Perspectives of pregnant women on broadening the scope of noninvasive prenatal testing from screening for foetal aneuploidies to prediction of adverse pregnancy outcomes: A qualitative study.

OBJECTIVE: To explore the perspectives of pregnant women on broadening the scope of noninvasive prenatal testing (NIPT) from screening for foetal aneuploidies to prediction of adverse pregnancy outcomes. METHODS: Four online focus groups (n = 23 participants) and 14 individual semi-structured interviews were conducted. Participants included pregnant women with and without a history of adverse pregnancy outcomes. RESULTS: Both women at low and high risk of adverse pregnancy outcomes had a positive attitude towards using NIPT to predict adverse pregnancy outcomes. Perceived benefits included the possibility to potentially improve maternal and foetal outcomes by taking risk-reducing measures and/or intensified monitoring during pregnancy and the ability to mentally prepare for the potential adverse outcome. Perceived concerns included anxiety and stress caused by a high-risk test result, a false sense of control over pregnancy, and potential false reassurance. Additionally, women reasoned that broadening the scope of NIPT could increase the complexity of prenatal screening and raised concerns on the combined screening aims in one test (prediction of adverse pregnancy outcomes to improve foetal and maternal health vs. screening for foetal aneuploidies to increase reproductive autonomy). On a societal level, considerations on the risk of medicalising pregnancy and overall pressure to opt for NIPT were mentioned. CONCLUSION: In general, pregnant women have a positive attitude towards broadening the scope of NIPT to the prediction of pregnancy outcomes, although some concerns are acknowledged.

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.

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

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.

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.

Factors involved in the decision to decline prenatal screening with noninvasive prenatal testing (NIPT).

OBJECTIVE: To investigate factors involved in the decision to decline prenatal screening with noninvasive prenatal testing (NIPT). METHOD: A questionnaire study was conducted among 219 pregnant women in the Netherlands who had declined prenatal screening with NIPT (TRIDENT-2 study). Respondents were selectively recruited from three hospitals and 19 midwifery practices, primarily located in or near socioeconomically disadvantaged neighborhoods. 44.3% of the respondents were of non-Western ethnic origin and 64.4% were religious. RESULTS: Most respondents (77.2%) found the decision to decline NIPT easy to make, and 59.8% had already made the decision before information about NIPT was offered. These respondents were more often religious, multigravida, and had adequate health literacy. The main reasons to decline NIPT were "I would never terminate my pregnancy" (57.1%) and "every child is welcome" (56.2%). For 16.9% of respondents, the out-of-pocket costs (175 euros) played a role in the decision, and the women in this group were more often nonreligious, primigravida, and had inadequate health literacy. CONCLUSION: The primary factors involved in the decision to decline NIPT were related to personal values and beliefs, consistent with autonomous choice. Out-of-pocket costs of NIPT hinder equal access for some pregnant women.

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.

How to improve preconception care in a local setting? Views from Dutch multidisciplinary healthcare providers.

OBJECTIVE: To explore healthcare providers' views on improving preconception care in their region. DESIGN: Mixed-methods study. SETTING: Working conferences aimed to educate healthcare providers on preconceptional risk factors and conduct a region-specific analysis of barriers and facilitators for implementing preconception care, were organised in ten municipalities in the Netherlands. PARTICIPANTS: 250 healthcare providers of various disciplines attended a working conference and participated in the study. MEASUREMENTS AND FINDINGS: Participants were asked to both fill out a questionnaire concerning statements and experiences with preconception care and to participate in a workshop, to identify barriers and facilitators for the implementation of a local preconception care program. Almost all healthcare providers suggested that the responsibility for providing preconception care consultations lies within primary care (general practitioners (n = 239; 95.6%) and midwives (n = 236; 94.4%)). Professionals other than midwives found it significantly more difficult to start a conversation about a wish to conceive compared to midwives (26.8% versus 20.2%, p-value = 0.006) and felt less competent to provide preconceptional information (32.3% versus 15.1%, p-value = <0.001). Innovative facilitators were mentioned to improve reaching the target population with preconceptional information, i.e. the use of social media and local ambassadors. KEY CONCLUSION: While the responsibility for providing preconception care consultations is best suited with primary care, many other healthcare providers involved may act as referrers towards preconception care. Still, approximately 1 in 7 midwives (strongly) disagree with the statement that it is part of their job to provide preconceptional information to couples with a wish to conceive. IMPLICATIONS FOR PRACTICE: There is a need for integrating preconception care in many curricula and postgraduate courses, especially for non-midwives, to improve the delivery of preconception care. Insights in the suggested barriers and facilitators can improve the implementation of (local) preconception care programs.

Routinization of prenatal screening with the non-invasive prenatal test: pregnant women's perspectives.

Due to the favorable test characteristics of the non-invasive prenatal test (NIPT) in the screening of fetal aneuploidy, there has been a strong and growing demand for implementation. In the Netherlands, NIPT is offered within a governmentally supported screening program as a first-tier screening test for all pregnant women (TRIDENT-2 study). However, concerns have been raised that the test's favorable characteristics might lead to uncritical use, also referred to as routinization. This study addresses women's perspectives on prenatal screening with NIPT by evaluating three aspects related to routinization: informed choice, freedom to choose and (personal and societal) perspectives on Down syndrome. Nationwide, a questionnaire was completed by 751 pregnant women after receiving counseling for prenatal screening. Of the respondents, the majority (75.5%) made an informed choice for prenatal screening as measured by the multidimensional measure of informed choice (MMIC). Education level and religious affiliation were significant predictors of informed choice. The main reason to accept screening was "seeking reassurance" (25.5%), and the main reason to decline was "every child is welcome" (30.6%). The majority of respondents (87.7%) did not perceive societal pressure to test. Differences between test-acceptors and test-decliners in personal and societal perspectives on Down syndrome were found. Our study revealed high rates of informed decision-making and perceived freedom to choose regarding fetal aneuploidy screening, suggesting that there is little reason for concern about routinization of NIPT based on the perspectives of Dutch pregnant women. Our findings highlight the importance of responsible implementation of NIPT within a national screening program.

Study design of a stepped wedge cluster randomized controlled trial to evaluate the effect of a locally tailored approach for preconception care - the APROPOS-II study.

BACKGROUND: In a previous feasibility study (APROPOS) in a single municipality of the Netherlands, we showed that a locally tailored preconception care (PCC) approach has the potential to positively affect preconceptional lifestyle behaviours. Therefore, we designed a second study (APROPOS-II) to obtain a more robust body of evidence: a larger group of respondents, more municipalities, randomization, and a more comprehensive set of (clinical) outcomes. The aim of this study is to assess the effectiveness and the implementation process of a local PCC-approach on preconceptional lifestyle behaviours, health outcomes and the reach of PCC among prospective parents and healthcare providers. METHODS: This study is an effectiveness-implementation hybrid type 2 trial. This involves a stepped-wedge cluster randomized controlled trial design aiming to include over 2000 future parents from six municipalities in the Netherlands. The intervention has a dual-track approach, focusing on both the uptake of PCC among future parents and the provision of PCC by healthcare providers. The PCC-approach consists of 1) a social marketing strategy directed towards prospective parent(s) and 2) a local care pathway to improve interdisciplinary collaboration. Data will be collected before and after the introduction of the intervention through questionnaires and medical records in each of the participating municipalities. The primary outcome of this study is change in lifestyle behaviours (e.g. folic acid use, smoking and alcohol use). Secondary outcomes are pregnancy outcomes (e.g. miscarriage, preterm birth, gestational diabetes) and the uptake of PCC. Moreover, a process evaluation will be performed, providing information on the efficacy, feasibility, barriers and facilitators regarding the implementation of the intervention. DISCUSSION: The APROPOS-II study introduces a locally tailored PCC-approach in six municipalities in the Netherlands that will contribute to the body of evidence regarding the effectiveness of PCC and its implementation. If this intervention has a positive effect on lifestyle behaviour changes, leading to improved pregnancy outcomes and the future health of prospective parents and their offspring, it could subsequently be upscaled to (inter)national implementation. TRIAL REGISTRATION: Dutch Trial register: NL7784 (Registered June 6th, 2019).

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.

What Do Parents of Children with Down Syndrome Think about Non-Invasive Prenatal Testing (NIPT)?

This study explores the attitudes of parents of children with Down syndrome towards non-invasive prenatal testing (NIPT) and widening the scope of prenatal screening. Three focus groups (n = 16) and eleven individual interviews with Dutch parents (and two relatives) of children with Down syndrome were conducted. Safety, accuracy and earlier testing were seen as the advantages of NIPT. Some participants were critical about the practice of screening for Down syndrome, but acknowledged that NIPT enables people to know whether the fetus is affected and to prepare without risking miscarriage. Many feared uncritical use of NIPT and more abortions for Down syndrome. Concerns included the consequences for the acceptance of and facilities for children with Down syndrome, resulting in more people deciding to screen. Participants stressed the importance of good counseling and balanced, accurate information about Down syndrome. Testing for more disorders might divert the focus away from Down syndrome, but participants worried about "where to draw the line". They also feared a loss of diversity in society. Findings show that, while parents acknowledge that NIPT offers a better and safer option to know whether the fetus is affected, they also have concerns about NIPT's impact on the acceptance and care of children with Down syndrome.

Determining Pre-Conception Risk Profiles Using a National Online Self-Reported Risk Assessment: A Cross-Sectional Study.

AIM: To measure the prevalence of health risk factors in women who are preparing for pregnancy, using an online publicly available questionnaire aimed at identifying personal and pre-conception risks and at providing tailored information. METHODS: A nation-wide available, free, web-based, self-reported questionnaire for pre-conception use (in Dutch). Between May 2006 and August 2009, 89,946 questionnaires were completed (78,732 were from unique respondents) and available for research purposes, from which those of non-pregnant women (n = 66,617) were selected. Socio-demographic subgroups were distinguished by age, ethnicity, urban living area and living in a deprived neighbourhood. The four pre-conception risk domains were lifestyle, medical, reproductive and family history; together they were defining the risk profile. χ(2) tests were used to compare the risk profiles among the subgroups. RESULTS: The prevalences of the reported risk factors are given. The risk factor profiles revealed that the average, responding, non-pregnant, Dutch woman is exposed to a substantial number of risk factors. Different risk profiles were observed in the different socio-demographic subgroups. Women older than 36 years, of non-Western origin, living in urban areas and those in deprived neighbourhoods showed higher risk profiles, based on a larger number of risks, with significantly higher prevalences. CONCLUSION: Self-reported data from a large, self-selected, non-pregnant population who actively visited a web-site for reproductive information suggest the need for active general pre-conception care as risk factors were abundant. A considerable increase in attention for pre-conception care is justified; different subpopulations most likely require adapted approaches.

[Preconceptual care should include looking at the effect of working conditions on pregnancy]. / Effecten van arbeidsomstandigheden op de zwangerschap verdienen aandacht binnen de preconceptiezorg.

Working conditions are amongst the exogenous factors that can lead to pregnancy complications. Attention within preconceptual care to the working conditions experienced by women who plan to become pregnant can change this, by influencing exposure to harmful working conditions. Until now, relatively little attention has been given to working conditions within preconceptual care, and the subject is often not discussed in daily midwifery practice. The most relevant literature on this topic is summarized in this article. Occupational exposure to certain chemicals, stressful work and nightshifts during early pregnancy increase the risk of spontaneous abortion. There is also an increased risk of congenital malformations if the mother has been exposed to solvents or pesticides during early pregnancy, or the father has been exposed to these substances before or shortly after conception. We conclude that the occupational physician should be involved in the preconceptual consultation in order to contribute to the prevention of pregnancy complications.