IntroductionSenior Research Fellow Dr Susan Kelly reflects on recent professional recommendations regarding NIPT/NIPD.
A position and a policy statement, respectively, on non-invasive prenatal testing (NIPT) developments have recently been published by two important professional clinical organisations, the International Society for Prenatal Diagnosis (ISPD) and the American College of Medical Genetics (ACMG.1 Senior Research Fellow Dr Susan Kelly has concerns about each of them.
These statements are timely (writes Dr Kelly), as several commercial forms of this test, for certain chromosome abnormalities, are entering practice in the US and Europe, as well as other locations worldwide. The potential for foetal loss following invasive procedures for foetal diagnosis has driven the search for non-invasive approaches. NIPT analyses cell free foetal DNA (cffDNA) in the maternal circulation, and has been under development also for implementation in public health systems such as the UK NHS. In the case of the NHS, NIPT has to date been offered to women who are at high risk of a specific genetic disorder, (such as identifying foetal sex when there is risk of a sex linked disorder, foetal blood type in Rh negative mothers, or some single gene disorders) (There has been much discussion in clinical communities and in relevant literatures concerning whether NIPT for chromosome abnormalities such as Down Syndrome should be implemented within existing screening pathways, with the offer of invasive diagnostic testing following a high risk result, or whether it should be implemented as a diagnostic test (likely still with ultrasound). Both the ISPD and ACMG policy statements take measured approaches to this debate, noting limitations with current forms of cffDNA-based aneuploidy testing, and come down firmly for implementation within existing screening protocols.
I have two concerns about these statements. The first is that disability concerns that have been widely aired in social science and ethics literatures are not part of the discussion in either of them, particularly regarding the role of NIPT in intensifying surveillance of pregnancies for Down Syndrome My second concern is that both statements conflate NIPT (or NIPS – non-invasive prenatal screening, as the ACMG labels the technology) for screening and high risk uses. Having evaluated existing experiential evidence, I feel strongly that there are profound clinical justifications for offering cffDNA based NIPTs to women with pregnancies at high risk of a genetic disorder, in a clinical genetics context. The ease of the tests, administration early in pregnancy, and avoidance of miscarriage risk have been found to have significant benefits for pregnant women in terms of relieving anxiety, enabling earlier decision-making, and forming an early attachment to an unaffected pregnancy.
However, it is not helpful to conflate this use of NIPT technology with commercial NIPTs for Down Syndrome and other chromosomal abnormalities. There is a vast disconnect between high risk applications, such as those mentioned above, and the way in which NIPT is being strongly marketed and developed with a narrow focus on chromosome abnormalities, particularly Down Syndrome. While the issue of screening versus diagnosis has not yet been resolved, the policy statements focus heavily on technical aspects of the technology (e.g., sensitivity, specificity) and leave aside (in the sense of missing completely) the opportunity to initiate a dialogue or assessment of the social impacts and implications of these practices. The lack of reflection about what this intensification might mean for people with Down Syndrome and their families is a striking omission. It is also striking that there is noreflection on the commercial drivers of this particular application of the technology.
For example, the recent ISPD position statement devotes no space at all to education of women about Down Syndrome or other chromosome abnormalities. In fact, it gives more space to detailing the committee members’ conflicts of interest than to discussing informed consent, counselling and education. It does detail how complex such risk determination has become in pregnancy, and the kinds of information prospective parents are confronted with on a routine basis, but pays no attention to the important question of what life as a parent of a child with Down Syndrome might be like. Further, the position statement is limited to the use of cffDNA for chromosome abnormality detection, and although it suggests limiting this application to high risk women, and mentions the possible use of the technology for single gene disorders, it does not address these in any depth. While the use of cffDNA technologies for Down Syndrome diagnosis is not recommended by either body, that is clearly the direction in which implementation of the technology is headed. That no space at all is dedicated to recognition, much less discussion, of the many ethical and social debates that have been raised by such uses of this technology, is disturbing. It is long past time to recognise that prenatal aneuploidy screening and diagnosis are far more than narrow technical practices.
The ACMG policy statement does reference educational materials available to assist prospective parents and professionals facing a Down Syndrome diagnosis. This is to be welcomed and one can but hope that the importance of these materials is not lost in the overwhelmingly clinical tone of the statement. This tone, in fact, exemplifies one of the concerns often voiced by a range of ethics and clinical observers of developments in NIPT for Down Syndrome; that the offer of such testing by professionals is itself taken as endorsement of its importance, as a signal that responsible pregnant women should accept such testing. While it might be asking too much of professional clinical bodies to grapple with ethical and social concerns with testing (the principle of distributive justice related to test cost and insurance is the only mention of anything approaching these), it is disappointing that there is little if any acknowledgement of concerns about social pressure to test, of the difficulties of informed consent, and of difficulties of educating prospective parents about Down Syndrome or related conditions in the midst of antenatal care screening and diagnosis. It appears likely that NIPT (or NIPS) for chromosome abnormalities will enter clinical practice without the opportunity for measured evaluation of priorities regarding antenatal testing – in fact, according to the ACMG policy statement, it has already arrived.
1 Benn P., Borell A., Chiu R., Cuckle H., Dugoff L., Faas B., et al. Position statement from the aneuploidy screening committee on behalf of the board of the international society for prenatal diagnosis, April 2013; Gregg, A.R., Gross, S.J., Best, R.G., Monaghan, K.G., Baja, K., Skokto, B.G., Thompson, B.H. and Watson, M.S. (The Noninvasive Prenatal Screening Work Group of the American College of Medical Genetics and Genomics) ACMG policy statement on noninvasive prenatal screening for fetal aneuploidy, 2013.