Development of an Optimal Approach to Return of Results for Families Undergoing Next-generation Sequencing for Prenatal Diagnosis

Although whole exome sequencing (WES) was first used for identification of the genetic cause
of a disease only in 2009 and whole genome sequencing (WGS) in 2010, and questions remain
about their performance as clinical tests, they are already being offered to patients and
doctors as a clinical test by several laboratories certified by the US government (14 labs
for WES and 5 labs for WGS). The results from WES and WGS can be complex and confusing, even
for doctors and scientists who work with this technology on a daily basis; for patients, the
process of deciding whether to have WES or WGS testing, undergoing the testing, receiving
the results, and trying to use the results for further decision-making could be quite
stressful. Currently, this process occurs in an unstandardized fashion, with some patients
receiving extensive education and counseling, and others receiving almost none. There is a
critical need to identify patient needs and desires in this area, and to develop strategies
to satisfy them. The primary goal of this project is to gain knowledge about how patients
undergoing prenatal diagnosis for a fetal abnormality understand and react to WGS testing,
so that we can develop a more ethical and responsible approach to patient education,
counseling, and return of results for patients . In order to do this, we need to evaluate
parents' understanding of the utility and limitations of the technology, parents'
preferences regarding the types of results they want to receive, and the psychological
impact of receiving results from this technology. We will enroll 30 families consisting of a
woman carrying a fetus with a major abnormality identified by ultrasound, and the father of
the fetus, who have opted for amniocentesis for standard prenatal diagnostic testing
(karyotyping, fluorescence in situ hybridization (FISH) and/or microarray testing). Half of
the families will serve as controls, who will only have standard prenatal diagnostic
testing. For the other half of the families, WGS will be performed in addition to standard
diagnostic testing. For all 30 cases, we will perform psychosocial evaluations (including
assessments of the subjects' mood, understanding of the technology and preferences for
return of results) at the time of enrollment, at the time of return of CLIA-certified
genetic testing results (karyotype, FISH, microarray, and/or WGS), and after completion of
the pregnancy. In this way, we will learn whether participants are receiving adequate
education about next-generation sequencing to make informed choices, what the range of
preferences are for return of results in a prenatal population (and whether this changes
when new methods for prenatal diagnosis are employed), and whether the use of WGS imposes
additional psychological stress compared to standard prenatal diagnostic tests. This study
will be carried out in a stepwise and carefully monitored environment, with progress
overseen by an Independent Data Monitoring Committee in order to maximize the knowledge
gained while minimizing potential harms.

Inclusion Criteria:

- Subject(s) 18 years or older (both mom and father of baby (FOB)

- Subject is undergoing prenatal testing for a major fetal anomaly

Exclusion Criteria:

- Mothers or fathers of the affected fetus are under the age of 18 years