Neurodevelopmental screening in children with early-onset spinal muscular atrophy in the treatment era: a strengths-based cohort study

With transformative advances in diagnostic and therapeutic approaches in spinal muscular atrophy, the long-term neurodevelopmental outcomes of children with, or predicted to have, spinal muscular atrophy type 1 are essential to evaluate. In this single-centre cross-sectional study, development in children with/at-risk of spinal muscular atrophy type 1, aged 1-66 months, was assessed using parent-reported Ages and Stages Questionnaires® (ASQ-3™). Risk of autism spectrum disorder (ASD), parental distress, sociodemographic and clinical characteristics were also evaluated. Associations between exploratory variables and developmental risk were analysed within a bioecological model of health. Adaptive least absolute shrinkage and selection operator (LASSO) was used to identify variables most predictive of developmental acquisition. Thirty-seven children with spinal muscular atrophy participated (response rate: 90.2%, girls: 54.0%). Clinical characteristics varied with modality of diagnosis, survival motor neuron 2 (<i>SMN2</i>) copies and clinical status at initiation of survival motor neuron (SMN)-augmenting therapy. ASQ-3 scores were indicative of no/low developmental risk in 16/37 (43.2%), isolated gross-motor delay consistent with spinal muscular atrophy phenotype in 8/37 (21.6%), isolated non-gross-motor delay in 3/37 (8.1%), and global developmental delay (≥2 domains) in 10/37 (27.0%). The majority of children (21/24, 87.5%) screened negative on Modified Checklist for Autism in Toddlers Revised (M-CHAT-R), indicating low risk of autism spectrum disorder. Almost one-third (32.4%) of parents reported high levels of distress. Factors associated with better developmental performance included three <i>SMN2</i> copies, diagnosis through newborn bloodspot screening and clinical silent status, absence of bulbar dysfunction, higher motor function at the time of initiation of SMN-augmenting therapy, parental well-being (absence of mental health condition and no distress) and parental attainment of tertiary education. An absence of a mental health condition in parents and three <i>SMN2</i> copy genotype in the child were identified as the strongest predictors of no/low developmental risk, with odds ratios of 4.7 and 1.4, respectively. The study findings demonstrate diverse neurodevelopmental profiles in treated children with/at-risk of spinal muscular atrophy type 1 associated with the magnitude and duration of SMN deficiency. The SMN-associated neurodevelopmental disorders may be amenable to modification by targeting bioecological factors of health. Namely, newborn screening and expedient initiation of SMN-augmenting therapies are central to targeting the neurodevelopmental window in children with/at-risk of spinal muscular atrophy type 1. Best practice includes the incorporation of proactive developmental screening for all children with/at-risk of spinal muscular atrophy type 1, with an integrated model of psychosocial support provided for families.