Clinical Effectiveness of Newborn Screening for Spinal Muscular Atrophy
Oliver Schwartz, Katharina Vill, Michelle Pfaffenlehner, Max Behrens, Claudia Weiß, Jessika Johannsen, Johannes Friese, Andreas Hahn, Andreas Ziegler, Sabine Illsinger, Martin Smitka, Arpad von Moers, Heike Kölbel, Gudrun Schreiber, Nadja Kaiser, Ekkehard Wilichowski, Marina Flotats‐Bastardas, Ralf A. Husain, Matthias Baumann, Cornelia Köhler, Regina Trollmann, Annette Schwerin-Nagel, Astrid Eisenkölbl, Mareike Schimmel, Martin Fleger, Birgit Kauffmann, Gert Wiegand, Manuela Baumgärtner, Christian Rauscher, Sebahattin Çırak, Dieter Gläser, Günther Bernert, Tim Hagenacker, Susanne Goldbach, Kristina Probst-Schendzielorz, Hanns Lochmüller, Wolfgang Müller‐Felber, Ulrike Schara‐Schmidt, Maggie C. Walter, Janbernd Kirschner, Astrid Pechmann, SMARTCARE study group, Petra Baum, Moritz Metelmann, Fiona Zeiner, Wolfgang N. Löscher, Veronika Pilshofer, Kathrin Mörtlbauer, Elke Pernegger, Anna Elmecker, Tanja Neimair, Verena Angermair, Mika Rappold, A. Ille, Magdalena Gosk - Tomek, Anna Wiesenhofer, Katia Vettori, A. Hüpper, Theresa Stadler, Astrid Bertsche, Josefine Pauschek, Markus Blankenburg, Christof Reihle, Michael Schroth, Sarah Braun, Eva‐Maria Wendel, Julia Haverkamp, Daniela Banholzer, Annette Karolin Homma, Jonas Denecke, Joenna Driemeyer, Deike Weiss, Paula-Sophie Steffens, Jila Taherpour, Marcus Deschauer, Paul Lingor, Luisa Semmler, Gerrit Machetanz, Matthias Eckenweiler, Bettina Henzi, C. Müller, Thorsten Langer, Sabine Wider, Juliane Hug, Sabine Stein, Sibylle Emilie Vogt, Katharina Dörnbrack, Christina Saier, Adrian Tassoni, Franziska Wenzel, Tim Kampowski, Axel Gebert, Elisabeth Steiner, Manuel Pühringer, Sandra Baumann, Andrea Dall, Christina Bant, Tabea Reinhardt, Michael Zemlin, Sabine Hettrich
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.