What knowledge is required for an informed choice related to non-invasive prenatal screening?

Non-invasive prenatal screening (NIPS) using cell-free DNA is a screening test for fetal aneuploidy offered by a variety of prenatal healthcare providers. Guidelines for genetic screening consistently recommend that providers facilitate informed choices, which have been associated with better psychological and clinical outcomes than uninformed choices. The multidimensional measure of informed choice (MMIC) is a widely used and theory-based measure that combines knowledge, values, and behavior to classify decisions as either informed or uniformed. We implemented a previously validated version of the MMIC for women offered NIPS to describe the choices made by women receiving prenatal care at the Vanderbilt University Medical Center. The survey included the Ottawa Decisional Conflict scale, an outcome measure used for validation of choice categorization. We found that most women (87%) made an informed choice about NIPS. Of the women categorized as uninformed, 67% had insufficient knowledge, and 33% had an attitude discordant with their decision. The vast majority of respondents (92.5%) underwent NIPS and had a positive attitude toward screening (94.3%). Ethnicity (p = 0.04) and education (p = 0.01) were found to be significantly associated with informed choice. Decisional conflict was extremely low among all participants, with only 5.6% of all participants demonstrating any form of decisional conflict, and all being categorized as having made an informed choice. This study suggests that pre-test counseling by a genetic counselor results in high rates of informed choice and low-decisional conflict amongst women offered NIPS by genetic counselors, though more research is required to determine if rates of informed choice remain high when NIPS is offered by other prenatal providers.

The COVID-19 pandemic and reproductive genetic counseling: Changes in access and service delivery at an academic medical center in the United States.

The COVID-19 pandemic widely disrupted the delivery of healthcare services, including genetic counseling. To ensure continuity of care, the reproductive genetic counselors at a large academic medical center in the United States rapidly transitioned their practice from 90% in-person patient consultations to a predominantly telehealth model. The present study describes this transition in regard to patient access to genetic counseling and genetic screening. A chart review of patients seen by the reproductive genetic counselors from January 2020 to August 2020 was completed. The time frame included the three months prior to the COVID-19 pandemic and the first five months during COVID-19. Patient demographics and clinical and appointment data were compared between the pre-COVID-19 and during-COVID-19 timeframes. Overall, 88.6% of patients were seen via telehealth during COVID-19 and there was no significant difference based upon patient age (p = .20), indication for appointment (p = .06), or gestational age (p = .06). However, non-English speaking patients were more often seen in-person than by telehealth (p < .001), and more patients residing farther from the clinic were seen via telehealth (p = .004). During-COVID-19 results for prenatal cell-free DNA screening and expanded carrier screening were delayed (p < .001). Additionally, after consenting to screening, patients seen during COVID-19 were more likely to not complete a sample collection for their intended screening when compared to those seen pre-COVID-19 (OR = 6.15, 95% CI = 1.43-26.70, p = .015). Overall, this study supports that access to genetic counseling services and genetic screening can be maintained during a global pandemic like COVID-19. Genetic counselors are well-equipped to pivot swiftly during challenging times; however, they must continue to work to address other barriers to accessing genetic services, especially for non-English speaking populations. Future studies are needed to pose solutions to the obstacles confronted in this service delivery model during a global pandemic.

Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in the etiology of ACDMPV.