Table 1 Characteristics of articles included.

Wilfond [32]

1990

US

Theoretical paper

To review past American experiences and problems with mass screening programs and explore the potential for similar problems with a program for cystic fibrosis.

Cystic fibrosis

The author states that screening programs should be designed to minimize error, confusion, stigmatization and discrimination and maximize the transfer of understandable information. Benefits and risks should be investigated in pilot studies.

Achterbergh [37]

2007

Netherlands

Sociotechnical analysis

To get insight into the process of implementation of a preconception screening program to identify carrier couples for cystic fibrosis and hemoglobinopathies.

Cystic fibrosis & haemoglobinopathies

The authors conclude that successful implementation of preconceptional carrier screening will have to include the establishment of a new preconceptional healthcare setting and a visible public health authority that can coordinate, monitor and evaluate the initiative.

Kalokairinou [7]

2008

Cyprus

Case description

To describe the preconception screening program for the prevention of β-thalassemia in Cyprus.

ß-Thalassemia

The author concludes that, although the PCS program in Cyprus proved a successful model for the management of ß-thalassemia, the program bears no resemblance to eugenics.

Raz [6]

2008

Israel

Qualitative interview study with ultra-orthodox women and matchmakers (N = 24)

To explore the views of members of the ultra-orthodox Jewish community regarding premarital carrier matching in the Dor Yeshorim program.

Expanded

This study indicates that participants in the Dor Yeshorim program have many misunderstandings regarding the genetic basis of carrier matching and that the experiences differ from the original design and public messages of the program. While Dor Yeshorim aimed to reduce individual stigmatization, the program also reproduces stigmatization by a culture of ignorance and fear.

Lakeman [42]

2008

Netherlands

Screening offer evaluation using quantitative surveys among participants originating from Europe, North America or Australia (N = 97) and participants originating from other parts of the world (N = 46) before, shortly after and three months after receiving screening results

To study psychological outcomes, knowledge, recall and understanding of test results, satisfaction, and reproductive intentions of participants in preconceptional carrier screening.

Cystic fibrosis & hemoglobin-pathies

No major adverse psychological or social effects were found. Participants participating in the carrier screening offer did not report major feelings of discrimination or stigmatization. No differences were found between the study groups in this regard.

Zlotogora [56]

2009

Israel

Literature review

To provide an overview of the advantages and disadvantages of population genetic screening programs.

Thalassemia, spinocerebellar ataxia, Tay-Sachs disease

Both mandatory and voluntary screening programs exist worldwide. For voluntary programs, a major problem is that in many cases awareness about the existence of screening tests is very sparse.

Zlotogora [57]

2009

Israel

Program description

To describe Israel’s national genetic screening program, based on the experience of the first five years.

Thalassemia & Tay-Sachs disease

The author concludes that the community program directed toward couples in their reproductive period does not seem to have led to stigmatization at either the individual or the community level.

Cowan [4]

2009

Cyprus

Program description

To describe the development of the quasi-mandated screening program for ß-thalassemia in Cyprus.

ß-Thalassemia

The author argues that the Cypriot program does not have a eugenic aim as it involves mandated premarital carrier screening combined with voluntary prenatal diagnosis and voluntary termination of afflicted pregnancies.

Modra [34]

2010

Australia

Theoretical paper

To examine how cystic fibrosis carrier screening should be offered if Australia were to initiate a universal carrier screening program.

Cystic fibrosis

The authors state that offering carrier testing before pregnancy is preferable given the ethical advantages, while screening during pregnancy should also be offered. Establishing the screening program in a non-clinical setting is recommended to reach the preconception population.

Frumkin [55]

2011

Israel

Qualitative interview study with modern-religious Ashkenazi Jewish adults (N = 23)

To report on attitudes of modern-religious Ashkenazi Jewish adults in Israel toward anonymous carrier matching by Dor Yeshorim and to examine decision-making about carrier screening.

Small

The findings show a significant gap between the modern-religious respondents’ attitudes and family planning strategies and the method of confidential carrier matching.

De Wert [20]^b

2012

Netherlands

Theoretical paper

To review ethical issues of both individual preconception genetic counseling and of systematically offered PCS to couples or individuals in the reproductive age.

Small & expanded

The authors state there are moral reasons for regarding enhancement of reproductive autonomy as preferable to prevention as the primary objective of preconception carrier screening. In case of avoiding serious suffering, prevention may be a morally acceptable objective of preconception carrier screening. If preconception carrier screening is offered for cost reduction, reproductive freedom is under threat, possibly leading to pressure to also avoid the birth of children with minor or treatable conditions.

Jans [41]

2012

Netherlands

Sociotechnical analysis & qualitative witness seminar with stakeholders, including clinicians, scientists and policymakers (N = 14)

To explore the decision-making process of the past concerning preconceptional and prenatal carrier screening for hemoglobinopathies.

Hemoglobino-pathies

Based on witness reports, screening in general never appeared high on the policy agenda. Participants shared that registration of ethnicity remains sensitive due to the current political climate. Complexities related to carrier screening are a challenge in Dutch healthcare.

Ready [30]

2012

US

Quantitative survey study women’s healthcare providers (N = 203)

To determine women’s HCPs’ knowledge and attitudes regarding genetic ECS.

Expanded

Participants generally had good knowledge and positive attitudes about genetic conditions and expanded genetic screening. Very few participants disagreed with the notion of carrier screening as socially responsible behavior.

Aspinall [35]

2013

UK

Theoretical paper

To evaluate the appropriateness, operationalization and efficacy of decision instruments that utilize origins-based concepts of race, ethnicity, or ancestry to determine genetic carrier screening status.

Small & expanded

Several potential deleterious consequences of using origins-based concepts can be identified. Any such usage to describe individuals as high risk by virtue of their group membership risks potential offense, stigmatization and discrimination.

McGowan [29]

2013

US

Qualitative focus group study (N = 6 groups) with 40 medical geneticists and genetic counselors

To describe genetics professionals’ perceptions of the benefits and challenges of expanding prenatal carrier screening and to situate these in the social debates about integration of new risk assessment technologies into prenatal care.

Expanded

Participants believed that clinicians and pregnant women will likely face logistical and psychosocial challenges similar to those that have arisen in the context of universal carrier screening for single gene disorders and other forms of prenatal screening.

Massie [33]

2014

Australia and New Zealand

Literature review

To describe prenatal and preconception population carrier screening for cystic fibrosis in Australia and to consider progress toward establishing a universal program.

Cystic fibrosis

Literature identified showed support for prenatal and preconception cystic fibrosis carrier screening by the community, health professionals and relevant professional bodies in Australia. The barriers to development of a national screening program could be overcome with more physician engagement and government support.

Rose [31]

2015

US

Theoretical paper

To reflect on the ethical implications of ECS.

Expanded

The author argued that it is reasonable to offer ECS to all patients. ECS should remain voluntary in any form and requires informed pre-test counseling, independently derived guidelines and oversight from professional organizations.

Langlois [28]

2015

Canada/US

Theoretical paper

To describe an authors’ debate on whether preconception ECS should replace current prenatal screening for specific gene disorders.

Expanded

The authors argue that although preconception ECS maximizes reproductive options for at-risk couples, prenatal screening would need to remain an integral part of prenatal care as long as there is a significant proportion of pregnant women who do not receive regular medical care prior to pregnancy.

Kihlbom [14]^b

2016

Sweden

Theoretical paper

To provide a conceptual framework that may enhance ethical debate of preconception care in general and (preconception) ECS specifically.

Expanded

A universal offer of (preconception) ECS raises several ethical issues around justice (including prioritization, discrimination and stigmatization), consequences (including medicalization) and autonomy (including informed consent and routinization). The author also argues that it is ethically problematic to have a discrepancy between an official aim of ECS offers and what really drives development.

Van der Hout [2]^b

2016

Netherlands

Qualitative interview study with Dutch key stakeholders working in the field of carrier screening (N = 17)^c

To gain insight into professionals’ opinion on EUCS and to provide a balanced picture of the potential pros and cons of EUCS.

Expanded

Stakeholders perceived potential benefits of EUCS offers. However, they also had numerous concerns. The findings of this study indicate that if certain concerns do not receive proper attention, EUCS may do more harm than good.

Henneman [5]

2016

Europe

Expert consensus paper, with members of the Public and Professional Policy Committee of the European Society of Human Genetics

To contribute to the public and professional discussion regarding responsible implementation of ECS and to arrive at better clinical and laboratory practice guidelines.

Expanded

The experts advise that to minimize potential adverse psychological and social implications and ensure the quality of tests, carrier screening tests should comply with quality control and information standards. They also state that research into the financial aspects of ECS into public health systems is needed. It is recommended that the primary purpose of ECS should be to enhance reproductive autonomy, there should be sufficient evidence before ECS is initiated, it should ideally be offered preconceptionally, that psychosocial support and genetic counseling is provided, that the model for reaching informed consent is evaluated, that participation in ECS should be voluntary and informed, that HCPs should be educated and trained and governments and that public health authorities should adopt an active role in discussing responsible ECS implementation.

Azimi [25]

2016

US

Cost-effectiveness analysis based on published literature, population surveys and expert opinion

To evaluate the cost-effectiveness of carrier screening using NGS versus genotyping for 14 of the recessive disorders for which medical society guidelines recommend screening.

Expanded

The findings of this study indicate that NGS-based ECS offers in multi-ethnic populations show greater benefit in clinical outcomes and lower total healthcare costs compared to current genotyping-based carrier screening, although these findings are sensitive to assumptions with regard to mutation detection rates and carrier frequencies in multi-ethnic populations.

Holtkamp [38]

2016

Netherlands

Quantitative survey study with individuals from the Dutch Jewish community (N = 145)

To explore attitudes of people from the Jewish community regarding ancestry-based and pan-ethnic ECS.

Small & expanded

Slightly more than half of the respondents favored EUCS over ancestry-based screening. Important reasons in favor of a EUCS were that everyone has a right to be tested, the fear of stigmatization when offering ancestry-based panels and difficulties in identifying risk based on mixed backgrounds. Prevention of high healthcare costs was considered the most important reason against EUCS.

Ekstrand Ragnar [50]

2016

Sweden

Quantitative survey study with expecting couples (N = 777)

To investigate parents’ (future) interest and motives toward preconception ECS and factors associated with interest in preconception ECS.

Expanded

Most participants expressed uncertainty about whether they would consider preconception ECS in the future, but women more often expressed motives against preconception ECS, including being concerned about negative consequences and being opposed to such a way of child selection.

Matar [53]

2016

Sweden

Qualitative interview study with HCPs (N = 11), including clinicians, geneticists, a midwife, and a genetic counselor

To explore Swedish HCPs’ views on preconception ECS.

Expanded

Participants raised concerns about ethical issues including medicalization, reproductive autonomy, parental responsibility, discrimination against those with disease or carrier status, prioritization of health resources and uncertainty concerning what to test for and how to interpret the results.

Holtkamp [39]

2017

Netherlands

Qualitative interview study with Dutch key stakeholders working in the practical and scientific field of carrier screening (N = 17)^c

To identify general and population-specific barriers and needs reflected by stakeholders regarding the implementation of ECS in a changing landscape.

Expanded

Barriers were identified on cultural level (including uncertainty about the desirability of screening and lack of priority), on a structural level (including need for guidelines, financial structure, and practical tools for overcoming challenges during counseling and need to train and educate HCPs) and practical barriers (including lack of demand for screening by the public and need for a division of responsibilities).

Molster [3]^b

2017

International

International workshop with experts (N = 41)

To identify key public policy issues related to preconception ECS that governments should consider when deciding whether to publicly fund such programs.

Expanded

Participants raised a range of issues that require careful examination prior to implementing ECS. Based on the workshop outcomes, new criteria need to be developed that inform whether to initiate preconception ECS. Participants felt it was needed to consider equitable availability and downstream effects on and costs of follow-up interventions for those identified as carriers.

Holtkamp [40]

2017

Netherlands

Literature review & case descriptions

To identify critical factors involved in successful implementation of ECS from a user perspective and by learning from implemented initiatives.

Expanded

This study indicates that factors contributing to successful implementation of carrier screening include familiarity with genetic diseases, its availability, high perceived benefits of screening, acceptance of reproductive options, perceived risk of being a carrier and low perceived social barriers such as stigmatization. High social cohesion in a community would also facilitate implementation.

Janssens [54]

2017

Belgium

Qualitative interview study European clinical and molecular geneticists with expertise in carrier screening (N = 16)

To explore geneticists’ attitudes about the implementation of ECS for monogenic recessive disorders.

Expanded

In considering ECS implementation, participants perceived benefits (including greater access to screening) but also identified major challenges, including limited benefit for most couples in the general population, lack of public and HCP education on ECS, potential negative societal implications (including slippery slope, effects for people living with conditions screened) and limited economic resources. Participants called for more extensive discussion of the societal effects of EUCS offers.

Chokoshvili [10]

2017

Belgium

Literature review

To highlight the distinct issues associated with three different types of ECS offers (direct-to-consumer, physician-mediated and clinic-based testing).

Expanded

Although all the three models (direct-to-consumer, physician-mediated and clinic-based testing) for ECS offers are characterized by different challenges, it was found that, in practice, physician-mediated ECS offers appear to be the most problematic, warranting greater regulatory scrutiny into these kind of testing offers.

Mathijssen [43]

2018

Netherlands

Screening offer evaluation using quantitative surveys among members of a Dutch founder population (N = 319; 182 attendees at an outpatient clinic and 137 non-attendees) and qualitative semi-structured interviews with 7/8 identified carrier couples

To evaluate experiences with a PCS offer for four recessive disorders in a Dutch founder population.

Expanded

Almost all screened individuals reported being very satisfied with screening. Genetic counseling prior to screening was preferred. Before consultation, three individuals expected to be seen differently if they turned out to be a carrier. None of the participants perceived screening as discrimination. Fear of stigmatization was not an issue for carrier couples.

Van der Hout [45]

2018

Netherlands

Theoretical paper

To provide an ethically sustainable account of the aims of EUCS.

Expanded

Enhancing autonomy appears the most appropriate aim of prenatal screening offers. However, with offers in the preconception phase, a wider range of reproductive options is available. Therefore, the authors argue that to the extent that 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 just enhancing reproductive autonomy.

Kraft [27]

2019

US

Theoretical paper

To report on the current landscape of ECS and to identify potential challenges that should be addressed.

Expanded

The authors describe different challenges for ECS offers, including lack of demand from the public, low prioritization of health systems, potential for pressure to undergo screening, the possibility of disability-based discrimination, needed adaptations to pre- and post-test counseling, technical limitations and the evolving technological and socio-political landscape.

Beauchamp [26]

2019

US

Cost-effectiveness analysis comparing minimal screening and a 176-condition ECS panel

To model the clinical impact and cost-effectiveness of preconception ECS.

Small & Expanded

This study demonstrates that, relative to minimal screening, preconception ECS reduces the affected birth rate and is estimated to be cost-effective (<$50,000 incremental cost per life-year).

Nijmeijer [44]

2019

Netherlands

Quantitative survey study with members of the Dutch general population (N = 781) in the reproductive age

To assess the attitudes of the general Dutch population toward preconception ECS and to investigate which factors influence these attitudes.

Expanded

This study indicates an overall positive attitude toward ECS. 55% believed that ECS should be offered to all prospective parents. About one third of participants perceived adverse societal implications, including slippery slope, discrimination and societal pressure.

Matar [51]^a

2019

Sweden

Qualitative interview study with Swedish healthcare policymakers (N = 10)

To explore how healthcare policymaking experts perceive ethical and social aspects of preconception ECS.

Expanded

Participants believed that Sweden is currently not ready to implement ECS due to several ethical and social concerns, such as risks of stigmatization and discrimination, and potential long-term effects, such as a change of the public mind-set from tolerance and societal responsibility for the disabled to intolerance and attitudes of blame.

Matar [52]^a

2019

Sweden

Qualitative interview study with Swedish healthcare policymakers (N = 10)

To explore values and value conflicts that healthcare experts recounted in relation to the discussion of implementation and use of preconception ECS in Sweden.

Expanded

Participants described values and value conflicts with regard to EUCS implementation related to solidarity (including equality, justice and social care) and respect for individuals (including autonomy, integrity and privacy).

Delatycki [21]^b

2019

International

Case descriptions

To describe reproductive carrier screening offers across the globe.

Expanded

The authors describe carrier screening programs around the world that target different groups, as does the governance structure. Differences relate to geographical variation in carrier frequencies of genetic conditions and local healthcare, financial, cultural and religious factors.

Dive [13]

2020

Australia

Theoretical paper

To reflect on the ethical implications of large scale ECS offers in Australian healthcare.

Expanded

This article describes many ethical implications of ECS offers, related to its aim, gene selection, consent, funding and reporting of results. The authors argue that future delivery of a national ECS program in Australia will need to recognize and respond to this diversity while also upholding the values that motivate the program.

Rowe [36]

2020

UK

Literature review

To evaluate the existing evidence for EUCS programs, and to appraise the potential benefits and challenges of implementation within a publicly funded healthcare system.

Expanded

Literature identified indicates that although preconception screening would maximize the potential benefits from EUCS, the resource implications of different modes of delivery need to be carefully evaluated and balanced against maximizing reproductive autonomy and ensuring equity of access.

Cornel [47]

2021

Netherlands

Theoretical paper

To demonstrate how the dynamics and expansions in NBS and carrier screening have challenged four well-known screening criteria (treatment, test, target population and program evaluation), and the decision-making based on them.

Expanded

The authors argue that that shifting perspectives on screening criteria for NBS as well as carrier screening lead to converging debates in these fields.

Conijn [46]

2021

Netherlands

Qualitative focus group study with members of the general population (N = 18) and relatives of MPS III patients (N = 23)

To obtain insight into the perspectives of relatives of MPS III patients and potential users from the general population on ECS.

Expanded

Participants, both relatives of MPS III patients and individuals from the Dutch general population, support implementation of preconception ECS to prospective parents in the general population. However, important barriers for ECS implementation were identified. The concept of EUCS showed to be difficult to understand, particularly for participants from the general population.

Van Dijke [48]

2021

Netherlands

Quantitative survey study with high-risk participants (N = 89) and general-risk participants (N = 43)

To evaluate the experiences of couples that participated in an expanded carrier screening offer.

Expanded

Most individuals participating in the carrier screening program showed to have made an informed choice, showed no or limited negative psychological impact, and were satisfied with the screening although they considered the cost of the test too high.

Dive [13]

2021

Australia

Theoretical paper

To describe the relevance of public health ethics for implementation of reproductive genetic carrier screening programs.

Expanded

The authors argue that EUCS has sufficient features in common with other public health screening programs that it becomes important also to attend to public health implications of EUCS. It is stated that not attending public health implications may affect the capacity of people to exercise their reproductive autonomy.

Morberg Jamterud [49]

2021

Netherlands

Qualitative interview article with general practitioners (N = 7), compared with a theoretical bioethical analysis study

To present an empirical bioethics analysis of the PECS practice from the perspective of GPs.

Expanded

Two themes were identified in the analysis: (1)‘Choice and its complexity’, which suggests that medical, moral, social and psychological aspects co-shape the complexity of choice regarding EUCS and (2) EUCS as prompting existential concerns’, indicating that it is not possible to analyse existential issues raised by EUCS solely on the level of the couple or family but that a societal level must be included, since these levels affect each other (referred to as ‘entangled existential genetics’).

Bonneau [58]

2022

France

Quantitative survey article among members of the general population (N = 1568)

To collect French general population opinion on the implementation of preconception genetic testing and explore the factors associated with a difference of opinion.

Expanded

In this study, 91% of participants was favorable to ECS and 57% declare to be willing to participate in screening. A medical prescription by a general practitioner or a gynecologist was considered best to offer screening for 73%, with a reimbursement from insurance. However, 19% declared not to be willing to participate because of ethic or moral convictions, and the fear that the outcome would question becoming pregnant. Otherwise, most participants considered the test medical progress despite the risk of an increased medicalization of the pregnancy.