Clinical Effectiveness of Newborn Screening for Spinal Muscular Atrophy
Authors: Schwartz Oliver , Vill Katharina , Pfaffenlehner Michelle , Behrens Max , Weiß Claudia , Johannsen Jessika , Friese Johannes , Hahn Andreas , Ziegler Andreas , Illsinger Sabine , Smitka Martin , von Moers Arpad , Kölbel Heike , Schreiber Gudrun , Kaiser Nadja , Wilichowski Ekkehard , Flotats-Bastardas Marina , Husain Ralf A. , Baumann Matthias , Köhler Cornelia , Trollmann Regina , Schwerin-Nagel Annette , Eisenkölbl Astrid , Schimmel Mareike , Fleger Martin , Kauffmann Birgit , Wiegand Gert , Baumgartner Manuela , Rauscher Christian , Cirak Sebahattin , Gläser Dieter , Bernert Günther , Hagenacker Tim , Goldbach Susanne , Probst-Schendzielorz Kristina , Lochmüller Hanns , Müller-Felber Wolfgang , Schara-Schmidt Ulrike , Walter Maggie C. , Kirschner Janbernd , Pechmann Astrid ,   SMARTCARE study group, Baum Petra , Metelmann Moritz , Zeiner Fiona , Löscher Wolfgang , Pilshofer Veronika , Mörtlbauer Kathrin , Pernegger Elke , Elmecker Anna , Neimair Tanja , Angermair Verena , Rappold Mika , Ille Alexandra , Gosk - Tomek Magdalena , Wiesenhofer Anna , Vettori Katia , Hüpper Anna , Stadler Theresa , Bertsche Astrid , Pauschek Josefine , Blankenburg Markus , Reihle Christof , Schroth Michael , Braun Sarah , Wendel Eva-Maria , Haverkamp Julia , Banholzer Daniela , Homma Annette Karolin , Denecke Jonas , Driemeyer Joenna , Weiss Deike , Steffens Paula-Sophie , Taherpour Jila , Deschauer Marcus , Lingor Paul , Semmler Luisa , Machetanz Gerrit , Eckenweiler Matthias , Henzi Bettina , Müller Cornelia , Langer Thorsten , Wider Sabine , Hug Juliane , Stein Sabine , Vogt Sibylle , Dörnbrack Katharina , Saier Christina , Tassoni Adrian , Wenzel Franziska , Kampowski Tim , Gebert Axel , Steiner Elisabeth , Pühringer Manuel , Baumann Sandra , Dall Andrea , Bant Christina , Reinhardt Tabea , Zemlin Michael , Hettrich Sabine , Holzwarth Dorothea , Geitmann Stephanie , Dworschak Gabriel , Busch Franziska , Baur Ute , Richmann Marion , Geis Tobias , Wittmann Wolfgang , Goldhahn Klaus , Theophil Manuela , von Moers Arpad , Müller-Kaempffer Katharina , Zeisler Daniela , Bühner Kathrin , Nicolai Sylke , Groß Martin , Kappel Stefan , Günther René , Freigang Maren , Lapp Hanna Sophie , Dittes Isabelle , Wessel Maria , Stolte Benjamin , Brakemeier Svenja , Thimm Andreas , Lipka Jaqueline , Schlag Melina , Martakis Kyriakos , Gehrke Tascha , Quinten Lisa , Hackemer Andrea , Ruß Lena , Atta Omar , Lang Annina , Hamelmann Eckard , Classen Georg , Ntemiris Klearchos , Albers Kristina , Plugge Loreen , Horber Veronka , Roland-Schäfer Doris , Bevot Andrea , Jansen Eva , Küpper Hanna , Meßmer Birgit , Steuernagel Daniela , Borowski Sabine , Bretschneider Christa , Roth Erdmute , Müller Anja , de Vries Heike , Hartmann Hans , Ramadan Barbara , Kamm Christoph , Fischer Sophie , Wermuth Marieke , Hustedt Ulf , Koch Jan Christoph , Muhandes Mohamad Tareq , Baum Tobias , Hotter Anna , Ludolph Albert , Uzelac Zeljko , Witzel Simon , Dorst Johannes , Schuster Joachim , Wollinsky Kurt , Martin Pascal , Mensch Alexander , Naegel Steffen , Schneider Ilka , Kendzierski Thomas , Koelsch Anna , Meyer zu Hörste Gerd , Wiethoff Sarah , Akova-Oztürk Esra , Blaschek Astrid , Hannibal Iris , Warken-Madelung Birgit , Well Therese , Rotenfusser Elisabeth , Nitzsche Maren , Neuwirth Christoph , Braun Nathalie , Dibrani Zylfie , Bischofberger Jasmin , Petri Susanne , Bjelica Bogdan , Wohnrade Camilla , Riesmeier Tilman , Schwippert Michaela , Leinert Antonia , Oscmanovic Alma , Schreiber-Katz Olivia , Eisenkölbl Astrid , Rathmann Imke , Schäfer Dorothee , Della-Marina Adela , Gangfuß Andrea , Holtkamp Britta , Andres Barbara , Renger Isabelle , Angelova-Toshkina Daniela , Jung Lisa , Schrank Bertold , Wilken Bernd , Osmanovic Alma , Fiedler Barbara , Deba Timo , Johann to Settel Eva , Köbbing Katja , Omran Heymut , Guillemot Hélène , Plecko Barbara , Zobel Joachim , Grässl Michael , Claeys Sander , von der Hagen Maja , Schallner Jens , Fiebig Susan , Foerster Sandy , Claus Nicole , Lehnert Ilka , Hammer Julie , Steinbach Meike , Tomforde Maike , Stoffels Johannes , Voelkl Thomas , Kraut Christina , Hollerauer Carmen , Seeber Lea , Grünwedel Mike , Topakian Raffi , Müller Petra , Vollmann Peter , Krahwinkler Ina , Behring Bettina , Schüssler Stephanie , Türk Matthias , Vorgerd Matthias , Güttsches Anne , Roeder Melanie , Lange Irene , Reilich Peter , Hiebeler Miriam , Montagnese Federica , Thiele Simone , Hagenmeyer Anna , Grimm Laura , Wirner-Piotrowski Corinna , Weiler Markus , Wick Wolfgang , Berberich Nicole , Mann-Richter Marcel , Rochau-Trumpp Heidi , Schnurr Marion , Stocker Guido , Stoltenburg Corinna , Schneider Joanna , Wagner Alexandra , George Annette , Dukic Vladimir , Kaindl Angela M. , van der Stam Lieske , Wunderlich Gilbert , Wurster* Claudia Diana , Dorst* Johannes , Schuster* Joachim , Ludolph* Albert Christian , Zeller Daniel , Bellut Julia , Brauner Brigitte , Leypold Christine , Hoffmann Georg Friedrich , Kölker Stefan , Saffari Afshin , Niesert Moritz , Specht Sabine , Hoevel Annegret , Bongartz Anke , Zöller Daniela , Binder Harald , Hackenberg Maren 
Published: April 2024

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