Newborn screening for SMA leads to more children being able to walk at two years post diagnosis, new study finds

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Didu Kariyawasam

Newborn screening (NBS) for spinal muscular atrophy (SMA), when combined with early treatment, results in better movement ability in affected children, including the ability to walk, when compared to children who are diagnosed once symptoms develop. This is according to a new Australian study, published in The Lancet: Child and Adolescent Health journal, by Didu Kariyawasam (Sydney Children’s Hospital Network, Sydney, Australia) et al.

The prospective non-randomised cohort study, which was funded by the Brain Foundation and Australian National Health and Medical Research Council, found that 11 out of 14 children with SMA diagnosed via newborn screening and given early access to treatment were walking independently or with assistance two years after diagnosis, compared with one out of 16 of children diagnosed with SMA based on clinical symptoms, which presented on average at around four months of age.

Arlene D’Silva, who works at the University of New South Wales’ Paediatric Neurology Research Group (Sydney, USA), said: “Newborn screening has been proposed as the gateway to early diagnosis and more-timely access to treatment for SMA, however before now there was a lack of evidence on the impact of newborn screening for SMA beyond the non-diverse populations in clinical trials.

“Our study is the first to look at real-world data on how children with SMA diagnosed via newborn screening fare compared to children diagnosed after symptoms develop. We believe our findings justify broader implementation of newborn screening for SMA.”

The study took place at Sydney Children’s Hospital Network (Sydney, Australia), and included children younger than 16 years with homozygous exon 7 deletions of survival motor neuron 1 gene (SMN1) mutations, non-selectively assigned to a screening group (incident population diagnosed by newborn screening) from 1 August 2018, to 1 August 2020, or a comparator group (incident population diagnosed by clinical referral) from 1 August 2016, to 31 July 2018.

Infants with compound heterozygous SMN1 mutations and those participating in ongoing and unpublished clinical trials were excluded. Effectiveness of newborn screening for SMA was compared using motor development milestone attainment defined by WHO Multicentre Growth Reference Study at two years post diagnosis.

In addition, secondary outcome measures included mortality and change in Hammersmith Infant Neurological Examination-2 (HINE-2) score, ventilation requirements, and enteral requirements two years from the time of diagnosis.

A total of 34 children met the study inclusion criteria, but 33 children were included in the study population after one neonate was excluded due to participation in an ongoing unpublished clinical trial. In all, 15 children were included in the screening group (seven [47%] male and eight [53%] female; median age 2.1 weeks [interquartile range (IQR) 1.9–2.7]) and 18 children (nine [50%] male and nine [50%] female) were included in the comparator group (median age 47.8 weeks [13–99.9]).

The two-year survival rate was 93% (14 of 15 children) in the screening group and 89% (16 of 18) in the comparator group. Among survivors, 11 (79%) of 14 walked independently or with assistance in the screening group, compared with one (6%) of 16 children in the comparator group (χ2=16.27; p<0·0001).

A significantly greater change in motor function was observed in the screening group compared with the comparator group over two years (HINE-2 score group difference, 12.32; p<0·0001).

The requirement for non-intensive ventilation or feeding support at follow-up was higher in the comparator group than in the screening group (odds ratio 7.1 [95% confidence interval 0.7–70.2]).

Significant predictors of functional motor outcomes as determined by HINE-2 score at two years post diagnosis were HINE-2 score (p=0.0022), CHOP-INTEND (p=0.0001), compound muscle action potential (CMAP; p=0.0006), and disease status (p=0.023) at diagnosis.

“Our study suggests that newborn screening for SMA reduces the current delays in children being diagnosed and treated for SMA”, noted Kariyawasam. “Early screening and diagnosis are essential to giving children with SMA better health outcomes and quality of life. It’s extremely promising that the majority of children diagnosed via newborn screening in our study were able to walk after two years, compared to those children diagnosed through symptoms who were mostly only able to sit unassisted,” she added.

Kariyawasam continues: “Although we are seeing pilot programmes rolled out, only a small number of countries have fully introduced newborn screening for SMA, with fewer than 2% of newborns across the world currently screened for the condition. Our study offers further evidence of the value of newborn screening for SMA and encourage wider implementation of this effective intervention.”

The authors acknowledge some limitations to their study, including that the trial was non-randomised meaning it could be prone to selection bias, however this was mitigated by the chronological enrolment of children as they were referred to the service. Additionally, it was not possible to match the two groups by age, due to the inherent diagnostic delays associated with a clinically based diagnosis.

The Australian NBS for SMA pilot study is designed to speed up and enable equitable access to diagnosis and treatment. Therefore, these findings may not be generalisable to areas where there are delays in the screening to treatment process, including challenges in accessing appropriate health services and treatment.


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