ESHG and ASHG call for “responsible innovation” in non-invasive prenatal screening

The European Society of Human Genetics (ESHG) and the American Society of Human Genetics (ASHG) yesterday issued a joint position document calling for “responsible innovation” in the development, translation and clinical implementation of non-invasive prenatal genetic screening (NIPGS). In a lengthy statement authored by international experts (including Wybo Dondorp, Diana Bianchi, and Lyn Chitty), the two professional societies explored many of the ethical issues raised by NIPGS, issuing ten recommendations for addressing these issues, summarized here:

1. Positive results from NIPGS should always be confirmed if a woman is considering ending her pregnancy based on this information. (This issue was highlighted in a recent article by the New England Center for Investigative Reporting.)
2. All women should be given adequate pre-test counseling/information before having NIPGS, and the information offered should be responsive to those women’s needs and any linguistic, educational, or cultural barriers. (Our PRINCESS project is highlighting many of the same needs and makes similar recommendations.)
3. Clear policies should be put in place for dealing with incidental findings from NIPGS, and women should be informed about this possibility and given a choice, insofar as this is possible.
4. NIPGS for sex chromosome aneuploidies and chromosomal microdeletions is currently not recommended, because of the challenges for counseling and increased follow-on testing. (See more on this below.)
5. Every effort should be made to separate–conceptually, if not physically–prenatal screening for preventable maternal/fetal health problems from prenatal screening aimed at detecting fetal genetic conditions for the purposes of reproductive decision-making.
6. Governments choosing to offer prenatal screening for fetal genetic conditions as a public health program should implement responsible governance for quality control, education and counseling, equity of access, and future innovation.
7. Decisions about clinical or public health implementation of NIPGS should take into account not only economics, but also the values and needs of pregnant women and families, and the larger society. (The editorial of a recent special issue of Bioethics makes a similar argument–not surprisingly, since it’s also by Dondorp.)
8. More research is needed on informed choice in prenatal screening and interventions to achieve informed choice. (Several of PIRC’s research projects focus on the quality of informed decision-making for NIPGS, and we are heartened to see that several groups are working on interventions.)
9. Professionals and the larger society should engage in forward-looking discussions about the future scope of prenatal screening, particularly considering the pending development of tests for genetic conditions that do not pose a serious or immediate threat to the fetus or young child.
10. More ethical analysis is needed on the relationship between prenatal screening and potential fetal therapies.

This document is a major step forward in the ongoing effort to develop professional guidelines and societal policies around NIPGS. It is particularly striking because it has emerged not from a bioethics society, a patient-led group, or even a primarily clinical organization–but from two professional organizations of human geneticists, representing both clinical geneticists and basic scientists.

I am particularly struck by recommendation #4, bolded above. The issue of low positive predictive values for NIPGS for microdeletions, along with the meager justification for offering screening for sex chromosome aneuploidies with often very mild phenotypes, has increasingly troubled us here at PIRC, along with other observers of the rapidly expanding scope of NIPGS. (Megan Allyse and Shubha Chandrasekharan’s commentary on this topic just appeared today, though it’s behind a paywall. They are also presenting a poster based on their commentary next week.)

The recommendations should generate a good deal of interesting conversation, especially at next week’s meeting of the American College of Medical Genetics and Genomics (ACMG). The ACMG did not sign on to this policy statement–and we don’t know if they were asked–but NIPGS has been a major topic at the last several ACMG meetings. Now the ESHG and ASHG have pushed the conversation to a new (and arguably higher) level, and it will be fascinating to see the response from all sides.