Julia Wynn

The role of a cancer genetic counselor includes communication about emotions, thoughts, and decision‐making related to prophylactic surgery. No prior study has fully evaluated the preferences of young adults who are BRCA1, BRCA2 (BRCA1/2) , or PALB2 positive and their communication preferences on discussing prophylactic surgery in a genetic counseling session. We addressed this through semi‐structured interviews with 13 individuals who were assigned female sex at birth, aged 18–30 during the time of genetic counseling, had seen a genetic counselor in the past 7 years, and tested positive for a BRCA1/2 or PALB2 pathogenic or likely pathogenic variant. Coding by two researchers and reflexive thematic analysis by three researchers was conducted to explore preferences of this population. Five major themes were constructed in analysis: (1) care personalized for life stage and identity; (2) personal and community factors impacting decision‐making; (3) communication about gene‐positive medical management; (4) healthcare system concerns; and (5) preferences for genetic counselor post‐test counseling and follow‐up. Young adult participants discussed that life‐stage considerations such as body image, sexuality, and childbearing were important factors in their emotions and decision‐making around prophylactic surgery, differing from previous literature on older populations. Participants desired more follow‐up, better support and education around practical and emotional considerations for prophylactic surgery, and acknowledgment of personal and community factors that impacted them. Genetic counselors can personalize each visit to the patient and their needs by extensively contracting and bringing up topics that may be relevant and adjusting based on their preferences and values.

Introduction: In this study we performed a retrospective chart review of alloimmunized pregnancies undergoing monitoring for hemolytic disease of the fetus and newborn (HDFN) in a cohort with known fetal antigen (FA) status. The objective was to compare fetal monitoring with titers and middle cerebral artery peak systolic velocity Doppler (MCA‐PSV Doppler) in FA‐negative and FA‐positive pregnancies and to understand downstream impacts of screening with titers in FA‐negative pregnancies. Methods: Retrospective chart review of alloimmunized pregnant patients who underwent FA cell‐free DNA (cfDNA) analysis and participated in a registry in which neonatal genotyping was performed to confirm FA cfDNA results. Patients were divided into FA‐positive or FA‐negative cohorts based on the FA genotypes. Medical records were reviewed to characterize monitoring for anemia, titer results, MCA‐PSV Doppler results, and whether interventions were performed. Fischer's exact or chi‐square tests were performed as appropriate to ascertain differences between the cohorts. Results: Sixty‐nine alloimmunized pregnant individuals were included. Forty pregnancies (58%) were FA positive. Of 29 FA‐positive pregnancies who had titers more than once, 20 (69%) had titers that rose over two or more time points. There were 29 FA‐negative pregnancies (42%). Of 20 FA‐negative pregnancies that underwent titers more than once, 10 (50%) had titers that rose over two or more time points. The FA‐positive and FA‐negative cohorts had similar proportions of pregnancies that reached critical titers—70% (28/40) and 69% (20/29), respectively. In the FA‐positive cohort 14 of 34 participants who underwent MCA‐PSV Doppler reached greater than 1.5 multiples of the median (MoM), suggestive of fetal anemia. One patient in the FA‐negative cohort reached 1.5 MoM. Conclusions: Titers frequently yield elevations that, while reflective of maternal alloimmunization, are not indicative of positive FA status or risk for HDFN in antigen‐negative pregnancies. Such results lead to unnecessary monitoring, including MCA‐PSV Doppler as well as invasive interventions. These outcomes can be avoided using methods including FA cfDNA, which has been shown to be highly accurate. These results suggest that monitoring for fetal anemia should be discontinued if FA cfDNA has determined the FA status is negative, as this will reduce downstream burdens and risks to alloimmunized patients who are not at risk for HDFN.

Genetic testing is recommended as part of an autism assessment, and most parents support genetic testing for their minor children. However, the impact on parents of receiving a monogenetic/ copy number variant diagnosis for autism in their child is not well understood. To explore this, we surveyed and interviewed parents of children in the SPARK study, a study of autism that includes genetic testing. Surveys were administered one month before and one and 12 months after parents received their child’s genetic result. Interviews were conducted approximately one month after results disclosure. A genetic diagnosis (GD) for their child appeared to reduce parents’ sense of self-blame and feelings of guilt, and this impact was relatively stable. The data also indicate a modest impact on parents’ actions related to the condition, perceptions of themselves, and some aspects of life planning for their child, as measured by quantitative instruments at one month and 12 months after receipt of results. Other measures of parental identity and expectations for their child, in contrast, showed little change following receipt of genetic findings. Overall, parents who were told that no GD was identified showed minimal changes in their responses over time. These results suggest a discernable but relatively limited impact of genetic test results on parents of children with autism. These results should be reassuring to clinicians caring for children with autism and are consistent with studies in other areas of medicine that have suggested that genetic results tend to have fewer effects—negative or positive—than were anticipated.

Objective: Carrier screening with reflex to single‐gene noninvasive prenatal testing (sgNIPT) is an alternative approach for identifying pregnancies at risk for inherited autosomal recessive conditions without the need for a sample from the reproductive partner. This study is the largest clinical validation of this approach in a general population setting.Methods: The clinical performance of carrier screening with reflex to sgNIPT for cystic fibrosis, spinal muscular atrophy, alpha thalassemias, and beta hemoglobinopathies was assessed by collecting pregnancy outcome data on patients who underwent this testing and comparing the neonatal outcome to the assay‐predicted fetal risk.Results: Of 42,067 pregnant individuals who underwent screening, 7538 carriers (17.9%) had reflex sgNIPT, and neonatal or fetal outcomes were obtained for 528 cases, including 25 affected pregnancies. Outcomes demonstrated high concordance with sgNIPT, for example, all pregnancies with 9 in 10 personalized fetal risk results were affected (positive predictive value (PPV) of 100% for the sub‐group) and the sgNIPT assay showed a sensitivity of 96.0% (95% CI: 79.65%–99.90%), specificity of 95.2% (95% CI: 92.98%–96.92%), average PPV of 50.0% (95% CI: 35.23%–64.77%), and negative predictive value (NPV) of 99.8% (95% CI: 98.84%–99.99%). The end‐to‐end performance of carrier screening with reflex to sgNIPT was calculated to have a sensitivity of 92.4% and specificity of 99.9%, which are unaffected by partner carrier screening or misattributed paternity unlike a traditional carrier screening workflow, which has a 35% sensitivity and a maximum of 25% PPV (1 in 4) in a real‐life setting.Conclusion: This study builds upon earlier findings to confirm that carrier testing with reflex to sgNIPT is highly accurate for general population screening. Given this high accuracy and an NPV of 99.8%, this workflow should be considered as an option for most of the general pregnant population. When the biological partner sample is unavailable, this workflow should be recommended as the first‐line approach.