The first implementation of a new genetic testing service in the south-east region of the UK National Health Service (NHS) has resulted in the rapid diagnosis of fetal genetic abnormalities and early reassurance for pregnant women with normal test results, report authors of a study in this week’s issue of THE LANCET.
Pregnant women are routinely offered an invasive prenatal test for chromosome abnormalities (such as trisomy 21, associated with Down’s syndrome) if they are identified as being at high risk (eg. as a result of indications from blood or ultrasound tests, increased maternal age, or family history of chromosome abnormalities). Consequently, around 40 000 women a year in the UK NHS are given full chromosome assessment (karyotype analysis), which identifies genetic abnormalities in around 7% of fetuses. However, women have to wait for around two weeks for karyotype results, with implications for the decision to continue or terminate pregnancy. A different testing procedure, quantitative fluorescence (QF) polymerase chain reaction (PCR), has been shown to provide a rapid and effective analysis of autosomal trisomies (abnormalities characterised by the presence of an extra chromosome), which account for around 80% of all prenatal genetic abnormalities.
Caroline Ogilvie, Kathy Mann, and colleagues from Guy's and St Thomas' Hospital NHS Trust, London, UK, have developed and implemented the first QF PCR trisomy testing service in the UK NHS. They report the data for the first year of the service, in which 1148 amniotic fluid samples, 188 chorionic villus samples, and 37 fetal tissue samples were tested. All samples were also assessed by karyotype analysis. QF-PCR results were obtained and reported on 1314 (98%) of the prenatal samples; the remaining 22 (2%) were uninformative because of maternal-cell contamination. There were no misdiagnoses as confirmed by karyotype analysis. The average reporting time for the last 4 months of data collection was 1.25 working days.
Caroline Ogilvie comments: “Rapid testing of all prenatal samples for autosomal trisomies has been widely welcomed by health professionals and pregnant women. First and foremost, the fast turnaround time means that women with normal results receive prompt reassurance, and abnormalities are identified earlier, leading to better pregnancy management. Our experience indicates that the service itself is low-cost and efficient in terms of labour and consumables, with potential for high-throughput of samples involving minimum extra investment in staff time. Logically, therefore, all prenatal samples from a large region could be tested at a single centre. A nationwide discussion concerning the provision of QF-PCR rapid trisomy testing for all at-risk pregnancies and the identification of appropriate testing centres is now urgently required.”
In an accompanying Commentary (p 1030) Matteo Adinolfi from University College London, UK, states: “…Mann and colleagues suggest that QF-PCR should always be followed by conventional cytogenetic tests until such time that there are sufficient data to establish that full karyotype can be reserved for special cases. This view was supported by the majority of people who attended a special meeting of the British Society for Human Genetics in York on Sept 10, 2001, at which votes on this issue were cast. However, since numerical disorders of chromosomes 21, 18, 13, X, and Y are the commonest causes of aneuploidies, with the use of multiplexes with several markers for each chromosome, only a small percentage of affected fetuses may not be diagnosed. Out of every 100 mothers aged over 36 years who are investigated, only about 2-3% are expected to have fetuses with chromosome disorders; of these nearly 98% will have chromosome abnormalities that can be diagnosed by QF-PCR.”
Contact: Dr Caroline Ogilvie, c/o Kate Oake, Communications Department, Guy's and St. Thomas' Hospital, Trust, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK; T) 44-20-7922-8120; F) 44-20-7633-0347; E) kate.oake@gstt.sthames.nhs.uk
Professor Matteo Adinolfi, Galton Laboratory and Department of Obstetrics and Gynaecology, University College London, ,London NW1 2HE, UK; F) 44-20-7387-3496; E) matteo@galton.ucl.ac.uk
Journal
The Lancet