Parental questions about sex chromosome aneuploidies regarding sex, gender, and sexual orientation as reported by genetic counselors in a prenatal setting.

The introduction of cell-free DNA screening has resulted in increased prenatal identification of sex chromosome aneuploidies (SCAs). This study aimed to evaluate genetic counselor experiences disclosing SCAs positive prenatal screening or testing results and genetic counselor-reported parental questions regarding sex, gender, and sexual orientation. Forty-eight prenatal genetic counselors completed the survey. When asked to quantify their experiences, 97.9% of counselors reported disclosing a SCAs positive screen result within the previous year, and 81.3% disclosed a diagnostic result. Of those counselors, 53.8% reported always or often receiving parental questions about sex, 33% always or often about gender, and 25% always or often regarding sexual orientation. Counselors were asked to share examples of parental questions following a positive screen or diagnostic testing for SCAs. Parental questions were stratified by karyotype and content analysis revealed questions about the fetus' sex, anatomy, reproduction, being cisgender, gender expression, behavior, being transgender, and sexual orientation. The examples of parental questions provided by genetic counselors suggested some parents may have misconceptions about the intersection of SCAs with sex, gender, and sexual orientation following prenatal screening or diagnostic testing. The majority of counselors (83.3%) agreed to some extent that they desired further education on responding to parental questions about SCAs. Findings from this research suggest a need for genetic counseling strategies that accurately and respectfully discuss SCAs in the context of sex, gender, and sexual orientation with prenatal patients.

The Medical Process in Pregnancy Terminations for Fetal Anomaly: An Analysis of Counselling and Bereavement.

OBJECTIVES: Pregnancy termination for fetal anomaly (TOPFA) is a possible outcome of a pregnancy complicated by a fetal anomaly detected during routine prenatal care. Limited research is available on the quality of the counselling offered to women, in terms of enabling them to make an informed decision. The goal of this descriptive cohort study was to examine the medical process offered to a cohort of 151 women who underwent TOPFA in 2018 in a single tertiary mother and child hospital to identify areas for potential quality improvement. METHODS: Statistical analysis comprised basic statistical tests, Pearson's χ2 test, and logistic regression. Counselling was evaluated by two fetal health specialists. RESULTS: The counselling process was found to be minimal in 42% of cases. Counselling referrals to pediatric specialists were made in 26% of cases, with many potential explanations for this finding. Complicated bereavement was present in 39% of cases. Risk factors for complicated bereavement were explored and were found to be insufficient social support (odds ratio [OR] 6.5; 95% CI 2.0-21.0, P < 0.001), history of a mood disorder (OR 3.4; 95% CI 1.3-8.8, P < 0.01), and history of another TOPFA (OR 6.2; 95% CI 1.2-31.0, P = 0.01). Viewing the fetus after termination was not correlated with a significant reduction in complicated bereavement. CONCLUSION: The evaluation of the counselling as minimal in 42% of cases and the high prevalence of complicated bereavement call for quality improvement in the process for women who undergo TOPFA. Clinicians should be able to screen women most at risk for complicated bereavement to best orient preventive care.

Prenatal genetic counseling practices regarding recommendations for cancer genetic counseling: A retrospective chart review from two academic institutions.

Prenatal and preconception genetic counselors are trained to take patient pedigrees to evaluate for potential risks for genetic conditions, including hereditary cancer syndromes. However, little research has been published on how often prenatal/preconception genetic counselors provide recommendations for cancer genetic counseling solely based on a family history of cancer. Therefore, this study sought to (a) characterize the types of cancers recognized for a cancer genetic counseling recommendation, (b) analyze appointment indications associated with discussion documentation, and (c) investigate how often National Comprehensive Cancer Center (NCCN) genetic testing criteria for Hereditary Breast and Ovarian Cancer syndrome (HBOC) and Lynch syndrome were met and how often a recommendation for cancer genetic counseling was made. A retrospective chart review and pedigree analysis were performed for prenatal/preconception genetic counseling patients with a family history of cancer seen at two academic institutions between August 10, 2019, and December 1, 2019. In the 170 charts included, a recommendation for cancer genetic counseling was documented in 40% of all genetic counseling summaries and in 59.2% of summaries when NCCN genetic testing criteria for HBOC and/or Lynch syndrome was met. Using chi-squared and logistic regression analysis, these data support that individuals were significantly more likely to receive a recommendation when NCCN genetic testing criteria were met (OR = 5.01, p < .001) or when the family history contained two or more types of cancer (OR = 2.24, p = .02). Overall, this study identified the NCCN genetic testing criteria for HBOC and Lynch syndrome for which recommendations for cancer genetic counseling were commonly missed. This characterization suggests that continuing education for prenatal and preconception genetic counselors on updated NCCN guidelines may be helpful for improving rates of cancer genetic counseling referrals, uptake of genetic testing, and cancer screening recommendations.

To offer or request? Disclosing variants of uncertain significance in prenatal testing.

The use of genomic testing in pregnancy is increasing, giving rise to questions over how the information that is generated should be offered and returned in clinical practice. While these tests provide important information for prenatal decision-making, they can also generate information of uncertain significance. This paper critically examines three models for approaching the disclosure of variants of uncertain significance (VUS), which can arise from forms of genomic testing such as prenatal chromosomal microarray analysis (CMA). Contrary to prevailing arguments, we argue that respect for reproductive autonomy does not justify adopting a model on which an offer to disclose VUS is a routine part of genetic counselling. Instead, we contend that a commitment both to solidarity between healthcare providers and pregnant women and to the acceptance of a novel principle of caution under normative uncertainty means that we should instead adopt a model of VUS disclosure that imposes a strong presumption against offering to disclose VUS. The upshot of this is that it should be standard practice to only offer to disclose VUS when this is requested by the woman undergoing CMA. We defend our position against claims that arise from an alleged right to such information and that a presumption against an offer will lead to inequity.

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.

Ante-natal counseling in phacomatoses.

OBJECTIVES: Phacomatoses are a group of neuro-oculo-cutaneous syndromes/ neurocutaneous disorders, involving structures arising from the embryonic ectoderm. Most of phacomatoses including the most common ones:, neurofibromatosis type I and type II (NF1, NF2) and tuberosclerosis complex (TSC), are autosomal dominant genetic disorders with full penetrance and variable expression. As no effective treatment exists, the only way to prevent the disease, is by prenatal genetic diagnosis (either chorionic villus sampling-CVS or amniocentesis-AC) and termination of pregnancy or performing preimplantation genetic testing (PGT). As the risk for an affected offspring is 50% in every pregnancy of an affected parent, prenatal, and preimplantation testing are of great importance. However, those procedures are associated with technical and ethical concerns. This chapter shortly reviews the common phacomatoses emphasizes their genetics and inheritance. We will review the common methods for prenatal and preimplantation diagnoses and discuss its use in common phacomatoses. CONCLUSION: Phacomatoses are common autosomal dominant genetic conditions with variable expression. Ante-natal genetic diagnosis is an appropriate approach for family planning in individuals affected by phacomatosis or parents of an affected child.

Genetic counselor and proxy patient perceptions of genetic counselor responses to prenatal patient self-disclosure requests: Skillfulness is in the eye of the beholder.

Research demonstrates some genetic counselors self-disclose while others do not when patients' request self-disclosure. Limited psychotherapy research suggests skillfulness matters more than type of counselor response. This survey research assessed perceived skillfulness of genetic counselor self-disclosures and non-disclosures. Genetic counselors (n = 147) and proxy patients, women from the public (n = 201), read a hypothetical prenatal genetic counseling scenario and different counselor responses to the patient's question, What would you do if you were me? Participants were randomized either to a self-disclosure study (Study 1) or non-disclosure study (Study 2) and, respectively, rated the skillfulness of five personal disclosures and five professional disclosures or five decline to disclose and five redirecting non-disclosures. Counselor responses in both studies varied by intention (corrective, guiding, interpretive, literal, or reassuring). Participants also described what they thought made a response skillful. A three-way mixed ANOVA in both studies analyzed skillfulness ratings as a function of sample (proxy patient, genetic counselor), response type (personal, professional self-disclosure, or redirecting, declining non-disclosure), and response intention. Both studies found a significant three-way interaction and strong main effect for response intention. Responses rated highest in skillfulness by both genetic counselors and proxy patients in Study 1 were a guiding personal self-disclosure and a personal reassuring self-disclosure. The response rated highest in skillfulness by both samples in Study 2 was a redirecting non-disclosure with a reassuring intention. Proxy patients in both studies rated all literal responses as more skillful than genetic counselors. Participants' commonly described a skillful response as offering guidance and/or reassurance. Counselor intentions and response type appear to influence perceptions, and counselors and patients may not always agree in their perceptions. Consistent with models of practice (e.g., Reciprocal-Engagement Model), genetic counselors generally should aim to convey support and guidance in their responses to prenatal patient self-disclosure requests.

Use of a novel computerized decision aid for aneuploidy screening: a randomized controlled trial.

PURPOSE: To assess whether knowledge following use of a decision aid (DA) for aneuploidy screening and testing is inferior to knowledge in women who saw a genetic counselor (GC) only. METHODS: This is a randomized controlled noninferiority trial of pregnant women at ≤22 weeks. Women who were scheduled for GC were randomly allocated to use a DA before GC or to GC alone. The primary outcome was knowledge score, comparing women who had used the DA only to those who saw GC alone. Analysis was by intent to treat. RESULTS: Between January and October 2017, 197 women were randomized, 105 to GC only and 92 to DA use before GC. Demographics and baseline knowledge were similar between groups. Mean knowledge score following DA use was not inferior to mean knowledge score following GC only (10.4 vs. 10.6, p = 0.306). Decisional conflict was similar following completion of the DA to following GC only, but was reduced following completion of both the DA and GC compared with GC only (0.22 vs. 1.74, p = 0.003). CONCLUSION: Knowledge surrounding aneuploidy screening in women who used a DA was not inferior to knowledge in women who underwent GC. Use of the DA in addition to GC reduced decisional conflict.

Prospective observations study protocol to investigate cost-effectiveness of various prenatal test strategies after the introduction of noninvasive prenatal testing.

BACKGROUND: Among the non-invasive screening methods for the identification of fetal aneuploidy, NIPT (non-invasive prenatal testing) shows the highest sensitivity and specificity in high-risk pregnancies. Due to the low false positive rate of NIPT, it is assumed that the implementation of NIPT as a primary screening method may reduce the number of invasive fetal tests and result in a similar or lowered cost in the overall detection of Down syndrome. However, most previous studies are based on theoretical economic analysis. This study aims to determine the cost effectiveness of various prenatal test strategies, including NIPT, in real clinical settings in both low risk and high risk pregnancies. METHODS/DESIGN: In this prospective observational study, women (< 24 weeks) with singleton or twin pregnancies will be enrolled in 12 different healthcare institutions. The participants will be grouped based on the risks of fetal chromosomal abnormalities and will be counseled on the various screening or diagnostic methods, including NIPT, according to the aneuploidy risk. The final decision on screening or diagnostic methods will be made by patients after counseling. Questionnaires regarding factors affecting the decision on prenatal test will be answered by the participants and physicians. The economic analysis on final total costs will be compared according to the various prenatal test strategies. DISCUSSION: The results of present study are expected to have a significant impact on national policies in determining Korean prenatal screening test strategies and to help in developing novel and effective prenatal screening tests in the future.

Choosing between Higher and Lower Resolution Microarrays: do Pregnant Women Have Sufficient Knowledge to Make Informed Choices Consistent with their Attitude?

Developments in prenatal testing allow the detection of more findings. SNP arrays in prenatal diagnosis (PND) can be analyzed at 0.5 Mb resolution detecting more clinically relevant anomalies, or at 5 Mb resolution. We investigated whether women had sufficient knowledge to make informed choices regarding the scope of their prenatal test that were consistent with their attitude. Pregnant women could choose between testing at 5 or at 0.5 Mb array. Consenting women (N = 69) received pre-test genetic counseling by phone and filled out the Measure of Informed Choice questionnaire designed for this study. Choices based on sufficient knowledge and consistent with attitude were considered informed. Sixty-two percent of the women made an adequately informed choice, based on sufficient knowledge and attitude-consistent with their choice of microarray resolution. Women who made an informed choice, opted for 0.5 Mb array resolution more often. There were no differences between women making adequately informed or less informed choices regarding level of experienced anxiety or doubts. Over time on T0 and T1, anxiety and doubts significantly decreased. While previous studies demonstrated that knowledge is an important component in informed decision-making, this study underlines that a consistent attitude might be equally important for decision-making. We advocate more focus on attitude-consistency and deliberation as compared to only a strong focus on knowledge.

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.

Genesurance Counseling: Patient Perspectives.

Genetic counselors (GCs) have reported an increase in discussion of insurance-related, or "genesurance," topics during genetic counseling sessions. Despite increasing frequency, there have been no studies examining patient expectations of GCs in these discussions. This study aimed to explore patient expectations of GCs in these discussions, as well as examine factors that may impact expectations. A 38-item survey was administered prior to patients receiving prenatal or cancer genetic counseling at 11 clinic sites across UTHealth, Baylor College of Medicine, and Sanford Health, with 360 responses analyzed. Key variables were analyzed using descriptive statistics, chi-square analysis, and multivariate logistic regression to assess associations between factors and control for potential confounders. Over 75% of patients expected GCs to discuss genesurance topics during a genetic counseling session. The majority of patients (78%) expected GCs to provide an estimated out-of-pocket cost, know if a test is a covered benefit (77%), and provide referral information for further questions (76%). Two additional expectations, considered to be unrealistic in most clinical settings, included expecting GCs to know the patient's specific insurance plan and coverage information (57%) and provide an exact out-of-pocket cost (41%). Ethnicity was the only significant predictor of response for these two expectations, as African Americans and Hispanics were more likely than Caucasians to have these beliefs. While the patient participants felt that GCs were primarily responsible for initiating these conversations, they also reported a personal sense of responsibility for raising questions. This study demonstrates that patients may expect GCs to address genesurance topics in a genetic counseling session, with specific expectations about the cost and coverage of genetic tests. Further studies will establish the most effective way to communicate this information to patients and examine whether and where within the scope of GC practice, genesurance discussions fall.

Attitudes Toward Discussing Approved and Investigational Treatments for Cystic Fibrosis in Prenatal Genetic Counseling Practice.

This project aimed to explore the attitudes of prenatal genetic counselors toward discussion of novel approved and experimental CF treatments in the prenatal setting, and to assess how knowledge of genotype-specific, targeted treatments may influence their current practices. Targeted treatments have the potential to impact the health-related quality of life of individuals affected with CF and therefore, knowledge of the availability of such treatments may influence the decision-making process of parents who receive a fetal diagnosis of CF. Using the 2012 FDA approval and introduction of ivacaftor into CF clinical practice as a case study, a survey was designed to explore the opinions and practices of prenatal genetic counselors with regard to counseling for a prenatal diagnosis of CF, and how those practices might be impacted by the availability of a new genotype-specific treatment. Approximately 800 genetic counselors were sent questionnaires in January of 2013. Respondents were provided information about this treatment and were asked to rate its perceived benefits, along with the likelihood that they would discuss potential benefits and limitations with parents receiving a prenatal diagnosis of CF. One-hundred sixty-nine prenatal genetic counselors (21.1 %) responded to the survey. Results indicated that 80 % of respondents 'never heard of the drug', or they were 'not exactly sure' what it was. After reading the materials provided, counselors felt the new treatment would have 'some' or a 'significant' impact on an affected individual's life. Their opinions varied on what information about this treatment they would choose to discuss with their patients; even if the treatment is currently FDA approved and clinically available for affected individuals with the genotype of the fetus. However, they would 'definitely' refer these patients to a specialist to discuss targeted treatments further. Most prenatal genetic counselors indicated there are certain scenarios in the prenatal setting which warrant a discussion of targeted treatments for CF, at least on some level. Counselor's views on sharing information about new treatment options are shaped by their familiarity with the treatment and their perception of its benefits and limitations, their comfort discussing these subjects, and their interpretation of the genetic counselor's role. Most genetic counselors had never heard of ivacaftor or Kalydeco™ prior to taking the survey. Therefore, counselors need to be better educated about the availability of CFTR mutation-based treatments before they will be able to incorporate discussion of new treatment options into their counseling.

Spiritual Exploration in the Prenatal Genetic Counseling Session.

Religion and spirituality (R/S) are important components of many individuals' lives, and spirituality is often employed by women coping with pregnancy complications. To characterize how prenatal genetic counselors might address spiritual issues with patients, 283 English and Spanish speaking women receiving prenatal genetic counseling in Houston, Texas were surveyed post-counseling using both the Brief RCope and questions regarding interest in spiritual exploration. Genetic counselors were concurrently surveyed to identify religious/spiritual language used within sessions and perceived importance of R/S. Genetic counselors were significantly more likely to identify R/S as important to a patient when patients used religious/spiritual language (p < 0.001). Conversely, when no religious/spiritual terms were present, the counselor felt uncertain about the importance of R/S 63 % of the time. However, 67 % of patients reported that they felt comfortable sharing their faith as it relates to their pregnancy, and 93 % reported using positive religious coping. Less than 25 % reported a desire for overt religious actions such as prayer or scripture exploration. Therefore, most patients' desires for spiritual exploration center in the decision making and coping processes that are in line with the genetic counseling scope of practice. Thus, counselors should feel empowered to incorporate spiritual exploration into their patient conversations.

Clients' Perception of Outcome of Team-Based Prenatal and Reproductive Genetic Counseling in Serbian Service Using the Perceived Personal Control (PPC) Questionnaire.

This is the first study in Serbia and the region of South-East Europe dedicated to clients' perception of outcome and efficiency of prenatal and reproductive genetic counseling. The primary aim of this study was to assess overall value and success of genetic counseling in prenatal and reproductive care with regard to perceived personal control of clients, reflecting also in a part patient comprehension, knowledge retention, and empowerment in decision-making. The standardized Perceived Personal Control questionnaire (PPC) was used for the assessment of 239 female participants. First, we performed a complete validation of the psychometric characteristics of the Serbian-language version of the PPC questionnaire. The validation of the questionnaire permits other researchers from Serbian-speaking regions of South-East Europe to use this standard instrument to assess the effectiveness of prenatal genetic counseling in their communities and analyze advantages and disadvantages of their counseling models. We also measured social and demographic characteristics of participants. Further, we analyzed effects of our team-based prenatal and reproductive genetic counseling model through (a) calculation of PPC scores at three different stages (before initial, after initial, and before second counseling session), and (b) by assessing participants' responses by indication for referral (advanced maternal age, abnormal biochemical screening, family history of hereditary disorders, maternal exposure to drugs, exposure to radiation, exposure to infective agents, infertility or recurrent abortions, and miscellaneous). The results indicate that participants' knowledge after initial counseling increased significantly and after that remained stable and sustainable. A satisfactory level of confidence among participants had been achieved, in that many felt an increased sense of control over their situation and emotional response to it. Indirectly, these results indicate the success of a team-based prenatal genetic counseling model, which has not been assessed in the literature to date.

"We are just not sure what that means or if it's relevant": Uncertainty when gathering family history information in South African prenatal genetic counseling consultations.

Uncertainty impacts the process of health communication. The management and tolerance of uncertainty during healthcare discussions have gained renewed focus due to the growing challenge of obtaining and delivering complex health information, and the offer of health services in diverse contexts. Prenatal genetic counseling (GC) provides education, support and testing options for patients and couples facing a genetic or congenital diagnosis or risk during pregnancy. Gathering detailed and accurate family history information is essential to determine a patient's genetic risk. In South Africa, contextual factors such as patient literacy, language diversity, limited written patient health records, and a lack of familiarity with GC services may increase the potential for misunderstandings during GC consultations. This study uses a qualitative sociolinguistic approach to analyse 9 video-recorded South African prenatal GC consultations to understand the impact of uncertainty on the process of gathering family history information. The findings reveal uncertainty is introduced in different ways during family history taking. This includes when patients have no knowledge about their family history; when they have some knowledge but the details are unclear; or when patients have knowledge but the details are confusing. Uncertainty can lead to interactional trouble in the form of knowledge asymmetries, interrogative questioning, reversals in epistemic authority, and the potential for mistrust. Suggestions are made for how genetic specialists can manage uncertainty in GC family history taking. These include recognizing contextual sources of uncertainty, understanding how patients may respond to uncertainty and being aware of personal responses to moments of discomfort. Specific communication training recommendations and video-based sociolinguistic methods to enhance reflection and communication practice are highlighted. These approaches may enhance the effectiveness of GC communication and strengthen patient-specialist relationships, especially in diverse settings.

Incidence of occult cleft palate on prenatal magnetic resonance images obtained for non-cleft indications.

Prenatal diagnosis of craniofacial anomalies has improved family education and preparedness. Isolated cleft palate, however, remains difficult to identify sonographically. The aim of this study was to investigate the rate of incidental cleft palate identified on fetal magnetic resonance imaging (MRI) following the ultrasound detection of non-cleft abnormalities. This was a retrospective study of pregnant women who had fetal MRI performed between 2003 and 2017. To be included, the woman had to have been referred for fetal imaging for a non-cleft indication, with subsequent identification of an isolated cleft palate on MRI. Fetuses with a postnatal diagnosis of Robin sequence were excluded. The study sample included 30 women. Mean gestational age at MRI was 24 weeks 4 days± 38 days. Most referrals (76.7%) were for non-cleft craniofacial anomalies, of which micrognathia was the most common (63.3%). The annual incidence of occult cleft palate diagnosis was 0.4%, and a genetic syndrome was suspected based on imaging findings in 76.7%. Although rare, isolated cleft palate found incidentally on fetal imaging led to concern for a genetic syndrome in a high percentage of cases. This suggests that early referral for fetal MRI may provide critical information when sonographic fetal anomalies have been identified.

Genetic Evaluation of the Parents Following Demise of the Index Case: Report of a Family with Fucosidosis.

It is common in obstetric practice to encounter couples who seek prenatal genetic counseling and testing in view of history of known or suspected genetic disorders in the previous offspring or in other family members. Recent advances in genetic testing techniques, especially the availability of the next-generation sequencing (NGS) technology, have greatly facilitated genetic evaluation of the proband and/or the consultand couple and enabled provision of accurate genetic counseling and prenatal genetic testing in such clinical scenarios. However, even in this era of NGS, comprehensive clinical history taking and detailed phenotype characterization through clinical examination and thorough perusal of available medical records, are very important and essential for accurate diagnosis, as reiterated by this report of a 30-year-old third gravida, who was referred for prenatal genetic counseling and testing, in view of history of death of the first offspring due to a suspected neurogenetic disorder. Retrospective clinical diagnosis for the deceased index child with the help of available medical records and reports, followed by relevant NGS-based clinical exome sequencing of the couple, helped to arrive at a definitive diagnosis of fucosidosis, based on which accurate prenatal genetic testing could be done.

Case Report: Prenatal Genetic Counseling to Parents of Fetuses Suspected of Having Ambiguous Genitalia.

The occurrence of fetuses suspected of having ambiguous genitalia will likely increase in the future. Currently, the impact of prenatal genetic counseling on parents' understanding and psychological preparedness has not been addressed. We provided prenatal genetic counseling to parents of two fetuses suspected of ambiguous genitalia. Case 1: At 22 weeks of gestation, swelling of the labia majora, and a clitoris-like structure were noted despite 46,XY detected in amniotic fluid cells. Case 2: At 28 weeks of gestation, bladder exstrophy and a scrotum-like structure were noted. At 32 weeks (Case 1) and 37 weeks (Case 2) of gestation, we shared information with parents regarding the possible difficulty of legal sex assignment at birth, and a scenario for registration of the birth certificate. At birth, both babies presented with ambiguous genitalia. For both cases, the parents remained calm on seeing their baby's genitalia for the first time. After a month, we shared medical information with parents, including karyotype, testosterone production capacity, and surgical schedule. In both cases parents assigned their respective baby's legal sex as male. Several months later, parents were questioned on prenatal genetic counseling. Case 1: Mother, "I was prepared to address our baby's genitalia calmly." Father, "I understood the procedure of legal sex assignment." Case 2: Mother, "Without counseling, I would have been more upset and worried." Father, "We were assured that multidisciplinary experts would support us." Prenatal genetic counseling provides reassurance to parents, who remain informed and emotionally secure throughout the legal sex assignment of their child.

A Randomized Controlled Trial on the Influence of Prenatal Counseling on the Attitudes and Preferences Toward Invasive Prenatal Testing Among Women in Their First Trimester of Pregnancy (INVASIVE).

OBJECTIVE: To assess the impact of prenatal genetic counseling on the attitudes and preferences toward invasive testing in first-trimester pregnant women. METHODS: This is a randomized open-label study, of pregnant women undergoing first trimester combined screening for aneuploidies. Women were divided into the experimental or control groups in a 1:1 design. The intervention consisted of 15-min extra counseling about prenatal screening and diagnosis. The main outcome was the desire to choose an invasive testing as their first prenatal testing option which was measured as absolute risk. RESULTS: After excluding those with incomplete data, 75 women remained in the experimental group and 75 as controls. Women receiving counseling were 32% more likely to choose an invasive prenatal testing as their first-line option after extra 15-min extensive counseling, reducing the first-trimester combined screening by 20% and the cell-free DNA by 12%. If given the opportunity, 59% of the women would like to be able to choose the prenatal test that suits their needs. CONCLUSION: Women given an extensive prenatal counseling are more likely to choose an invasive testing as their first-line test in spite of the concerning risks. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT04119349.