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EACH study: Evaluation of Array Comparative genomic Hybridisation and non-invasive prenatal diagnosis using cell free fetal DNA in prenatal diagnosis of fetal anomalies

Funder: UK Research and InnovationProject code: MC_PC_12031
Funded under: MRC Funder Contribution: 1,506,200 GBP

EACH study: Evaluation of Array Comparative genomic Hybridisation and non-invasive prenatal diagnosis using cell free fetal DNA in prenatal diagnosis of fetal anomalies

Description

All pregnant women are offered scans at 12 and 20 weeks of pregnancy to confirm the dates and detect fetal abnormalities, many of which are due to chromosome imbalances (i.e. gains or losses of part or all of a chromosome). Babies with chromosomal abnormalities have complex problems, often associated with developmental disability. Parents faced with this knowledge have to make difficult choices; some opt not to continue the pregnancy. Testing for chromosome problems involves an 'invasive' procedure (e.g. amniocentesis) which can sometimes cause a miscarriage. Major chromosomal abnormalities (e.g. Down's syndrome) can be detected using a technique called PCR (Polymerase Chain Reaction). Smaller and less common imbalances require the baby's cells to be grown and examined. This procedure (karyotyping) is slow, labour intensive and only detects large imbalances that can be seen down the microscope. Array comparative genomic hybridisation (aCGH) is a new molecular test that can rapidly detect smaller (sub-microscopic) imbalances. When used in children with undiagnosed developmental disability it has detected imbalances (not detected by karyotyping) in 10% of cases. There is very little experience of using aCGH on fetal samples but small studies suggest it may detect 5-10% more imbalances than karyotyping. However, performing and interpreting array CGH is complex as not all imbalances cause problems - some are inherited from a parent and others appear not to have any adverse effect, so more tests are needed to understand the significance of a newly detected imbalance. We now know that the baby’s genetic material (DNA) is present in the mother’s blood and research has shown that this DNA can be used to diagnose Down’s syndrome. This means that we may be able to detect babies with this condition non-invasively by taking a sample of the mother’s blood, thereby avoiding the miscarriage risk associated with invasive testing (NIPD). This study will recruit 1500 fetuses being karyotyped because of an abnormality detected on a scan. NIPD will be performed using the mother’s blood sample. Arrays will be performed on villi and amniotic fluid cells in 6 genetics laboratories using agreed guidelines. In addition to the standard karyotype information, clinicians/parents will be informed of imbalances detected by aCGH where the significance is known (based on similar cases reported in the medical literature). We need costs for the arrays and the scientists to perform them. NHS costs are requested for midwives to recruit parents. In addition, we will find out what parents, health professionals and commissioners think of the new technology. We will make recommendations as to whether array CGH should replace fetal karyotyping.

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