EACH study: Evaluation of Array Comparative genomic Hibridisation in prenatal diagnosis of foetal anomalies

ISRCTN	ISRCTN01058191
DOI	https://doi.org/10.1186/ISRCTN01058191
Secondary identifying numbers	11729

Submission date: 24/06/2013
Registration date: 24/06/2013
Last edited: 20/10/2017

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Pregnancy and Childbirth

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Stephen Robson
Scientific

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

Phone	+44 (0)191 282 4132
Email	s.c.robson@ncl.ac.uk

Study information

Study design	Non-randomised; Interventional; Design type: Diagnosis, Process of Care
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Other
Study type	Diagnostic
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	EACH study: Evaluation of Array Comparative genomic Hibridisation in prenatal diagnosis of foetal anomalies
Study acronym	EACH
Study objectives	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(s)	04/01/2012, ref: 11/NE/0331
Health condition(s) or problem(s) studied	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
Primary outcome measure	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 study start date	01/05/2012
Completion date	01/09/2014

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	Planned Sample Size: 3000; UK Sample Size: 3000; Description: 1500 Maternal Consents 1500 Paternal Consents
Key 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
Key exclusion criteria	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
Date of first enrolment	01/05/2012
Date of final enrolment	01/09/2014

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Institute of Cellular Medicine

Newcastle Upon Tyne
NE1 7RU
United Kingdom

Sponsor information

Newcastle upon Tyne Hospitals NHS Foundation Trust (UK)
Hospital/treatment centre

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

"ROR"	https://ror.org/05p40t847

Funders

Funder type

Government

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

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/02/2017		Yes	No

Editorial Notes

20/10/2017: Publication reference added.