Look Before You Leap

Abstract

There are a number of new genetic tests and a variety of recommendations for obstetrician-gynecologists. In recent years, screening of low-risk pregnant women with noninvasive prenatal testing has been proposed as well as universal BRCA1 and BRCA2 screening of all women regardless of risk status. Both proposed genetic screening tests raise complicated issues relating to predictive value, cost, and consequences after screening to both the health care system as a whole as well as serious potential adverse consequences for the patient. In addition, there are significant barriers relating to clinician education in proper use of these genetic tests as well as logistic issues of performing adequate genetic counseling in a busy general practice. We recommend that pregnant women offered noninvasive prenatal testing be informed of its advantages and disadvantages compared with standard screening with the caveat that positive noninvasive prenatal tests must be confirmed with further, invasive testing. We recommend against population genetic screening of all women for BRCA1 and BRCA2 mutations until there are comprehensive data regarding harms and benefits as well as cost-effectiveness. Finally, we recommend that new educational models for genetics be developed for obstetrics and gynecology residency training so that future health care providers will be prepared for the opportunities and challenges that genetic testing creates.

Personal Genome Sequencing in Ostensibly Healthy Individuals and the PeopleSeq Consortium

“…However, there are significant challenges to be addressed. Implementing PPGS involves all the same interpretation challenges as diagnostic testing but with generally increased scope and without the benefit of a strong prior probability for genetic disease [ 13 , 14 , 15 , 16 , 19 , 32 , 33 ]. As more healthy individuals with detailed phenotypes are sequenced, our understanding of variant penetrance and disease expressivity, which are currently biased by ascertainment in affected individuals, will change.…”

“…There is intense and evolving debate about if and how to most effectively and appropriately apply sequencing technologies for predispositional population screening [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 19 , 32 , 33 , 80 ]. The promise of genome sequencing is the ability to implement a single genomic test that can detect both known and novel disease-associated variants for a variety of medical uses.…”

“…There are also numerous concerns when returning PGS results to participants, particularly with the increased scope and complexity of GS [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 31 ]. The results could be distressing without any corresponding clinical or personal benefit.…”

“…As defined here PPGS is a form of population screening, and will likely be judged by similar criteria as other genetic and public health screening tests [ 13 , 14 , 15 , 16 , 19 , 32 , 33 ]. At present there is very limited data on the medical outcomes of sequencing unselected ostensibly healthy individuals.…”

“…And there can also be ethical and other non-health-related motivations to return genomic data to project participants independent of any potential health benefits. But at this moment in time, the use of PGS for population screening in ostensibly healthy individuals is controversial, with the preponderance of experts and professional organizations recommending caution and calling for more research, given large gaps in evidence around penetrance, clinical validity and clinical utility [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. However, there is also a convergence of forces that are accelerating PPGS for persons who would not meet the current criteria for diagnostic sequencing.…”