Challenges of using whole genome sequencing in population newborn screening

In the UK, newborn screening is offered under the oversight of the National Screening Committee.1 Heel prick blood spots are currently tested biochemically for nine conditions for which early treatment, before symptoms, improves outcome. The NHS embedded Newborn Genomes Programme (recently renamed the Generation Study) aims to “detect hundreds more rare, treatable diseases in [the] first years of life”2 and builds on the ambition outlined by the UK health secretary in 2019 “that eventually every child will be able to receive whole genome sequencing along with the heel prick test … We will give every child the best possible start in life.”3

The Generation Study aims to screen at least 100 000 newborn babies for several hundred potentially treatable rare diseases that are likely to present by the age of 5 years. The offer of this screening will be contingent on parental consent to the baby’s genome being linked to their health records to enable research into genetic links to disease.4

In aspiring to fulfil both aims simultaneously, the Generation Study fuses separate elements: one focusing on newborn screening for rare conditions; one exploring how a baby’s genetic code relates to their life trajectory. Because these two elements are run under the same study, the newborn screening aspect cannot consider what assay would be best for that purpose alone. It has to be whole genome sequencing, even though the screening proposed could be obtained from more focused genetic testing. However, the offer of “extra” screening is likely to attract parents and overshadow considerations around the pros and cons of enrolling …