Clinical Effectiveness of Newborn Screening for Spinal Muscular Atrophy: A Nonrandomized Controlled Trial

Schwartz O, Vill K, Pfaffenlehner M, Behrens M, Weiß C, Johannsen J, Friese J, Hahn A, Ziegler A, Illsinger S, Smitka M, Von Moers A, Kölbel H, Schreiber G, Kaiser N, Wilichowski E, Flotats-Bastardas M, Husain RA, Baumann M, Köhler C, Trollmann R, Schwerin-Nagel A, Eisenkölbl A, Schimmel M, Fleger M, Kauffmann B, Wiegand G, Baumgartner M, Rauscher C, Cirak S, Gläser D, Bernert G, Hagenacker T, Goldbach S, Probst-Schendzielorz K, Lochmüller H, Müller-Felber W, Schara-Schmidt U, Walter MC, Kirschner J, Pechmann A (2024)

Publication Type: Journal article

Publication year: 2024

Journal

DOI: 10.1001/jamapediatrics.2024.0492

Abstract

Importance: There 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. Objective: To compare data obtained on patients with SMA diagnosed through newborn screening and those diagnosed after clinical symptom onset. Design, Setting, and Participants: This 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. Exposure: Patients 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 Outcomes: The primary end point was the achievement of motor milestones. Results: A 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 Relevance: This 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 Registration: German Clinical Trials Register: DRKS00012699.

Authors with CRIS profile

Involved external institutions

Universität Salzburg (Paris Lodron Universität Salzburg) Austria (AT) genetikum – Genetische Beratung & Diagnostik Germany (DE) Universitätsklinikum des Saarlandes (UKS) Germany (DE) Kepler Universitätsklinikum (KUK) Austria (AT) Sozialmedizinisches Zentrum Süd - Kaiser-Franz-Josef-Spital und Gottfried von Preyer'schem Kinderspital und Geriatriezentrum Favoriten Austria (AT) Universitätsklinikum Augsburg Germany (DE) Universitätsklinikum Essen Germany (DE) Deutsche Gesellschaft für Muskelkranke (DGM) Germany (DE) Landeskrankenhaus Bregenz Austria (AT) Children's Hospital of Eastern Ontario (CHEO) / Centre hospitalier pour enfants de l'est de l'Ontario Canada (CA) Klinikum der Universität München Germany (DE) Universität Duisburg-Essen (UDE) Germany (DE) Universitätsklinikum Freiburg Germany (DE) Universitätsklinikum Münster Germany (DE) Universitätsklinikum Jena Germany (DE) Charité - Universitätsmedizin Berlin Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Universitätsklinikum Bonn Germany (DE) Justus-Liebig-Universität Gießen Germany (DE) Universitätsklinikum Heidelberg Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) Deutsches Rotes Kreuz e.V. (DRK) Germany (DE) Medizinische Universität Innsbruck Austria (AT) Katholisches Klinikum Bochum (St. Josef- und St. Elisabeth-Hospital gGmbH) Germany (DE) Klinikum Kassel GmbH Germany (DE) Asklepios Kliniken Germany (DE) Ordensklinikum Linz - Elisabethinen Austria (AT) Universitätsklinikum Tübingen Germany (DE) Medizinische Universität Graz Austria (AT) Universitätsklinikum Göttingen Germany (DE) Universitätsklinikum Ulm Germany (DE)

How to cite

APA:

Schwartz, O., Vill, K., Pfaffenlehner, M., Behrens, M., Weiß, C., Johannsen, J.,... Pechmann, A. (2024). Clinical Effectiveness of Newborn Screening for Spinal Muscular Atrophy: A Nonrandomized Controlled Trial. JAMA Pediatrics. https://doi.org/10.1001/jamapediatrics.2024.0492

MLA:

Schwartz, Oliver, et al. "Clinical Effectiveness of Newborn Screening for Spinal Muscular Atrophy: A Nonrandomized Controlled Trial." JAMA Pediatrics (2024).

BibTeX: Download