Preconception carrier screening in 2025: what’s next?

Introduction

When a child is diagnosed with a severe (autosomal) recessive condition, parents often ask the question: “Could we have known before that both of us are carrier of this condition?” Technically speaking, the answer to this question is “yes”, but in practice preconception carrier screening is not accessible to most couples worldwide. When Mackenzie was diagnosed with Spinal Muscular Atrophy, a severe inherited neuromuscular condition, her parents asked this question to many doctors and policy makers in Australia, which was the driver behind a large scale offer of carrier screening in Australia (Kirk et al. 2024). The three year research study ended enrolment in 2022 and results are now becoming available. Thus preconception carrier screening is more topical than ever. The Journal of Community Genetics already had a long-standing interest, and decided to start a collection on the topic: Preconception carrier screening.

The start

Decades ago, screening offers started for haemoglobin disorders in the Mediterranean area as well as for Tay Sachs disease, a severe progressive lethal neurodegenerative condition, among Ashkenazi Jewish people (Antonarakis 2019). Recent years have made it possible to move from ancestry-based screening for one condition to pan-ethnic or universal screening for a larger number of conditions (Cornel et al. 2021). This is partly driven by technological innovations, especially next-generation sequencing (Rowe and Wright 2020), and partly by ethical reasons, avoiding stigmatization and discrimination and improving equity. The very recent Australian initiative offered a test for > 1000 genetic conditions to > 9000 couples in the government funded project Mackenzies Mission, and 1.9% were identified as carrier couples (Kirk et al. 2024). More than 75% of the newly identified carrier couples planned to avoid the birth of an affected child (Kirk et al. 2024). As a consequence, suffering as well as costs might be avoided.

Aim: reproductive autonomy or prevention?

The aim of preconception carrier screening has often been discussed, and the Journal of Community Genetics has a tradition of stressing the importance of offering screening to increase reproductive autonomy (Schmidtke and Cornel 2020; Cornel et al. 2021). However, offering carrier screening to enable couples to make an informed reproductive choice may lead to a reduced prevalence of the recessive conditions involved. Thus prevention may be a consequence of a screening offer. Other authors have also described the latter as an important goal to implement carrier screening programs (Sinha et al. 2020). Especially in India the increasing possibilities for treatment of haemoglobin disorders, which lead to a longer and healthier life of patients with hemoglobinopathies such as thalassemia and sickle cell disease, also lead to public health expenditure that is increasingly seen as problematic (Modell 2020). If thalassemia patients are diagnosed early and treated with blood products adequately, “budgetary requirements… would account for over 19% of the current National Health Budget” (Sinha et al. 2020). Therefore “The Government of India is presently engaged in the implementation of a prevention and control programme for thalassaemia major and sickle cell disease, with guidelines for their prevention and management” (Sinha et al. 2020). A study “to explore the knowledge, awareness, and attitude of premarital genetic counselling and screening” in Odisha, a state in Eastern India, showed room for improvement in knowledge and awareness (Bindhani et al. 2020). Parents of children with Sickle Cell Anaemia in Tanzania often found out about carrier screening after the diagnosis of their child (Kisanga et al. 2021). They support an offer of premarital carrier screening, some even consider that this should be compulsory. Also in The Netherlands in a focus group study, both relatives of mucopolysaccharidosis III patients and participants from the general population supported offering carrier screening, in particular for severe, childhood-onset disorders (Conijn et al. 2021). In the United States, while not an organized program, professional organizations of Obstetricians and Gynaecologists as well as Geneticists have recommended carrier screening for many years (Reed-Weston et al. 2020). While Ashkenazi Jewish people are relatively well informed on their risk of Tay-Sachs disease, amongst others, other minority groups such as the Latino community is less well served, while also interested to receive genetic test results (Reed-Weston et al. 2020).

Organizing a program

Apart from India, also other countries have organized carrier screening programs, such as Oman (Al Zeedi and Al Abri 2021). Here, a premarital screening and counselling program has been organized. Couples who were engaged were the majority of users. The engagement was cancelled in 23% of couples with positive results (Al Zeedi and Al Abri 2021). In Israel, high risk groups can be screened for other conditions than the general population. For instance, for Arab Bedouins, who have a high percentage of consanguineous marriages, the Ministry of Health developed a targeted screening program including education and raising awareness (Singer et al. 2020).

Countries struggle to decide on the implementation of carrier screening programs in a public health setting (Rowe and Wright 2020). This is partly because of the definitions of “severe”, “serious” or “profound” conditions to be included in the gene panel, but also uncertainty on cost, uptake and reproductive options being available (Rowe and Wright 2020). Screening tests differ in the conditions included and offers of carrier screening in care setting or public health care programs differ.

Conclusion

Although there are many questions related to preconception carrier screening, the evidence from pilot programs is increasingly becoming available and implementation in care settings as well as public health care programs needs to be considered again. The recent publication on Mackenzie’s mission is a major achievement that will inform many policy makers globally. Approaches may differ. Stakeholders can use this collection of the Journal of Community Genetics to help discuss and shape the future.