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
+44 191 282 4132
s.c.robson@ncl.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
11729
Study information
Scientific title
EACH study: Evaluation of Array Comparative genomic Hibridisation in prenatal diagnosis of foetal anomalies
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
04/01/2012, ref: 11/NE/0331
Study design
Non-randomised; Interventional; Design type: Diagnosis, Process of Care
Primary study design
Interventional
Secondary study design
Non randomised study
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
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