Service Evaluation for Newborn Screening for Spinal Muscular Atrophy

Spinal Muscular Atrophy (SMA) is a disease that causes progressive muscle weakness. There are many types- the most severe and most common, type 1, affects very young babies, and is life-threatening if untreated. Other types can cause significant disability. Most cases are caused by a missing part of the survival motor neuron 1 (SMN1) gene. Another related gene, SMN2, can partially compensate for this affected gene. With more copies of SMN2 broadly leading to a milder disease.

Three new treatments can slow or prevent symptoms, but they work best when given before symptoms appear. This has led to many countries, including the USA and much of Europe, introducing newborn screening (NBS) for SMA, so that affected babies can be treated as early as possible. The investigators ran a UK pilot project that screened nearly 33,000 babies and found the test to be accurate and practical, but this pilot was too small to show whether screening improves outcomes or is good value for money for the NHS. The UK National Screening Committee would also like to know how acceptable NBS for SMA is for different groups of people. This study is designed to answer those questions.

Screening will be introduced across seven NHS screening laboratories, most of which already screen for another rare condition, severe combined immunodeficiency (SCID). About 400,000 babies are born in the areas covered by these laboratories every year. Screening will be introduced gradually, so that the investigators can compare babies born before and after screening starts, with screening between the autumn of 2026 and autumn 2027.

This will be followed by a period of only SMA NBS which will continue until autumn 2030. This will be compared to a period of no screening from autumn 2024 until autumn 2027 to include babies born before any laboratory starts screening and where the screening laboratories have not yet opened during the study.

The study has two phases:

Phase 1 will examine how successfully SMA NBS can be delivered through the NHS, and will look at:

• Whether screening can accurately identify SMA
• How quickly screening results are returned
• Whether babies diagnosed through SMA NBS start treatment earlier than those diagnosed because of symptoms
• How many parent(s)/guardian(s)/guardians agree to take part in screening
• How different groups feel about SMA NBS and whether there are any areas of the process that need to be improved

Phase 2 will examine whether SMA NBS improves children's lives and will look at:

• Longer-term health outcomes, including whether treated children with SMA diagnosed by NBS or standard of care (SoC) can walk independently by 24 months
• Quality of life for children and families with SMA diagnosed by NBS or SoC
• Evaluate overall costs and benefits for the NHS

How will the study work?

• It will be led by the University of Oxford, with input from hospitals, laboratories, patient groups, and experts across the UK.
• Parent(s)/guardian(s) will be asked for consent when their baby has the routine heel-prick blood test. No extra blood will be needed.
• A national clinical network called SMA REACH, will provide information about the milestones babies reach and their general health.
• All other information will be asked for directly from parent(s)/guardian(s) with children who have SMA
• Health economists will use information collected to update an existing mathematical model on cost-effectiveness. This will estimate whether the benefits of early diagnosis and treatment outweigh the costs of screening.

The study will give the UK National Screening Committee (UK NSC) clear, high-quality evidence on whether newborn screening for SMA is feasible, acceptable, beneficial for children and families, and good value for the NHS.