番茄社区

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 .

Increasingly, countries are "introducing newborn screening for spinal muscular atrophy," Kirschner told 番茄社区 in an email. In the U.S., SMA newborn screening has been . 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 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 . "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 [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."

Comment