Non-invasive prenatal testing for Down’s syndrome: psychologically speaking, what else do we need to know?

Risk of miscarriage is the main reason that pregnant women give for not choosing a diagnostic test following a positive screening result for Down’s syndrome (Green, Hewison, Bekker, Bryant, & Cuckle, 2004) and a non-invasive diagnostic test for the condition has long been considered the ‘holy grail’ of prenatal testing. The discovery that fragments of cell-free fetal DNA circulate in maternal plasma has led to the rapid development of non-invasive prenatal testing (NIPT) for a range of clinical applications, including identification of fetal Rhesus-D status and determining fetal sex for sex-linked genetic conditions (Chitty, Hill, White, Wright, & Morris, 2012).

However, there have been a number of false dawns in relation to the development of a fully diagnostic, non-invasive maternal blood test for Down’s syndrome, and although validation studies of NIPT for the condition report detection rates of over 98% sensitivity and a low false-positive rate of 0.1%, the tests cannot yet be considered fully diagnostic (Twiss, Hill, Daley, & Chitty, 2013). Invasive testing – amniocentesis or Chorionic Villus Sampling – should therefore still be offered following a positive NIPT result (American College of Obstetricians and Gynecologists 2012). For this reason, NIPT can be used as an advanced early screening test for Down’s syndrome around 10 week’s gestation.

NIPT for Down’s syndrome is rapidly being taken up in the commercial health sector across the world, particularly in Hong Kong, China and the United States, where much of the research and development of the technology has taken place. Evidence from large studies using NIPT as an advanced screening test in all-risk populations report promising results but the full utility as a universal screening test is not yet known (Twiss et al., 2013). The test is currently available through private screening services in the UK, but a study funded by the National Institute of Health Research to evaluate how NIPT compares with current NHS testing practice has just begun at London’s Great Ormond Street Hospital. Due to the costs involved it is unlikely that NIPT will replace current screening tests immediately and instead will be used as a contingent screening test for pregnancies identified as being at high risk for Down’s syndrome via conventional screening (Chitty et al., 2012). This sequential screening process has the potential to significantly reduce the number of invasive diagnostic tests carried out and therefore the number of iatrogenic miscarriages; a key goal of the UK Fetal Anomaly Screening Programme.

There have, of course, been concerns raised about the routine implementation of NIPT. Prenatal testing is a contentious social issue which provokes strong views. For example, it has been argued that NIPT will lead to the trivialisation of early abortion (Kelly & Farrimond, 2011). It is possible that some health professionals may view an early termination as a less significant event than one conducted later in pregnancy; however, the evidence clearly shows that while the opportunity for an early procedure is preferred by women, termination for fetal anomaly is never a psychologically trivial event (Nazaré, Fonseca, & Canavarro, 2013). Concerns about ensuring informed consent to NIPT have been raised and research in this area conducted (Chitty et al., 2012; van den Heuvel et al., 2010). Ensuring that women’s decisions about NIPT accord with their values is, as ever, paramount, particularly for women in parts of the world where a paternalistic approach to practicing medicine is still the norm (Ahmed, Bryant, Tizro, & Shickle, 2012). Women offered NIPT must be aware that while the test poses no physical risk to themselves or their baby, the implications and potential consequent decisions of a positive result are essential to consider in advance. While this issue is not a new one, the relative ease with which NIPT can be conducted would require existing informed consent guidelines to be examined afresh.

Currently absent from the NIPT literature is an evidence-based psychosocial critique. Informed choice is not the only psychological issue of interest here, and we know from past experience with amniocentesis and screening for neural tube defects in the 1980s that unanticipated psychological consequences can occur with new prenatal testing technologies (Green, 1990; Rothman, 1986). There are a number of issues specific to NIPT and its implementation that have not yet been addressed.

Women’s views towards the availability of NIPT as an alternative to current screening tests are generally favourable (Lewis, Silcock, & Chitty, 2013). If NIPT is added to the current NHS screening test repertoire as a contingent test, this would, however, mean some women will undergo four prenatal testing procedures before receiving a definitive diagnosis: a nuchal fold scan and a blood test, a NIPT test if the result is higher than the cut-off risk, and a subsequent invasive test if they receive a positive NIPT result. For some women, termination of pregnancy may actually take place at a later stage in the pregnancy than with current screening protocols. Will women feel as favourably towards NIPT once it is situated within this proposed pathway? The psychological burden of these multiple tests for pregnant women and their partners is unknown. What is known is that a screen positive result frequently provokes clinically significant levels of anxiety in pregnant women (Green et al., 2004). Women who receive a positive result from NIPT will know that their baby has an extremely high likelihood of being affected by a chromosomal condition and anxiety is also likely to be extremely high. While a 98% detection rate is not considered a definitive test in scientific terms, it is likely to be seen as such by women on the receiving end of the result. Breaking the news to and counselling women in this situation will require high levels of skill. Some women may not wish to undergo the stress of further invasive testing and may ask for a termination before a definitive result is given. Psychologically informed protocols will be an essential component of a women-centred NIPT programme.

Another consideration is the context in which NIPT is presented so that, as far as possible, decisions about uptake can be made within a non-biasing frame. The ideal characteristics of a prenatal test are early, accurate and safe, and for many women the safety of a prenatal test is the priority (Hill, Fisher, Chitty, & Morris, 2012). This can make the idea of NIPT highly attractive and it is no accident that the NIPT test currently marketed by private health services in Hong Kong is called ‘safe T21’. The effect of test characteristics and the social context in which they are offered has been one of the least researched topics in the psychology of screening. We know that the technology used to test for fetal anomaly plays an important factor in decision-making for some conditions (Miller, Hewison, & Morley, 2012). We know that ultrasound scans are very popular with women, but we do not know to what extent this might make a screening test that incorporates a scan more attractive than one that does not. We do not yet know the answers to these questions for current prenatal testing technology and we have no idea at all of how the psychosocial context of NIPT, including its high media profile, will impact on the decisions of individual women. Therefore, while research to learn more about how informed decisions can be supported is essential, it is unlikely to reveal systematic biases inherent in the way tests are presented or perceived. Research on psychosocial aspects of NIPT that go well beyond individual informed choice is urgently required to address these critical questions.

As with NIPT, difficult decisions and decision-making are a key aspect of many research studies in the area of reproductive psychology. This is clear in many papers published in the Journal and this edition is no exception, with papers by Jarvholm and colleagues on pre-implantation diagnosis, by Baccino and colleagues on disclosing their type of conception to offspring conceived by gamete or embryo donation and Dembriska’s paper on the emotional aspects of treatment for infertility. In all these different but related areas the choices offered and the associated decisions and psychological consequences continue to be an important source of research questions and hypotheses that need to be addressed.

Louise Bryant
Leeds Institute of Health Sciences, University of Leeds
Email: [email protected]