5-Year Review Further Bolsters Support for Newborn SMA Screening

The initiation of newborn screening (NBS) in spinal muscular atrophy (SMA) continues to benefit both treatment efficacy and patient outcomes, according to new results from a 5-year review published in the International Journal of Neonatal Screening. Presymptomatic treatment in newborns with SMA was possible thanks to NBS and helped many of these patients reach developmental and motor milestones that can otherwise be drastically hindered in this condition.¹

Over the years, a growing body of literature continually suggests the benefits of early treatment interventions as gene-modifying therapies became available. As novel therapeutics such as nusinersen (Sprinraza), risdiplam (Evrysdi), and onasemnogene abeparvovec (Zolgensma) were developed in the past decade, their clinical use has dramatically altered the natural history of SMA and led to life-changing outcomes as patients may experience less-intense symptoms and maximize their motor potential.

Newborn screening, such as a blood spot test, can provide numerous benefits for infants who may have unknown conditions or complications | image credit: Peakstock - stock.adobe.com

To be placed onto a newborn screening panel, states are informed by recommendations from the secretary of HHS’ Recommended Uniform Screening Panel (RUSP).² While the RUSP provides a list of recommended conditions to include on a panel, NBS inclusion is not the same throughout all states as each state weighs factors including screening cost, implications of the illness, available treatments, and more. Blood spot screening is one of the standard procedures of NBS; here, a couple drops of blood are taken from the newborn’s heel, dried on a card, and sent to the laboratory for testing. Results can typically be expected within 7 days.

Utah became the first state to initiate state- and population-wide NBS for SMA in 2018—and later that year, SMA ended up being added to the RUSP.¹ In light of these efforts, NBS for SMA continues to serve as a valuable tool for identifying those who may need/benefit the most from earlier treatment. In this retrospective study, investigators reviewed patients’ and their families’ experiences with NBS for SMA in Utah, as well as evaluated 5-year follow-up data.

A total of 239,844 infants underwent NBS for SMA between January 2018 and January 2023; 13 of these tests came back positive for SMA. The NBS assay consisted of a quantitative polymerase chain reaction test to find whether an infant’s SMN1 gene had exon 7. This test was conducted within 2 days of birth and repeated around 2 weeks later.

Positive screening results were available after a median of 6 days (range, 3-18 days) from the infant’s birth, with a median time of 5 days from the sample collection until the positive results. The researchers estimated that the prevalence of SMA in Utah at this time was 1 in 20,000 live births. Of the 13 newborns with SMA, 4 (31%) were found to have heightened levels of anti–adeno-associated virus 9 (AAV9), which was successfully resolved within 4 months for those affected. Other treatment decisions included gene replacement therapy (in clinical trials), nusinersen, and onasemnogene abeparvovec.

Researchers used the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the third edition of the Bayley Scaled of Infant and Toddler Development (BSID) to evaluate clinical outcomes and motor functioning. According to these measures, patients with 2 copies of SMN2 achieved developmental milestones at an early rate than the natural course of SMA typically predicts, and patients with 3 or 4 copies of SMN2 who were treated hit these milestones at the expected timeline.

“The majority of the treated NBS-identified patients demonstrated gross motor development between the 5th and 95th percentiles as compared to neurotypical age-matched peers as measured using BSID growth scores,” the authors wrote, with CHOP INTEND scores ranging from 35 to 51 at baseline, and infants largely reaching a score of 64 by the 8-month mark.

The authors concluded by iterating how their findings showcase the value of prompt treatment prior to symptom onset in SMA, and the benefits that NBS provides for identifying patients in need. “Due to these complexities of newborn screening follow-up, a multidisciplinary team, including close communication with the newborn screening program, is required to facilitate diagnosis and treatment in a timely manner; thus, continued efforts to further expedite diagnostic testing, evaluation, and treatment are essential as the landscape of SMA diagnosis and treatment continue to evolve,” they wrote.

At present, all newborns are screened for SMA throughout the US.

References

1. Wong KN, McIntyre M, Cook S, et al. A five-year review of newborn screening for spinal muscular atrophy in the state of Utah: lessons learned. Int J Neonatal Screen. 2024;10(3):54. doi:10.3390/ijns10030054

2. Newborn screening process. Health Resources & Services Administration. December 2023. Accessed October 3, 2024. https://newbornscreening.hrsa.gov/newborn-screening-process#:~:text=To%20help%20states%20decide%20which,Recommended%20Uniform%20Screening%20Panel%20page