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Trial registered on ANZCTR


Registration number
ACTRN12620000446965p
Ethics application status
Submitted, not yet approved
Date submitted
22/02/2020
Date registered
6/04/2020
Date last updated
6/04/2020
Date data sharing statement initially provided
6/04/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Childhood outcomes of fetal genomic variants: the PrenatAL Microarray (PALM) cohort
Scientific title
Childhood outcomes of fetal genomic variants: the PrenatAL Microarray (PALM) cohort
Secondary ID [1] 300197 0
None
Universal Trial Number (UTN)
Trial acronym
PALM cohort
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fetal genomic copy number variants 315753 0
Condition category
Condition code
Human Genetics and Inherited Disorders 314034 314034 0 0
Other human genetics and inherited disorders
Reproductive Health and Childbirth 314035 314035 0 0
Fetal medicine and complications of pregnancy

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
1) Women who have undergone a prenatal chromosomal microarray during pregnancy and have a live child will be asked to complete 3 parent completed questionnaires - telephone, online or hardcopy, from 15-30 minutes each, can be completed at single time, or over several months as preferred. These 3 questionnaires are all completed one time only.
2) Psychologist assessment of participants whose child is aged 2 years 7 months or older at the time of recruitment - Wechsler Preschool and Primary School Intelligence Score (WPPSI-IV). The WPPSI-IV takes approximately 30 minutes to complete. This assessment is completed one time only.
3) A one off clinical review by study paediatrician (30-45 minutes) for history and examination
No biosamples will be collected, no painful or invasive procedures for child
Intervention code [1] 316472 0
Diagnosis / Prognosis
Comparator / control treatment
Prenatal diagnosis with no clinically significant copy number variant detected on chromosomal microarray.
Control group
Active

Outcomes
Primary outcome [1] 322438 0
Intellectual functioning as assessed by the Wechsler Preschool and Primary Scale of Intelligence IV (WPPSI-IV)
Timepoint [1] 322438 0
Single assessment between the ages of 2 years 6 months to 7 years 7 months, at the discretion of researcher and participants.
Primary outcome [2] 322439 0
Adaptive and social functioning as assessed by the Vineland-II Adaptive Behavior Scale (VABS)
Timepoint [2] 322439 0
Single time point between the ages of 2 years 7 months to 7 years 7 months at the discretion of researcher and participants
Primary outcome [3] 322440 0
Maternal perceptions of child health, behaviour and development as assessed by the Brief Infant-Toddler Social and Emotional Assessment (BITSEA) questionnaire
Timepoint [3] 322440 0
Single time point when child is aged 12 months or more, at the discretion of researcher and participants
Secondary outcome [1] 378551 0
The proportion of prenatally-ascertained variants of uncertain significance that are reclassified as benign or pathogenic following reanalysis 2 or more years since initial diagnosis. This will be a composite outcome.

This will be done using the clinical standard laboratory software and resources in use during 2020-21. This includes use of platform specific software (such as Affymetrix ChAS), literature review and the DECIPHER [http://decipher.sanger. ac.uk/.] and ISCA [https://www.iscaconsortium.org/] databases. We will compare the classifications given at the time of issue of the prenatal report and the current classifications in 2020-21 according to the issuing laboratory’s protocols.
Timepoint [1] 378551 0
At least 2 years after the index prenatal diagnosis report, at the discretion of researcher.

Eligibility
Key inclusion criteria
Women resident in Victoria with a prenatal chromosomal microarray (CMA) record in the Victorian Prenatal Diagnosis Data collection (VPDD) between 2013 and 2019, and who have a live child from that pregnancy.
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Non-English speaking women
Prenatal diagnosis performed in a multiple pregnancy
No live child from the index pregnancy
Unable to give informed consent
Not resident in VIC
Unable to complete parental questionnaire

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Case control
Timing
Prospective
Statistical methods / analysis
The primary outcome is the WPPSI-IV full IQ score. The WPPSI-IV is standardized to be normally distributed with a mean of 100 and standard deviation of 15 in the general population (variance of 30). We are therefore able to perform the primary analysis as a single group comparison by t-test of the WPPSI-IV full IQ score in the children enrolled in this study with the population norm. We will also perform a between group analysis of the WPPSI-IV from the study and control cohorts. We will analyse the results from the children with variants of uncertain significance (VUS) separately from those with pathogenic copy number variants.
If 300 VUS cases are enrolled, this will yield > 95% power and 95% confidence to detect a 3 point difference (0.2SD) in mean IQ from the norm assuming that the standard deviation is 15.
Our study cohort of women are a heterogenous group with varying indications for testing. As the presence of a fetal structural abnormality is likely to be a modifier of all assessed outcomes, we will perform a stratified analysis of participants with and without this indication for prenatal diagnosis.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 15576 0
Mercy Hospital for Women - Heidelberg
Recruitment hospital [2] 15577 0
The Royal Women's Hospital - Parkville
Recruitment hospital [3] 15578 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [4] 15947 0
Sunshine Hospital - St Albans
Recruitment postcode(s) [1] 28960 0
3084 - Heidelberg
Recruitment postcode(s) [2] 28961 0
3052 - Parkville
Recruitment postcode(s) [3] 28962 0
3168 - Clayton
Recruitment postcode(s) [4] 29431 0
3021 - St Albans

Funding & Sponsors
Funding source category [1] 304629 0
Government body
Name [1] 304629 0
National Health and Medical Research Council
Address [1] 304629 0
16 Marcus Clarke St, City West, Canberra, ACT 2601
Country [1] 304629 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Murdoch Children's Research Institute
Address
50 Flemington Rd
Parkville VIC 3052
Country
Australia
Secondary sponsor category [1] 304924 0
None
Name [1] 304924 0
Address [1] 304924 0
Country [1] 304924 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 305049 0
Royal Children's Hospital HREC
Ethics committee address [1] 305049 0
50 Flemington Rd
Parkville 3052
Ethics committee country [1] 305049 0
Australia
Date submitted for ethics approval [1] 305049 0
15/02/2020
Approval date [1] 305049 0
Ethics approval number [1] 305049 0

Summary
Brief summary
To establish and follow up a Victorian cohort of children who had a prenatal diagnosis of a genomic copy number variant from 2013-2019. Children aged 12 months to 7 years will be assessed for developmental, social-emotional and health outcomes using validated, age-appropriate measures.

Objectives:
1. To compare the developmental, social-emotional and health status of children with prenatal CNVs to children with normal prenatal CMA results.
2. To measure the impact of a prenatal diagnosis of a VUS on parental perceptions of their child.
3. To determine the proportion of prenatally-ascertained VUS that are reclassified as benign or pathogenic after 2 or more years.
Trial website
Trial related presentations / publications
Public notes
Consumer input into the study participant information was kindly provided by SWAN (Syndrome Without a Name) https://swanaus.org.au/

Contacts
Principal investigator
Name 99098 0
A/Prof Lisa Hui
Address 99098 0
Reproductive Epidemiology Group
Level 5
Murdoch Children's Research Institute
Royal Children's Hospital
Flemington Road, Parkville Victoria 3052 Australia

Country 99098 0
Australia
Phone 99098 0
+61 3 9936 6766
Fax 99098 0
Email 99098 0
lisa.hui@mcri.edu.au
Contact person for public queries
Name 99099 0
Ms Joanne Kennedy
Address 99099 0
Murdoch Children's Research Institute
Reproductive Epidemiology Group
Level 5
50 Flemington Rd
Parkville 3052
Country 99099 0
Australia
Phone 99099 0
+61 3 9936 6766
Fax 99099 0
Email 99099 0
joanne.kennedy@mcri.edu.au
Contact person for scientific queries
Name 99100 0
A/Prof Lisa Hui
Address 99100 0
Reproductive Epidemiology Group
Level 5
Murdoch Children's Research Institute
Royal Children's Hospital
Flemington Road, Parkville Victoria 3052 Australia

Country 99100 0
Australia
Phone 99100 0
+61 3 9936 6766
Fax 99100 0
Email 99100 0
lisa.hui@mcri.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD sharing status undetermined. Ethics approval for IPD not yet sought.
What supporting documents are/will be available?
No other documents available
Summary results
No Results