Condition category
Pregnancy and Childbirth
Date applied
24/06/2013
Date assigned
24/06/2013
Last edited
24/06/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Stephen Robson

ORCID ID

Contact details

Institute of Cellular Medicine
Claremont Road
Newcastle Upon Tyne
NE1 7RU
United Kingdom
s.c.robson@ncl.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

11729

Study information

Scientific title

Acronym

EACH

Study hypothesis

All pregnant women are offered ultrasound scans to detect fetal abnormalities, many of which are due to chromosome imbalances. Babies with chromosomal abnormalities have complex problems, usually resulting in developmental disability. Parents faced with this knowledge have to make difficult choices. Testing for chromosome problems involves an 'invasive' procedure (e.g. amniocentesis) which can cause miscarriage. Major chromosomal abnormalities can be detected quickly by a technique called PCR. Less common imbalances require the baby's cells to be grown (karyotyping) which is slow, labour intensive and only detects large (microscopic) imbalances. Array comparative genomic hybridisation (CGH) is a new molecular test that can rapidly detect smaller (sub-microscopic) imbalances. In children with developmental disability, array CGH has detected imbalances in 10% of cases. Limited experience of array CGH on fetal samples suggests it may detect 5-10% more chromosome imbalances than karyotyping. However performing and interpreting arrays is complex. The size of imbalances that can be detected depends on array design and not all imbalances cause problems some are inherited from a parent. Understanding the significance of a newly detected imbalance requires further tests on fetal and parental DNA. This study will recruit 1500 fetuses undergoing karyotyping because of a scan abnormality. Arrays will be performed and interpreted in 7 Genetics laboratories according to agreed guidelines. Clinicians/parents will be informed of large imbalances detected by array CGH but only where the outcome of such imbalance is known (based on the medical literature). In addition to determining if array CGH detects harmful chromosomal imbalances more often, more quickly and at less cost than karyotyping, the study will find out what parents and health professionals think of the new technology.

Ethics approval

11/NE/0331; First MREC approval date 04/01/2012

Study design

Non-randomised; Interventional; Design type: Diagnosis, Process of Care

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Other

Trial type

Diagnostic

Patient information sheet

Not provided at time of registration

Condition

Topic: Genetics Research and Congenital Disorders, Reproductive Health and Childb; Subtopic: Genetics Research and Congenital Disorders (all subtopics), Reproductive Health and Childb (all Subtopics); Disease: Genetics Research and Congenital Disorders, Reproductive Health & Childbirth

Intervention

Diagnosis & management of care, comparision of karyotyping test with Array CGH; Study Entry: Registration only

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

Detection of pathogenic Copy number variants (CNVs); Timepoint(s): detection of pathogenic CNVs and chromosomal imbalances by array CGH and/or karyotyping

Secondary outcome measures

Not provided at time of registration

Overall trial start date

01/05/2012

Overall trial end date

01/09/2014

Reason abandoned

Eligibility

Participant inclusion criteria

1. Fetuses (singleton or dichorionic twin) undergoing conventional karyotyping by amniocentesis or Chorionic villus sampling (CVS) for clinical indications with:
1.1. one or more structural anomalies identified on an ultrasound scan* or
1.2. an isolated nuchal translucency (NT) =3.5 mm identified at the 11+2 to 14+1 wk ultrasound screening scan.
* Includes fetal growth restriction (defined as abdominal circumference >2 standard deviations below the mean for gestational age)
2. Only those fetuses with a normal qfPCR result, fetuses with a sex chromosome aneuploidy that is unlikely to explain the ultrasound anomaly e.g. XXX, XXY and XYY will undergo array CGH. This group has the highest risk of unbalanced chromosomal rearrangements [25] and recent array CGH studies suggest that they have the highest risk of pathogenic CNVs.

Cases will be recruited from selected Fetal Medicine Units (FMUs) in England and Wales.
Target Gender: Male & Female; Upper Age Limit 65 years ; Lower Age Limit 16 years

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 3000; UK Sample Size: 3000; Description: 1500 Maternal Consents 1500 Paternal Consents

Participant exclusion criteria

Exclusion criteria include cases where:
1. Single or multiple ultrasound variants (or markers). In this context fetal cerebral ventriculomegaly (atrium = 10 mm) is classed as a structural anomaly not a normal variant.
2. Structural anomaly identified outside the time frame specified in the inclusion criteria
3. Participant declines to take part in the study
4. Participant is under the age of 16 years
5. Participant is unable to read English and understand the study information leaflet
6. Those fetuses with Triploidy, the common aneuploidies (Trisomy 13, 18, 21), or Monosomy X will be excluded from the study

Recruitment start date

01/05/2012

Recruitment end date

01/09/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Institute of Cellular Medicine
Newcastle Upon Tyne
NE1 7RU
United Kingdom

Sponsor information

Organisation

Newcastle upon Tyne Hospitals NHS Foundation Trust (UK)

Sponsor details

Northern Centre for Cancer Care
Freeman Road
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

NIHR Evaluation, Trials and Studies Coordinating Centre; Grant Codes: 10/06/03

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes