Microarrays as a diagnostic tool in prenatal screening strategies: ethical reflection

Abstract

Genomic microarray analysis is increasingly being applied as a prenatal diagnostic tool. Microarrays enable searching the genome at a higher resolution and with higher sensitivity than conventional karyotyping for identifying clinically significant chromosomal abnormalities. As yet, no clear guidelines exist on whether microarrays should be applied prenatally for all indications or only in selected cases such as ultrasound abnormalities, whether a targeted or genome-wide array should be used, and what these should include exactly. In this paper, we present some ethical considerations on the prenatal use of microarrays. There is a strong consensus, at least in Western countries, that the aim of prenatal screening for foetal abnormalities should be understood as facilitating autonomous reproductive choice for prospective parents. The tests offered should be valid and useful to reach that purpose. Against this background, we address several ethical issues raised by the prenatal application of microarrays. First, we argue that the general distinction between a targeted and a genome-wide microarray needs to be scrutinised. Then we examine whether microarrays are 'suitable tests' to serve either a screening or a diagnostic purpose. Given the wide range of findings possibly generated by microarrays, the question arises whether microarrays actually promote or interfere with autonomous reproductive decision-making. Moreover, if variants of unknown clinical significance are identified, this adds to the burden and complexity of reproductive decision-making. We suggest a qualified use of microarrays in the prenatal context.

Pre- and post-test genetic counseling for chromosomal and Mendelian disorders

“…1, 94,95 Specific concerns include the possibility of detecting copy number variants (CNVs) of uncertain clinical significance (VOUS), the detection of CNVs associated with conditions with variable expression or penetrance, and incidental findings including CNVs associated with an increased risk for adult-onset conditions or neuropsychiatric disorders. 95, 96, 97 These findings complicate pre-test counseling and when detected, cause significant distress and difficulty with decision-making.…”

“…Although more information can be known, this information may be ambiguous, complicating decision-making and raising ethical issues. 1,2 …”

“…1, 4–5 Discussion has focused on the extent to which the accessibility of these new tests will routinize their use, erode informed consent and stigmatize individuals living with certain disabilities. 6 It is likely that genetic screening in the future will include testing for more disorders.…”

Defining and managing incidental findings in genetic and genomic practice

“…Much of the debate around whether or not IFs should be disclosed to patients/research participants/consumers is focused around the clinical utility of the finding, which has been defined in a variety of different ways 20 – 23. Broadly speaking, clinical utility refers to whether the finding could lead to a medical intervention (ie, treatment, risk-reducing surgery and/or surveillance) that could improve health outcomes.…”

The Psychological Impact of Prenatal Diagnosis and Disclosure of Susceptibility Loci: First Impressions of Parents’ Experiences

“…It has been argued that pregnant couples may wish not to be informed on findings of uncertain expression (Hillman et al 2013) and that such findings should be withheld in order not to put burden on the pregnant couple (Rigter et al 2013; de Jong et al 2014). It has also been said, both for susceptibility loci and VOUS, that reporting them may create a false sense of autonomy (Brady et al 2013), because an overload of information could deteriorate reproductive autonomy, or raise possible emotional harm such as distress (McGillivray et al 2012).…”