New guidance from a trio of maternal-fetal medical groups recommends against routine use of genome-wide sequencing (GWS) as a prenatal diagnostic test because this method as of now has not been validated sufficiently and not enough is known about its benefits and pitfalls. However, the International Society for Prenatal Diagnosis (ISPD), the Society for Maternal-Fetal Medicine and the Perinatal Quality Foundation outlined circumstances when fetal genomic testing might be appropriate. One example is when ultrasound shows anomalies potentially of genetic origin, but standard genetic testing does not clarify the cause of these abnormalities. GWS might also be applicable when couples who previously had an affected fetus, stillborn, or newborn for whom a genetic diagnosis had not been made have a new pregnancy showing a similar pattern of anomalies.
The joint position statement also offers specific recommendations to labs and clinicians on interpreting DNA variants, ensuring test quality, and returning results to parents.
DNA sequencing has grown in importance as a diagnostic tool in flagging genetic diseases, particularly in fetuses. The joint statement published in Prenatal Diagnosis offers advice both to clinicians and laboratorians on how to use this developing technology in prenatal testing. “We envision this as the beginning of similar future collaborations that will benefit prenatal care providers and patients in the current rapidly evolving genomic era,” said ISPD president Ignatia Van den Veyver, MD, a maternal-fetal medicine specialist, in a statement.
Prenatal genetic testing should only take place in accredited diagnostic labs that know how to conduct and interpret these types of tests, the groups advised. They also outlined what information a clinician should provide to a lab before a genetic test takes place.
“Clinical information must be submitted by the referring clinician in a standardized format, preferentially using human phenotype ontology terms. In addition, clinicians should provide imaging data … to support the fetal phenotypic findings,” they recommended. Labs in turn should set up systems to make it easier for clinicians to submit this type of information.
Diagnostic labs should take on any initial variant annotation or classification. However, “interpretation of pathogenicity and attributed clinical significance should be informed by the fetal phenotype and other relevant clinical information,” the groups suggested. This type of analysis should incorporate a team-based approach that involves a variety of experts such as clinical geneticists, scientists and counselors, and those with prenatal diagnosis expertise. Labs and referring clinicians, perhaps in conjunction with other clinical experts, should discuss any final or possible revision of the interpretation of results.
The guidance discusses what types of lab results should be addressed in pretest and post-test counseling. Examples include variants of uncertain significance in strong candidate disease genes for the fetal phenotype, or any pathogenic variant that may lead to moderate or severe childhood- or adult-onset disorders. “Strategies for disclosure of results on parental samples should be addressed during pretest counseling and in the informed consent process,” the guideline authors recommended.
Any inconclusive sequencing results involving a prior fetus, infant, or other family member that could heighten the risk of a planned pregnancy should undergo a review. Additionally, all communications about results, genetic counseling or reproductive options should be communicated to parents in written language that they’ll understand.