Will UK Public Approval of Whole Genome Sequencing for Newborn Screenings Lead to National Rollout?

The following article is an opinion piece written by Sukhvinder Nijhar Nicklen. The views and opinions expressed in this article are those of the author and do not necessarily reflect the official position of Technology Networks.

Following a series of public consultations on the topic of whole genome sequencing (WGS), Genomics England – the Department of Health and Social Care’s genome-sequencing hub – recently announced that public support for WGS has reached the point where the prospect of its national rollout on the NHS could soon be a reality. 

The news comes as advances in technology and scientists’ growing knowledge of WGS make this analysis more affordable and effective enough to be incorporated into standardized newborn screening (NBS) procedures in the UK.

There are, nonetheless, still a number of critical questions that need to be answered before WGS becomes a staple of neonatal care in the NHS. What are its benefits? What are the costs involved? What potential ethical issues does it incur? 

The current state of NBS in the UK

At present, screening in neonatal care involves four drops of blood being taken from the babies’ heel, approximately five days after birth. Biochemical blood tests are then performed on the dried blood sample (DBS) in order to diagnose a number of serious disorders. The current scope of these tests covers nine different conditions, including sickle cell disease (SCD), congenital hypothyroidism (CH) and phenylketonuria (PKU), which, if identified in the early stages of a person’s life, can be treated effectively as soon as possible. Currently in the UK, babies are only screened for metabolic disorders that can be treated.

WGS by no means represents a replacement for the biochemical tests currently part of the UK’s NBS programme, but it would offer a richer level of important information relating to any conditions identified by biochemical testing. For example, the enriched phenotypic data yielded by WGS can be used to understand more precisely disease variants and to rapidly deliver insights that are relatively likely to affect early treatment and management decisions. If introduced, WGS will offer an additional layer of screening for a wide range of genetic markers associated with rare disorders. 

Factors affecting the scope of NBS

While WGS has the capability to test for a wider range of conditions, there are a number of considerations to take into account before doing so. The method by which NBS is carried out in the UK today is based on the stipulations of the Wilson and Jungner criteria advocated by the World Health Organization, which include: 

• the condition is adequately understood; 

• facilities for diagnosis and treatment are available; 

• clinical management of the condition should be optimized in all healthcare providers. 

Screening for disorders that do not meet these criteria (i.e. those for which effective clinical treatment and management is not available) could cause severe emotional and/or psychological distress to parents upon receiving news of a diagnosis. This further underlines the importance of using WGS to deepen the understanding of disorders identified by biochemical testing as opposed to a replacement diagnostic test.

The impact of WGS on funding & resources

Thanks to advances in genome-related laboratory technology, the cost of WGS has dropped considerably over the past few years – a trend we can expect to continue for the foreseeable future. That said, we’re still a long way off from WGS costs falling to a level equivalent to current biochemical tests. Any major changes to newborn screening must be affordable in a public health setting, which makes it imperative to deeply analyze the involved cost versus benefits. So, with a national rollout representing a significant jump in the cost of NBS, how can the introduction of WGS be justified?

The answer lies in the potential cost savings that WGS could bring to diagnostic processes overall. From a purely financial point of view, treating the recurrent symptoms of a patient with an undiagnosed disorder over the years could cost the NHS hundreds of thousands of pounds. If the disorder can instead be diagnosed using WGS and an appropriate treatment administered early on, the overall cost of doing so would be significantly lower.

The same argument can be made from a resourcing perspective. The treatment of undiagnosed illnesses often requires specialist equipment, staff, and hospital space, and may not always be available in the location in which it is needed, presenting a further logistical challenge. With COVID-19 having put the topic of NHS resourcing in the spotlight, any initiatives that could free these resources up certainly present a compelling argument.

As clear as the economic advantages of WGS in NBS could be, these pale in comparison to the impact that such a change could bring to patient wellbeing. In some cases, a disorder diagnosed earlier on in life could help kickstart a treatment programme before the disorder itself creates irreversible damage to the patients’ health, and could lead to an invaluable reduction in the physical and emotional cost of a patient undergoing years of treatment.

Ethical issues surrounding WGS

Perhaps one of the most important issues to overcome in any widespread rollout of WGS is to ensure tests remain accurate for individuals of different ethnic backgrounds. Studies have shown that genetic markers for condition-causing variants are not uniform across different ethnic groups, which opens the possibility for misdiagnosis under WGS, especially for individuals of an ethnic minority within a larger population.

To avoid these issues, it is essential that the datasets used within WGS to determine what a “healthy” individual’s genome looks like incorporate data of individuals from under-represented groups. Collecting more diverse data will enable us to broaden our definition of “normal” variation beyond that of majority groups to provide individuals in these groups with the same level of care as the rest of the population. Only then can genomic databases be diversified enough so that everyone can benefit equally.

The future of WGS for NBS

When it comes to whether or not WGS for NBS should be introduced on a national scale, the arguments on both sides are complex and compelling. With a potential immediate impact on the wellbeing of future generations and the access to healthcare moving forward, the most important factor today is to ensure that the public is well-informed about WGS and has the ability to engage in open discussions on its introduction.

We are still at the beginning of a very extensive process. It’s one that will need a lot of consultation with both professionals and the public but will ultimately help advance our ability to treat people affected by serious conditions and improve patient wellbeing overall.

About the author: Sukhvinder Nijhar Nicklen PhD, is Market Development Leader at PerkinElmer.