Clinical Effectiveness of Newborn Screening for Spinal Muscular Atrophy

Abstract

ImportanceThere is increasing evidence that early diagnosis and treatment are key for outcomes in infants with spinal muscular atrophy (SMA), and newborn screening programs have been implemented to detect the disease before onset of symptoms. However, data from controlled studies that reliably confirm the benefits of newborn screening are lacking.ObjectiveTo compare data obtained on patients with SMA diagnosed through newborn screening and those diagnosed after clinical symptom onset.Design, Setting, and ParticipantsThis nonrandomized controlled trial used data from the SMARTCARE registry to evaluate all children born between January 2018 and September 2021 with genetically confirmed SMA and up to 3 SMN2 copies. The registry includes data from 70 participating centers in Germany, Austria, and Switzerland. Data analysis was performed in February 2023 so that all patients had a minimal follow-up of 18 months.ExposurePatients born in 2 federal states in Germany underwent screening in a newborn screening pilot project. All other patients were diagnosed after clinical symptom onset. All patients received standard care within the same health care system.Main OutcomesThe primary end point was the achievement of motor milestones.ResultsA total of 234 children (123 [52.6%] female) were identified who met inclusion criteria and were included in the analysis: 44 (18.8%) in the newborn screening cohort and 190 children (81.2%) in the clinical symptom onset cohort. The mean (SD) age at start of treatment with 1 of the approved disease-modifying drugs was 1.3 (2.2) months in the newborn screening cohort and 10.7 (9.1) months in the clinical symptom onset cohort. In the newborn screening cohort, 40 of 44 children (90.9%) gained the ability to sit independently vs 141 of 190 (74.2%) in the clinical symptom onset cohort. For independent ambulation, the ratio was 28 of 40 (63.6%) vs 28 of 190 (14.7%).Conclusions and RelevanceThis nonrandomized controlled trial demonstrated effectiveness of newborn screening for infants with SMA in the real-world setting. Functional outcomes and thus the response to treatment were significantly better in the newborn screening cohort compared to the unscreened clinical symptom onset group.Trial RegistrationGerman Clinical Trials Register: DRKS00012699

Concerns About Clinical Effectiveness of Newborn Screening for Spinal Muscular Atrophy—Reply

“…Finally, Cheng and Hsu commented on the proportion of symptomatic infants with 2 SMN2 copies within the NBS cohort at the initiation of treatment. Our data showed that 11 of 31 patients with 2 SMN2 copies were symptomatic at the start of treatment . This reflects the real-world experience with NBS for SMA and corresponds well to a systematic review by Aragon-Gawinska et al, which reported that approximately 50% of patients with 2 SMN2 copies identified by NBS were symptomatic at treatment initiation.…”

“…In Reply We appreciate the comments from Cheng and Hsu regarding our study on the clinical effectiveness of newborn screening (NBS) for spinal muscular atrophy (SMA). Their observations bring valuable perspectives that merit further discussion.…”

Concerns About Clinical Effectiveness of Newborn Screening for Spinal Muscular Atrophy

“…To the Editor It was with great interest and appreciation that we read the article by Schwartz et al, which reported that functional outcomes and, thus, the response to treatment for spinal muscular atrophy (SMA) were significantly better in the newborn screening cohort than in the unscreened clinical symptom onset group. However, this study had some limitations.…”

“…A nonrandomized cohort study in Australia analyzed, in addition to the above 2 methods, Hammersmith Infant Neurological Examination-2 (HINE-2) scores and compound muscle action potential data. These 2 assessments were included in the medical assessment section of the SMARTCARE protocol . However, the authors did not present the relevant data or analyses for these assessments.…”

“…Third, in the study’s Results section, the authors mentioned that the SMN2 copy number and presymptomatic status were closely associated because 35% of children in the newborn screening subgroup with 2 SMN2 copies were already symptomatic at the start of treatment . However, the authors discussed possible causes of avoidable delays, including communication barriers after positive screening results, additional diagnostic tests, limited hospital resources, parental concerns, and required health insurance coverage for disease-modifying therapies . Thus, we are concerned that factors causing treatment delays may increase the proportion of patients who are symptomatic at the start of treatment.…”