This document discusses the ethical challenges posed by new developments in prenatal genetic testing. It outlines the traditional moral framework for prenatal screening based on principles of respect for persons, non-maleficence, beneficence, and justice. New tests like NIPT are replacing older risk assessment methods and broadening the scope of information available, complicating informed consent. There are also debates around the right not to know of future children, redefining reproductive autonomy given increasing choices, and whether the aim of screening should be facilitating reproductive decisions or moving toward prevention. The conclusion is that the content of standard test offers is no longer obvious and reproductive autonomy must be rephrased in this new context.

1. Ethical aspects in the new era of
reproductive genetic diagnosis
Antina de Jong antina.dejong@planet.nl
Symposium on reproductive & non-invasive prenatal
genetic diagnostics
Madrid, 8-9 June 2017

2. Outline
• Moral framework for prenatal screening and diagnosis
• Prenatal screening: then and now
• Challenges of new developments for moral framework
NIPT (T21, 18, 13)
Standard broad screening / diagnostic test
PGD or PGS?
Broadening the scope of prenatal testing
Several purposes of prenatal testing
• Right not to know of future children
• Redefining reproductive autonomy
• Conclusion

3. Moral framework for prenatal screening
• Unsollicited test offer
• Aim: Facilitate well-informed autonomous reproductive choice
(not: prevention)
• General ethical principles
Respect for persons
Non-maleficence / Beneficence
(distributive) Justice
• Requirements prenatal screening
Condition: important health problem
Proportionality: benefits > drawbacks
Test method: suitable
Informed consent: capacity, information, voluntariness
Justice: cost-effectiveness, equal access
Willson and Jungner 1968; Nuffield 1993; Health Council of The Netherlands 2001; Beauchamp and Childress 2009

4. Prenatal screening: then and now
< 24 wks
abortion allowed
9 14 15 partusconception 18
40 wks
9-14 maternal
serumscreening
11
Diagnostics
15 181111 15
15-18
amniocentesis
9-14
CVS
Risk-assessment
karyotyping

5. Prenatal tests: then and now
< 24 wks
abortion allowed
partusconception
40 wks
Diagnostics
15-18
amniocentesis
9-14
CVS
Risk-assessment
11-... ultrasound scans
9-14 maternal
serumscreening
11-14
NT-measurement
RAD karyotyping
array-CGH
WGS / WES
9 14 15 221811 15 181111 15 18
…
NIPT
NIPT

6. NIPT (T21, 18, 13) as risk-assessment test
24 wks
abortion allowed
9 14 15 22 partusconception 18 19
40 wks
15-24
amniocentesis
7-22: fetal ultrasound scans
9-14
CVS
9-14 maternal
serumscreening
7 11
11-14 NT-measurement
NIPT 21, 18, 13
NIPT replacing risk-assessment:
• Offer to all pregnant women
• Remains 2-step testing
• Less invasive procedures
• Higher uptake?
• Earlier in pregnancy: ↓ burden choice
•What happens to NT-measurement?
• Scope of follow-up invasive PD?

7. Standard broad test offer
ArrayCGH/microarray – Whole Genome/Exome Sequencing/Analysis
• Diagnosis or screening?
• Equal Access?
• Too much information -> incapacitates choice
• Informed consent -> generic consent?
Categories of abnormalities
• Really facilitates well-informed decision-making?

8. Preimplantation diagnosis or screening?
• Preimplantation diagnosis (PGD)
For what indication?
Mainly decided on national level
• Preimplantation screening (PGS)
Screening instead of diagnostic tool?
From a choice to a prevention paradigm?

9. Broadening the scope of prenatal testing
• What (not) to include?
- no consensus on a list to justify testing / selective abortion
- severity evaluated differently
- who decides, on what grounds?
• How to guarantee informed decision-making?
- classic interpretation informed consent: every single abnormality
- infeasible, information overload
- alternative of ‘generic consent’
- adequate way of ensuring autonomous choice?

10. ‘Right not to know’ of future children
• Profiling newborns morally unjustified (HGC 2005)
• Amounts to de facto profiling future children?
• ‘Right not to know’ future children may be violated (Feinberg 1980)
e.g. by knowledge of late(r)-onset diseases
- only conditional access?
- avoid these findings by: use filters, targeted arrays/algorithms?
- … not limit access to relevant information for reproductive decision-making

11. Several purposes of prenatal testing
Heterogeneous, compound test offer
• Different purposes (NIPT, ultrasound scans)
Pregnancy-related complications (RhD-status) vs
Fetal abnormalities (continue or terminate pregnancy)
• Simultaneous or separate offer?
• Informed consent
• Directive vs undirective counselling

12. Redefining reproductive autonomy
• Qualified (health related nature)
• Feasibility of informed, adequate choice: categories
Too many choices incapacitate -> limit options for sake of
autonomy
“libertarian paternalism” (Sunstein & Thaler)
• Future child’s right not to know
• Aim of screening: reproductive interest
> Test what you are willing to abort / not-implant for…?

13. Conclusion
• Traditionally: accept/decline standard test offer
• Scope & number : content test offer no longer obvious
• Reproductive choice: not unlimited nor unconditional
• Rephrasal reproductive autonomy

14. Antina de Jong
antina.dejong@planet.nl
Thank you for your attention