Screening for SMA in Newborns Alleviates Functional Burden, Associated Comorbidities

A study found that screening for spinal muscular atrophy (SMA) in newborns paired with early access to disease-modifying therapies was effective in alleviating the burden and comorbidities of the disease.

The burden and comorbidities of spinal muscular atrophy (SMA) can be mitigated through early screening for the disease and early access to disease-modifying therapies, according to results published in The Lancet: Child & Adolescent Health.

SMA is a motor neuron disease that affects muscle weakness, which leads to reduced survival and disability. There are 3 therapies that have been used to treat SMA in the past, and early diagnosis and intervention have shown benefits in clinical trials. This study investigated how effective newborn screening was when coupled with disease-modifying treatment as an intervention for SMA.

The single-center, prospective, nonrandomized cohort study included incident newborns aged from birth to 6 weeks, infants aged between 6 weeks and 12 months, and children aged between 12 months and 16 years. All participants had the homozygous exon 7 deletions of survival motor neuron 1 gene (SMN1).

Children included were from the Sydney Children’s Hospital Network in Australia, and they were eligible for inclusion regardless of their survival motor neurone 2 (SMN2) copy number, their disease status, functional ability, and the presence of comorbidities. Infants who had compound heterozygous SMN1 mutations and those participating in ongoing and unpublished trials were excluded.

All newborns were screened for SMA if they were born in New South Wales and the Australian Capital Territory from August 1, 2018. This study included those who were screened from August 1, 2018, to August 1, 2020. The comparison group consisted of children and infants who had a diagnosis of SMA after having clinical referrals in the 2 years prior to newborn screening (August 1, 2016, to July 31, 2018).

Participants in the screening group were separated into 2 groups: newborn screening and presymptomatic, and newborn screening and symptomatic. Outcome measures were evaluated 2 years after diagnosis. Motor milestone attainment was measured using the WHO Multicentre Growth Reference Study (WHO-MRGS), which includes a scale from 1 to 6 measuring the motor function of participants, from sitting without support (1) to walking alone (6). The secondary outcome of survival and change in ventilatory and feeding requirements was measured using the Hammersmith Infant Neurological Examination-2 (HINE-2) score, which ranges from 0 to 26.

There were 33 participants included in the study population, with 15 children making up the screening group and 18 children making up the comparison group. There were 7 boys and 8 girls in the screening group and the comparison group was evenly split. Age of treatment was different in the newborn screening and symptomatic subgroups.

There were 6 children who were symptomatic within the first weeks of their life in the screening group, presenting symptoms by a median (IQR) of 2.9 (1.9-3.7) weeks.

There were 14 children in the screening group and 16 in the comparison group who were alive after 2 years of diagnosis. A total of 11 of 14 children were walking independently or with assistance in the study group compared with 1 in the comparison group (P < .0001). The highest motor milestone achieved by the comparison group after a median chronological age of 2.84 years was sitting ability, which was observed in 9 children.

A greater change in HINE-2 score was found in the screening group (group difference, 12.3 [95% CI, 9.5-16.2]). A steep and early rise in HINE-2 scores was found in the screening group in the first 6 months of diagnosis with ongoing motor gains, albeit slower, found in the first 10 months. The comparison group had a lower mean HINE-2 score at follow up but had a wider variability compared with younger counterparts in the screening group (mean [SD] HINE-2 score, screening group, 23.0 [4.2]; comparison group, 15.1 [6.7]).

Significant changes were found in the correlation effects of motor function gain between the screening and comparison groups. The screening group had increases in HINE-2 scores (r = 0.08) and WHO motor milestones (r = 0.25) as age at diagnosis increased, whereas negative correlations were found with increasing age at diagnosis in the comparison group in HINE-2 scores (r = –0.37) and WHO motor milestone measures (r = –0.22).

Newborn screening and symptomatic children had smaller gains in motor function if they had delays in therapeutic intervention compared with children in the newborn screening and presymptomatic (mean [SD] HINE-2 score, 17.0 [3.7] vs 21.7 [1.9], respectively).

There was a limitation to this study, in that it is difficult to generalize these findings to places where these screening processes do not exist.

The researchers concluded that their study findings determined variables at diagnosis that could be useful for prognosis of SMA and could inform best practices around access to therapeutics and clinical trial design.


Kariyawasam DS, D’Silva AM, Sampaio H, et al. Newborn screening for spinal muscular atrophy in Australia: a non-randomised cohort study. Lancet Child Adolesc Health. Published online January 17, 2023. doi:10.1016/s2352-4642(22)00342-x

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