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A recent front page article describing a risk-free blood test for Down syndrome in pregnancy (see The Times, 21^st June) has generated considerable online discussion, primarily centring on the worth of individuals with Down syndrome and the ethics of abortion.

 

The technique in question detects cell-free fetal nucleic acids (DNA and RNA), from the placenta, which can be extracted from maternal blood from around 7 weeks gestation to determine the genetic status of the fetus. There are a number of potential applications of the technique for antenatal care in addition to testing for Down syndrome, including sex determination (for families with inherited sex-linked diseases), diagnosis of certain single gene disorders, and blood Rhesus factor status (in the case of Rhesus D-negative mothers).

 

A number of different methods have been developed for non-invasive prenatal diagnosis (NIPD) of Down syndrome based on cell-free fetal nucleic acids. Perhaps the most promising method detects circulating RNA from genes that are only expressed during pregnancy by the placenta [Lo et al. Nat. Med. (2007) 13: 218-213]. Recently, the company Sequenom® announced that it has achieved 100% accuracy in a trial of 200 clinical samples (see press release), although much larger trials will be needed to definitively establish the clinical validity of the test relative to the current gold standard.

 

Whilst the article itself provides an informative overview, much of the public debate has focused on the ethical questions raised by this technique in isolation, rather than in comparison with current Down syndrome screening programmes. In the UK, pregnant women are routinely offered a battery of blood screening tests for different purposes, one of which is to assess their risk of carrying a fetus with Down syndrome. Test results are combined with maternal age to estimate this risk, and women at high risk are offered an invasive procedure to sample fetal cells (normally amniocentesis) for diagnostic testing during the second trimester. However, the screening tests are only accurate in around 85% of cases, and the subsequent invasive diagnostic test is not only unpleasant for the mother, but also results in miscarriage in around 1% of cases. Some women therefore opt out of diagnostic testing because of the risk to a potentially unaffected fetus.

 

NIPD for Down syndrome should be looked at simply as a replacement technology, in which diagnosis (rather than risk prediction) is achieved earlier in pregnancy and without risk to health of the fetus. Key ethical issues are therefore centred not on whether or not offering testing for Down Syndrome is acceptable – current UK practice is based on the assumption that it is, although any woman can choose not to undergo testing – but rather the differences that NIPD would make relative to the current status quo. By offering early non-invasive diagnosis, as opposed to later risk assessment and the option for invasive diagnosis, will the relative ease of such a test result in more terminations of Down syndrome fetuses? Will there be increased social pressure to have the test and terminate the pregnancy if it is positive? What will be the effect of direct-to-consumer testing?

 

Comment: The PHG Foundation is currently undertaking a project on NIPD, looking at the technical issues and the ethical, legal and social implications of each of the applications of cell-free fetal nucleic acids. The project was commissioned by the Joint Committee for Medical Genetics and is being led by an expert steering group in conjunction with a working group of wider stakeholders. The project seeks to identify barriers to implementation of this technique within the NHS, and highlight the wider implications of NIPD both for the health service itself and to the public at large. The report is expected to be available by early 2009, following a second meeting of the working group in September 2008.