What is the meaning of a ‘genomic result’ in the context of pregnancy?

Abstract

Prenatal genetic testing and analysis in the past was usually only offered when a particular fetal phenotype was noted or suspected, meaning that filtering and interpretation of genetic variants identified could be anchored in attempts to explain an existing health concern. More recently, advanced genomic testing is increasingly being used in "low-risk" pregnancies, producing information on genotype adrift of the phenotypic data that is often necessary to give it meaning, thus increasing the difficulty in predicting whether and how particular genetic variants might affect future development and health. This presents an increasing challenge to healthcare scientists, clinicians, and parents in deciding what qualities prenatal genotypic variation should have in order to be constructed as a 'result'. At the same time, such tests are often re requested in order to make binary decisions about whether to continue a pregnancy or not. As a range of professional organisations develop guidelines on the use of advanced genomic testing during pregnancy we highlight the particular difficulties of discovering ambiguous findings such as variants with uncertain clinical significance, susceptibility loci for neurodevelopmental problems and susceptibility to adult-onset diseases and aim to foster international discussions about how decisions around disclosure are made and how uncertainty is communicated.

A qualitative interview study of the attitudes toward reproductive options of people with genetic visual loss

“…In general, participants were supportive of PGT and PND being available to people with genetic visual loss but felt they might be unlikely to use these techniques themselves. The attitudes toward reproductive options in our study show similarities to those described in other genetic conditions (Shkedi‐Rafid et al, 2021 ). For example, some with Huntington's disease report feeling morally obliged to prevent the inheritance of the condition by their children, with PND and PGT being viewed as acceptable (Decruyenaere et al, 2007 ).…”

Postpartum women's attitudes to disclosure of adult‐onset conditions in pregnancy

“…similar, more than others, less than others, and don't know); and 3) psychological domain: level of concern about fetal health (i.e. not concerned, concerned, very concerned) and level of psychological distress (based on the K6 scale, responses to each of the six questions were coded between 0 and 4, with a sum of 0-24 to all questions and applying the standard categorization of the score into 3 levels (non-distress (score≤4), moderate distress (5)(6)(7)(8)(9)(10)(11)(12), severe distress (score≥13)) or dichotomous (moderate or severe vs. low).…”

“…1,[8][9][10] Alongside the increased capacity of AGT to detect childhood-onset pathogenic findings, they can also identify risks for adult-onset (AO) conditions in the fetus. Detection of such findings challenges the traditional purpose of prenatal testing 11,12 and raises dilemmas typically related to predictive genetic testing in adults.…”

Not putting the cart before the horse: the complex social and ethical terrain of prenatal exome sequencing

“…Indeed, whilst Daum et al have emphasised the ‘false reassurance’ associated with use of CMA without PES, we argue that its inclusion could conversely introduce new uncertainties, decision conflict and distress amongst prospective parents, as has been demonstrated in other prenatal contexts where equivocal results have been identified [ 11 ]. In light of this, achieving valid consent for ES, will not only require counselling about the ‘limited phenotypic delineation of the foetus’ in variants with variable expression and incomplete penetrance (Daum et al, p. 4), but also discussion of the individual meaning of severity and disability for the woman/couple, the (uncertain and variable) meaning of pathogenicity in advanced genomic testing, and findings that go beyond the initially defined list of genetic conditions [ 12 ].…”