Key Points
Question Is early diagnosis through newborn screening associated with improved outcomes in infants with spinal muscular atrophy compared to those diagnosed after onset of symptoms?
Findings In this nonrandomized controlled trial within the SMARTCARE registry, patients identified by newborn screening showed better motor development with disease-modifying treatments than those who were diagnosed after onset of symptoms.
Meaning These results offer supporting evidence for the benefit of newborn screening for spinal muscular atrophy.
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.
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Children with spinal muscular atrophy (SMA) identified by newborn screening showed better motor development with disease-modifying treatment than those diagnosed after symptom onset, a German cohort study showed.
Nine out of 10 (90.9%) of kids identified with SMA on newborn screening gained the ability to sit independently at a median age of 9 months, compared with 74.2% of children diagnosed after symptom onset who could sit independently at a median age of 14 months, reported Janbernd Kirschner, MD, of the University of Freiburg in Germany, and colleagues.
The ability to walk independently was gained by 63.6% of patients in the newborn screening cohort at a median age of 17 months, compared with 14.7% of patients in the symptom onset group at a median age of 23.5 months, they noted in JAMA Pediatrics.
Increasingly, countries are "introducing newborn screening for spinal muscular atrophy," Kirschner told MedPage Today in an email. In the U.S., SMA newborn screening has been adopted in all 50 states. Though "good response with early initiation of treatment is evident from clinical experience and uncontrolled studies, this is the first study to evaluate the effect of newborn screening with a parallel control group," he said.
"The situation in Germany with a regional pilot project provided a unique opportunity to compare screened and unscreened patients within the same health system," he added.
Specifically, data from the SMARTCARE registry -- a registry for patients with SMA comprising 70 healthcare facilities in Germany, Austria, and Switzerland -- were used in the study. Patients born in two federal states in Germany underwent SMA screening for a newborn screening pilot project, and all other patients were diagnosed after clinical symptom onset. All patients received standard care within the same healthcare system.
Ultimately, data from the SMARTCARE registry were used to evaluate all children born between January 2018 and September 2021 with genetically confirmed SMA and up to three SMN2 copies, as onset is often later in children with more than three SMN2 copies. Analysis was performed in February 2023, in order for patients to have a minimum follow-up of 18 months.
"The SMARTCARE study group presents an important addition to the body of evidence supporting NBS [newborn screening] for SMA by looking at real-world effectiveness of NBS," Maryam Oskoui, MD, MSc, of Montreal Children's Hospital in Canada, and colleagues wrote in an accompanying editorial. "Effectiveness will include infants who are treated late and are already symptomatic, i.e., infants who would have otherwise been excluded from the presymptomatic clinical trials."
"When counseling families of infants identified through SMA NBS programs or when building a health economic model for these programs, it is important to consider potential outcomes based on effectiveness studies rather than efficacy in presymptomatic treatment trials," they added.
A total of 234 children were included in the analysis: 44 from the newborn screening cohort, and 190 in the clinical symptom onset cohort.
Mean CHOP-INTEND [Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders] scores -- for which higher scores indicate better motor function -- at 18 months were 59.5 in the newborn screening cohort and 47.7 in the symptom onset group. At 34 months, scores were 62.6 and 52.2, respectively.
Before treatment, 5.8% of patients in the symptom onset cohort required permanent ventilator support and 10.6% used occasional ventilation. In the same group, 2.6% of patients started permanent ventilation after treatment, and 16.8% required intermittent ventilation. In the newborn screening cohort, 6.8% of patients depended on intermittent ventilation.
Once under treatment, 4.5% of patients in the newborn screening cohort and 3.2% of patients in the symptom onset cohort could be weaned from ventilator support.
Additionally, before treatment, exclusive tube feeding was required by 7.4% of patients in the symptom onset cohort and supplemental tube feeding was required by 4.7%. In the newborn screening cohort, 2.3% of patients required supplemental tube feeding.
After the start of treatment, one patient diagnosed via newborn screening required exclusive tube feeding and 29 patients in the symptom onset group began to use tube feeding (12 exclusively and 17 supplementally). None of the patients stopped tube feeding during follow-up.
Limitations of the study included that data from the minimum follow-up to 18 months of age were not available from all patients within the SMARTCARE registry, which could introduce survival bias.
Still, the study provides evidence supporting newborn screening for SMA, and is "important for prognostication and to counsel families with regard to treatment expectations," the researchers said.
"While patients still asymptomatic at treatment initiation have a good chance of achieving independent ambulation," they wrote, "this is rather unlikely for those who already exhibited clear symptoms of SMA at treatment onset."
https://www.medpagetoday.com/pediatrics/generalpediatrics/109560
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