Transgender and gender diverse individuals' perspectives on discussions of fetal sex chromosomes in obstetrics care.

In the past decade, prenatal cell-free DNA screening (cfDNA) has become ubiquitous as a screening tool for fetal aneuploidy and sex chromosomes. Healthcare provider (HCP) discussions and public perceptions of sex and gender uniquely impact transgender and gender diverse (TGD) individuals, and existing cfDNA guidelines lack recommendations regarding how to discuss sex and gender prenatally. The aim of this exploratory qualitative study was to examine TGD individuals' opinions regarding fetal sex chromosome disclosure sessions. Twelve semi-structured virtual interviews were conducted with TGD individuals regarding their perspectives on the discussion of fetal sex chromosomes by HCPs within the prenatal setting. Interviews were coded and analyzed using a reflexive thematic approach, generating four major themes: (1) Current practices in prenatal care exclude gender diverse people; (2) HCPs' responsibility to de-gender discussions of sex chromosomes in prenatal care; (3) HCPs' responsibility to acknowledge gender diversity; and (4) HCPs' influence on societal perceptions of sex and gender. More guidance is needed from professional societies regarding best practices for HCP discussions of sex chromosomes, sex, and gender. Participants recommended HCPs educate patients about sex chromosomes and their relevance to health while avoiding the conflation of sex and gender terms. Additionally, there is an acute need for trans-inclusive prenatal healthcare. Ultimately, HCPs' and organizations are in a prime position to deconstruct rigid gender binaries and promote societal inclusion of TGD people.

Postnatal genetic testing on cord blood for prenatally identified high-probability cases.

OBJECTIVE: To evaluate the utility of postnatal genetic testing on umbilical cord blood (CB) for prenatally identified high-probability fetuses. METHOD: CB for genetic testing was offered to individuals who met one of the following criteria: (i) fetal anomaly, (ii) positive non-invasive prenatal screening by cfDNA or biochemical analysis, or (iii) family history. Individuals with diagnostic testing, but not microarray, were also included when recommended by society guidelines. CB was collected at Brigham and Women's and Emerson Hospitals between 2016 and 2021. RESULTS: 448 individuals consented for cord blood testing (370 (82.6%) for fetal anomalies, 51 (11.4%) for high-probability cfDNA, and 27 (6.0%) for family history) and a total of 393 (87.7%) samples were analyzed. Genetic testing yielded a diagnosis in 92 (23.4%) neonates by karyotype (n = 37), chromosomal microarray (CMA) (n = 32), and other molecular analysis (n = 23). Testing averaged 10.3 days (range 1-118 days). 68 (73.9%) diagnoses potentially impacted neonatal management. MCC could not be definitively excluded in only 1.4% (6/418) of samples. CONCLUSION: Prenatal identification of high-probability fetuses and genetic testing on CB facilitates timely genetic diagnoses and neonatal management. Testing provides reassurance and reduces a postnatal diagnostic odyssey for high-probability neonates.

Single gene non-invasive prenatal screening for autosomal dominant conditions in a high-risk cohort.

PURPOSE: To determine the utility of single gene non-invasive prenatal screening (NIPS-SGD) in a high-risk reproductive genetics clinic. METHODS: A clinical pilot for NIPS-SGD was conducted from March 2020 to November 2021. A NIPS-SGD panel assessing pathogenic variants in 30 genes was offered to pregnant individuals for the following indications: (1) advanced sperm age ≥40 years, (2) nuchal translucency (NT) ≥ 3.5 mm, (3) fetal anomaly, or (4) family history of a condition covered by the panel. Diagnostic testing was offered concurrently. RESULTS: NIPS-SGD was ordered for 253 individuals: 88 (34.8%) for fetal anomalies, 96 (37.9%) for advanced sperm age, 37 (14.6%) for increased NT, and 5 (2.0%) for family history. Among 228 (90.1%) completed tests, 8 (3.5%) were positive. Diagnostic testing for 78 individuals revealed no false positive or negative results. Of 41 (25.9%) individuals who received a molecular diagnosis, 34 (82.9%) were outside the scope of NIPS-SGD. Positive NIPS-SGD altered medical management in five cases. CONCLUSIONS: NIPS-SGD in a high-risk population can lead to earlier prenatal diagnosis, enhanced surveillance, and targeted genetic analysis, but should not replace clinically indicated diagnostic testing. Potential incidental findings include parental diagnoses and misattributed parentage.

Genetic counseling for fetal sex prediction by NIPT: Challenges and opportunities.

Non-invasive prenatal testing (NIPT) has grown in ubiquity in the last decade and is now endorsed by Society for Maternal Fetal Medicine and American College of Obstetricians and Gynecologists as a screening tool for aneuploidy in all patients. Past studies have demonstrated a tendency among obstetrics patients to focus on the ability of NIPT to predict fetal sex chromosomes; however, data on the experiences of genetic counselors (GCs) counseling on NIPT and fetal sex prediction are limited. This mixed-methods study aimed to explore how GCs counsel about NIPT and fetal sex prediction, as well as the use of gender-inclusive language in this setting. A 36-item survey with multiple choice, Likert scale, and open-ended questions was distributed to GCs who currently offer NIPT to patients. Quantitative data were analyzed using R and qualitative data were manually analyzed and coded via inductive content analysis. A total of 147 individuals completed at least some portion of the survey. A majority of participants (68.5%) reported frequent interchangeable use of the terms 'sex' and 'gender' by patients. A majority (72.9%) of participants reported that they rarely or never discuss the difference between these terms in sessions (Spearman's rho = 0.17, p = 0.052). Seventy-five respondents (59.5%) indicated that they had taken continuing education courses on inclusive clinical practices for trans and gender-diverse (TGD) patients. Several themes arose from free responses; the most frequently identified themes were the need for thorough pretest counseling that properly describes the scope of NIPT and the challenge of discrepant pretest counseling by other healthcare providers. Results from our research identified challenges and misconceptions GCs face when offering NIPT and various tactics implemented to mitigate these. Our study highlighted the need for the standardization of pretest counseling regarding NIPT, additional guidance from professional organizations, and continuing education focused on gender-inclusive language and clinical practices.

Somatic tumor mutations in moderate risk cancer genes: Targets for germline confirmatory testing.

BACKGROUND: Recent changes in oncology practice guidelines indicate that mutations in cancer susceptibility genes identified on tumor genomic profiling (TGP) should prompt confirmatory germline testing. Our study aimed to determine the proportion of patients with TGP-identified mutations in moderate risk breast and ovarian cancer genes who previously would not have been considered for germline testing. METHODS: From January 2013 to September 2020, 7468 adult Stanford Health Care patients underwent TGP on solid tumor samples and 166 had TGP-identified mutations in moderate risk breast and ovarian cancer susceptibility genes (ATM, BRIP1, CHEK2, PALB2, RAD51C and RAD51D). Retrospective chart reviews were performed on 160 patients. Cases were analyzed to determine eligibility for germline testing using established NCCN criteria, and somatic and germline results were compared where both were available. RESULTS: Nearly half (45.3% [73/160]) of patients would not have been eligible for germline testing if not for a TGP-identified mutation in a moderate risk breast or ovarian cancer gene. Of the 64 cases that underwent germline testing, about half (51.5% [33/64]) had results that confirmed germline origin of the TGP finding. High rates of germline confirmation were found in PALB2 (100% [5/5]), ATM (40% [14/35]), CHEK2 (61.5% [8/13]), and BRIP1 (57.1% [4/7]). CONCLUSION: Our study shows that the presence of TGP-identified mutations in moderate risk breast and ovarian cancer genes increases eligibility for germline testing beyond those that would be eligible based largely on personal and family history criteria alone. Additionally, results of germline testing in these newly eligible cases supports that this expanded eligibility captures individuals with hereditary cancer syndromes that would not have otherwise been identified.