Efficacy of newborn screening for SMA

In a transformational era for spinal muscular atrophy (SMA), research conducted by Sydney Children’s Hospitals Network (SCHN) and UNSW Sydney has shown newborn bloodspot screening (NBS) leads to better health outcomes for children diagnosed with the devastating genetic condition.

The study, published in The Lancet Child & Adolescent Health, found children with SMA are more likely to walk, be more functionally independent and free of respiratory and feeding support when screened, diagnosed and treated shortly after birth.

Dr Didu (Sandi) Kariyawasam and Professor Michelle Farrar, paediatric neurologists at the Network, led the study. It is one of the first to investigate the efficacy of NBS for SMA beyond clinical trial populations, with the findings providing an impetus for the implementation of this testing in the broader population.

“It’s an important study for building the evidence base that newborn screening is an approach that leads to better health outcomes for children with spinal muscular atrophy and is impactful enough to justify widespread adoption,” Prof Farrar said.

SMA is an early-onset motor neuron disorder characterised by progressive muscle weakness and wasting, leading to substantial disability and reduced survival.

Until a few years ago, SMA was the leading cause of death in infants under two years old, occurring in 1 in 10,000 births. The introduction of novel gene therapies, such as the development of genetic replacement drug Zolgensma®, has transformed SMA from a lethal to a treatable disease.

While there is currently no cure for SMA, recent advances in the effectiveness of genetic treatments have opened the possibility for a test for SMA to be included in NBS.

“While the development of genetic therapies has been crucial, having a proactive model for early diagnosis is equally as important as an intervention,” Dr Kariyawasam said.

“The earlier the diagnosis, the earlier treatment can begin, which is where newborn screening comes in.”

Participants in the study included 15 children diagnosed with SMA using NBS (screening group) and 18 children diagnosed by clinical referral (comparator group) for two years post diagnosis. Children within both groups had the potential to access disease-modifying therapeutics.

The two-year survival rate was 93 per cent in the screening group and 89 per cent in the comparator group. But of the survivors, 11 could walk independently or with assistance in the screening group, compared with just one child diagnosed via a traditional clinical pathway.

In addition, the study found the need for respiratory and feeding support was also seven times less in the screening group than the comparator group.

“Even though they are younger, the newborn screening group were almost always more functionally able and had fewer co-morbidities than those in the comparator group who were older,” Dr Kariyawasam said.

“It shows that changing the paradigm of diagnosis to being more proactive can improve the lives of children born with spinal muscular atrophy.”

In light of its findings, the research leads said NBS for SMA reduces clinical uncertainties that come with delayed diagnosis and help to identify the right treatment pathways.

“The burden of care and the morbidity of SMA was drastically lower in the newborn screening group, which has a huge effect on the quality of life for children and their families,” Prof Farrar said.

“NBS for SMA allows us to provide more precise care and set realistic expectations about the likely health outcomes, which can help families deal with some of the uncertainty that comes with such a shocking diagnosis.”

More than 400,000 babies have been screened for SMA in the NSW NBS program since 2018. NSW was the first jurisdiction in Australia to pilot testing for SMA in the NSW NBS program and has since committed $1.3 million annually to ongoing screening.

From 1 July 2022, parents of all new babies born in NSW and the ACT are offered free tests for SMA within 48-72 hours of birth. SMA screening has now been recommended by the Australian Government to be rolled out nationally with support from the research team, who will help develop standardised guidelines.