Active NBS Study: Decentralised Monitoring Motor Development in Children With Duchenne Muscular Dystrophy or Spinal Muscular Atrophy Identified by Newborn Screening

Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) are severe, progressive, and life-limiting neuromuscular disorders that manifest during early childhood. Both conditions are characterized by motor function decline, leading to severe disability and premature mortality. The availability of disease-modifying therapies has dramatically changed the clinical landscape, but their effectiveness is strongly dependent on very early initiation, ideally before symptom onset.

Newborn screening (NBS) for SMA has now been implemented in several countries, enabling the identification of affected infants at birth. This shift creates a new challenge: the need to monitor presymptomatic or minimally symptomatic children over time with sensitive, reliable, and age-appropriate tools. Conventional motor function scales were designed for older children and are not sufficiently adapted for infants and toddlers. As a result, there is a critical gap in longitudinal assessment during the first years of life, a period when therapeutic interventions may have the greatest impact.

The Active NBS study was designed to address this unmet need. This is a monocentric, fully remote, academic, observational study that leverages wearable digital technologies to monitor motor development in very young children with SMA or DMD. The study is conducted entirely at a distance, with no requirement for hospital visits, thereby reducing the burden on families and improving accessibility.

Study Objectives:

The primary objective is to validate digital biomarkers of early motor development in children diagnosed with SMA or DMD. Secondary objectives include the early detection of motor deficits, quantification of developmental delays according to genetic subtype, and modeling of motor trajectories during the first years of life. Exploratory objectives focus on gait analysis, including stride velocity 95th centile (SV95C), and comparisons of motor outcomes across genetic backgrounds and treatment exposure.

Study Design and Procedures:

Up to 100 children will be enrolled, including infants identified by NBS, family testing, or incidental diagnosis. Enrollment and informed consent are performed remotely using secure electronic platforms. Participants are followed prospectively for up to 30 months, with assessments every 6 months through structured questionnaires and video consultations with the study team.

Two wearable devices will be employed, depending on the child's age and motor status:

• MAIJU® (Motor Assessment of Infants with a Jumpsuit): a sensorized garment designed for non-ambulant infants, capturing spontaneous movement and generating a composite biomarker (Babacloud Infant Motility Score, BIMS).
• Syde®: a wearable ankle sensor validated in ambulant children, enabling precise gait monitoring and calculation of SV95C, a regulatory-accepted endpoint in DMD.

Data collected include digital motor endpoints, routine clinical information, and quality of life metrics (PedsQL). Families are instructed on the correct use of devices and can install and remove them independently at home. No travel or in-person assessments are required, making this approach particularly suitable for rare disease populations.

Scientific Rationale:

Traditional motor scales, while validated in older children, lack sensitivity to detect subtle developmental changes in infancy and early childhood. Digital endpoints derived from continuous movement monitoring have the potential to provide richer, objective data on motor development. By validating these measures in a presymptomatic or early symptomatic population, this study aims to establish novel tools for both clinical practice and future interventional trials. Importantly, the study also addresses the practical and ethical challenges of long-term follow-up in very young children by implementing a fully remote design.

Expected Impact:

The Active NBS study is expected to generate the first large-scale, longitudinal dataset on motor development in presymptomatic and early symptomatic children with SMA and DMD. The validation of digital endpoints such as SV95C and BIMS will contribute to the development of sensitive outcome measures for clinical trials and may support regulatory acceptance in the future. Beyond its immediate scientific goals, the study demonstrates the feasibility and acceptability of decentralized follow-up in rare pediatric populations, setting the stage for broader applications of digital health technologies in neuromuscular disorders.

Inclusion criteria

Genetically confirmed SMA and avalaible MSNA2 copy number:

• Identified by newborn screening,
• Identified by family screening, or incidental diagnosis in pre-symptomatic stage
• Treated (or follow-up possible for patients with 4 SMN2 copies)

Genetically confirmed DMD:

• Identified by newborn screening,
• Identified by family screening, or incidental diagnosis in pre-symptomatic stage
• Age < 4 years at inclusion

Legal guardian able to provide informed consent

Exclusion criteria

• Any acute or chronic condition that, in the investigator's opinion, significantly interferes with assessments and/or motor development.
• Participation in a therapeutic trial.
• Lack of internet connection.