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Expanded carrier screening (ECS) intends to broadly screen healthy individuals to determine their reproductive chance for autosomal recessive (AR) and X‐linked (XL) conditions with infantile or early‐childhood onset, which may impact reproductive management (Committee Opinion 690, Obstetrics and Gynecology, 2017, 129, e35). Compared to ethnicity‐based screening, which requires accurate knowledge of ancestry for optimal test selection and appropriate risk assessment, ECS panels consist of tens to hundreds of AR and XL conditions that may be individually rare in various ancestries but offer a comprehensive approach to inherited disease screening. As such, the term "equitable carrier screening" may be preferable. This practice guideline provides evidence‐based recommendations for ECS using the GRADE Evidence to Decision framework (Guyatt et al., BMJ, 2008, 336, 995; Guyatt et al., BMJ, 2008, 336, 924). We used evidence from a recent systematic evidence review (Ramdaney et al., Genetics in Medicine, 2022, 20, 374) and compiled data from peer‐reviewed literature, scientific meetings, and clinical experience. We defined and prioritized the outcomes of informed consent, change in reproductive plans, yield in identification of at‐risk carrier pairs/pregnancies, perceived barriers to ECS, amount of provider time spent, healthcare costs, frequency of severely/profoundly affected offspring, incidental findings, uncertain findings, patient satisfaction, and provider attitudes. Despite the recognized barriers to implementation and change in management strategies, this analysis supported implementation of ECS for these outcomes. Based upon the current level of evidence, we recommend ECS be made available for all individuals considering reproduction and all pregnant reproductive pairs, as ECS presents an ethnicity‐based carrier screening alternative which does not rely on race‐based medicine. The final decision to pursue carrier screening should be directed by shared decision‐making, which takes into account specific features of patients as well as their preferences and values. As a periconceptional reproductive risk assessment tool, ECS is superior compared to ethnicity‐based carrier screening in that it both identifies more carriers of AR and XL conditions as well as eliminates a single race‐based medical practice. ECS should be offered to all who are currently pregnant, considering pregnancy, or might otherwise biologically contribute to pregnancy. Barriers to the broad implementation of and access to ECS should be identified and addressed so that test performance for carrier screening will not depend on social constructs such as race. [ABSTRACT FROM AUTHOR]

Cell-free DNA is an advancing technology with increasing applications in screening, diagnosis, and treatment for several disease processes. The shared physiologic, genetic, and epigenetic characteristics of placental physiology and tumor development have become apparent to both clinicians and researchers. Maternal malignancy has been reported as a cause of false-positive prenatal cell-free DNA screening results. The detection of multiple aneuploidies or a single autosomal monosomy increases the chance for an underlying maternal malignancy when the result is discordant with fetal diagnostic testing. There is currently no consensus guideline on counseling and evaluation of patients with concern for malignancy from cell-free DNA testing. Furthermore, laboratories differ significantly in reporting policies, terminology, and in reporting strategies and methods used for unexpected or incidental findings. The ordering practitioner is therefore tasked to understand the policies of their laboratory of choice to provide adequate pretest and posttest genetic counseling. In pretest counseling, the potential for incidental or unexpected findings or nonreportable results should be explained. With an abnormal, unanticipated, or nonreportable result, posttest counseling should include a description of possible fetal or maternal diagnoses, including malignancy. Health care professionals should explain options for further evaluation and management, including a recommendation for fetal diagnostic testing. The medical workup recommended by various authors to evaluate cancer risk is based on consensus, experience, and expert opinion. These strategies should incorporate the patient's desire for information, cost, and family and personal medical history. Ongoing research and multi-disciplinary collaboration in this area is critical to identify best practices in management of complex results from this increasingly common screening test. [ABSTRACT FROM AUTHOR]

Objective: To determine the yield of prenatal testing and screening options after identification of fetal structural abnormalities using a novel mathematical model. 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. A novel mathematical model was used to determine and compare the predicted diagnostic yields of prenatal testing and screening options. Results: Over a quarter of patients with at least one structural abnormality (28.1%, n = 222) had a genetic aberration identified that explained their phenotype. Chromosomal microarray (CMA) had the highest predicted diagnostic yield (26.8%, P <.001). Karyotype (20.8%) had similar yields as genome wide NIPT (21.2%, P =.859) and NIPT with select copy number variants (CNVs) (17.9%, P =.184). Among individuals with an isolated structural abnormality, whole exome sequencing (25.9%) and CMA (14.9%) had the highest predicted yields. Conclusion: This study introduces a novel mathematical model for predicting the potential yield of prenatal testing and screening options. This study provides further evidence that CMA has the highest predicted diagnostic yield in cases with structural abnormalities. Screening with expanded NIPT options shows potential for patients who decline invasive testing, but only in the setting of adequate pre‐test counseling. [ABSTRACT FROM AUTHOR]

Objective: To describe uptake of carrier screening by male reproductive partners of prenatal and preconception patients.Methods: A retrospective database review of all prenatal and preconception patients seen for genetic counseling in Maternal Fetal Medicine clinics was performed. Descriptive statistics and chi-square analysis were used on the data set.Results: Within the study period, 6087 patients were seen for genetic counseling, of whom 661 were identified as a carrier of an autosomal recessive disorder by their referring provider or genetic counselor. Despite guidelines recommending partner testing for risk clarification when a woman is known to be a carrier of an autosomal recessive condition, only 41.5% male partners elected carrier screening to clarify the couple's reproductive risk, with a majority of males (75%) having screening consecutively. Of all assessed variables, the only significant predictors of male carrier screening uptake were female parity and earlier gestational age (p < .0001, and p = .001, respectively).Conclusion: With less than half of male partners pursuing carrier screening when indicated, its utility becomes severely diminished. More research is needed to explore reasons why males elect or decline carrier screening. [ABSTRACT FROM AUTHOR]

The introduction of cell‐free DNA screening, or non‐invasive prenatal testing (NIPT), for chromosome abnormalities has greatly impacted prenatal care since its introduction in late 2011. We aimed to evaluate the association between the introduction of cell‐free DNA screening and indication and referral patterns for genetic counseling at a large US academic medical center by comparing the percentage of each counseling indication between the time period prior to the introduction of cell‐free DNA screening (2006–2011) and following its introduction (2012–2016) using multivariable Poisson regression models. Genetic counseling indications for positive carrier screens, average risk patients, abnormal ultrasound findings, and family history indications were significantly higher following the introduction of NIPT while advanced maternal age and abnormal maternal serum screening indications dropped significantly. We also showed that the uptake of amniocentesis dropped significantly after the introduction of cell‐free DNA screening, while chorionic villus sampling uptake increased. These results provide evidence that the introduction of new genetic screening technologies is associated with a shift in genetic counseling referral indications and an increased uptake in genetic screening. Additional research is needed to explore the impact of expanded testing options on the need for genetic counseling services. [ABSTRACT FROM AUTHOR]

Non-invasive prenatal screening provides a risk assessment for aneuploidies by utilizing cell-free DNA (cfDNA). It is recommended that cell-free DNA screening (cfDNA screening) be offered to all pregnant people regardless of a priori risk for aneuploidy. In the absence of an increased risk, alternative motives for electing cfDNA screening and different levels of informed decision making may arise. Therefore, our study aimed to characterize low-risk patients' motivations for cfDNA screening election, determine how often informed decisions are being made, and compare motivations between informed and uninformed decision makers. A survey that included a modified, validated measure of informed choice (MMIC) and questions to assess patients' motivations for cfDNA screening was offered at four MFM clinics following genetic counseling. It was found that 44% of participants (n = 100) made an uninformed decision about testing. Participants with private insurers were 4.25 times more likely to make an informed decision (95% CI = 1.10-16.37). Informed decision makers scored avoiding invasive procedures higher (p = 0.007) and ranked doing what family/friends desire lower (p = 0.005) than uninformed decision makers. While most participants scored receiving information about genetic conditions highest, 12% of participants reported fetal sex disclosure as a priority. However, this was not found to be associated with uninformed decision making. This study ultimately established that following genetic counseling, a low-risk population shared motivations with high-risk populations which highlights the importance of complete pre-test counseling for all. Future research should investigate the effect of modifying variables, such as socioeconomic status, on the performance of informed choice measures and critically evaluate the parameters that determine informed choice., (© 2024 National Society of Genetic Counselors.)

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., (© 2021 John Wiley & Sons Ltd.)

This article outlines a framework for the process of genetic counseling in the primary obstetric and gynecologic setting. Specifics regarding risk assessment, family history evaluation, genetic testing, and pretest and posttest counseling are discussed. Additionally, the article provides strategies for counseling patients effectively and addresses when a referral for additional genetic counseling by a specialized genetics provider should be considered., (Copyright © 2017 Elsevier Inc. All rights reserved.)