Impact of Newborn Screening for Spinal Muscular Atrophy

Source: Schwartz O , Vill K , Pfaffenlehner M , et al . Clinical effectiveness of newborn screening for spinal muscular atrophy: a nonrandomized controlled trial. JAMA Pediatr. 2024;178(6):540-547; doi: 10.1001/jamapediatrics.2024.0492.Investigators from multiple institutions conducted a cohort study to evaluate the clinical effectiveness of newborn screening for spinal muscular atrophy (SMA). For the study, they reviewed data in the SMARTCARE clinical registry that includes information on patients with SMA treated at 1 of 70 centers in Germany, Austria, and Switzerland. Data on patient demographics, diagnosis, SMA genotype, treatment with disease-modifying medications, neuromuscular development milestones, and standardized testing results were recorded on standardized case report forms for the registry. Study participants were children with genetically confirmed SMA and up to 3 SMN2 copies who were born between January 2018 and September 2021, included in the registry, and had follow-up through at least 18 months age. The study patients were divided into 2 cohorts; 1 cohort included children diagnosed with SMA after onset of symptoms, and the other consisted of patients diagnosed through a newborn screening program implemented at 3 centers in Germany. The main study outcomes were ability to sit independently and walk independently. Kaplan-Meier curves were used to calculate probability of gaining the ability to sit or walk independently. Study patients also were assessed with the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) when they were 18 months of age and mean scores of those in the 2 cohorts calculated. CHOP INTEND is a validated assessment designed for children with SMA and includes 16 items for a total possible score of 64 points. Higher scores indicate better motor function.A total of 234 children with SMA were included in the analysis. The newborn screening cohort consisted of 44 patients (18.8%), and the clinical diagnosis group included 190 (81.2%). The mean ages at start of disease-modifying treatment were 1.3 ±2.2 months for those in the newborn screening cohort and 10.7 ±9.1 months for those diagnosed clinically. The ability to sit independently was achieved by 90.9% of those in the newborn screening group at a median age of 9 months and in 74.2% of those in the clinical diagnosis cohort at a median age of 14 months. A total of 28 (63.6%) children in the newborn screening cohort gained the ability to walk at a median age of 17 months, compared to 28 (14.7%) patients in the clinical diagnosis group who were able to walk at a median age of 23.5 months. At 18 months of age, mean CHOP INTEND scores were 59.5 ±1.2 and 47.7 ±0.9, respectively, for children in the newborn screening and clinical diagnosis cohorts.The authors conclude that the results of the study demonstrated the effectiveness of newborn screening for SMA.Dr Thompson has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.SMA is a devasting progressive degenerative neuromuscular disorder. Historically, children with SMA were clinically diagnosed after the onset of symptoms (eg, muscle weakness, wasting); definitive diagnosis required muscle biopsy.1 Currently, SMA is diagnosed via blood sample genetic testing. In the past, treatment was symptomatic and palliative, with death occurring in early childhood. Recent advances in genetic diagnosis and emerging treatments have dramatically altered the landscape for this once uniformly fatal condition.2 The effectiveness of these new treatment modalities is largely dependent upon their administration early in the course of illness, prior to the presence of significant symptoms.Other childhood diseases have dismal prognoses similar to SMA. The implementation of widespread newborn screening has allowed for the early diagnosis and treatment of a vast number of these illnesses, such as hypothyroidism and phenylketonuria.3 These advancements have led to diminished morbidity and mortality associated with these diseases.Many children have benefited from early genetic diagnosis and administration of novel therapies for SMA. The first to be approved was nusinersen in 2016 (administered with repeated doses given intrathecally).4 Onasemnogene abeparvovec (a single intravenous dose) and risdiplam (a daily oral medication) have since been added.5 These disease-modifying therapies have been shown to provide improved motor function, especially when given to presymptomatic patients.5 Nusinersin especially has been shown to improve ventilatory function.6The current authors investigated the impact of newborn screening and early treatment for SMA using a proven metric (CHOP INTEND).7 Considering the economic costs, emotional burden on patients and families, and quality of life issues of disease progression without early treatment, the results of the current study provide compelling support for newborn screening for SMA.8Newborn screening for SMA, now mandatory in all 50 US States,9 is associated with improved outcomes as compared to infants diagnosed after onset of symptoms.