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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 performed in a low-risk population as part of a nationwide prenatal screening program is unknown. Potential benefits of the first-trimester anomaly scan include early detection of fetal anomalies, providing parents with more time for reproductive decision-making. OBJECTIVE: 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 of 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 of gestation. RESULTS: The first-trimester anomaly scan uptake was 74.9% (129,704/173,129). In 1.0% (1313/129,704), 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), intrauterine 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 of gestation) were found, with 1 case having an unknown outcome. 0.9% (n=1164) of all cases with a normal first-trimester anomaly scan 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% (537/1312); 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% (1164/1701). The median time to diagnosis for structural anomalies was 20 days (6-43 days; median gestational age 16+3), for genetic anomalies 17 days (8.5-27.5 days; median gestational age 15+6 weeks), and for first-trimester major congenital anomalies 9 days (5-22 days; median gestational age 14+6 weeks). CONCLUSION: The performance of a newly introduced nationwide first-trimester anomaly scan 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 of gestation for referred cases. To evaluate the balance between benefits and potential harm of the first-trimester anomaly scan 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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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 Prenatal , Ultrasonografía Prenatal , Embarazo , Humanos , Femenino , Primer Trimestre del Embarazo , Países Desarrollados , Diagnóstico Prenatal/métodos , UltrasonografíaRESUMEN
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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Expanded universal carrier screening (EUCS) entails a population-wide screening offer for multiple disease-causing mutations simultaneously. Although there is much debate about the conditions under which EUCS can responsibly be introduced, there seems to be little discussion about its aim: providing carrier couples with options for autonomous reproductive choice. While this links in with current accounts of the aim of foetal anomaly screening, it is different from how the aim of ancestry-based carrier screening has traditionally been understood: reducing the disease burden in the population. The reasons why the aim of EUCS is presented in terms of 'autonomy' rather than 'prevention' have not been spelled out in the literature. This paper seeks to fill this gap by considering the morally relevant similarities and dissimilarities between foetal anomaly screening, ancestry-based carrier screening and EUCS. When carrier screening is performed in the prenatal period, enhancing autonomy appears the most appropriate aim of EUCS, as the alternative of 'prevention through selective abortion' would urge women to terminate wanted pregnancies. However, when screening is conducted in the preconception period, carrier couples can avoid the birth of affected children by other means than selective abortion, for instance preimplantation genetic diagnosis. To the extent that this increased control over passing on a genetic disorder raises questions of parental responsibility, it seems necessary that the account of the aims of EUCS is wider than only in terms of enhancing reproductive autonomy.
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Tamización de Portadores Genéticos/ética , Heterocigoto , Obligaciones Morales , Padres , Autonomía Personal , Beneficencia , Femenino , Humanos , Masculino , Atención Preconceptiva , Embarazo , Diagnóstico Prenatal , Derechos Sexuales y Reproductivos/éticaAsunto(s)
Pruebas Genéticas , Diagnóstico Prenatal , Embarazo , Femenino , Humanos , Diagnóstico Prenatal/ética , Pruebas Genéticas/éticaRESUMEN
Expanded carrier screening (ECS) entails a screening offer for multiple recessive disorders at the same time, and allows testing of individuals or couples regardless of ancestry or geographic origin. Children of consanguineous couples have a higher-than-average risk of manifesting autosomal recessive disorders. This study aims to contribute to the responsible implementation of ECS for consanguineous couples. Seven semi-structured interviews were conducted with consanguineous couples who had recently participated in Whole Exome Sequencing (WES)-based ECS at Maastricht University Medical Center (MUMC+), the Netherlands. The test offered at MUMC+ covers a large number of disease-related genes (~2000), including severe, relatively mild, early- and late-onset disorders. Respondents were interviewed about their views on, and experiences with participation in WES-based ECS. Overall, participation was experienced as worthwhile: it enabled respondents to make informed choices with regard to family planning as well as to take on the presumed parental responsibility to deliver their children as healthy as possible. Furthermore, our findings suggest that (1) true consent for having this test requires timely information about the possible implications of a positive test result for specific categories of findings, as well as about the success rates of the available reproductive options; (2) the clinical geneticist can play a pivotal part in informing participants as well as providing clear information about autosomal recessive inheritance; (3) more research is needed to explore what type of genetic risk information is considered 'meaningful' by participants and actually contributes to reproductive decision-making.
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Padres , Conducta Social , Niño , Humanos , Consanguinidad , Países Bajos , Patrón de Herencia , Tamización de Portadores Genéticos , Pruebas GenéticasRESUMEN
[This corrects the article DOI: 10.1093/hropen/hoaa063.].
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Expanded carrier screening (ECS) entails a screening offer for carrier status for multiple recessive disorders simultaneously and allows testing of couples or individuals regardless of ancestry or geographic origin. Although universal ECS-referring to a screening offer for the general population-has generated considerable ethical debate, little attention has been given to the ethics of preconception ECS for patients applying for assisted reproduction using their own gametes. There are several reasons why it is time for a systematic reflection on this practice. Firstly, various European fertility clinics already offer preconception ECS on a routine basis, and others are considering such a screening offer. Professionals involved in assisted reproduction have indicated a need for ethical guidance for ECS. Secondly, it is expected that patients seeking assisted reproduction will be particularly interested in preconception ECS, as they are already undertaking the physical, emotional and economic burdens of such reproduction. Thirdly, an offer of preconception ECS to patients seeking assisted reproduction raises particular ethical questions that do not arise in the context of universal ECS: the professional's involvement in the conception implies that both parental and professional responsibilities should be taken into account. This paper reflects on and provides ethical guidance for a responsible implementation of preconception ECS to patients seeking assisted reproduction using their own gametes by assessing the proportionality of such a screening offer: do the possible benefits clearly outweigh the possible harms and disadvantages? If so, for what kinds of disorders and under what conditions?
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Expanded universal carrier screening (EUCS) entails a twofold expansion of long-standing (preconception) carrier screening programmes: it not only allows the simultaneous screening of a large list of diseases ('expanded'), but also refers to a pan-ethnic screening offer ('universal'). Advocates mention three main moral advantages of EUCS as compared with traditional (targeted and/or ancestry-based) forms of carrier screening: EUCS will (1) maximise opportunities for autonomous reproductive choice by informing prospective parents about a much wider array of reproductive risks; (2) provide equity of access to carrier testing services; (3) reduce the risk of stigmatisation. This empirical ethics study aims to widen this account and provide a balanced picture of the potential pros and cons of EUCS. Semi-structured interviews were conducted with 17 health (policy) professionals and representatives of patient organisations about their views on carrier screening including a possible EUCS scenario. Stakeholders acknowledged the potential benefits of EUCS, but also expressed five main moral concerns: (1) Does EUCS respond to an urgent problem or population need? (2) Is it possible to offer couples both understandable and sufficient information about EUCS? (3) How will societal views on 'reproductive responsibility' change as a result of EUCS? (4) Will EUCS lead to a lower level of care for high-risk populations? (5) Will EUCS reinforce disability-based stigmatisation? While having the potential to overcome some moral limits inherent in traditional carrier screening, EUCS comes with moral challenges of its own. More research is needed to (further) anticipate the ethical and practical consequences of EUCS.
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Tamización de Portadores Genéticos , Pruebas Genéticas/ética , Heterocigoto , Tamizaje Neonatal/ética , Femenino , Humanos , Recién Nacido , Masculino , Factores de RiesgoRESUMEN
Every field of science, but especially biology, contains particular conceptions of nature. These conceptions are not merely epistemological or ontological, but also have normative dimensions; they provide an ethos, a framework for moral orientation. These normative dimensions, whilst often remaining 'hidden' and inarticulate, influence the way in which biologists practice their profession. In this paper, I explore what happens when different versions of these implicit normative frameworks collide. To do so, I will focus on a case study from the field of ecological genomics as it has evolved in one particular country, namely the Netherlands. During an important inaugural meeting, the director of one of the most sizeable Dutch ecogenomics centres gave a presentation in which he introduced the term 'nature mining'. Part of the audience immediately embraced the term, but others were very reluctant. This mixed response is generally explained as a culmination of growing tension about the future direction of the field: due to new funding demands, a shift had occurred from fundamental research to research more interested in 'valorisation'.In addition to this current interpretation, I will argue that the turmoil caused by the use of the term 'nature mining' also reveals a more fundamental difference between the various parties involved in the Dutch ecogenomics community. This term is part of a vocabulary that emphasises the beneficial 'goods' produced by nature. Whereas part of the audience saw no harm in this commodification of nature, others had difficulties with the reduction of nature to a reservoir to be exploited using the latest technologies. I will conclude by arguing that, although at present, the core of Dutch ecogenomics research reflects a more or less instrumental attitude towards nature, the field also harbours other interpretations of nature as a significant and meaningful order. For instance, ecogenomics might further develop the image of land as a 'collective organism', as proposed by Aldo Leopold.
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The emerging field of ecological genomics promises to bring about a marriage between ecological and laboratory-based, genomic investigations. In this paper, I will reflect on this promise by exploring how ecology and genomics are integrated in the two approaches that currently dominate this field: the organism-centred approach, focusing on individual (model) organisms, and the metagenomic approach, concentrating on (the metagenome of) entire microbial communities composed of a variety of species. I will show that both approaches have already taken some important steps in bridging the gap between genomics and ecology. Since the introduction of next-generation sequencing methodology in 2007, the organism-centred approach does not need to stick to classical model organisms like Arabidopsis anymore. Instead, it is now able to apply genomic tools to ecologically interesting species (e.g. amphibians, reptiles, birds) as well. The metagenomic approach has been able to give ecology a more prominent place in its investigations, in another way. Contrary to classical microbiology (the field from which it originates), it does not study microbial communities under controlled laboratory settings, but under nature's own conditions. However, in the marriage between genomics and ecology, genomics still appears to be the dominant partner, especially in the case of the organism-centred approach that continues to study the new ecological models in artificial lab environments. Moreover, the organism-centred and metagenomic approaches employ a gene-centred perspective in understanding critical ecological interactions, thus strengthening a reductionist rather than a holistic (systems-oriented) approach.