27th November 2023
Discussing Newborn Screening: A hot topic for BSGM in 2023.
Jen Willows, Editor at PET (the Progress Educational Trust)
Earlier this year, the BSGM dedicated four of its popular 'Lunch and Learn' webinars to the subject of newborn screening.
Here we provide a very brief overview of the sessions, as well as highlighting some of the shared themes that recurred across the different presentations.
The UK blood spot test
The first session provided a review of the current newborn blood spot screening programme in the UK. It featured Dr David Elliman, who is Clinical Lead for national newborn bloodspot screening programme and infant physical examination programme, and Nick Meade, Director of Policy ant Genetic Alliance UK.
Dr Elliman provided an introduction to the idea of screening, and the reasons why decisions about screening apparently healthy people differ from those regarding tests for patients who have presented with some kind of symptoms.
He gave an overview of the history of the blood spot screening test, which conditions are included in different parts of the UK, and what factors the UK National Screening Committee (UKNSC) considers when deciding to recommend a condition be included.
Nick Mead spoke from the perspective of Genetic Alliance's members – families affected by genetic, rare or undiagnosed conditions. He compared the number of conditions included in UK screening programmes with other countries, particularly in Europe, many of which screen for around twice as many.
The second and third sessions in the series focused on newborn screening in Europe and California respectively.
The second session, A Review of Newborn Screening Bloodspot Programmes in Europe featured presentations from Peter Schielen from the International Society for Newborn Screening (ISNS) and Editor in Chief of the International Journal of Newborn Screening. He talked about the changes in neonatal screening across Europe since 2010 and the current situation.
The second presentation featured a perspective from the Netherlands, from Eugenie Dekkers, who manages the Newborn Screening Programme at the Centre for Population Screening Rijksinstitut voor Volksgezondheid en Milieu.
The third session, Review of Newborn Blood Spot Screening in California opened with Dr Lisa Fechtbaum from the California Department of Public Health, who presented an overview of the current screening programme in her state.
This was followed by a presentation on genome sequencing for newborn screening from
Professor Robert Nussbaum, who is Clinical Professor of Medicine at the University of California San Francisco. His talk explained how genomic screening can be used to reduce the number of false positives that are generated by even very high specificity tests when screening for ultra-rare conditions.
The final presentation in the series returned the focus to the UK, but continued discussion of whole genome sequencing as an approach to newborn screening.
An update on Genomics England's Newborn Genomes Programme was given via a joint presentation from Genomics England's Chief Medical Officer (currently acting CEO) Dr Rich Scott, and Clinical Lead for Genetic Counselling Amanda Pichini.
Amanda Pichini introduced the research part of the programme, now called the Generation Study, which will use whole genome sequencing in 1000,000 newborns to assess the feasibility and clinical utility of WGS to screen for a larger number of conditions. It also aims to understand the possible impacts and benefits of storing a baby's genome for use in medical care throughout their life, as well as attitudes of patients and health professionals to this possibility.
The presentation also included a 'deep dive' into how the project plans to interpret and return results to participants.
Some themes cropped up repeatedly in the different presentations, particularly issues around evidence, consent and what sorts or conditions should be screened for.
Nick Mead pointed out that for rare and ultra-rare conditions, obtaining 'robust' evidence of an effective treatment is very difficult, because there are too few patients to run a randomised controlled trial in a useful timeframe.
Dr Elliman agreed and said that in these cases they have to work on lower levels of evidence that they would require in other conditions, but also constantly monitor new evidence as it emerges. However, he qualified that they do need to be 'reasonably confident' that the screening test will be beneficial, as it is very difficult to discontinue a screening programme once it is stablished.
One of the main aims of the Generation study is to gather evidence: "We are wanting to ask not just how [WGS] might be implemented, but whether there is evidence to support implementing genome sequencing as part of newborn screening," said Pichini
One of the issues raised by Dr Elliman was that of informed consent. The current UK blood spot test looks for nine conditions, and health professionals are able to explain the risks and benefits of screening for these conditions, but
"Informed consent …is going to be an increasing problem whether or not we go with whole genome sequencing. Because how much is it fair to expect a pregnant family to understand of each individual condition? … As the numbers [of conditions] increase that's not going to be practical," he said.
The Generation study, by necessity, takes a much broader approach to consent. Not only will it screen for over 200 conditions, but parents are asked to consent to all aspects of the study, including storage of their child's genomic data and heath records, and allowing that (de-identified) data to be used in research. The children will be reconsented at 16 for their data to be held in the National Genomics Research Library, or can choose to withdraw from the programme.
Treatable v actionable: Who benefits?
The UKSC only screens for 'treatable' conditions, specifically those for which there is effective treatment or intervention available in the UK. Similarly, the
Generation Study (which has released the list of conditions it will screen for since the webinar took place) will only screen for conditions where 'Early or pre-symptomatic intervention for the condition has been shown to lead to substantially improved outcomes' and where these interventions 'are equitably accessible for all'.
This approach was contrasted by that of Rare Diseases Europe (EURORDIS), which takes a wider view of what is classed as 'actionable', which encompasses benefits to the child, family and society.
Nick Mead pointed out that even when a condition Is not treatable, a diagnosis has great value to Genetic Alliance's members, in that it may enable the child to have fewer clinic visits and tests, or enable them to participate in research or clinical trials. There are benefits for the family as well, such as planning care, making informed reproductive choices, and accessing support and connecting with other affected families.
The issue of broader, and indirect benefit to the child was illustrated by a discussion of familial hypercholesterolaemia in the Q&A part of the first session. Dr Elliman explained that children with this condition would not normally be given drug treatment before the age of eight, although dietary approaches can be employed. However, he mentioned discussions that took place around a study (that UKNSC are not involved in) that suggested that one of the benefits of screening children would be identifying the condition in their parent(s) as well. The idea is that the adult would benefit, but the child could also benefit indirectly by reducing the risk that their parent could die prematurely.
These are only a few of the facets of this fascinating subject that were raised, and a short article like this one cannot come close to covering the depth of content in these presentations.
All four webinars are available to view on the BSGM website for members who missed them, or who would like to watch again.