Pandora's pregnancy: NIPT, CMA, and genome sequencing-A new era for prenatal genetic testing.

OBJECTIVES: We delineate in this article a shift from the "traditional" technologies of karyotyping in PND to the current phase of advanced genetic technologies including noninvasive prenatal testing (NIPT), chromosomal microarray analysis (CMA), and whole-exome sequencing (WES) with their higher detection rate and related abundance of uncertain data. METHODS: Conceptual analysis based on seminal works that shaped the socioethical discourse surrounding the experiences of parents as well as professionals with prenatal diagnosis in the last 30 years. RESULTS: We consider the implications of this new era of PND for patients and health professionals by drawing on previous studies documenting how probability and uncertainty affect informed consent/choice, health risks communication, customer satisfaction and decision making, and parent-child bonding. CONCLUSIONS: We argue that these changes move us beyond the idioms and realities of the tentative pregnancy and moral pioneering, to uncertainty, probability-based counseling, and moral/translational gambling. We conclude by discussing what is needed to maintain hope in the era of Pandora's pregnancy.

[Array-comparative genomic hybridization is a new and promising method for prenatal chromosomal diagnosis]. / Array-komparativ genomisk hybridisering er en ny og lovende metode til prænatal kromosomundersøgelse .

Array-comparative genomic hybridization (array-CGH) is a very sensitive method for identifying chromosomal imbalances and is now used on a clinical basis for prenatal diagnosis. This article reviews the advantages and disadvantages of the method, the ethical considerations and the current recommendations for prenatal use in Denmark according to a new national guideline from The Danish Society of Foetal Medicine and the Danish Society of Medical Genetics.

Chromosomal microarray analysis and prenatal diagnosis.

Chromosomal microarray analysis (CMA) assesses chromosomal copy number alterations and affords higher resolution when compared with standard karyotype. This review provides the obstetric provider with an update on the technology, use, and controversies concerning CMA utilization in prenatal diagnosis. Chromosomal microarray analysis offers increased resolution for copy number abnormalities compared with traditional karyotype. There is high-quality evidence for the added detection of clinically significant copy number alterations with CMA in prenatal diagnosis when the traditional karyotype is normal. Other potential advantages of CMA include a quicker turnaround time and utilization in clinical situations with a high probability of nondividing cells (ie, intrauterine fetal demise, spontaneous miscarriage, and third-trimester amniocentesis). Chromosomal microarray analysis may be beneficial when prenatally detected structural anomalies are associated with specific microdeletions and microduplications or to assess for copy number variants when a de novo balanced rearrangement or marker chromosome is diagnosed. Use of CMA includes the detection of copy number variants of uncertain significance. In light of these issues, large prospective cohort studies are needed to illustrate the diagnostic utility of CMA for detection of prenatal chromosomal abnormalities in low-risk populations before routine clinical use of CMA is recommended in all circumstances of prenatal diagnosis.

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

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.

Ethical controversies in prenatal microarray.

PURPOSE OF REVIEW: Chromosome microarray (CMA) analysis enables genome interrogation at a much higher resolution than is possible with conventional karyotyping. CMA is considered 'standard of care' for postnatal genetic testing, yet its introduction into the prenatal setting has been delayed, in part because of ethical concerns about possible psychosocial harm and deficits in informed consent. RECENT FINDINGS: The findings of several large trials have now been reported, allowing preliminary quantification of the relative benefits and harms of CMA in prenatal diagnosis. Qualitative studies have also provided insights into the patient experience particularly in cases in which results of uncertain significance are provided. In an attempt to minimize potential harms, some professional guidelines have suggested limiting access to CMA to patients with fetal abnormality on ultrasound, limiting the diagnostic power of CMA by using targeted platforms or limiting reporting. SUMMARY: We provide an overview of the relative benefits and harms of prenatal CMA, and critically examine the strategies proposed to minimize harms in the context of other important ethical issues such as patient autonomy, justice and equity of access. We advocate for improved patient consent, counselling and support so that patients can fully benefit from the improved diagnostic yield of CMA despite the challenges that are intrinsic to the prenatal setting.