Views of patients and parents of children with genetic disorders on population-based expanded carrier screening

Objective Faster and cheaper next generation sequencing technologies have enabled expansion of carrier screening for recessive disorders, potentially facilitating population-based implementation regardless of ancestry or family history. Little is known, however, about the attitudes regarding population-based carrier screening among families with genetic disorders. This study assessed views among parents and patients with a recessive disorder and parents of children with Down syndrome (DS) on expanded carrier screening (ECS). Method In total, 85 patients with various recessive disorders, 110 parents of a child with a recessive disorder and 89 parents of a child with DS participated in an online survey in the Netherlands. Severity of recessive disorders was classified as mild/moderate or severe/profound. Results The majority of the (parents of) patients with a recessive disorder had a positive attitude towards population-based ECS, including screening for their own or their child's disorder. DS parents were significantly less positive towards ECS. Subgroup analyses showed that the severity of the disorder, rather than being a patient or parent, influences the attitudes, beliefs and intention to participate in ECS. Conclusion Our findings have important implications for future implementation initiatives as they demonstrate the different perspectives from people with experiential knowledge with genetic disorders

A qualitative study on stakeholders’ views on the participation of pregnant women in the APOSTEL VI study: a low-risk obstetrical RCT

Abstract Background Bioethicists argue that inclusion of pregnant women in clinical research should be more routine to increase the evidence-base for pregnant women and foetuses. Yet, it is unknown whether pregnant women and others directly involved are willing to be routinely included. Therefore, we first need to establish what these stakeholders think about research participation in regular pregnancy-related research. However, studies on their views are scarce. In our study, we piggy-backed on a relatively conventional RCT, the APOSTEL VI study, to identify the views of stakeholders on inclusion of pregnant women in this study. Methods We conducted a prospective qualitative study using 35 in-depth semi-structured interviews and one focus group. We interviewed pregnant women (n = 14) recruited for the APOSTEL VI study, in addition to healthcare professionals (n = 14), Research Ethics Committee members (RECs) (n = 5) and regulators (n = 7) involved in clinical research in pregnant women. Results Three themes characterise stakeholders’ views on inclusion of pregnant women in the APOSTEL VI study. Additionally, one theme characterises stakeholders’ interest in inclusion of pregnant women in clinical research in general. First, pregnant women participate in the APOSTEL VI study for potential individual benefit and secondarily for altruistic motives, contrary to hypothetical studies. Second, a gatekeeping tendency hampers recruitment of pregnant women who might be eligible and willing, and questions about pregnant women’s decisional capacities surface. Third, healthcare professionals sometimes use the counselling conversation to steer pregnant women in a direction. Fourth, all stakeholders are hesitant about inclusion of pregnant women in clinical research in general due to a protective sentiment. Conclusions Pregnant women are willing to participate in the APOSTEL VI study for potential individual benefit and altruistic motives. However, an underlying protective sentiment, resulting in gatekeeping and directive counselling, sometimes hampers recruitment in the APOSTEL VI study as well as in clinical research in general. While bioethicists claim that inclusion of pregnant women should be customary, our study indicates that healthcare professionals, regulators, RECs and pregnant women themselves are not necessarily interested in inclusion. Advancing the situation and increasing the evidence-base for pregnant women and foetuses may require additional measures such as investing in the recruitment and feasibility of RCTs and stimulating pregnant women’s decisional capacities

A qualitative study on stakeholders' views on the participation of pregnant women in the APOSTEL VI study: a low-risk obstetrical RCT

BACKGROUND: Bioethicists argue that inclusion of pregnant women in clinical research should be more routine to increase the evidence-base for pregnant women and foetuses. Yet, it is unknown whether pregnant women and others directly involved are willing to be routinely included. Therefore, we first need to establish what these stakeholders think about research participation in regular pregnancy-related research. However, studies on their views are scarce. In our study, we piggy-backed on a relatively conventional RCT, the APOSTEL VI study, to identify the views of stakeholders on inclusion of pregnant women in this study. METHODS: We conducted a prospective qualitative study using 35 in-depth semi-structured interviews and one focus group. We interviewed pregnant women (n = 14) recruited for the APOSTEL VI study, in addition to healthcare professionals (n = 14), Research Ethics Committee members (RECs) (n = 5) and regulators (n = 7) involved in clinical research in pregnant women. RESULTS: Three themes characterise stakeholders' views on inclusion of pregnant women in the APOSTEL VI study. Additionally, one theme characterises stakeholders' interest in inclusion of pregnant women in clinical research in general. First, pregnant women participate in the APOSTEL VI study for potential individual benefit and secondarily for altruistic motives, contrary to hypothetical studies. Second, a gatekeeping tendency hampers recruitment of pregnant women who might be eligible and willing, and questions about pregnant women's decisional capacities surface. Third, healthcare professionals sometimes use the counselling conversation to steer pregnant women in a direction. Fourth, all stakeholders are hesitant about inclusion of pregnant women in clinical research in general due to a protective sentiment. CONCLUSIONS: Pregnant women are willing to participate in the APOSTEL VI study for potential individual benefit and altruistic motives. However, an underlying protective sentiment, resulting in gatekeeping and directive counselling, sometimes hampers recruitment in the APOSTEL VI study as well as in clinical research in general. While bioethicists claim that inclusion of pregnant women should be customary, our study indicates that healthcare professionals, regulators, RECs and pregnant women themselves are not necessarily interested in inclusion. Advancing the situation and increasing the evidence-base for pregnant women and foetuses may require additional measures such as investing in the recruitment and feasibility of RCTs and stimulating pregnant women's decisional capacities

Experiences of pregnant women with genome-wide non-invasive prenatal testing in a national screening program

Pregnant women’s perspectives should be included in the dialogue surrounding the expanding offers of non-invasive prenatal testing (NIPT), especially now that technological possibilities are rapidly increasing. This study evaluated women’s experiences with the offer of genome-wide (GW) first-tier NIPT in a national screening program. A nationwide pre-and post-test questionnaire was completed by 473 pregnant women choosing between targeted NIPT (trisomies 21, 18 and 13 only) and GW-NIPT (also other findings) within the Dutch TRIDENT-2 study. Measures included satisfaction, reasons for or against choosing GW-NIPT, anxiety, and opinion on the future scope of NIPT. Most respondents (90.4%) were glad to have been offered the choice between GW-NIPT and targeted NIPT; 76.5% chose GW-NIPT. Main reasons to choose GW-NIPT were ‘wanting as much information as possible regarding the child’s health’ (38.6%) and ‘to be prepared for everything’ (23.8%). Main reasons to choose targeted NIPT were ‘avoiding uncertain results/outcomes’ (33.7%) and ‘not wanting to unnecessarily worry’ (32.6%). Nearly all respondents received a low-risk NIPT result (98.7%). No differences were found in anxiety between women choosing GW-NIPT and targeted NIPT. Most respondents were favorable toward future prenatal screening for a range of conditions, including life-threatening disorders, mental disabilities, disorders treatable in pregnancy and severe physical disabilities, regardless of their choice for GW-NIPT or targeted NIPT. In conclusion, women who chose first-tier NIPT were satisfied with the choice between GW-NIPT and targeted NIPT, and most women were favorable toward a broader future screening offer. Our results contribute to the debate concerning the expansion of NIPT

Experiences of pregnant women with genome-wide non-invasive prenatal testing in a national screening program

Pregnant women’s perspectives should be included in the dialogue surrounding the expanding offers of non-invasive prenatal testing (NIPT), especially now that technological possibilities are rapidly increasing. This study evaluated women’s experiences with the offer of genome-wide (GW) first-tier NIPT in a national screening program. A nationwide pre-and post-test questionnaire was completed by 473 pregnant women choosing between targeted NIPT (trisomies 21, 18 and 13 only) and GW-NIPT (also other findings) within the Dutch TRIDENT-2 study. Measures included satisfaction, reasons for or against choosing GW-NIPT, anxiety, and opinion on the future scope of NIPT. Most respondents (90.4%) were glad to have been offered the choice between GW-NIPT and targeted NIPT; 76.5% chose GW-NIPT. Main reasons to choose GW-NIPT were ‘wanting as much information as possible regarding the child’s health’ (38.6%) and ‘to be prepared for everything’ (23.8%). Main reasons to choose targeted NIPT were ‘avoiding uncertain results/outcomes’ (33.7%) and ‘not wanting to unnecessarily worry’ (32.6%). Nearly all respondents received a low-risk NIPT result (98.7%). No differences were found in anxiety between women choosing GW-NIPT and targeted NIPT. Most respondents were favorable toward future prenatal screening for a range of conditions, including life-threatening disorders, mental disabilities, disorders treatable in pregnancy and severe physical disabilities, regardless of their choice for GW-NIPT or targeted NIPT. In conclusion, women who chose first-tier NIPT were satisfied with the choice between GW-NIPT and targeted NIPT, and most women were favorable toward a broader future screening offer. Our results contribute to the debate concerning the expansion of NIPT

Psychological impact of additional findings detected by genome-wide Non-Invasive Prenatal Testing (NIPT):TRIDENT-2 study

In the Netherlands, genome-wide non-invasive prenatal testing (NIPT) is offered to all pregnant women as part of the nationwide TRIDENT-2 study. Findings other than trisomy 21, 18, or 13, which are called “additional findings”, are reported only on request of the pregnant woman. This study examined: (1) women’s pre-test perceptions and reasons to opt for additional findings and (2) women’s experiences with- and the psychological impact of being informed about an additional finding. A questionnaire, consisting of the anxiety measure State-Trait Anxiety Inventory (STAI), distress measure Impact of Event Scale (IES) and questions developed specifically for this study, was retrospectively administered to 402 women who received an additional finding. A total of 227 (56.5%) women completed the questionnaire. Most (60.2%) chose to know additional findings because they wanted as much information as possible about the health of their fetus. Almost all (92%) stated that receiving the additional finding was unexpected, a shock, and/or they were in disbelief, for 85% it caused a lot of worry. Post-test, high anxiety (STAI) levels were reported in 15.5% of women, and 7.5% reported severe distress (IES). Women who gave birth to an affected child (n = 10) experienced most psychological impact (STAI and IES). Eighty-six percent of women with a fetal aberration would opt for additional findings again, compared to 49.2% of women whose result was confined to the placenta. Pre-test counseling should focus on explaining the different results NIPT can generate. Post-test counseling should focus on guiding pregnant women through this uncertain and anxious time.</p

Psychological impact of additional findings detected by genome-wide Non-Invasive Prenatal Testing (NIPT):TRIDENT-2 study

In the Netherlands, genome-wide non-invasive prenatal testing (NIPT) is offered to all pregnant women as part of the nationwide TRIDENT-2 study. Findings other than trisomy 21, 18, or 13, which are called “additional findings”, are reported only on request of the pregnant woman. This study examined: (1) women’s pre-test perceptions and reasons to opt for additional findings and (2) women’s experiences with- and the psychological impact of being informed about an additional finding. A questionnaire, consisting of the anxiety measure State-Trait Anxiety Inventory (STAI), distress measure Impact of Event Scale (IES) and questions developed specifically for this study, was retrospectively administered to 402 women who received an additional finding. A total of 227 (56.5%) women completed the questionnaire. Most (60.2%) chose to know additional findings because they wanted as much information as possible about the health of their fetus. Almost all (92%) stated that receiving the additional finding was unexpected, a shock, and/or they were in disbelief, for 85% it caused a lot of worry. Post-test, high anxiety (STAI) levels were reported in 15.5% of women, and 7.5% reported severe distress (IES). Women who gave birth to an affected child (n = 10) experienced most psychological impact (STAI and IES). Eighty-six percent of women with a fetal aberration would opt for additional findings again, compared to 49.2% of women whose result was confined to the placenta. Pre-test counseling should focus on explaining the different results NIPT can generate. Post-test counseling should focus on guiding pregnant women through this uncertain and anxious time.</p

Informed choice and routinization of the second-trimester anomaly scan: a national cohort study in the Netherlands

Abstract Background Since 2007 all pregnant women in the Netherlands are offered the second-trimester anomaly scan (SAS) in a nationwide prenatal screening program. This study aims to assess the level of informed choice of women opting for the SAS and to evaluate the presence of routinization 16 years after its implementation. It further explores decisional conflict and women’s decision making. Methods This prospective national survey study consisted of an online questionnaire which was completed after prenatal counseling and before undergoing the SAS. Informed choice was measured by the adapted multidimensional measure of informed choice (MMIC) and was defined in case women were classified as value-consistent, if their decision for the SAS was deliberated and made with sufficient knowledge. Results A total of 894/1167 (76.6%) women completed the questionnaire. Overall, 54.8% made an informed choice, 89.6% had good knowledge, 59.8% had deliberated their choice and 92.7% held a positive attitude towards the SAS. Women with low educational attainment (p=0.004) or respondents of non-Western descent (p=0.038) were less likely to make an informed choice. Decisional conflict was low, with a significantly lower decisional conflict score in women that made an informed choice (p<0.001). Most respondents (97.9%) did not perceive pressure to undergo the SAS. Conclusions Our study showed a relatively low rate of informed choice for the SAS, due to absence of deliberation. Therefore, some routinization seem to be present in the Netherlands. However, most women had sufficient knowledge, did not perceive pressure and experienced low decisional conflict