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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. [ABSTRACT FROM AUTHOR]

Genomic microarray may detect susceptibility loci (SL) for neurodevelopmental disorders such as autism and epilepsy, with a yet unquantifiable risk for the fetus. The prenatal disclosure of susceptibility loci is a topic of much debate. Many health care professionals fear that reporting susceptibility loci may put a psychological burden on pregnant couples. It is our policy to disclose prenatal susceptibility loci as we recognize them as actionable for prospective parents. The aim of this report was to evaluate the psychological impact of disclosing a prenatal diagnosis of susceptibility loci. The psychological impact of disclosing susceptibility loci was evaluated in the first patients who received such results. Eight out of 15 women who had a susceptibility locus disclosed and four of their partners consented to share their experiences through a telephonic evaluation ( n = 12). Follow-up time ranged from 3 to 15 months after their prenatal test result. The reporting of susceptibility loci was initially 'shocking' for five parents while the other seven felt 'worried'. Ten out of 12 participants indicated they would like to be informed about the susceptibility locus again, two were unsure. Most had no enduring worries. Participants unanimously indicated that pregnant couples should have an individualized pre-test choice about susceptibility loci (non)disclosure. We observed no negative psychological impact with the prenatal diagnosis and disclosure of SL on participants. A key factor in mitigating parental anxiety with SL disclosure appears to be post-test genetic counseling. Our report confirms that pregnant women and their partners prefer an individualized choice regarding the scope of prenatal testing. [ABSTRACT FROM AUTHOR]

Frontotemporal dementia (FTD) is the second most prevalent dementia after Alzheimer’s disease (AD). We compared 29 FTD and 90 AD caregivers with respect to burden, health-related quality of life (HQoL) and coping. FTD caregivers were more burdened than AD caregivers, and caregivers of patients who were demented for shorter duration had lower HQoL. We furthermore compared the 29 FTD caregivers with 34 caregivers of institutionalized FTD patients to understand their specific caregiver issues. Caregivers of FTD patients institutionalized after shorter dementia duration were most burdened and affected in their HQoL. Overall, passive coping strategies were associated with increased burden and decreased HQoL. We recommend that FTD caregivers be offered more support than AD caregivers. Furthermore, we suggest that interventions target passive coping strategies. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Given the potential large ethical and societal implications of human germline gene editing (HGGE) the urgent need for public and stakeholder engagement (PSE) has been repeatedly expressed. In this short communication, we aim to provide directions for broad and inclusive PSE by emphasizing the importance of futures literacy, which is a skill to imagine diverse and multiple futures and to use these as lenses to look at the present anew. By first addressing "what if" questions in PSE, different futures come into focus and limitations that arise when starting with the "whether" or "how" questions about HGGE can be avoided. Futures literacy can also aid in the goal of societal alignment, as "what if" questions can be answered in many different ways, thereby opening up the conversation to explore a multitude of values and needs of various publics. Broad and inclusive PSE on HGGE starts with asking the right questions., (© 2023. The Author(s).)

Public engagement for Human Germline Genome Editing (HGGE) has often been called for, for example by the WHO. However, the impact of public engagement remains largely unknown. This study reports on public engagement outcomes in the context of a public dialogue project about HGGE in the Netherlands; the DNA-dialogue. The aim was to inquire opinions and opinion change regarding HGGE. A questionnaire was distributed on a national level (n = 2381) and a dialogue level (n = 414). The results indicate that the majority of the Dutch population agrees with the use of HGGE to prevent severe genetic diseases (68.6%), unlike the use to protect against infectious diseases (39.7%), or for enhancement (8.5%). No indications of change in these acceptance rates as a result of dialogue participation were found. The results did provide a tentative indication that participation in dialogue may lead to less negative opinions about HGGE (χ 2 (1) = 5.14, p = 0.023, OR = 0.56, 95% CI [0.34, 0.93]). While it was not a goal of the project to make people more accepting towards HGGE, this might be the effect of exposure to opinions that are less often heard in the global debate. We conclude that dialogue may lead to different outcomes for different people, depending on their characteristics and their entrance attitude, but does not appear to systematically direct people towards a certain opinion. The self-reported, impacts of dialogue participation included no impact, strengthening of opinion, enabling of forming a first opinion, more insight into the potential implications of HGGE, and a better understanding of other people's perspectives., (© 2022. The Author(s), under exclusive licence to European Society of Human Genetics.)

Objective: We conducted a survey-based discrete-choice experiment (DCE) to understand the test features that drive women's preferences for prenatal genomic testing, and explore variation across countries., Methods: Five test attributes were identified as being important for decision-making through a literature review, qualitative interviews and quantitative scoring exercise. Twelve scenarios were constructed in which respondents choose between two invasive tests or no test. Women from eight countries who delivered a baby in the previous 24 months completed a DCE presenting these scenarios. Choices were modeled using conditional logit regression analysis., Results: Surveys from 1239 women (Australia: n = 178; China: n = 179; Denmark: n = 88; Netherlands: n = 177; Singapore: n = 90; Sweden: n = 178; UK: n = 174; USA: n = 175) were analyzed. The key attribute affecting preferences was a test with the highest diagnostic yield (p < 0.01). Women preferred tests with short turnaround times (p < 0.01), and tests reporting variants of uncertain significance (VUS; p < 0.01) and secondary findings (SFs; p < 0.01). Several country-specific differences were identified, including time to get a result, who explains the result, and the return of VUS and SFs., Conclusion: Most women want maximum information from prenatal genomic tests, but our findings highlight country-based differences. Global consensus on how to return uncertain results is not necessarily realistic or desirable., (© 2022 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Prenatal DNA tests, such as chromosomal microarray analysis or exome sequencing, increase the likelihood of receiving a diagnosis when fetal structural anomalies are identified. However, some parents will receive uncertain results such as variants of uncertain significance and secondary findings. We aimed to develop a set of attributes and associated levels for a discrete-choice experiment (DCE) that will examine parents' preferences for tests that may reveal uncertain test results. A two phase mixed-methods approach was used to develop attributes for the DCE. In Phase 1, a "long list" of candidate attributes were identified via two approaches: 1) a systematic review of the literature around parental experiences of uncertainty following prenatal testing; 2) 16 semi-structured interviews with parents who had experienced uncertainty during pregnancy and 25 health professionals who return uncertain prenatal results. In Phase 2, a quantitative scoring exercise with parents prioritised the candidate attributes. Clinically appropriate levels for each attribute were then developed. A final set of five attributes and levels were identified: likelihood of getting a result, reporting of variants of uncertain significance, reporting of secondary findings, time taken to receive results, and who tells you about your result. These attributes will be used in an international DCE study to investigate preferences and differences across countries. This research will inform best practice for professionals supporting parents to manage uncertainty in the prenatal setting., Competing Interests: The authors have read the journal’s policy and have the following competing interests: JB received travel support from Illumina to attend conferences. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Even if the predominant model of science communication with the public is now based on dialogue, many experts still adhere to the outdated deficit model of informing the public., (© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

For years, calls for public involvement in the debate concerning the acceptability of human germline genome editing (HGGE) have been made. A multidisciplinary consortium of 11 organizations in the Netherlands organized a broad societal dialogue to inquire about the views of Dutch society toward HGGE. The project aimed to reach a wide and diverse audience and to stimulate a collective process of deliberative opinion forming and reflection. To that end, several instruments and formats were developed and employed. We present the results of 27 moderated dialogues organized between October 2019 and October 2020. Overall, participants of the dialogues were capable of assessing and discussing the subject of HGGE in a nuanced way. Analysis of these dialogues shows that in general, participants had no fundamental and absolute objections toward HGGE technology. However, they only deemed HGGE to be acceptable when it is used to prevent serious heritable diseases and under strict conditions, without affecting important (societal) values. There was a small group of participants who found HGGE fundamentally unacceptable because it would cross natural, socio-ethical, or religious boundaries.

Objectives: To conduct qualitative interviews with healthcare providers working in different countries to understand their experiences of dealing with uncertain results from prenatal chromosome microarray analysis (CMA) and exome sequencing (ES)., Methods: Semi-structured interviews with 31 healthcare providers who report or return prenatal CMA and/or ES results (clinicians, genetic counsellors and clinical scientists) in six countries with differing healthcare systems; Australia (4), Denmark (5), Netherlands (6), Singapore (4), Sweden (6) and United Kingdom (6). The topic guide explored the main sources of uncertainty and their management., Results: There was variation in reporting practices both between and across countries for variants of uncertain significance, however, there was broad agreement on reporting practices for incidental findings. There was also variation in who decides what results are reported (clinical scientists or clinicians). Technical limitations and lack of knowledge (to classify variants and of prenatal phenotypes) were significant challenges, as were turnaround times and lack of guidelines., Conclusion: Health professionals around the globe are dealing with similar sources of uncertainty, but managing them in different ways, Continued dialogue with international colleagues on ways of managing uncertain results is important to compare and contrast the benefits and limitations of the different approaches., (© 2021 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

For a number of prospective parents, uncertainty during pregnancy starts when an anomaly is found during a routine fetal anomaly scan. This may be followed by numerous tests to determine the etiology and nature of the anomaly. In this study, we aimed to understand how prospective parents perceive and manage uncertainty after being confronted with a structural anomaly during their routine ultrasound. Han's taxonomy of uncertainty was used as a framework to identify and understand the different types of uncertainty experienced. Interviews were held in the UK (n = 8 women and n = 1 male partner) and in the Netherlands (n = 7 women) with participants who had experienced uncertainty in their pregnancy after a fetal scan. Data were analyzed using thematic analysis, and the uncertainties experienced by parents were mapped against the dimensions of the Han taxonomy (sources, issues, and locus). Participants' experience of uncertainty was relevant to all dimensions and subcategories of the Han taxonomy, showing its applicability in the prenatal setting. Sources of uncertainty included receiving probabilistic or ambiguous information about the anomaly, or information that was complex and challenging to understand. Issues of uncertainty included were those that were scientific-such as a probable diagnosis with no further information, personal-such as the emotional impact of uncertainty, and practical-such as limited information about medical procedures and practical aspects of care. Additionally, participants described what helped them to manage uncertainty. This included active coping strategies such as searching for information on the Internet, external coping resources such as seeking social support, and internal coping resources such as using positivity and hope. Several recommendations for the healthcare professional to minimize uncertainty and help the patient deal with uncertainty have been proposed based on these findings., (© 2020 The Authors. Journal of Genetic Counseling published by Wiley Periodicals LLC on behalf of National Society of Genetic Counselors.)

Introduction: A common concern regarding the introduction of chromosomal microarray in prenatal testing is the concomitant identification of an uncertain copy number variant (CNV) where significance and clinical implication for the unborn child can be difficult or impossible to predict. Following the identification of an uncertain CNV, prospective parents may decide to continue the pregnancy. The aim of this study was to explore how prospective parents manage uncertainty and experience pregnancy in light of an uncertain CNV result., Material and Methods: Qualitative interviews with 16 women and 10 partners who had received a prenatally diagnosed, uncertain CNV. Participants were recruited from the Aarhus University Hospital, Denmark and most were interviewed in their homes 1-14 weeks after birth. Data were analyzed using thematic analysis., Results: Following the CNV diagnosis, some couples focused on the severe syndromes ruled out by the result, whereas others were more concerned with the new potential risks, for example, learning disabilities. Most couples did not remember the actual diagnosis, but all described a number of attention points generated by the CNV result. During pregnancy, the couples used various strategies to limit worry and enjoy their pregnancy, such as limiting information seeking, reducing talk of the CNV, and deferring thoughts of potential consequences. Furthermore, ultrasound was considered a valuable resource for reducing worry as it provided reassurance about the development of the baby. Inherited CNVs caused relief on one hand, but also feelings of responsibility for the child's potential challenges. After birth, worry decreased considerably, but all couples paid some extra attention to the child's development, while also being alert to the risk of wrongfully interpreting the child's development in terms of the CNV. Eleven couples expressed satisfaction with knowing about the child's CNV, whereas five couples would rather not have known., Conclusions: The results indicate that health professionals should be mindful of terminology, remember to point out what has been ruled out by the CNV result, and discuss potential coping strategies with the couple. Furthermore, these couples may have a higher need for ultrasound during pregnancy to help reduce worry. More research is needed on the families' long-term coping., (© 2020 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: Two technological innovations in the last decade significantly influenced the diagnostic yield of prenatal cytogenetic testing: genomic microarray allowing high resolution analysis and noninvasive prenatal testing (NIPT) focusing on aneuploidy. To anticipate future trends in prenatal screening and diagnosis, we evaluated the number of invasive tests in our center and the number of aberrant cases diagnosed in the last decade., Methods: We retrospectively analyzed fetal chromosomal aberrations diagnosed in 2009-2018 in 8,608 pregnancies without ultrasound anomalies., Results: The introduction of NIPT as the first-tier test led to a substantial decrease in the number of invasive tests and a substantially increased diagnostic yield of aneuploidies in the first trimester. However, we have also noted a decreased detection of submicroscopic aberrations, since the number of invasive tests substantially decreased. We have observed that pregnant women were interested in broader scope of prenatal screening and diagnosis than detection of common trisomies., Conclusion: Since the frequency of syndromic disorders caused by microdeletions/microduplications is substantial and current routine NIPT and ultrasound investigations are not able to detect them, we suggest that a noninvasive test with resolution comparable to microarrays should be developed, which will also meet patient's needs., (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Background: Whole genome array testing not only provides an increased diagnostic yield of pathogenic causative findings, but it may also reveal so called susceptibility loci (SL) for neurodevelopmental disorders. The goal of this study was to evaluate the pregnancy outcomes in SL cases and to establish a protocol for pregnancy management, follow-up and additional investigations., Methods: Fifty seven cases were evaluated: 34 with and 23 without ultrasound anomalies at referral. Each pregnant couple received pretest counseling and extensive posttest genetic counseling., Results: After diagnosis of SL, parental testing and an additional ultrasound examination were offered. The severity of the ultrasound anomalies and not the diagnosis of SL was the most important factor contributing to the decision on pregnancy continuation. In the majority of cases with milder or no ultrasound anomalies, the pregnancy was continued and a normal outcome after birth was observed., Conclusions: The diagnosis of a SL did not seem to be a reason for termination of pregnancy. Most patients were able to cope with the uncertainty and were interested in both prenatal and postnatal actionability of SL. Long-term follow-up is crucial to assess the actual risks for neurodevelopmental disorders, especially in families with unremarkable history. © 2016 John Wiley & Sons, Ltd., (© 2016 John Wiley & Sons, Ltd.)

Pregnant couples tend to prefer a maximum of information about the health of their fetus. Therefore, we implemented whole genome microarray instead of conventional karyotyping (CK) for all indications for prenatal diagnosis (PND). The array detects more clinically relevant anomalies, including early onset disorders, not related to the indication and more genetic anomalies of yet unquantifiable risk, so-called susceptibility loci (SL) for mainly neurodevelopmental disorders. This manuscript highlights the psychological challenges in prenatal genetic counselling when using the array and provides counselling suggestions. First, we suggest that pre-test decision counselling should emphasize deliberation about what pregnant couples wish to learn about the future health of their fetus more than information about possible outcomes. Second, pregnant couples need support in dealing with SL. Therefore, in order to consider the SL in a proportionate perspective, the presence of phenotypes associated with SL in the family, the incidence of a particular SL in control populations and in postnatally ascertained patients needs highlighting during post-test genetic counselling. Finally, the decision that couples need to make about the course of their pregnancy is more complicated when the expected phenotype is variable and not quantifiable. Therefore, during post-test psychological counseling, couples should concretize the options of continuing and ending their pregnancy; all underlying feelings and thoughts should be made explicit, as well as the couple's resources, in order to attain adequate decision-making. As such, pre- and post-test counselling aids pregnant couples in handling the uncertainties that may accompany offering a broader scope of genetic PND using the array.

Objective: The sense of competence (SC) of informal caregivers of frontotemporal dementia (FTD) patients is important for their task but has rarely been assessed. Here, the relationship between caregiver burden and SC and the differential value of SC in understanding caregiver suffering were studied., Methods: At 24 months of follow-up patient behavioural problems, dementia severity, caregiver SC, burden, psychological complaints and quality of life were inspected cross-sectionally in 46 caregiver/care recipient dyads., Results: SC was unrelated to dementia severity and patient behavioural problems. Principal component analysis of SC revealed 3 dimensions: 'emotions', 'attributions' and 'sacrifice'. Sacrificing one's personal life to caregiving was associated with more psychological complaints and a worse physical and mental quality of life, as found in structural equation modelling., Conclusions: Caregiver suffering comprised an unbalance between self-care and caring for the FTD patient. FTD caregivers may benefit from psycho-education on self-care and methods to create time for their personal needs.

Background/aims: The current study examined the change of caregiver burden and the development of the quality of the partner relation in frontotemporal dementia (FTD)., Methods: During a 2-year period, deterioration, behavioural problems, caregiver burden, general psychopathology, quality of life, social support, coping strategies and relationship quality were inspected in 63 FTD caregiver-care recipient dyads., Results: After 2 years patients reached maximum dementia severity with stable Neuropsychiatric Inventory levels. Contrary to expectations, caregiver burden decreased and psychological well-being remained stable. Coping style and social support changed unfavourably. Relationship closeness and getting along were preserved, whereas communication and sharing viewpoint on life were dramatically reduced., Conclusions: FTD caregivers need support in coping with the increasingly hopeless situation of their patients. Future research methods into caregiver burden should address response shift as a means for psychological adjustment., (Copyright 2008 S. Karger AG, Basel.)