Clinical Effectiveness of Newborn Screening for Spinal Muscular Atrophy
Authors: 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 Baumgartner, Christian Rauscher, Sebahattin Cirak, 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, Petra Baum, Moritz Metelmann, Fiona Zeiner, Wolfgang Löscher, Veronika Pilshofer, Kathrin Mörtlbauer, Elke Pernegger, Anna Elmecker, Tanja Neimair, Verena Angermair, Mika Rappold, Alexandra Ille, Magdalena Gosk - Tomek, Anna Wiesenhofer, Katia Vettori, Anna 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, Cornelia Müller, Thorsten Langer, Sabine Wider, Juliane Hug, Sabine Stein, Sibylle 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, Dorothea Holzwarth, Stephanie Geitmann, Gabriel Dworschak, Franziska Busch, Ute Baur, Marion Richmann, Tobias Geis, Wolfgang Wittmann, Klaus Goldhahn, Manuela Theophil, Arpad von Moers, Katharina Müller-Kaempffer, Daniela Zeisler, Kathrin Bühner, Sylke Nicolai, Martin Groß, Stefan Kappel, René Günther, Maren Freigang, Hanna Sophie Lapp, Isabelle Dittes, Maria Wessel, Benjamin Stolte, Svenja Brakemeier, Andreas Thimm, Jaqueline Lipka, Melina Schlag, Kyriakos Martakis, Tascha Gehrke, Lisa Quinten, Andrea Hackemer, Lena Ruß, Omar Atta, Annina Lang, Eckard Hamelmann, Georg Classen, Klearchos Ntemiris, Kristina Albers, Loreen Plugge, Veronka Horber, Doris Roland-Schäfer, Andrea Bevot, Eva Jansen, Hanna Küpper, Birgit Meßmer, Daniela Steuernagel, Sabine Borowski, Christa Bretschneider, Erdmute Roth, Anja Müller, Heike de Vries, Hans Hartmann, Barbara Ramadan, Christoph Kamm, Sophie Fischer, Marieke Wermuth, Ulf Hustedt, Jan Christoph Koch, Mohamad Tareq Muhandes, Tobias Baum, Anna Hotter, Albert Ludolph, Zeljko Uzelac, Simon Witzel, Johannes Dorst, Joachim Schuster, Kurt Wollinsky, Pascal Martin, Alexander Mensch, Steffen Naegel, Ilka Schneider, Thomas Kendzierski, Anna Koelsch, Gerd Meyer zu Hörste, Sarah Wiethoff, Esra Akova-Oztürk, Astrid Blaschek, Iris Hannibal, Birgit Warken-Madelung, Therese Well, Elisabeth Rotenfusser, Maren Nitzsche, Christoph Neuwirth, Nathalie Braun, Zylfie Dibrani, Jasmin Bischofberger, Susanne Petri, Bogdan Bjelica, Camilla Wohnrade, Tilman Riesmeier, Michaela Schwippert, Antonia Leinert, Alma Oscmanovic, Olivia Schreiber-Katz, Astrid Eisenkölbl, Imke Rathmann, Dorothee Schäfer, Adela Della-Marina, Andrea Gangfuß, Britta Holtkamp, Barbara Andres, Isabelle Renger, Daniela Angelova-Toshkina, Lisa Jung, Bertold Schrank, Bernd Wilken, Alma Osmanovic, Barbara Fiedler, Timo Deba, Eva Johann to Settel, Katja Köbbing, Heymut Omran, Hélène Guillemot, Barbara Plecko, Joachim Zobel, Michael Grässl, Sander Claeys, Maja von der Hagen, Jens Schallner, Susan Fiebig, Sandy Foerster, Nicole Claus, Ilka Lehnert, Julie Hammer, Meike Steinbach, Maike Tomforde, Johannes Stoffels, Thomas Voelkl, Christina Kraut, Carmen Hollerauer, Lea Seeber, Mike Grünwedel, Raffi Topakian, Petra Müller, Peter Vollmann, Ina Krahwinkler, Bettina Behring, Stephanie Schüssler, Matthias Türk, Matthias Vorgerd, Anne Güttsches, Melanie Roeder, Irene Lange, Peter Reilich, Miriam Hiebeler, Federica Montagnese, Simone Thiele, Anna Hagenmeyer, Laura Grimm, Corinna Wirner-Piotrowski, Markus Weiler, Wolfgang Wick, Nicole Berberich, Marcel Mann-Richter, Heidi Rochau-Trumpp, Marion Schnurr, Guido Stocker, Corinna Stoltenburg, Joanna Schneider, Alexandra Wagner, Annette George, Vladimir Dukic, Angela M. Kaindl, Lieske van der Stam, Gilbert Wunderlich, Claudia Diana Wurster*, Johannes Dorst*, Joachim Schuster*, Albert Christian Ludolph*, Daniel Zeller, Julia Bellut, Brigitte Brauner, Christine Leypold, Georg Friedrich Hoffmann, Stefan Kölker, Afshin Saffari, Moritz Niesert, Sabine Specht, Annegret Hoevel, Anke Bongartz, Daniela Zöller, Harald Binder, Maren Hackenberg
Journal: JAMA Pediatrics (2024)

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