Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening

Abstract

This paper contains a joint ESHG/ASHG position document with recommendations regarding responsible innovation in prenatal screening with non-invasive prenatal testing (NIPT). By virtue of its greater accuracy and safety with respect to prenatal screening for common autosomal aneuploidies, NIPT has the potential of helping the practice better achieve its aim of facilitating autonomous reproductive choices, provided that balanced pretest information and non-directive counseling are available as part of the screening offer. Depending on the health-care setting, different scenarios for NIPT-based screening for common autosomal aneuploidies are possible. The trade-offs involved in these scenarios should be assessed in light of the aim of screening, the balance of benefits and burdens for pregnant women and their partners and considerations of cost-effectiveness and justice. With improving screening technologies and decreasing costs of sequencing and analysis, it will become possible in the near future to significantly expand the scope of prenatal screening beyond common autosomal aneuploidies. Commercial providers have already begun expanding their tests to include sex-chromosomal abnormalities and microdeletions. However, multiple false positives may undermine the main achievement of NIPT in the context of prenatal screening: the significant reduction of the invasive testing rate. This document argues for a cautious expansion of the scope of prenatal screening to serious congenital and childhood disorders, only following sound validation studies and a comprehensive evaluation of all relevant aspects. A further core message of this document is that in countries where prenatal screening is offered as a public health programme, governments and public health authorities should adopt an active role to ensure the responsible innovation of prenatal screening on the basis of ethical principles. Crucial elements are the quality of the screening process as a whole (including non-laboratory aspects such as information and counseling), education of professionals, systematic evaluation of all aspects of prenatal screening, development of better evaluation tools in the light of the aim of the practice, accountability to all stakeholders including children born from screened pregnancies and persons living with the conditions targeted in prenatal screening and promotion of equity of access.

Patient choice and clinical outcomes following positive noninvasive prenatal screening for aneuploidy with cell-free DNA (cfDNA)

“…Testing for sex chromosome aneuploidies has not been recommended, but may be performed if requested. 10,17 False positive cfDNA results have been demonstrated due to confined placental mosaicism (CPM), maternal low-level mosaicism, twin demise and rarely, maternal cancer. [18][19][20][21] All patients with positive cfDNA were offered prenatal diagnostic testing, and almost two-thirds of women had either a CVS or amniocentesis.…”

Preferences for prenatal tests for Down syndrome: an international comparison of the views of pregnant women and health professionals

“…22 With NIPT now available through commercial companies in more than 60 countries 8 and evaluation of implementation in the public sector underway, [23][24][25] this exploration of cross-cultural variation in women's and HPs' preferences for prenatal tests is timely. Overall, women placed greater emphasis on test safety and having comprehensive information than HPs, who placed more emphasis on accuracy and early testing than women.…”

Trial by Dutch laboratories for evaluation of non‐invasive prenatal testing. Part II—women's perspectives

“…The ability to make an informed choice has been shown to be associated with beneficial psychological outcomes such as less decisional conflict regarding the choice 11, 12. To safeguard the process of informed decision‐making, the need for comprehensive counseling on NIPT has been emphasized 9, 13…”