Expanded carrier screening in the United States: A systematic evidence review exploring client and provider experiences.

The aim of carrier screening is to identify prospective parents at risk of having a pregnancy affected with an autosomal recessive or X-linked disorder. Though minimal guideline-based screening is available, expanded carrier screening (ECS) is quickly becoming a feasible option for the general population due to its growing availability and affordability. However, the impact of ECS on clients and providers remains relatively unexplored. We performed a systematic evidence review to identify publications describing client-, provider-, and test-related outcomes. We searched several biomedical databases for articles published between January 1, 2003 and May 31, 2021. Studies were eligible for inclusion if they described genetic counseling and/or genetic testing for carrier screening (minimal guideline-based or ECS) in a prenatal or preconception setting in the United States. Title and abstract screening were performed using the Raayan web application or customized Google Forms. Full-text review and data extraction of included articles were performed using custom Google Forms. Two researchers performed a multistep selection process independently for validation purposes. Of 5413 unique articles screened, 36 studies were included with several studies contributing to multiple outcomes. Twenty described outcomes relating to patients/clients, 10 described provider-based outcomes, and 16 described test-based outcomes. Findings suggest that client and provider perceptions of ECS and minimal guideline-based carrier screening are multifaceted. Though clients have expressed desire for ECS, clinical uptake and impact on reproductive decision-making varies. Additionally, though genetic counselors seem to be comfortable with ECS, most other reproductive care providers seem to prefer minimal guideline or ancestry-based screening due to perceived barriers, such as time needed for ECS results disclosure and follow-up, as well as the desire to have panels set by professional societies/recommendations. There are limitations within the gathered literature, leading to potential uncertainty in the generalizability of our review. We outline several recommendations for future studies, including the need to examine variant interpretation and use of next-generation sequencing.

Utility of expanded carrier screening in pregnancies with ultrasound abnormalities.

OBJECTIVE: Explore the utility of expanded carrier screening in evaluating heritable causes of congenital anomalies detected by prenatal ultrasound. METHOD: A retrospective chart review was conducted to collect structural abnormality and genetic testing data on infants who were evaluated postnatally by a medical geneticist. These were used to determine if expanded carrier screening could have determined the etiology prior to delivery. Additionally, recessive and X-linked conditions on clinically available carrier screening panels were evaluated to determine the number of conditions associated with abnormal ultrasound findings. RESULTS: Our retrospective chart review found 222 patients with genetic etiologies, including eight unique autosomal recessive conditions and six X-linked conditions in the 23% who underwent exome sequencing. Of these 14 unique conditions detected, three were included on a list of 271 conditions for which screening was available in 2019 and five were included on a 500 condition panel available in 2020. A literature review was performed on the list of 271 conditions and 88 were reported to be associated with one or more ultrasound abnormalities. CONCLUSION: This study demonstrates limited but potential utility for expanded carrier screening to determine the underlying etiology of congenital anomalies.

Attitudes Toward and Uptake of Prenatal Genetic Screening and Testing in Twin Pregnancies.

The rate of twinning is rising and since the introduction of non-invasive prenatal testing, interest in and uptake of genetic screening and testing in twin pregnancies has not been investigated. This study aimed to explore the attitudes toward and uptake of current prenatal genetic screening and diagnostic testing options for fetal aneuploidy in twin pregnancies. Women being seen for genetic counseling with twin gestations were recruited for participation in a descriptive study with questionnaire (n = 42) and semi-structured phone interview (n = 15). Women were significantly more in favor of screening than diagnostic testing (p = 0.049). Sixty-nine (n = 25) percent elected screening, while one participant had a diagnostic procedure. Women were interested in screening for preparation or reassurance despite having concerns about accuracy and uncertainty. Most women (86%) felt they would make the same decision in a singleton pregnancy. Despite this, 48% cited twin pregnancy as influential to some degree. Information learned from providers, past experiences, and family and friends were also cited as influencing and anchoring factors, suggesting that tailoring prenatal genetic counseling sessions for twins might parallel that of singletons. No significant differences between natural and assisted conception patients were found. Although it did not alter patient decisions, genetic counseling was used as a platform to raise concerns and gather information.

Finding Middle Ground in Constructing a Clinically Useful Expanded Carrier Screening Panel.

Expanded carrier screening for autosomal-recessive conditions effectively identifies more carrier couples than traditional guideline-based carrier screening. However, clinically available expanded carrier screening panels include numerous conditions, some of which have questionable clinical utility as a result of very low carrier frequency, low or unknown testing sensitivity, and mild or incompletely penetrant phenotypes. Using the 2013 American College of Medical Genetics and Genomics Position Statement on Prenatal and Preconception Expanded Carrier Screening and the 2017 American College of Obstetricians and Gynecologists' Committee Opinion on Carrier Screening in the Age of Genomic Medicine as guidance, we propose specific criteria for the development of expanded carrier screening panels that will maximize clinical utility and minimize patient stress, unnecessary cost of follow-up testing, and clinician time spent facilitating and performing follow-up counseling and testing. We identified 96 conditions that meet our proposed criteria, far more than current guidelines recommend. On the other hand, a considerable percentage (73%) of conditions on current expanded carrier screen panels does not meet our proposed criteria. The purpose of this commentary is to acknowledge the benefits of expanded panels, but to also recognize that in their current state, we are putting patients at risk for undue stress and spending excessive time and money on follow-up testing for remarkably rare or mild conditions and conditions with low screening performance. We encourage laboratories and clinicians to work together to create the most clinically useful screening panels for patients desiring reproductive risk information.