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 () 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 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 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.