The NHS is aiming to test up to 100,000 newborn infants in a study to understand whether improvements can be made in diagnosing and treating genetic conditions.

The results will add to the evidence that will inform future decisions about the use of whole genome sequencing to support newborn screening.

NHS to Test up to 100,000 Newborns for Genetic Conditions

Peter Russell | 09 October 2024

The NHS is aiming to test up to 100,000 newborn infants in a study to understand whether improvements can be made in diagnosing and treating genetic conditions.

Newborn blood spot screening, often referred to as the "heel prick test", is currently offered to parents to test their baby for any of nine rare but serious health conditions.

The Generation Study, led by Genomics England, is using whole genome sequencing to look for changes in genes associated with more than 200 individual conditions caused by genetic changes in around 500 different genes. The results will add to the evidence that will inform future decisions about the use of whole genome sequencing to support newborn screening.

More than 500 blood samples have been taken so far from newborns at 13 NHS hospitals across England as part of the Generation Study. The NHS plans to scale this up to around 40 hospitals to reach approximately 105,000 infants by March 2025.

Scope of the Study

There are over 6000 known rare diseases, with eight out of 10 having a genetic cause. Almost all genetic conditions, meanwhile, are classed as rare. However, the study will look only for disorders that develop in the first few years of life, that can be improved if caught early, and which can be treated by the NHS.

Sequencing can identify treatable conditions soon after birth, rather than when symptoms appear later in childhood, NHS England said in a statement.

Nick Meade is a member of the Ethics Working Group of the study and director of policy at Genetic Alliance UK, which supports people with genetic, rare, and undiagnosed conditions. He told Medscape News UK , “We want to understand to what extent this tool — genome sequencing — is a valuable tool to use and how effective it is, as well as assessing whether some of these conditions that we don't screen for at the moment might be potential candidates for the future."

Dr David Elliman, clinical adviser to the UK National Screening Committee and newborn blood spot screening programme, and a consultant at Great Ormond Street Hospital, said it might seem like a "no-brainer" that the NHS should offer this to all infants. However, he cautioned that there is currently very limited experience of testing babies before they have symptoms and predicting what might have happened if they were not treated.

"Even if it works, we're probably not going to abandon the routine screening that we would do, but it may help some people, and we should look at it as an important development that needs further examination," Elliman told Medscape News UK.

Protocol

At participating hospitals, expectant parents are told about the study during pregnancy, and if they are interested, a research midwife will have a detailed discussion with them to decide whether they want to take part. Shortly after the birth, an NHS doctor, nurse, or midwife will confirm with the parents that they are still happy for their baby to be tested. If so, a blood sample will be taken, usually from the umbilical cord, for whole genome sequencing.

The results are then reviewed by NHS genomic scientists, with the aim of informing parents within 28 days if a condition is suspected, or within a few months if no condition is suspected.

If a newborn infant is found to have a treatable childhood condition through the genome sequencing, families and carers will be offered further testing to confirm the diagnosis, as well as ongoing support and treatment, NHS England said.

Challenges and Concerns

Elliman acknowledged that whole genome sequencing "holds out promise of a whole new world". However, he cautioned: "We still need to look at not just the principle of whether we can do this, but for each individual condition, whether there is a balance of harms and benefits that is in favour of the benefits. And what we have with the conditions that we currently screen for is a big evidence bank that the benefits outweigh the harms at reasonable costs."

According to Elliman, while some children will benefit from testing, others could end up being treated for a condition they do not have or for which they would not have needed treatment. Also, there may be some cases where the outcome of the test will be inconclusive, leaving parents with ongoing uncertainty about their child’s future health.

"Is it really worth — and I don't mean now in terms of money — human anxiety, emotional cost, that we're following up a lot of children and inevitably changing their views of life to some extent, when a lot of them — in fact, the majority — may not profit from that?", he asked.

"There will inevitably be some false-positives," acknowledged Meade, of Genetic Alliance UK. "Hopefully that number will be small, and then we can also understand to what extent that is a damaging process to go down." He suggested that the broader question would be "do we tolerate a small number of false-positives to be in a health environment where we catch serious, rare conditions early? That's the balance we have to strike."

Case Example: Adrenoleukodystrophy

Among the conditions being screened for is adrenoleukodystrophy (ALD), in which the gene responsible for activating the normal chemical processes of breaking down fatty acids in cells is faulty, resulting in damage to the adrenal glands, brain cells, and myelin.

Sara Hunt, founder of the leukodystrophy charity Alex, welcomes the Generation Study, which she said had been a "long time coming". Her oldest son, after whom the charity was named, died at age 19 years, 12 years after being diagnosed with ALD. His younger brother, who had also inherited the genetic disorder, was scanned every year and underwent a bone marrow transplant.

"He's now 24, working in my charity," Hunt told Medscape News UK. "You wouldn't know there was anything wrong with him. He leads a very healthy, very normal life. These conditions are incredibly preventable."

The contributors have disclosed no relevant financial relationships.

Peter Russell has been a journalist for 40 years covering international news, health, medicine, and national politics on radio, TV, and online.

Medscape UK

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