Screening for SMA in neonates reduces functional burden and associated complications

burden and complications of spinal muscular atrophy According to results published in , (SMA) can be mitigated by early screening of the disease and early access to disease-modifying therapies. of The Lancet: Childhood and Adolescent Health.

SMA is a motor neuron disease that affects muscle weakness, leading to poor survival and disability. There are three of his therapies 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 is when combined with disease-modifying treatments as an intervention for SMA.

A single-center, prospective, nonrandomized cohort study included neonates from birth to 6 weeks of age, infants from 6 weeks to 12 months of age, and children from 12 months to 16 years of age. All participants were homozygous for the exon 7 deletion of the survival motor neuron 1 gene (SMN1).

Included children were from the Sydney Children’s Hospital Network, Australia and were eligible for inclusion regardless of surviving motor neurons 2 (SMN2) copy number, disease status, functional capacity, presence of comorbidities.Compound heterozygous infant SMN1 Mutations and those participating in ongoing and unpublished trials were excluded.

All newborns were screened for SMA if born in New South Wales and the Australian Capital Territory after 1 August 2018. The study included neonates screened from 1 August 2018 until she was 1 August 2020. An infant diagnosed with SMA after receiving a clinical referral during her 2-year period (from 1 August 2016 until she was 31 July 2018) prior to neonatal screening.

Participants in the screening arm were divided into two groups: neonatal screening plus presymptomatic and neonatal screening plus symptomatic. Outcome measures were assessed 2 years after her diagnosis. Attainment of motor milestones was measured using the WHO Multicenter Growth Reference Study (WHO-MRGS). It contains a 1 to 6 scale that measures the motor function of the participants, ranging from sitting without support (1) to walking alone (6). Secondary outcomes of survival and changes in ventilation and feeding requirements were measured using the Hammersmith Infant Neurological Examination-2 (HINE-2) score ranging from 0 to 26.

The study population included 33 participants, with 15 children forming the screening group and 18 children forming the comparison group. She had 7 boys and her 8 girls in the screening group, and the comparison group was evenly split. Age of treatment differed between neonatal screening and symptomatic subgroups.

There were 6 children in the screening group who presented with symptoms within the first few weeks of life, with a median (IQR) of 2.9 (1.9-3.7) weeks of symptoms.

Fourteen children in the screening group and 16 children in the comparison group were alive two years after diagnosis. A total of 11 of the 14 children walked alone or with assistance in the study group compared with her one in the comparison group (P. < .0001). The highest motor milestone achieved by the comparison group after her median chronological age was 2.84 years was the ability to sit observed in 9 children.

Larger changes in HINE-2 scores were seen in the screening group (group difference, 12.3 [95% CI, 9.5-16.2]). A steep and early rise in HINE-2 scores was seen in the screened group in his first 6 months of diagnosis and was discovered in his first 10 months, albeit late, of ongoing exercise. It was an improvement in my ability.The comparison group had lower mean HINE-2 scores at follow-up, but had greater variability compared with younger screened counterparts (mean [SD] HINE-2 score, screened group, 23.0 [4.2]comparison group, 15.1 [6.7]).

There was a significant change in the correlated effects of motor gains between the screening and comparison groups. HINE-2 score (r = 0.08) and WHO motor milestones (r = 0.25) increased with increasing age at diagnosis in the screened group, whereas HINE-2 score comparison group showed an increase in age at diagnosis. Negative correlations were found with higher (r = –0.37) and WHO motor milestone measures (r = –0.22).

Newborn screened and symptomatic children had smaller improvements in motor function when intervention was delayed compared with newborn screened and asymptomatic children (mean [SD] HINE-2 score, 17.0 [3.7] vs 21.7 [1.9]Respectively).

A limitation of this study was that it was difficult to generalize these findings to locations where these screening processes did not exist.

The researchers concluded that the study results determined variables at diagnosis, which may aid prognosis in SMA, and inform best practices regarding treatment access and clinical trial design.

reference

Kariyawasam DS, DiSilva AM, Sampaio H, et al. Newborn screening for spinal muscular atrophy in Australia: a non-randomized cohort study. lancet child address healthPublished online January 17, 2023. doi:10.1016/s2352-4642(22)00342-x