ffDNA as a method of screening for Down’s syndrome is much more accurate than the current NHS screening tests
‘vanishing’ twin. This occurs when a demised trisomic twin is found alongside a live twin with normal chromosomes7
fetal DNA are very low in the maternal blood, so the condition is masked by maternal DNA1,4,6
. False negatives are extremely rare but can also still occur. This happens when the levels of . Overall, most
studies investigating ffDNA as a method of screening for Down’s syndrome, find a sensitivity and specificity close to 100%. It is therefore much more accurate than the current NHS screening tests (table 2). In twin pregnancies ffDNA doubles, therefore in monochorionic pregnancies ffDNA will be more effective than in singletons as the twins are genetically identical. In dichorionic pregnancies, where twins can be genetically different, a maternal blood sample would need fetal DNA levels of more than 8% in order to be processed as each twin would then contribute 4% of the total DNA1
.
Current status of ffDNA (UK and worldwide) ffDNA has been used for Down’s syndrome screening in the United States since 2011. In 2012, the American College of Obstetricians and Gynecologists advised it should be used only for high risk women. This included women over the age of 40, those who had had a previously affected fetus, or those who had a positive screening test or a known translocation in either parent1,4,6
. In 2013 the International Society for Prenatal
Diagnosis agreed it could be used for women at high risk of trisomy 21, 18 or 13 using the same criteria to define high risk patients1,6
. At that time, evidence about the accuracy of the test in low risk women did not
exist. The high sensitivities are now known to be the same in both high risk and low risk groups making it an excellent population screening tool6,9
. In the UK ffDNA is already used for fetal blood grouping in cases of rhesus alloimmunisation1 . However,
ffDNA testing for Down’s syndrome is not yet available within the NHS. It can be obtained privately at between £400-£8003
. A significant number of women are already accessing this test privately, so
healthcare professionals need to be aware of the issues surrounding it. Currently, tests are sent to the USA for processing as the UK does not yet have its own laboratory. With increasing public awareness through the media and social networking sites such as Mumsnet, the demand for this technology is likely to increase10
than for the current screening system3
. Limited evidence obtained within the UK suggests that uptake for ffDNA would be higher . The need for national policies on the use of this new screening tool
will be required, particularly when it starts to impact on or replace the national screening program already in place. These policies should be evidence based and driven by scientific research and not influenced purely by public demand.
-23-
Training impact As the numbers of amniocentesis and CVS decrease there would be fewer centres needed to perform these invasive tests and therefore fewer training opportunities for fetal medicine trainees to become skilled in these procedures. Ultrasonographers may also become deskilled at measuring nuchal thickness, which may reduce the detection of chromosomal abnormalities other than Down’s syndrome. New sonographers would have fewer opportunities to learn this skill if the nuchal thickness is no longer part of the national screening program, although in principle the training could still include nuchal thickness assessment. On the positive side, the first trimester scan will take less time after removing the nuchal element and this may enable
Service impact With the introduction of any new service comes a huge shift in the allocation of resources, including finance, technology, and people skilled to provide the service11
. Currently, there are two schools of thought as to
how ffDNA could be included in the NHS screening program. The first involves adding ffDNA into the screening program as it stands. All women would be offered the combined screening and those found to have a risk higher than 1 in 150 would then be offered ffDNA. If that test came back positive then the woman would be offered invasive testing. This would decrease the number of invasive tests, which may be enough to cover the costs of the more expensive ffDNA test. Assuming that the current threshold of 1 in 150 was used and that the price of ffDNA was £500 per patient this ‘contingent’ screening program would cost roughly the same as the current program3 more than £750 per pregnancy then ffDNA would not be cost effective to implement3 The second option would be to use ffDNA as a first line screening tool instead of the combined
. If the test cost .
screening in place now. The money currently spent on Down’s screening could then be put towards implementing the new system. Ultrasound in the first trimester would still be needed to confirm location, multiplicity, cardiac activity and to date the pregnancy5
, but the nuchal and biochemical element of the
screening would no longer be required. This would shorten the scan time, dramatically decrease the workload in the biochemistry screening laboratories, and also the cytogenetic labs which analyse the amniocentesis and CVS samples. It would involve setting up a new laboratory service in this country to analyse the ffDNA. This would ultimately make the test cheaper than it is now, as current costs include the expense of sending the serum overseas3 service.
Due to its low false positive rate, if ffDNA became a standard screening test there would be a decrease of around 50-89% in the number of invasive diagnostic procedures6,12
. However, there are large costs involved in setting up a new . This means the number
. As the test can be carried out after eight weeks, any terminations for positive results would also occur at earlier gestations potentially causing less distress for the patient, but also cutting costs for the NHS. A first trimester termination costs around £697 whereas in the second trimester costs rise to £8823
.
of miscarriages related to CVS or amniocentesis would be reduced. The fewer invasive tests being performed, the cheaper the screening program becomes. CVS or amniocentesis costs around £480 per test3
. However, despite these savings, replacing the current screening system with ffDNA would be more expensive for the NHS3
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