Whole genome sequencing for newborn screening

Today, all newborns aged between five days and one year are eligible for NBS screening for nine different conditions, including sickle cell disease, congenital hypothyroidism and phenylketonuria.

WGS does not represent a replacement for current tests but would instead offer a richer level of important information relating to any conditions identified by biochemical testing. For example, the enriched phenotypic data yielded via WGS can be used to understand disease variants more precisely and to rapidly deliver insights likely to impact early treatment and management decisions.

While WGS has the capability to test for a wider range of conditions, there are a number of aspects to take into account before doing so.

The current criteria for screening conditions in the UK are based on the stipulations of the Wilson and Jungner criteria advocated by the WHO, which include: the condition should be adequately understood; there should be facilities for diagnosis and treatment available; and clinical management of the condition should be optimised 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 families upon receiving news of a diagnosis.

This furthers the argument to use WGS to deepen the understanding of disorders identified by biochemical testing as opposed to a replacement diagnostic test.

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 being said, the cost of WGS is still much higher than, for instance, that of current biochemical tests. Clearly, any major changes to NBS must be affordable in a public health setting, and as a consequence, for the introduction of WGS to be justified it is imperative to investigate the health economic evidence related to it.

An important dimension of this are the potential cost savings that WGS could bring to diagnostic processes overall. From a purely financial point of view, treating a patient with an undiagnosed disorder over the years could cost the NHS hundreds of thousands of pounds.

If the disorder can be diagnosed sooner using WGS and an appropriate treatment can be administered early on, it may be possible that symptoms are less severe later in life, requiring less treatment, or potentially even curing the condition in its entirety. Impact on the patient’s quality of life notwithstanding, both of these outcomes represent enormous cost savings for the NHS.

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.

Covid-19 put the topic of NHS resourcing in the spotlight, so any initiatives that could free up these resources certainly present a compelling argument.

Needless to say, the economic advantages of WGS pale in comparison to the positive impact on patient wellbeing with early diagnosis, less invasive treatment and reduced pain and suffering.

When it comes to whether or not WGS for NBS should be introduced on a national scale, the arguments on both sides are equally complex and compelling.

With a potential immediate impact on the health, wellbeing and quality of life of citizens, 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 just at the beginning of a very extensive process. One which will need a lot of consultation with both professionals and the public but will ultimately help advance our ability to treat patients and improve their wellbeing overall.