A qualitative study looking at informed choice in the context of non-invasive prenatal testing for aneuploidy

OBJECTIVE: To explore women's attitudes towards non-invasive prenatal testing (NIPT) and determine factors influencing their decisions around uptake of NIPT. METHOD: We conducted qualitative interviews to assess knowledge, attitude and deliberation amongst women offered NIPT in a public health service. In total, 45 women took part in telephone interviews (79% participation rate). RESULTS: Most women could recount the key aspects of NIPT discussed during pre-test counselling but had variable knowledge about Down syndrome. Analysis of women's attitudes towards undergoing NIPT revealed three dominant factors they considered when reflecting on the test: (1) how NIPT compared with alternative testing options, (2) reflections on coping and (3) moral or religious values. Exploring the deliberative process revealed the different paths women take when making decisions. For some, it was an extension of the decision to have Down syndrome screening; some considered it early on following the booking-in appointment; others made step-wise decisions about NIPT when it became relevant to them. CONCLUSION: Our findings support the importance of personalised counselling, whereby women and their partners have the opportunity to reflect on the implications of the test results in the context of their own lives and values. Our data highlight the influence of personal circumstances on decision-making

Stakeholder attitudes and needs regarding cell-free fetal DNA testing

PURPOSE OF REVIEW: To explore stakeholder views on cell-free DNA testing and highlight findings important for successful implementation and the provision of best practice in counseling. RECENT FINDINGS: Noninvasive tests based on the analysis of cell-free fetal DNA are now widely available in clinical practice and applications are expanding rapidly. It is essential that stakeholder views are considered in order to identify and address any ethical and social issues. We provide an overview of stakeholder viewpoints and then focus on the key issues of informed decision making, test uptake, service delivery and information sources. SUMMARY: Stakeholders are positive about the introduction of cell-free fetal DNA testing into clinical practice. They describe both practical and psychological benefits arising from tests that are safe and can potentially be performed earlier in pregnancy. Key concerns, which include the potential for these tests to have a negative impact on informed decision making and increased societal pressure to have testing, can be addressed through careful parent-directed counseling. As applications for these tests expand it is increasingly important to develop innovative approaches to facilitate good understanding for parents who are offered noninvasive prenatal testing

Development and validation of a measure of informed choice for women undergoing non-invasive prenatal testing for aneuploidy.

Non-invasive prenatal testing (NIPT) using cell-free DNA for aneuploidy is a highly accurate screening test; however, concerns exist around the potential for routinisation of testing. The multidimensional measure of informed choice (MMIC) is a quantitative instrument developed to assess informed choice for Down syndrome screening (DSS). We have validated a modified MMIC for NIPT and measured informed choice among women offered NIPT in a public health service. The measure was distributed to women recruited across eight maternity units in the United Kingdom who had accepted DSS. Construct validity was assessed by simultaneously conducting qualitative interviews. Five hundred and eighty-five questionnaires were completed and 45 interviews conducted after blood-draw (or equivalent for those that declined NIPT). The measure demonstrated good internal consistency and internal validity. Results indicate the vast majority of women (89%) made an informed choice; 95% were judged to have good knowledge, 88% had a positive attitude and 92% had deliberated. Of the 11% judged to have made an uninformed choice, 55% had not deliberated, 41% had insufficient knowledge, and 19% had a negative attitude. Ethnicity (OR=2.78, P=0.003) and accepting NIPT (OR=16.05, P=0.021) were found to be significant predictors of informed choice. The high rate of informed choice is likely to reflect the importance placed on the provision of pre-test counselling in this study. It will be vital to ensure that this is maintained once NIPT is offered in routine clinical practice

Non-invasive prenatal testing for aneuploidy: a systematic review of Internet advertising to potential users by commercial companies and private health providers.

BACKGROUND: The development of non-invasive prenatal testing has increased accessibility of fetal testing. Companies are now advertising prenatal testing for aneuploidy via the Internet. OBJECTIVES: The aim of this systematic review of websites advertising non-invasive prenatal testing for aneuploidy was to explore the nature of the information being provided to potential users. METHODS: We systematically searched two Internet search engines for relevant websites using the following terms: 'prenatal test', 'antenatal test', 'non-invasive test', 'noninvasive test', 'cell-free fetal DNA', 'cffDNA', 'Down syndrome test' or 'trisomy test'. We examined the first 200 websites identified through each search. Relevant web-based text was examined, and key topics were identified, tabulated and counted. To analyse the text further, we used thematic analysis. MAIN RESULTS: Forty websites were identified. Whilst a number of sites provided balanced, accurate information, in the majority supporting evidence was not provided to underpin the information and there was inadequate information on the need for an invasive test to definitely diagnose aneuploidy. CONCLUSIONS: The information provided on many websites does not comply with professional recommendations. Guidelines are needed to ensure that companies offering prenatal testing via the Internet provide accurate and comprehensible information

Health professionals’ and coroners’ views on less invasive perinatal and paediatric autopsy: a qualitative study

OBJECTIVE: To assess health professionals’ and coroners’ attitudes towards non-minimally and minimally invasive autopsy in the perinatal and paediatric setting. METHODS: A qualitative study using semistructured interviews. Data were analysed thematically. RESULTS: Twenty-five health professionals (including perinatal/paediatric pathologists and anatomical pathology technologists, obstetricians, fetal medicine consultants and bereavement midwives, intensive care consultants and family liaison nurses, a consultant neonatologist and a paediatric radiologist) and four coroners participated. Participants viewed less invasive methods of autopsy as a positive development in prenatal and paediatric care that could increase autopsy rates. Several procedural and psychological benefits were highlighted including improved diagnostic accuracy in some circumstances, potential for faster turnaround times, parental familiarity with imaging and laparoscopic approaches, and benefits to parents and faith groups who object to invasive approaches. Concerns around the limitations of the technology such not reaching the same levels of certainty as full autopsy, unsuitability of imaging in certain circumstances, the potential for missing a diagnosis (or misdiagnosis) and de-skilling the workforce were identified. Finally, a number of implementation issues were raised including skills and training requirements for pathologists and radiologists, access to scanning equipment, required computational infrastructure, need for a multidisciplinary approach to interpret results, cost implications, equity of access and acceptance from health professionals and hospital managers. CONCLUSION: Health professionals and coroners viewed less invasive autopsy as a positive development in perinatal and paediatric care. However, to inform implementation a detailed health economic analysis and further exploration of parental views, particularly in different religious groups, are required

Delivering genome sequencing for rapid genetic diagnosis in critically ill children: parent and professional views, experiences and challenges

Rapid genomic sequencing (RGS) is increasingly being used in the care of critically ill children. Here we describe a qualitative study exploring parent and professional perspectives around the usefulness of this test, the potential for unintended harms and the challenges for delivering a wider clinical service. The Rapid Paediatric Sequencing (RaPS) study offered trio RGS for diagnosis of critically ill children with a likely monogenic disorder. Main and actionable secondary findings were reported. Semi-structured interviews were conducted with parents of children offered RGS (n = 11) and professionals (genetic clinicians, non-genetic clinicians, scientists and consenters) (n = 19) by telephone (parents n = 10/ professionals n = 1) or face-to-face (parents n = 1/professionals n = 18). We found that participants held largely positive views about RGS, describing clinical and emotional benefits from the opportunity to obtain a rapid diagnosis. Parental stress surrounding their child’s illness complicates decision making. Parental concerns are heightened when offered RGS and while waiting for results. The importance of multidisciplinary team working to enable efficient delivery of a rapid service was emphasised. Our findings give insight into the perceived value of RGS for critically ill children. Careful pre-test counselling is needed to support informed parental decision making. Many parents would benefit from additional support while waiting for results. Education of mainstream clinicians is required to facilitate clinical implementatio

Epsilon-aminocaproic acid for treatment of fibrinolysis during liver transplantation

In 97 adult patients receiving liver transplants, the coagulation system was monitored by thrombelastography and by coagulation profile including PT; a PTT; platelet count; level of factors I, II, V, VII, VIII, IX, X, XI, and XII; fibrin degradation products; ethanol gel test; protamine gel test; and euglobulin lysis time. Preoperatively, fibrinolysis defined as a whole blood clot lysis index of less than 80% was present in 29 patients (29.9%), and a euglobulin lysis time of less than 1 h was present in 13 patients. Fibrinolysis increased progressively during surgery in 80 patients (82.5%) and was most severe on reperfusion of the graft liver in 33 patients (34%). When whole blood clot lysis (F < 180 min) was observed during reperfusion of the graft liver, blood coagulability was tested by thrombelastography using both a blood sample treated in vitro with ε-aminocaproic acid (0.09%) and an untreated sample. Blood treated with ε-aminocaproic acid showed improved coagulation without fibrinolytic activity in all 74 tests. When whole blood clot lysis time was less than 120 min, generalized oozing occurred, and the effectiveness of ε-aminocaproic acid was demonstrated in vitro during the pre-anhepatic and post-anhepatic stages, ε-aminocaproic acid (1 g, single intravenous dose) was administered. In all 20 patients treated with ε-aminocaproic acid, fibrinolytic activity disappeared; whole blood clot lysis was not seen on thrombelastography during a 5-h observation period, and whole blood clot lysis index improved from 28.5 ± 29.5% to 94.8 ± 7.4% (mean ± SD, P < 0.001). None of the treated patients had hemorrhagic or thrombotic complications. In patients undergoing liver transplantation, the judicious use of a small dose of ε-aminocaproic acid, when its efficacy was confirmed in vitro, effectively treated the severe fibrinolysis without clinical thrombotic complications

Offering non-invasive prenatal testing as part of routine clinical service. Can high levels of informed choice be maintained?

OBJECTIVES: To assess rates of informed choice among women offered NIPT for aneuploidy as part of routine clinical care. METHODS: A cross-sectional survey was conducted across six antenatal clinics in England. Women with a high risk (≥1/150) Down syndrome screening result were offered NIPT, invasive testing or no further testing. Pre-test counselling was delivered as part of routine care by the local maternity team. Women were given a questionnaire containing a measure of informed choice immediately after pre-test counselling. RESULTS: In total, 220/247 women completed the questionnaire. Seventy six percent were judged to have made an informed choice, a significant decline from our previous study (89.0% v 75.6%; X(2) (2)=20.2, p<0.001). Of those making an uninformed choice, 46% had insufficient knowledge, 19% had not deliberated and 13% had made a value-inconsistent decision. Multivariate analysis showed women who were highly educated (OR 4.33; 95% CI 1.08-17.36) or had had screening in a previous pregnancy (OR 0.24; 95% CI 0.90-0.65) were significantly more likely to make an informed choice. CONCLUSIONS: The findings highlight the challenges of ensuring informed choice in routine prenatal care where NIPT is not discussed at multiple points, less time is available for counselling and written consent is not required

Young people's understanding, attitudes and involvement in decision-making about genome sequencing for rare diseases: A qualitative study with participants in the UK 100,000 genomes project

Genome sequencing (GS) will have a profound impact on the diagnosis of rare and inherited diseases in children and young people. We conducted 27 semi-structured interviews with young people aged 11-19 having GS through the UK 100,000 Genomes Project. Participants demonstrated an understanding of the role and function of genes and DNA, however the terms 'genome' and 'genome sequencing' were less well understood. Participants were primarily motivated to take part to get a diagnosis or identify the gene causing their condition. The majority of participants understood they might not receive a diagnostic result. Most were unconcerned about data security or access, however anxieties existed around what the results might show and the potential for disappointment if the result was negative. Signing an assent form empowered young people, formalised the process and instilled a sense of responsibility for their choice to participate. Most young people (≥16 years) had consented to receive secondary findings and had come to that decision without parental influence. Our research suggests that at least some young people are capable of making informed decisions about taking part in GS, and that involving them in discussions about testing can empower them to take responsibility over healthcare decisions that affect them

Living with Osteogenesis Imperfecta: A qualitative study exploring experiences and psychosocial impact from the perspective of patients, parents and professionals

BACKGROUND: Osteogenesis Imperfecta (OI) is a rare genetic condition characterised by increased bone fragility. Recurrent fractures, pain and fatigue have a considerable impact on many aspects of the life of a person affected with OI and their families. OBJECTIVE: To improve our understanding of the impact of OI on the daily lives of individuals and families and consider how the condition is managed so that support needs can be better addressed. METHODS: Semi-structured qualitative interviews (n = 56) were conducted with adults affected with OI, with (n = 9) and without children (n = 8), parents of children affected with OI (n = 8), health professionals (n = 29) and patient advocates (n = 2). Interviews were digitally recorded, transcribed verbatim and analysed using thematic analysis. RESULTS: Three overarching themes are described: OI is not just a physical condition, parenting and family functioning and managing the condition. Fractures, chronic pain and tiredness impact on daily life and emotional well-being. For parents with OI, pain, tiredness and mobility issues can limit interactions and activities with their children. Specialist paediatric health services for OI were highly valued. The need for more emotional support and improved coordination of adult health services was highlighted. CONCLUSIONS: Our findings allow a better understanding of the day-to-day experiences of individuals and families affected with OI. Supporting emotional well-being needs greater attention from policy makers and researchers. Improvements to the coordination of health services for adults with OI are needed and an in-depth exploration of young people's support needs is warranted with research focused on support through the teenage years