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In the TRIDENT-2 study, all pregnant women in the Netherlands are offered genome-wide non-invasive prenatal testing (GW-NIPT) with a choice of receiving either full screening or screening solely for common trisomies. Previous data showed that GW-NIPT can reliably detect common trisomies in the general obstetric population and that this test can also detect other chromosomal abnormalities (additional findings). However, evidence regarding the clinical impact of screening for additional findings is lacking. Therefore, we present follow-up results of the TRIDENT-2 study to determine this clinical impact based on the laboratory and perinatal outcomes of cases with additional findings. Between April 2017 and April 2019, additional findings were detected in 402/110,739 pregnancies (0.36%). For 358 cases, the origin was proven to be either fetal (n = 79; 22.1%), (assumed) confined placental mosaicism (CPM) (n = 189; 52.8%), or maternal (n = 90; 25.1%). For the remaining 44 (10.9%), the origin of the aberration could not be determined. Most fetal chromosomal aberrations were pathogenic and associated with severe clinical phenotypes (61/79; 77.2%). For CPM cases, occurrence of pre-eclampsia (8.5% [16/189] vs 0.5% [754/159,924]; RR 18.5), and birth weight <2.3rd percentile (13.6% [24/177] vs 2.5% [3,892/155,491]; RR 5.5) were significantly increased compared to the general obstetric population. Of the 90 maternal findings, 12 (13.3%) were malignancies and 32 (35.6%) (mosaic) pathogenic copy number variants, mostly associated with mild or no clinical phenotypes. Data from this large cohort study provide crucial information for deciding if and how to implement GW-NIPT in screening programs. Additionally, these data can inform the challenging interpretation, counseling, and follow-up of additional findings.
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Diagnóstico Pré-Natal , Trissomia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Mosaicismo , Placenta , Gravidez , Diagnóstico Pré-Natal/métodosRESUMO
Since its introduction in 2011, noninvasive prenatal testing (NIPT) has spread rapidly around the world. It carries numerous benefits but also raises challenges, often related to sociocultural, legal, and economic contexts. This article describes the implementation of NIPT in nine countries, each with its own unique characteristics: Australia, Canada, China and Hong Kong, India, Israel, Lebanon, the Netherlands, the United Kingdom, and the United States. Themes covered for each country include the structure of the healthcare system, how NIPT is offered, counseling needs and resources, and cultural and legal context regarding disability and pregnancytermination. Some common issues emerge, including cost as a barrier to equitable access, the complexity of decision-making about public funding, and a shortage of appropriate resources that promote informed choice. Conversely, sociocultural values that underlie the use of NIPT vary greatly among countries. The issues described will become even more challenging as NIPT evolves from a second-tier to a first-tier screening test with expanded use.
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Teste Pré-Natal não Invasivo , Austrália , Canadá , China , Feminino , Humanos , Gravidez , Diagnóstico Pré-Natal , Estados UnidosRESUMO
STUDY QUESTION: What is the current practice and views on (expanded) carrier screening ((E)CS) among healthcare professionals in medically assisted reproductive (MAR) practices in Europe? SUMMARY ANSWER: The findings show a limited support for ECS with less than half of the respondents affiliated to centres offering ECS, and substantial variation in practice between centres in Europe. WHAT IS KNOWN ALREADY: The availability of next-generation sequencing, which enables testing for large groups of genes simultaneously, has facilitated the introduction and expansion of ECS strategies, currently offered particularly in the private sector in the context of assisted reproduction. STUDY DESIGN, SIZE, DURATION: A cross-sectional survey evaluating practice and current views among professionals working in MAR practice in different European countries was designed using the online SurveyMonkey tool. The web-based questionnaire included questions on general information regarding the current practice of (E)CS in MAR and questions on what is offered, to whom the test is offered, and how it is offered. It consisted mostly of multiple-choice questions with comment boxes, but also included open questions on the respondents' attitudes/concerns relevant to (E)CS practice, and room to upload requested files (e.g. guidelines and gene panels). In total, 338 responses were collected from 8 February 2022 to 11 April 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: The online survey was launched with an invitation email from the ESHRE central office (n = 4889 emails delivered) and the European Society of Human Genetics (ESHG) central office (n = 1790 emails delivered) sent to the ESHRE and ESHG members, and by social media posts. The survey was addressed to European MAR centres or gamete banks and to centres located in non-European countries participating in the European IVF-monitoring Consortium. Two reminder emails were sent. After exclusion of 39 incomplete responses received (e.g. only background information), 299 respondents from 40 different countries were included for analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 42.5% (127/299) of respondents were affiliated to centres offering ECS. The perceived responsibility to enable prospective parents to make informed reproductive decisions and preventing suffering/burden for parents were the main reasons to offer ECS. A single ECS panel is offered by nearly 45% (39/87 received answers) of the centres offering ECS, 25.3% (22/87) of those centres offer a selection of ECS panels, and 29.9% (26/87) offer whole exome sequencing and a large in silico panel. Different ranges of panel sizes and conditions were included in the ECS panel(s) offered. Most of the respondents (81.8%; 72/88 received answers) indicated that the panels they offer are universal and target the entire population. Pathogenic variants (89.7%; 70/78 received answers), and to a lesser extent, likely pathogenic variants (64.1%%; 50/78 received answers), were included in the ECS report for individuals and couples undergoing MAR with their own gametes. According to 87.9% (80/91 received answers) of the respondents, patients have to pay to undergo an ECS test. Most respondents (76.2%; 61/80 received answers) reported that counselling is provided before and after the ECS test. Preimplantation genetic testing, the use of donor gametes, and prenatal diagnostic testing were the three main reproductive options discussed with identified carrier couples. The main reason, according to the respondents, for not offering ECS in their centre, was the lack of professional recommendations supporting ECS (52.5%; 73/139 received answers) and the high cost for couples or reimbursement not being available (49.6%; 69/139). The challenges and moral dilemmas encountered by the respondents revolved mainly around the content of the offer, including the variants classification and the heterogeneity of the panels, the counselling, and the cost of the test. LIMITATIONS, REASONS FOR CAUTION: Although the total number of respondents was acceptable, the completion rate of the survey was suboptimal. In addition, the heterogeneity of answers to open-ended questions and the ambiguity of some of the answers, along with incomplete responses, posed a challenge in interpreting survey results. It is also plausible that some questions were not easily understood by the respondents. For this reason, response and non-response bias are acknowledged as further limitations of the survey. WIDER IMPLICATIONS OF THE FINDINGS: The results of this survey could aid in identifying potential challenges or areas for improvement in the current practice of ECS in the MAR field and contribute to the discussion on how to address them. The results underline the need to stimulate a more knowledge-based debate on the complexity and the pros and cons of a possible implementation of ECS in MAR. STUDY FUNDING/COMPETING INTEREST(S): All costs relating to the development process were covered from European Society of Human Reproduction and Embryology and European Society of Human Genetics funds. There was no external funding of the development process or manuscript production. A.C. is full-time employee of Juno Genetics. L.H. declared receiving a research grant during the past 36 months from the Netherlands Organisation for Health Research and Development. She has also participated in a Health Council report of the Netherlands on preconception carrier screening and collaborated with the VSOP Dutch Genetic Alliance (patient umbrella organization on rare and genetic disorders). L.H. and C.v.E. are affiliated with Amsterdam University Medical Centre, a hospital that offers ECS in a non-commercial setting. R.V. received honoraria for presentations from Merck Academy and is unpaid board member of the executive committee of the Spanish Fertility Society. The other authors had nothing to disclose. TRIAL REGISTRATION NUMBER: N/A.
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Triagem de Portadores Genéticos , Técnicas de Reprodução Assistida , Humanos , Técnicas de Reprodução Assistida/estatística & dados numéricos , Estudos Transversais , Feminino , Europa (Continente) , Inquéritos e Questionários , Triagem de Portadores Genéticos/métodos , Testes Genéticos/métodos , Testes Genéticos/estatística & dados numéricos , Masculino , Adulto , Atitude do Pessoal de SaúdeRESUMO
RESEARCH QUESTION: What are the main arguments of reproductive healthcare providers in favour or against their involvement in offering expanded carrier screening (ECS) for recessive disorders at fertility clinics in the Netherlands? DESIGN: Semi-structured interview study with 20 reproductive healthcare providers between May 2020 and January 2021. Participants included 11 gynaecologists, seven fertility doctors, one nurse practitioner and one clinical embryologist, recruited from academic medical centres (nâ¯=â¯13), peripheral facilities associated with academic centres (nâ¯=â¯4), and independent fertility treatment centres (nâ¯=â¯3) in the Netherlands. An interview guide was developed, and thematic content analysis was performed using ATLAS.ti software. RESULTS: Arguments of reproductive healthcare providers in favour of their potential involvement in offering ECS included: (i) opportunities offered by the setting; (ii) motivation to assist in reproduction and prevent suffering; and (iii) to counter unwanted commercialization offers. Arguments against involvement included: (i) lack of knowledge and familiarity with offering ECS; (ii) insufficient staff and resources, and potential high costs for clinics and/or couples; (iii) the emotional impact it may have on couples; (iv) perceived complexity of counselling and expected elongation of waiting lists; and (v) expected low impact on reducing the burden of diseases. Participants felt that more evidence and research on the costs-benefits, implications and demand are needed prior to their involvement. CONCLUSION: While agreeing that the field of medically assisted reproduction provides a unique opportunity to offer ECS, reproductive healthcare workers feel a lack of capability and limited motivation to offer ECS to all or a selection of couples at their fertility clinics.
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Atitude do Pessoal de Saúde , Clínicas de Fertilização , Triagem de Portadores Genéticos , Pesquisa Qualitativa , Humanos , Feminino , Triagem de Portadores Genéticos/métodos , Masculino , Pessoal de Saúde/psicologia , Países Baixos , Adulto , Aconselhamento Genético/psicologiaRESUMO
BACKGROUND: A significant proportion of major fetal structural anomalies can be detected in the first trimester by ultrasound examination. However, the test performance of the first-trimester anomaly scan (FTAS) performed in a low-risk population as part of a nationwide prenatal screening program is unknown. Potential benefits of the FTAS include early detection of fetal anomalies, providing parents with more time for reproductive decision-making. OBJECTIVES: To investigate the uptake, test performance and time to a final prenatal diagnosis after referral. STUDY DESIGN: A nationwide implementation study was conducted in the Netherlands (November 2021-November 2022). The FTAS was performed between 12+3 and 14+3 weeks gestation by certified sonographers using a standard protocol. Women were referred to a tertiary care center if anomalies were suspected. Uptake, test performance and time to a final prenatal diagnosis (days between referral and date of final diagnosis/prognosis for reproductive decision-making) were determined. Test performance was calculated for first-trimester major congenital anomalies, such as anencephaly and holoprosencephaly and all diagnosed anomalies <24 weeks gestation. RESULTS: The FTAS uptake was 74.9% (129 704/173 129). In 1.0% (1 313/129 704), an anomaly was suspected, of which 54.9% (n=721) had abnormal findings on the detailed first-trimester diagnostic scan and 44.6% (n=586) showed normal results. In 0.5% (n=6), intra-uterine fetal death occurred. In the total group of 721 cases with abnormal findings, 332 structural anomalies, 117 genetic anomalies, 82 other findings (abnormal fetal biometry, sonomarkers, placental/umbilical cord anomaly, an-/oligohydramnios) and 189 cases with transient findings (defined as ultrasound findings which resolved <24 weeks gestation) were found, with one case having an unknown outcome. 0.9% (n=1164) of all cases with a normal FTAS were diagnosed with a fetal anomaly in the second trimester. Test performance included a sensitivity of 84.6% (126/149) for first-trimester major congenital anomalies and 31.6% (537/1701) for all types of anomalies. Specificity for all anomalies was 99.2% (98 055/98 830); positive predictive value 40.9% (537/1 312); negative predictive value 98.8% (98 055/99 219); positive likelihood ratio 40.3; negative likelihood ratio 0.7; false positive rate 0.8% (775/98 830) and false negative rate 68.4% (1 164/1 701). The median time to diagnosis for structural anomalies was 20 days (6-43 days; median GA 16+3), for genetic anomalies 17 days (8.5-27.5 days; median GA 15+6 weeks) and for first-trimester major congenital anomalies 9 days (5-22 days; median GA 14+6 weeks). CONCLUSIONS: The performance of a newly introduced nationwide FTAS in a low-risk population showed a high sensitivity for first-trimester major congenital anomalies and a lower sensitivity for all anomalies combined. The program was accompanied by a referral rate of 1.0%, of which 59.1% involved cases where anomalies were either not confirmed or resolved before 24 weeks gestation. Timing of diagnosis was around 16 weeks gestation for referred cases. To evaluate the balance between benefits and potential harm of the FTAS within a nationwide prenatal screening program, it is essential to assess the effectiveness of the program over time and to consider the perspectives of both women and their partners, as well as healthcare professionals.
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BACKGROUND: Noninvasive prenatal testing by cell-free DNA analysis is offered to pregnant women worldwide to screen for fetal aneuploidies. In noninvasive prenatal testing, the fetal fraction of cell-free DNA in the maternal circulation is measured as a quality control parameter. Given that fetal cell-free DNA originates from the placenta, the fetal fraction might also reflect placental health and maternal pregnancy adaptation. OBJECTIVE: This study aimed to assess the association between the fetal fraction and adverse pregnancy outcomes. STUDY DESIGN: We performed a retrospective cohort study of women with singleton pregnancies opting for noninvasive prenatal testing between June 2018 and June 2019 within the Dutch nationwide implementation study (Trial by Dutch Laboratories for Evaluation of Non-Invasive Prenatal Testing [TRIDENT]-2). Multivariable logistic regression analysis was used to assess associations between fetal fraction and adverse pregnancy outcomes. Fetal fraction was assessed as a continuous variable and as <10th percentile, corresponding to a fetal fraction <2.5%. RESULTS: The cohort comprised 56,110 pregnancies. In the analysis of fetal fraction as a continuous variable, a decrease in fetal fraction was associated with increased risk of hypertensive disorders of pregnancy (adjusted odds ratio, 2.27 [95% confidence interval, 1.89-2.78]), small for gestational age neonates <10th percentile (adjusted odds ratio, 1.37 [1.28-1.45]) and <2.3rd percentile (adjusted odds ratio, 2.63 [1.96-3.57]), and spontaneous preterm birth from 24 to 37 weeks of gestation (adjusted odds ratio, 1.02 [1.01-1.03]). No association was found for fetal congenital anomalies (adjusted odds ratio, 1.02 [1.00-1.04]), stillbirth (adjusted odds ratio, 1.02 [0.96-1.08]), or neonatal death (adjusted odds ratio, 1.02 [0.96-1.08]). Similar associations were found for adverse pregnancy outcomes when fetal fraction was <10th percentile. CONCLUSION: In early pregnancy, a low fetal fraction is associated with increased risk of adverse pregnancy outcomes. These findings can be used to expand the potential of noninvasive prenatal testing in the future, enabling the prediction of pregnancy complications and facilitating tailored pregnancy management through intensified monitoring or preventive measures.
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Ácidos Nucleicos Livres , Teste Pré-Natal não Invasivo , Resultado da Gravidez , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Adulto , Teste Pré-Natal não Invasivo/métodos , Ácidos Nucleicos Livres/sangue , Países Baixos/epidemiologia , Estudos de Coortes , Nascimento Prematuro/epidemiologia , Feto , Hipertensão Induzida pela Gravidez/epidemiologia , Recém-Nascido Pequeno para a Idade GestacionalRESUMO
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.
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Aneuploidia , Teste Pré-Natal não Invasivo , Resultado da Gravidez , Pesquisa Qualitativa , Humanos , Feminino , Gravidez , Adulto , Teste Pré-Natal não Invasivo/métodos , Resultado da Gravidez/epidemiologia , Grupos Focais , Gestantes/psicologia , Adulto JovemRESUMO
The introduction of rapid exome sequencing (rES) for critically ill neonates admitted to the neonatal intensive care unit has made it possible to impact clinical decision-making. Unbiased prospective studies to quantify the impact of rES over routine genetic testing are, however, scarce. We performed a clinical utility study to compare rES to conventional genetic diagnostic workup for critically ill neonates with suspected genetic disorders. In a multicenter prospective parallel cohort study involving five Dutch NICUs, we performed rES in parallel to routine genetic testing for 60 neonates with a suspected genetic disorder and monitored diagnostic yield and the time to diagnosis. To assess the economic impact of rES, healthcare resource use was collected for all neonates. rES detected more conclusive genetic diagnoses than routine genetic testing (20% vs. 10%, respectively), in a significantly shorter time to diagnosis (15 days (95% CI 10-20) vs. 59 days (95% CI 23-98, p < 0.001)). Moreover, rES reduced genetic diagnostic costs by 1.5% (85 per neonate). CONCLUSION: Our findings demonstrate the clinical utility of rES for critically ill neonates based on increased diagnostic yield, shorter time to diagnosis, and net healthcare savings. Our observations warrant the widespread implementation of rES as first-tier genetic test in critically ill neonates with disorders of suspected genetic origin. WHAT IS KNOWN: ⢠Rapid exome sequencing (rES) enables diagnosing rare genetic disorders in a fast and reliable manner, but retrospective studies with neonates admitted to the neonatal intensive care unit (NICU) indicated that genetic disorders are likely underdiagnosed as rES is not routinely used. ⢠Scenario modeling for implementation of rES for neonates with presumed genetic disorders indicated an expected increase in costs associated with genetic testing. WHAT IS NEW: ⢠This unique prospective national clinical utility study of rES in a NICU setting shows that rES obtained more and faster diagnoses than conventional genetic tests. ⢠Implementation of rES as replacement for all other genetic tests does not increase healthcare costs but in fact leads to a reduction in healthcare costs.
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Estado Terminal , Testes Genéticos , Recém-Nascido , Humanos , Sequenciamento do Exoma , Estudos Prospectivos , Estudos Retrospectivos , Países Baixos , Estudos de Coortes , Testes Genéticos/métodosRESUMO
OBJECTIVE: To perform a systematic review and meta-analysis of the available literature on low fetal fraction (LFF) in cell-free DNA (cfDNA) screening and the risk of fetal chromosomal aberrations. METHOD: We searched articles published between January 2010 and May 2021 in PubMed and EMBASE databases. Risk of bias was assessed using QUADAS-2. RESULTS: Twenty-seven studies met the inclusion criteria, comprising data of 243,700 singleton pregnancies. Compared to normal fetal fraction, LFF was associated with a higher risk of trisomy 13 (OR 5.99 [3.61-9.95], I 2 of heterogeneity = 0%, n = 22 studies), trisomy 18 (OR 4.46 [3.07-6.47], I 2 = 0%, n = 22 studies), monosomy X (OR 5.88 [2.34-14.78], I 2 = 18%, n = 10 studies), and triploidy (OR 36.39 [9.83-134.68], I 2 = 61%, n = 6 studies), but not trisomy 21 (OR 1.25 [0.76-2.03], I 2 = 36%, n = 23 studies). LFF was also associated with a higher risk of various other types of fetal chromosomal aberrations (OR 4.00 [1.78-9.00], I 2 = 2%, n = 11 studies). Meta-analysis of proportions showed that absolute rates of fetal chromosomal aberrations ranged between 1% and 2% in women with LFF. A limitation of this review is the potential risk of ascertainment bias because of differences in outcome assessment between pregnancies with LFF and those with normal fetal fraction. Heterogeneity in population characteristics or applied technologies across included studies may not have been fully addressed. CONCLUSION: An LFF test result in cfDNA screening is associated with an increased risk of fetal trisomy 13, trisomy 18, monosomy X, and triploidy, but not trisomy 21. Further research is needed to assess the association between LFF and other specific types of fetal chromosomal aberrations.
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Ácidos Nucleicos Livres , Síndrome de Down , Síndrome de Turner , Gravidez , Feminino , Humanos , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Síndrome da Trissomia do Cromossomo 13/diagnóstico , Triploidia , Diagnóstico Pré-Natal , Síndrome de Down/diagnóstico , Síndrome de Down/genéticaRESUMO
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.
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Síndrome de Down , Teste Pré-Natal não Invasivo , Feminino , Humanos , Gravidez , Custos e Análise de Custo , Síndrome de Down/diagnóstico , Países Baixos , Diagnóstico Pré-Natal , Recém-NascidoRESUMO
OBJECTIVES: First-trimester ultrasound screening is increasingly performed to detect fetal anomalies early in pregnancy, aiming to enhance reproductive autonomy for future parents. This study aims to display the current practice of first-trimester ultrasound screening in developed countries. METHOD: An online survey among 47 prenatal screening experts in developed countries. RESULTS: First-trimester structural anomaly screening is available in 30 of the 33 countries and is mostly offered to all women with generally high uptakes. National protocols are available in 23/30 (76.7%) countries, but the extent of anatomy assessment varies. Monitoring of scan quality occurs in 43.3% of the countries. 23/43 (53.5%) of the respondents considered the quality of first-trimester ultrasound screening unequal in different regions of their country. CONCLUSIONS: First-trimester screening for structural fetal anomalies is widely offered in developed countries, but large differences are reported in availability and use of screening protocols, the extent of anatomy assessment, training and experience of sonographers and quality monitoring systems. Consequently, this results in an unequal offer to parents in developed countries, sometimes even within the same country. Furthermore, as offer and execution differ widely, this has to be taken into account when results of screening policies are scientifically published or compared.
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Diagnóstico Pré-Natal , Ultrassonografia Pré-Natal , Gravidez , Humanos , Feminino , Primeiro Trimestre da Gravidez , Países Desenvolvidos , Diagnóstico Pré-Natal/métodos , UltrassonografiaRESUMO
BACKGROUND: The Netherlands and Belgium have been among the first countries to offer non-invasive prenatal testing (NIPT) as a first-tier screening test. Despite similarities, differences exist in counseling modalities and test uptake. This study explored decision-making and perspectives of pregnant women who opted for NIPT in both countries. METHODS: A questionnaire study was performed among pregnant women in the Netherlands (NL) (n = 587) and Belgium (BE) (n = 444) opting for NIPT, including measures on informed choice, personal and societal perspectives on trisomy 21, 18 and 13 and pregnancy termination. RESULTS: Differences between Dutch and Belgian women were shown in the level of informed choice (NL: 83% vs. BE: 59%, p < 0.001), intention to terminate the pregnancy in case of confirmed trisomy 21 (NL: 51% vs. BE: 62%, p = 0.003) and trisomy 13/18 (NL: 80% vs. BE: 73%, p = 0.020). More Belgian women considered trisomy 21 a severe condition (NL: 64% vs. BE: 81%, p < 0.001). Belgian women more frequently indicated that they believed parents are judged for having a child with trisomy 21 (BE: 42% vs. NL: 16%, p < 0.001) and were less positive about quality of care and support for children with trisomy 21 (BE: 23% vs. NL: 62%, p < 0.001). CONCLUSION: Differences in women's decision-making regarding NIPT and the conditions screened for may be influenced by counseling aspects and country-specific societal and cultural contexts.
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Síndrome de Down , Criança , Gravidez , Feminino , Humanos , Síndrome de Down/diagnóstico , Gestantes , Diagnóstico Pré-Natal/psicologia , Países Baixos , Bélgica , Síndrome da Trissomía do Cromossomo 18/diagnósticoRESUMO
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.
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Estudos de Coortes , Gravidez , Feminino , Humanos , Masculino , Países Baixos , Estudos Prospectivos , Segundo Trimestre da Gravidez , EscolaridadeRESUMO
BACKGROUND: Population-based expanded carrier screening (ECS) involves screening for multiple recessive diseases offered to all couples considering a pregnancy or during pregnancy. Previous research indicates that in some countries primary care professionals are perceived as suitable providers for ECS. However, little is known about their perspectives. We therefore aimed to explore primary care professionals' views on population-based ECS. METHODS: Four online focus groups with 14 general practitioners (GPs) and 16 community midwives were conducted in the Netherlands. RESULTS: Our findings highlight various perspectives on the desirability of population-based ECS. Participants agreed that ECS could enhance reproductive autonomy and thereby prevent suffering of the child and/or parents. However, they also raised several ethical, societal, and psychological concerns, including a tendency towards a perfect society, stigmatization, unequal access to screening and negative psychosocial consequences. Participants believed that provision of population-based ECS would be feasible if prerequisites regarding training and reimbursement for providers would be fulfilled. most GPs considered themselves less suitable or capable of providing ECS, in contrast to midwives who did consider themselves suitable. Nevertheless, participants believed that, if implemented, ECS should be offered in primary care or by public health services rather than as hospital-based specialized care, because they believed a primary care ECS offer increases access in terms of time and location. CONCLUSIONS: While participants believed that an ECS offer would be feasible, they questioned its desirability and priority. Studies on the desirability and feasibility of population-based ECS offered in primary care or public health settings are needed.
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The Netherlands launched a nationwide implementation study on non-invasive prenatal testing (NIPT) as a first-tier test offered to all pregnant women. This started on April 1, 2017 as the TRIDENT-2 study, licensed by the Dutch Ministry of Health. In the first year, NIPT was performed in 73,239 pregnancies (42% of all pregnancies), 7,239 (4%) chose first-trimester combined testing, and 54% did not participate. The number of trisomies 21 (239, 0.33%), 18 (49, 0.07%), and 13 (55, 0.08%) found in this study is comparable to earlier studies, but the Positive Predictive Values (PPV)-96% for trisomy 21, 98% for trisomy 18, and 53% for trisomy 13-were higher than expected. Findings other than trisomy 21, 18, or 13 were reported on request of the pregnant women; 78% of women chose to have these reported. The number of additional findings was 207 (0.36%); these included other trisomies (101, 0.18%, PPV 6%, many of the remaining 94% of cases are likely confined placental mosaics and possibly clinically significant), structural chromosomal aberrations (95, 0.16%, PPV 32%,) and complex abnormal profiles indicative of maternal malignancies (11, 0.02%, PPV 64%). The implementation of genome-wide NIPT is under debate because the benefits of detecting other fetal chromosomal aberrations must be balanced against the risks of discordant positives, parental anxiety, and a potential increase in (invasive) diagnostic procedures. Our first-year data, including clinical data and laboratory follow-up data, will fuel this debate. Furthermore, we describe how NIPT can successfully be embedded into a national screening program with a single chain for prenatal care including counseling, testing, and follow-up.
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Síndrome de Down/diagnóstico , Testes Genéticos/métodos , Genoma Humano , Implementação de Plano de Saúde , Diagnóstico Pré-Natal/métodos , Síndrome da Trissomia do Cromossomo 13/diagnóstico , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Adolescente , Adulto , Aberrações Cromossômicas , Síndrome de Down/epidemiologia , Síndrome de Down/genética , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Gravidez , Primeiro Trimestre da Gravidez , Prognóstico , Síndrome da Trissomia do Cromossomo 13/epidemiologia , Síndrome da Trissomia do Cromossomo 13/genética , Síndrome da Trissomía do Cromossomo 18/epidemiologia , Síndrome da Trissomía do Cromossomo 18/genética , Adulto JovemRESUMO
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.
Assuntos
Programas de Rastreamento , Pais , Criança , Família , Triagem de Portadores Genéticos , Humanos , Inquéritos e QuestionáriosRESUMO
PURPOSE: While neonatal bloodspot screening (NBS) for severe combined immunodeficiency (SCID) has been introduced more than a decade ago, implementation in NBS programs remains challenging in many countries. Even if high-quality test methods and follow-up care are available, public uptake and parental acceptance are not guaranteed. The aim of this study was to describe the parental perspective on NBS for SCID in the context of an implementation pilot. Psychosocial aspects have never been studied before for NBS for SCID and are important for societal acceptance, a major criterion when introducing new disorders in NBS programs. METHODS: To evaluate the perspective of parents, interviews were conducted with parents of newborns with abnormal SCID screening results (N = 17). In addition, questionnaires about NBS for SCID were sent to 2000 parents of healthy newborns who either participated or declined participation in the SONNET-study that screened 140,593 newborns for SCID. RESULTS: Support for NBS for SCID was expressed by the majority of parents in questionnaires from both a public health perspective and a personal perspective. Parents emphasized the emotional impact of an abnormal screening result in interviews. (Long-term) stress and anxiety can be experienced during and after referral indicating the importance of uniform follow-up protocols and adequate information provision. CONCLUSION: The perspective of parents has led to several recommendations for NBS programs that are considering screening for SCID or other disorders. A close partnership of NBS programs' stakeholders, immunologists, geneticists, and pediatricians-immunologists in different countries is required for moving towards universal SCID screening for all infants.
Assuntos
Implementação de Plano de Saúde , Triagem Neonatal , Pais/psicologia , Aceitação pelo Paciente de Cuidados de Saúde , Imunodeficiência Combinada Severa/epidemiologia , Implementação de Plano de Saúde/estatística & dados numéricos , Humanos , Recém-Nascido , Triagem Neonatal/métodos , Triagem Neonatal/psicologia , Países Baixos/epidemiologia , Vigilância em Saúde Pública , Encaminhamento e Consulta , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/etiologia , Estresse Psicológico/diagnóstico , Estresse Psicológico/etiologia , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Non-Invasive Prenatal Testing (NIPT) is increasingly being implemented worldwide. In public health programs, equitable access to healthcare is a fundamental principle which also applies to fetal aneuploidy screening. However, the out-of-pocket costs of NIPT may lead to sociodemographic disparities in uptake of screening. This study assessed whether there is a difference in the uptake of NIPT in socioeconomically disadvantaged neighborhoods compared to all other neighborhoods in the Netherlands, where NIPT is implemented in a national screening program (TRIDENT-2 study). METHOD: NIPT uptake, postal code and age of 156,562 pregnant women who received pre-test counselling for prenatal screening in 2018 were retrieved from the national prenatal screening database. Postal codes were used as a proxy to categorize neighborhoods as being either socioeconomically disadvantaged or other. The out-of-pocket costs for NIPT were 175. RESULTS: NIPT uptake in socioeconomically disadvantaged neighborhoods was 20.3% whereas uptake in all other neighborhoods was 47.6% (p < 0.001). The difference in NIPT uptake between socioeconomic disadvantaged neighborhoods and other areas was smaller for the youngest maternal age-group (≤25 years) compared to other age-groups. CONCLUSION: The variation in uptake suggest underlying disparities in NIPT uptake, which undermines the goals of a national fetal aneuploidy screening program of providing reproductive autonomy and equitable access. This has ethical and policy implications for ensuring fair and responsible implementation of fetal aneuploidy screening.
Assuntos
Teste Pré-Natal não Invasivo/estatística & dados numéricos , Gestantes/psicologia , Classe Social , Populações Vulneráveis/psicologia , Adulto , Estudos Transversais , Feminino , Humanos , Países Baixos , Teste Pré-Natal não Invasivo/métodos , Gravidez , Características de Residência/estatística & dados numéricos , Estudos Retrospectivos , Populações Vulneráveis/estatística & dados numéricosRESUMO
OBJECTIVES: To assess the association between low fetal fraction (FF) in prenatal cell-free DNA (cfDNA) testing and adverse pregnancy outcomes. METHODS: We conducted a retrospective cohort study of participants of the TRIDENT-2 study (Dutch nationwide government-supported study offering cfDNA screening for fetal aneuploidies) who received a failed test result due to low FF (<4%) between April 2017 until February 2018. Outcome measures included pregnancy-induced hypertension (PIH), pre-eclampsia (PE), small for gestational age neonates (SGA), spontaneous preterm birth (sPTB), gestational diabetes mellitus (GDM), chromosomal aberrations, and congenital structural anomalies. RESULTS: Test failure due to low FF occurred in 295 women (1.12% of tests performed). Information regarding pregnancy outcomes was available for 96.3% of these women. The incidence of PIH, PE, SGA, sPTB, and GDM was 11.2%, 4.1%, 7.3%, 5.1%, and 14.8%, respectively. The prevalence of chromosomal aberrations and congenital structural anomalies was 1.4% and 4.1%, respectively. Incidences of PIH, PE ≥ 34 weeks of gestation, GDM, and prevalence of aneuploidy and congenital structural anomalies were higher in women with low FF compared to the general Dutch obstetric population. CONCLUSION: Low FF is associated with adverse pregnancy outcomes. The value of FF in the prediction of these outcomes needs to be further established.
Assuntos
Ácidos Nucleicos Livres/análise , Resultado da Gravidez/genética , Adulto , Ácidos Nucleicos Livres/sangue , Estudos de Coortes , Feminino , Humanos , Gravidez , Resultado da Gravidez/epidemiologia , Diagnóstico Pré-Natal/métodos , Diagnóstico Pré-Natal/estatística & dados numéricos , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: Low fetal fraction (LFF) in prenatal cell-free DNA (cfDNA) testing is an important cause of test failure and no-call results. LFF might reflect early abnormal placentation and therefore be associated with adverse pregnancy outcome. Here, we review the available literature on the relationship between LFF in cfDNA testing and adverse pregnancy outcome. METHOD: A systematic literature search was conducted in MEDLINE and EMBASE up to November 1, 2020. RESULTS: Five studies met the criteria for inclusion; all were retrospective observational cohort studies. The cohort sizes ranged from 370 to 6375 pregnancies, with all tests performed in the first trimester or early second trimester. A 4% cutoff for LFF was used in two studies, two studies used the 5th and 25th percentiles, respectively, and one study used a variety of cutoff values for LFF. LFF in prenatal cfDNA testing was observed to be associated with hypertensive disease of pregnancy, small for gestational age neonates, and preterm birth. Conflicting results were found regarding the association between LFF and gestational diabetes mellitus. CONCLUSIONS: LFF in cfDNA testing is associated with adverse pregnancy outcome,specifically pregnancy-related hypertensive disorders, preterm birth, and impaired fetal growth related to placental dysfunction. Since the available evidence is limited, a large prospective cohort study on the relationship between fetal fraction and pregnancy outcomes is needed.