COLD SPRING HARBOR, NY (GenomeWeb News) – At an ethical, legal, and social implications, or ELSI, panel at the Biology of Genomes meeting here yesterday, a panel of ethicists, researchers, and legal experts mulled over some of the key ethical issues surrounding prenatal genetic testing — particularly non-invasive tests that take advantage of circulating fetal DNA in maternal blood.
Stanford University's Hank Greely moderated the panel discussion. Also participating were Ronald Wapner, director of reproductive genetics at Columbia University Medical Center; National Human Genome Research Institute bioethicist Benjamin Berkman; Mildred Cho, from Stanford University's Center for Biomedical Ethics; and Shubha Chandrasekharan, a researcher with the Institute for Genome Sciences and Policy at Duke University.
In opening the session, Greely predicted that the availability of non-invasive prenatal tests, or NIPT, — and the introduction of increasingly comprehensive tests on circulating fetal DNA — could dramatically change both the uptake of prenatal genetic testing and the sorts of genetic conditions considered for routine testing.
Currently, NIPTs offered by companies such as Ariosa Diagnostics, Natera, Sequenom, and Verinata Health are used to screen for chromosome 13, 18, or 21 trisomies as a means of prioritizing individuals for more invasive diagnostic testing by chorionic villus sampling or amniocentesis.
The latter tests are uncomfortable, carry a small miscarriage risk, and are not done particularly early in pregnancy — features that make them unappealing to many women, Columbia's Wapner explained. As such, the tests are typically reserved for those deemed at higher-than-usual risk of trisomy based on NIPT results, ultrasound results and/or advanced maternal age.
But women are expected to become more willing to undergo prenatal testing with the availability of non-invasive, blood-based tests. And the potential for such tests to expand from trisomy detection to the detection of smaller chromosomal changes, or even complete fetal genomes, has some mulling over the ethical and practical challenges that may arise in the future.
Even now, Wapner noted, the jump in information provided by microarrays and array comparative genomic hybridization relative to what could be deciphered by karyotyping DNA in amniocentesis or chorionic villus samples is presenting challenges for physicians as they try to convey accurate information to families.
Rather than finding a single fetal aneuploidy in every several hundred cases, microarrays uncover apparent genetic abnormalities in a far higher proportion of pregnancies, he said, including variants of unknown significance or disease risk factors with variable penetrance or expression.
Wapner was the lead author of a study published in December in The New England Journal of Medicine that posited that microarrays can provide more clinically relevant information than karyotyping and, thus, should become the standard for prenatal diagnostics moving forward.
The problem of accurately conveying prenatal test results to families could be compounded with the advent of more extensive analyses of circulating fetal DNA, according to NHGRI's Berkman, who summarized some of the key prenatal testing concerns being bandied about by ethicists.
If and when whole-genome sequencing on NIPT samples becomes routine, for example, he argued that researchers and clinicians will have to carefully consider the threshold for reporting findings to families, since no human genome is free from apparent abnormalities.
Berkman also emphasized the idea of future autonomy — a concept that he and his colleagues discussed in a Hastings Center Report article published last summer.
That ethical consideration centers on the idea that findings from comprehensive prenatal genetic tests could unearth information about future disease risks that might be conveyed to children after they are born without their own consent to that information.
To prevent that, Berkman argued that there should be an emphasis on providing parents-to-be with enough information to make reproductive decisions that are consistent with their own values, while protecting the future rights of children with respect to genetic data and disease risk profiles.
Depending on the scope of non-invasive prenatal tests developed and offered in the future, he argued that it may ultimately be beneficial to consider prenatal genetic testing guidelines in light of the guidelines being applied to genetic testing on children.
Meanwhile, Stanford University's Cho discussed key aspects of NIPT from the point of view of expecting parents, healthcare providers, and the societies to which they belong.
She noted that respondents to past surveys regarding NIPTs often focus on factors such as the tests' accuracy, safety for the fetus, cost, or clinical utility, though the results vary by geographical region and the groups of individuals involved.
For instance, an online study in the US suggested both physicians and members of the general public are concerned with the accuracy of prenatal tests, Cho said.
Whereas health care professionals tended to focus on false-negative test results, though, members of the broader public appeared to be more concerned with the prospect of false-positive tests.
Other surveys suggest that this range of values with respect to prenatal testing extends to other issues as well, she noted — from individuals' autonomy over whether to take such tests or not, to social pressures related to prenatal testing in various parts of the world.
Finally, Chandrasekharan from Duke discussed the current intellectual property, commercialization, and legal landscape faced by companies who are trying out their hand in the NIPT arena — from patent disputes and reviews to lawsuits between companies that have already entered the market.