessment is the non-directiveness subscale of the Manchester Assessment of Caregiver-Child Interaction (MACI). Linear regression will be used to model the effect of the intervention (independent variable: treatment vs control) on this outcome, with adjustment for the number of the mother’s previous children (0 vs 1 or more), family ‘liability’ level (’high liability’ vs ‘moderate liability’), social disadvantage (greater than or equal to the 40th percentile vs less than the 40th percentile of the Index of Relative Socio-economic Disadvantage, based on postcode), offspring chronological age at assessment (weeks), and the group size for participants that were enrolled into the treatment arm of the trial. Further adjustment variables may include sex of the child, maternal age, and other variables identified to be unbalanced across groups during the analysis. The beta coefficient and 95% confidence interval for the intervention term will be reported. If model fit is deemed poor or the assumptions of the model are violated, an ordinal regression model with the same adjustment variables will be explored; here, the odds ratio and 95% confidence interval for the intervention term will be reported.

Secondary analysis will include examining three other MACI subscales (caregiver sensitive responsiveness, infant attentiveness, and infant positive affect) together using a MANCOVA approach, with the intervention (treatment vs control) as the independent variable of interest and adjustments made for the number of the mother’s previous children, the degree of familial liability for autism, socioeconomic status, infant chronological age (weeks), and group size. If the MANCOVA test suggests between group difference exist, models for individual subscales may be pursued. Secondary outcomes that will also be analysed include Autism Observation Scale for Infants, Mullen Scales of Early Learning, Preschool Language Scale – 5th edition, Infant Behavior Questionnaire-Revised, MacArthur-Bates Communicative Development Inventory: Words and Gestures Form, Ages and Stages Questionnaire – 3rd edition, Ages and Stages Questionnaire: Social Emotional – 2nd edition, Communication and Symbolic Behaviour Scales Developmental Profile – Infant Toddler, Vineland Adaptive Behavior Scales – 3rd edition, Diamond Maternal Reflective Functioning Scale, Parenting Sense of Competence scale, and Perceived Maternal Parental Self-Efficacy using similar statistical methodologies to those outlined above, as appropriate.

The primary outcome variable at the follow-up (24-month assessment) is the Autism Diagnostic Observation Schedule - 2nd edition (ADOS-2). The ADOS-2 is a semi-structured, standardised assessment of communication, social interaction, play, and restricted and repetitive behaviours. Linear regression will be used to model the effect of the intervention (treatment vs control, the independent variable of interest) on ADOS-2; the model will be adjusted for the number of the mother’s previous children, the degree of familial liability for autism, socioeconomic status, and infant chronological age (weeks), and group size. The beta coefficient and 95% confidence interval for the intervention term will be reported.

Secondary outcomes that will also be analysed include Manchester Assessment of Caregiver-infant Interaction, Mullen Scales of Early Learning, Preschool Language Scale – 5th edition, Early Childhood Behavior Questionnaire-Revised, MacArthur-Bates Communicative Development Inventory: Words and Gestures Form, Ages and Stages Questionnaire – 3rd edition, Ages and Stages Questionnaire: Social Emotional – 2nd edition, Communication and Symbolic Behaviour Scales Developmental Profile – Infant Toddler, Vineland Adaptive Behavior Scales – 3rd edition, Diamond Maternal Reflective Functioning Scale, Parenting Sense of Competence scale, and Perceived Maternal Parental Self-Efficacy using similar statistical methodologies to those outlined above, as appropriate.

Recruitment

Recruitment status

Active, not recruiting

Date of first participant enrolment

Anticipated

20/01/2020

Actual

3/02/2020

Date of last participant enrolment

Anticipated

31/12/2022

Actual

14/03/2023

Date of last data collection

Anticipated

31/03/2025

Actual

Sample size

Target

150

Accrual to date

Final

130

Recruitment in Australia

Recruitment state(s)

WA,VIC

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Health and Medical Research Council

Address [1]

National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601

Country [1]

Australia

Primary sponsor type

Other

Name

Telethon Kids Institute

Address

Northern Entrance
Perth Children's Hospital
15 Hospital Ave
Nedlands WA 6009

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Ramsay Health Care WA | SA Human Research Ethics Committee (RHC WA | SA HREC)

Ethics committee address [1]

Research Ethics Dept
c/o CGU Building
PO Box 242
Joondalup WA 6919
http://www.ramsayhealth.com.au/Research/Research-Ethics

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

16/09/2019

Approval date [1]

12/12/2019

Ethics approval number [1]

1941

Summary

Brief summary

Parent-child interactions comprise one of the most profoundly influential experiences in a child’s development, and the quality of these interactions during early infancy in particular can have a lasting impact on neurodevelopment. This randomised controlled trial is a two-arm (Treatment vs Control), single blind (assessor) randomised controlled trial to test the efficacy of a new intervention designed to promote parent sensitivity and responsiveness to their newborns with a family liability for Autism Spectrum Disorder. We hypothesise that the newborn intervention will decrease parental directiveness and increase parental sensitivity during parent-infant interactions when measured when the baby is 9 months of age, and decreases the severity of autistic symptoms, and improve a range of child development outcomes, when measured when the baby is 2 years of age.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Andrew Whitehouse

Address

Telethon Kids Institute
Northern Entrance
Perth Children's Hospital
15 Hospital Ave
Nedlands WA 6009

Country

Australia

Phone

+61 08 6319 1000

Fax

[email protected]

Contact person for public queries

Name

Dr Jess Reynolds

Address

Telethon Kids Institute
Northern Entrance
Perth Children's Hospital
15 Hospital Ave
Nedlands WA 6009

Country

Australia

Phone

+61 8 6319 1266

Fax

[email protected]

Contact person for scientific queries

Name

Dr Jess Reynolds

Address

Telethon Kids Institute
Northern Entrance
Perth Children's Hospital
15 Hospital Ave
Nedlands WA 6009

Country

Australia

Phone

+61 8 6319 1266

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and Supplementary Material).

When will data be available (start and end dates)?

Immediately following publication; no end date

Available to whom?

Investigators whose proposed use of the data has been approved by an independent ethical review committee identified for the following purposes:
*Replication studies
*Individual participant data meta-analysis

Available for what types of analyses?

For replication studies and individual participant data meta-analysis

How or where can data be obtained?

Proposals should be directed to the Principal Investigator to gain access ([email protected]); data requestors will be required to sign a data access agreement.

What supporting documents are/will be available?

Doc. No.	Type	Other Details
6184	Study protocol	This will be submitted for publication (as an appe... [More Details]
6185	Statistical analysis plan	This will be submitted for publication (as an appe... [More Details]
6186	Informed consent form	Once the trial website is complete, the Informed C... [More Details]

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

Documents added manually

Documents added automatically