The fetus in the age of the genome

Abstract

Due to a number of recent achievements, the field of prenatal medicine is now on the verge of a profound transformation into prenatal genomic medicine. This transformation is expected to not only substantially expand the spectrum of prenatal diagnostic and screening possibilities, but finally also to advance fetal care and the prenatal management of certain fetal diseases and malformations. It will come along with new and profound challenges for the normative framework and clinical care pathways in prenatal (and reproductive) medicine. To adequately address the potential ethically challenging aspects without discarding the obvious benefits, several agents are required to engage in different debates. The permissibility of the sequencing of the whole fetal exome or genome will have to be examined from a philosophical and legal point of view, in particular with regard to conflicts with potential rights of future children. A second requirement is a societal debate on the question of priority setting and justice in relation to prenatal genomic testing. Third, a professional-ethical debate and positioning on the goal of prenatal genomic testing and a consequential re-structuring of clinical care pathways seems to be important. In all these efforts, it might be helpful to envisage the unborn rather not as a fetus, not as a separate moral subject and a second “patient”, but in its unique physical connection with the pregnant woman, and to accept the moral quandaries implicitly given in this situation.

Improving prenatal diagnosis through standards and aggregation

“…While progression towards this vision is generally accepted in the genomics community, it is essential in the prenatal space for several reasons. First, while large sequencing studies have been performed on postnatal cohorts, the coming years will bring a commensurate deluge of prenatal sequencing data, facilitated by the dropping cost of genomic sequencing, development of robust genome‐wide cell‐free DNA sequencing methods, and the cohesion of the prenatal community around the importance of genomics in patient care 67–72 . Second, the relationship between genotype and prenatal phenotype is not well understood and there is an opportunity to define the spectrum of prenatal phenotypes that exist for molecular diagnoses.…”

“…First, while large sequencing studies have been performed on postnatal cohorts, the coming years will bring a commensurate deluge of prenatal sequencing data, facilitated by the dropping cost of genomic sequencing, development of robust genome-wide cell-free DNA sequencing methods, and the cohesion of the prenatal community around the importance of genomics in patient care. [67][68][69][70][71][72] Second, the relationship between genotype and prenatal phenotype is not well understood and there is an opportunity to define the spectrum of prenatal phenotypes that exist for molecular diagnoses. This effort will drive gene discovery, given that molecular diagnoses are not identified in many prenatal cases, likely due to the lack of extensive sequencing to characterize "prenatal-specific" variation not observed postnatally.…”

Ethics experts and fetal patients: a proposal for modesty

“…the rights or interests of the future child) 1 without at the same time attributing a patient role to the fetus, we might be able to develop a sound normative foundation for prenatal medicine. But, so far, a generally accepted normative concept for physician–patient-interactions in prenatal medicine and the related professional ethos is still missing [ 28 , 30 ]. The ECS in our case example, accordingly, has no universally accepted guidelines at hand on how to handle conflicting interests of the pregnant woman and the future child in the prenatal situation.…”

“…Such circumstances may arise when investigations during the pregnancy may generate information that could harm the interests of the future child or when attempts at treatment may damage the fetus and lead to impairment of the future child. Especially in the light of the ever-growing diagnostic possibilities (for example through fetal whole genome sequencing and/or non-invasive prenatal testing [ 30 ]) and increasingly available therapeutic options, which may significantly affect the life of the future child, a facilitation process without any representation of this future child must seem incomplete.…”

Bioethics and Informed Consent in Prenatal Diagnostics

“…Prenatal diagnosis would be clearly contrary to moral standards when, depending on its outcome, an abortion would be envisaged. 12 It would be wrong to say that the main purpose of prenatal diagnosis is to detect embryonic or fetal diseases and birth defects, and consequently to terminate the pregnancy on that basis. 13 Advanced biomedical technology allows some treatments to begin in the womb; and in other cases, doctors can prepare to initiate treatment as soon as the child is born.…”