Two new papers provide insight into the genetic counseling issues that have arisen from the introduction of array-based prenatal testing.
Authored by two different research groups — one based in North America, the other based mostly in Australia and New Zealand — the papers have similar conclusions, calling for greater education of genetic counselors in reporting array-based findings, especially those of unknown clinical significance, and arguing that it would be unethical to withold information on such findings from women relying on chromosomal microarray analysis to make informed choices about their pregnancies.
The two opinion papers were included this month in a special issue of Prenatal Diagnosis that focused on new cytogenetic technologies, and array-based prenatal testing in particular (see related article, this issue).
George McGillivray, a consultant clinical geneticist with Genetic Health Services Victoria in Melbourne, Australia, is the lead author on the first paper, "Genetic counseling and ethical issues with chromosome microarray analysis in prenatal testing." The co-authors on the paper are Lynn Gilliam, academic director of the Children's Bioethics Centre in Melbourne; Mac Gardner, a medical geneticist at theUniversity of Otago in New Zealand; and Jill Rosenfeld, a genetic counselor at PerkinElmer subsidiary Signature Genomic Laboratories in Spokane, Wash.
According to the authors, there are "four key ethical questions" that must be addressed with regards to array-based prenatal testing. These are: Is there an unacceptable risk of harm to a woman or her fetus following the detection of a CNV of uncertain significance? How much information should be given to a woman about the result of her prenatal CMA—is it ethically justifiable to withhold information? What constitutes 'informed choice' when women are offered prenatal CMA? and Would clinicians be morally responsible for 'unnecessary' termination of pregnancy as a result of uncertain test results?
The authors argued that while the possibility of distress due to detection of a CNV of uncertain significance is real, it doesn't mean that such information should be withheld. Instead, the authors state that "steps should be taken to minimize distress and provide support" to pregnant mothers in such situations. The authors also believe that it is not ethically justifiable to withold information, despite the potential of causing distress, but acknowledge that some women might prefer a targeted array that is less likely to pick up such unclassified variants.
"We should strive to offer women the option of prenatal CMA that is most likely to find pathogenic changes that may be material to their decision making," the authors wrote. "This could include offering women the option of high-resolution genome-wide CMA with SNP markers, if there is an indication for prenatal testing, but also offering options for targeted studies to accommodate preferences for minimizing unclear results."
Noting that the "commonly accepted ethical standard for informed consent is a substantial understanding of the relevant information," the authors believe that informed consent can be achieved in the prenatal CMA setting.
Finally, they do not believe that clinicians are morally responsible for the unnecessary termination of a pregnancy based on uncertain results. "It would be paternalistic and inconsistent, with respect for a woman's autonomy, for a clinician to take on responsibility for that decision," the authors wrote.
McGillivray told BioArray News this week that the group's "four ethical questions" came from a synthesis of issues that have arisen in his clinical practice and those of the other authors, as well as the "concerns that have been expressed and considered in discussions with my geneticist and OBGYN colleagues," the clinical frameworks in bioethics that Gillam has brought to local discussions and debates about prenatal CMA.
According to McGillivray, his cytogenetic lab has processed more than 2,500 perinatal samples to date, including about 400 samples using the Affymetrix 2.7M array or the Illumina HumanCytoSNP12 BeadChip.
To arrive at answers to the four questions, McGillivray said he consulted existing literature about the ethics of prenatal diagnosis using established technologies, and "tested the principle of autonomy" through various scenarios to reach the conclusion that CMA can "ethically" be offered.
Of the group's opinion, McGillivray noted that being able to address women's distress caused by uncertain findings is "critical."
"I don't believe that laboratories should offer CMA or prenatal CMA to clinicians whose patients do not have access to genetic counseling services," he said. "There needs to be significant infrastructure in place prior to this sort of testing being made available prenatally."
A Second Opinion
The second paper in the special issue is called "Integration of microarray technology into prenatal diagnosis: counselling issues generated during the NICHD clinical trial." It was authored by Ron Wapner, director of reproductive genetics at New York Presbyterian Hospital-Columbia University Medical Center; Deborah Driscoll, professor of obstetrics and gynecology at the University of Pennsylvania School of Medicine; and Joe Leigh Simpson, chair of biomedical engineering at Florida International University in Miami.
Wapner is the principal investigator on the National Institute of Child Health and Human Development-funded study that demonstrated that arrays can detect more abnormalities than microscope-based karyotyping. A paper detailing those findings is expected later this year.
In the paper, the authors examined four cases, all evaluated in the NICHD prenatal microarray study, to "illustrate the challenges and subtleties of genetic counseling required with prenatal CMA testing." Noting that CMA's "improved diagnostic ability" to detect clinically relevant abnormalities compared to older methods is likely to lead to its "adaptation as a primary prenatal diagnostic tool," they admit that labs will face "frequent counseling dilemmas, as does the translation of any new technology into clinical care," but argue that "with time, education, and the development of appropriate care guidelines, these should become infrequent."
In particular, they urged increased counselor and practitioner education that includes "both an introduction to the science of interpreting array findings as well as development of improved approaches to uncertainty." To achieve this, the authors advocate "close collaboration between laboratories performing arrays, clinical geneticists with expert knowledge and expertise in the area, and counselors skilled in relating results to patients." A formal consent process for those requesting the testing is suggested, following pretest counseling.
The authors also stated that professional organizations, such as such as the American College of Medical Genetics and the American Congress of Obstetricians and Gynecologists, will "need to develop standardized guidelines for testing and reporting of results to minimize the uncertainty and ensure that patients and practitioners are provided with accurate information and appropriate counseling tools."
According to FIU's Simpson, much of this educational effort is the responsibility of organizations like ACMG and ACOG. "It comes back to the certification bodies," he told BioArray News this week. "The boards must make available educational modules that would fulfill these objectives." About overcoming genetic counseling issues for CMA, Simpson seemed optimistic. "It's really no different from any other molecular technology," he said. "People will learn and adapt."
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