乌鸦传媒

Newborn screening for spinal muscular atrophy (SMA) is effective and leads to better functional outcomes and treatment response, according to a report published in JAMA.¹

With 3 disease-modifying agents currently approved for the treatment of SMA, there is accumulating evidence demonstrating that early diagnosis and early treatment initiation are key to improving clinical outcomes, particularly in children who may have a severe phenotype of SMA. While findings are promising for clinical trials among patients with presymptomatic SMA as well as for genetic newborn screening pilot programs, controlled studies substantiating the advantage of newborn screening have been lacking.¹

Germany initiated newborn screening for SMA nationwide in 2021 after a large pilot project was first conducted at 3 German centers.² Capitalizing on the implementation of this newborn screening program, researchers from both Germany and Austria performed a nonrandomized, controlled trial to evaluate registry data on motor milestones among infants with SMA diagnosed early through newborn screening versus among those with SMA diagnosed after clinical onset of symptoms.¹

 鈥淭hese results offer supporting evidence for the benefit of newborn screening for spinal muscular atrophy,鈥� the authors concluded in their report.¹

Analyzing SMARTCARE data

The research team conducted a nonrandomized, controlled, parallel-group trial, using data from the SMARTCARE registry, which consists of 70 centers in Austria, Germany, and Switzerland, to evaluate all children born in January 2018 through September 2021 with genetically confirmed SMA and up to 3 SMN2 copies. Data were obtained from 30 neuropediatric departments in Germany and Austria. 

鈥淲hile the treatment strategy for children identified through newborn screening with 4 SMN2 copies is still debated, there is consensus that children with 2 or 3 SMN2 copies require immediate treatment,鈥� the authors explained in their report. For children with milder phenotypes (>3 SMN2 copies), they added, the follow-up period is still not long enough to yield meaningful results. 

All study participants had a minimum follow-up of 18 months. The researchers pointed out that this age reflected the 99th percentile for achieving independent walking during normal development. 

The authors considered the primary end point to be achievement of motor milestones on the basis of World Health Organization criteria. Clinical management, including disease-modifying treatment, was the same for both groups; identical algorithms and outcome measures also were employed in the SMARTCARE registry. 

The analysis included 234 children (52.6% female), including 44 (18.8%) who were diagnosed through newborn screening and 190 (81.2%) who were diagnosed after the onset of clinical symptoms. Mean age at treatment initiation with an approved disease-modifying agent was 1.3 months in the newborn screening group and 10.7 months in the clinical symptom onset group. The authors note that 11 patients with 2 SMN2 copies (25%) in the newborn screening group were symptomatic at the start of treatment.

Corresponding mean ages at the last follow-up visit was 32.3 and 36.2 months. Distribution of the various SMA agents was comparable between the 2 groups.

Newborn screening benefits substantiated

The probabilities of sitting independently and walking independently were significantly greater in the newborn screening group than in the clinical symptom onset group (90.9% [median age 9 months] vs 74.2% [median age 14 months] and 63.6% [median age 17 months] vs 14.7% [median age 23.5 months], respectively; P<.001). 

The authors pointed out that the number of children who achieved the motor milestone of independent ambulation was 4 times greater in the newborn screening group than in the clinical symptom onset group, commenting that this was plausibly 鈥渁 result of irreversible damage of motor neurons due to delayed treatment initiation.鈥�

Within the newborn screening group, the probability of sitting independently was not significantly different between those who were asymptomatic and those who were symptomatic at the start of therapy (P<.49). The probability of walking independently, however, was significantly greater for those who were asymptomatic at treatment initiation (P<.001). 

鈥淸O]ur results demonstrate that not all patients benefited equally from newborn screening,鈥� the authors commented. "While patients still asymptomatic at treatment initiation have a good chance of achieving independent ambulation, this is rather unlikely for those who already exhibited clear symptoms of SMA at treatment onset.鈥�

A total of 40.9% of children diagnosed through newborn screening were able to walk independently at 18 months of age (all of whom were asymptomatic at the start of therapy). In contrast, 5.8% of children in the clinical symptom onset group were able to walk at 18 months of age. 

Additionally, the probability of ventilation and tube feeding were significantly lower for the newborn screening group than for the clinical symptom onset group (P<.001). The researchers also observed that the newborn screening group had fewer adverse events compared to the clinical symptom onset group (mean per child: 0.3 vs 1.3). 

The research team concluded that the 鈥渂enefits of newborn screening identified in the study presented here encompass not only the achievement of motor milestones, but also a reduced need for ventilator support or tube feeding and a reduction in [adverse events].鈥� 

The challenge of diagnostic and treatment delays

The authors pointed out that mean age at treatment initiation was 1.3 months in the newborn screening group. Avoidable treatment delays, the researchers suggested, could be from communication issues after positive screening results, requirements for other diagnostic tests, concerns of parents, insufficient hospital resources, or lag period for confirmation of medical insurance coverage for disease-modifying agents. 

According to the authors of an accompanying editorial, 鈥淭he SMARTCARE study group present an important addition to the body of evidence supporting NBS [newborn screening] for SMA by looking at real-world effectiveness of NBS.鈥�³

鈥淚mmediate implementation of NBS in countries where [disease-modifying therapy] is available for SMA constitutes a medical, ethical, and economic emergency. It is also a matter of equity,鈥� they added, 鈥渁s diagnostic delays are impacted by both geographic and socioeconomic factors and NBS offers more equitable access to diagnosis and care.鈥�³

鈥淐onsequently, as symptoms of SMA can develop within weeks or even days,鈥� the authors of the SMARTCARE study wrote, 鈥渙ur study emphasizes that additional efforts are needed to facilitate early initiation of disease-modifying therapies.鈥� 

Published: May 15, 2024