Screening tests allow medical conditions, such as sickle cell disease and cystic fibrosis, to be identified as early as possible, ideally before symptoms onset. This then allows appropriate interventions and treatments to be given to ultimately improve patient outcomes.
In particular, screening newborn babies for rare genetic disorders in the first few days of life is one of the twentieth century’s most effective public health initiatives, as cited by the United States Centers for Disease Control and Prevention.
Traditionally, this is done by a ‘heel-prick’ test, where a few drops of the newborn’s blood are collected from their foot and sent for biochemical laboratory analysis.
The blood is analysed using tandem mass spectrometry (MS/MS), a biochemical test analysing metabolites of interest, which allows fast, simultaneous detection of multiple genetic diseases. Currently, in the UK, this approach allows detection of nine rare but serious conditions. The exact number of conditions screened for using this traditional blood spot biochemical test varies from county to country, for example, Greece screens for up to 30 diseases currently using this approach.
In Australia, newborn screening is performed at the state level - so the number of conditions screened for depends on the specific state/territory, with a maximum of 28 conditions being assessed. In the USA, the number of diseases tested for can also vary between states, with a core panel of 35 diseases being recommended for testing.
In some countries, newborn screening initiatives are beginning to take the first steps towards utilising large-scale genomics data (eg an individual’s whole genome) to diagnose an increasing number of disorders, including rare and genetic conditions.
Genomics is the study of a person’s complete set of DNA and has relevance to all medical specialities across all life stages. Increasingly, advances in our understanding of the genome are contributing to improvements in disease diagnosis, drug discovery and targeted therapeutics. Routine genomic sequencing of newborns can be considered the ultimate application of precision medicine and is a logical extension of more traditional screening of newborns for genetic diseases.
Several newborn genomic sequencing initiatives in the USA are already underway, including the Rady Children’s Institute’s BeginNGS initiative and the Boston Children’s Hospital and Brigham and Women’s Hospital BabySeq Project.
In Australia, the Murdoch Children’s Research Institute’s landmark Generation Victoria (GenV) initiative is currently trialling a new genomic newborn screening model on 1,000 babies to lay the foundation for a national-scale programme.
In Europe, Greece has begun a clinical trial as a partnership between PlumCare RWE and BeginNGS Greece, with Lifebit providing the trusted research environment for data analysis. Here, researchers will assess the outcomes of performing genomic newborn screening in an initial cohort of 1,000 newborns, with the aim of scaling to all newborns nationally by 2027.
In the UK, Genomics England’s Newborn Genomes Programme is currently co-designing and running a National Health Service (NHS) embedded research study to explore the benefits, challenges, and practicalities of sequencing and analysing the genomes of newborns to detect disease.
Dr Maria Chatzou Dunford, CEO of Lifebit, introducing the pioneering Greek Genome Project, to screen newborn babies for rare genetic conditions.
Genomic screening has several significant advantages compared to traditional biochemical screening approaches for genetic conditions in newborns.
These are:
While there are significant advantages to moving towards a genomic approach to newborn screening, these programmes also have challenges. These are summarised in the following table, alongside some ways that these issues are being addressed.
Newborn genomic screening allows early detection of genetic diseases, so appropriate early interventions can be given, allowing affected families to lead lives unaffected by disease. Improved care at a lower cost can ultimately be realised, provided technological advances and appropriate consideration of ELSI and subsequent PPIE and genetic counselling are leveraged.
These should be the first steps to ensuring that next-generation sequencing translates to next-generation care for newborns, ensuring healthier futures for all.