Receiving uncertain results from prenatal chromosomal microarray analysis: Women's decisions on continuation or termination of pregnancy.

BACKGROUND: Chromosomal microarray analysis (CMA) may detect variants of uncertain clinical significance (VUS) and susceptibility loci (SL) with incomplete penetrance for neurodevelopmental disorders. This qualitative study provides empirical data on women's experiences with receiving such findings in pregnancy and their decisions regarding continuation or termination of the pregnancy. METHODS: Semi-structured interviews were conducted with women who received a VUS and/or SL from prenatal CMA in the last 2-4 years and were analyzed using Grounded Theory. RESULTS: The vast majority of women recalled being stressed by the findings. All women sought further advice and information to be able to decide whether to continue or terminate their pregnancy. The three pregnancies that were terminated have in common a de novo SL with a 10%-20% penetrance. Similar reasoning (coping with uncertainty, the quest for a perfect child, and a chance for recurrence in future pregnancies) led different women to contradicting conclusions regarding their pregnancies. All women felt satisfied with their decisions. CONCLUSION: Although uncertain/probabilistic information commonly involves a psychological burden, it may also be perceived as valuable and actionable. Pre-test parental choice regarding the disclosure of such information could allow personalized utilization of advanced genomic tests in pregnancy.

Clinicians' attitudes towards parental choice in the era of advanced genomic tests in pregnancy.

OBJECTIVE: Israel is one of the first countries to incorporate chromosomal microarray analysis into routine prenatal care. We explored attitudes of Israeli healthcare professionals (HCPs) towards the disclosure of challenging findings: variants of uncertain clinical significance (VUS), susceptibility loci (SL) for neurodevelopmental disorders and variants associated with adult-onset (AO) conditions. Particularly, we sought their views on providing parental choice regarding the disclosure of these findings. METHODS: Twenty-nine in-depth interviews were conducted with genetic counselors (n = 19), medical geneticists (n = 4), medical geneticists that are trained in and practice fetal medicine (n = 3), and fetal medicine experts (n = 3). RESULTS: Most participants (n = 24) supported parental choice regarding uncertain genetic information. Engaging parents in disclosure decisions allows avoidance from potentially anxiety-provoking information, practicing parental autonomy, and better preparation in cases where uncertain findings are identified. HCPs believed that given appropriate preparation, parents can make informed decisions. Four participants believed that disclosure should be based on professional judgment and one supported full-disclosure. Unlike VUS or SL, all interviewees agreed that in cases of medically actionable AO conditions, the benefit of disclosure outweighs the damage. CONCLUSION: HCPs attitudes are largely in-line with the Israeli practice of involving parents in disclosure decisions regarding uncertain information. This may mitigate disclosure dilemmas and allow personalized disclosure based on parents' views.

Receiving Genomic Sequencing Results through the Victorian Undiagnosed Disease Program: Exploring Parental Experiences.

Rare diseases cumulatively affect a significant number of people, and for many, a diagnosis remains elusive. The Victorian Undiagnosed Disease Program (UDP-Vic) utilizes deep phenotyping, advanced genomic sequencing and functional studies to diagnose children with rare diseases for which previous clinical testing has been non-diagnostic. Whereas the diagnostic outcomes of undiagnosed disease programs have been well-described, here, we explore how parents experience participation in the UDP-Vic and the impact of receiving both diagnostic and non-diagnostic genomic sequencing results for their children. Semi-structured interviews ranging in length from 25 to 105 min were conducted with 21 parents of children in the program. Ten participants were parents of children who received a diagnosis through the program, and eleven were parents of children who remain undiagnosed. Although the experiences of families varied, five shared themes emerged from the data: (1) searching for a diagnosis, (2) varied impact of receiving a result, (3) feelings of relief and disappointment, (4) seeking connection and (5) moving towards acceptance. The findings demonstrate the shared experience of parents of children with rare disease both before and after a genomic sequencing result. The results have implications for genetic counselors and clinicians offering genomic sequencing and supporting families of children with rare diseases.