# Differences in swallowing efficacy of disease modifying treatment between infants receiving pre-symptomatic and symptomatic administration

## TL;DR

Infants with spinal muscular atrophy who receive treatment before symptoms show better swallowing outcomes compared to those treated after symptoms appear.

## Contribution

This study is the first to compare pre-symptomatic and symptomatic treatment effects on swallowing biomechanics and function in spinal muscular atrophy infants.

## Key findings

- Pre-symptomatic treatment is associated with fewer profound swallowing impairments compared to symptomatic treatment.
- Infants treated pre-symptomatically managed secretions well and consumed full nutrition without assistance.
- Pharyngeal biomechanical deficits were more common in infants treated after symptom onset.

## Abstract

Spinal muscular atrophy causes progressive motor neuron degeneration that impedes an infant's ability to maintain full oral nutrition and manage secretions. Development of pharmaceuticals that halt neuromuscular degeneration have enabled survival and improvement in motor function, with infants who receive treatment before symptoms exhibiting better outcomes than those who receive treatment after symptom onset. Little is known about the impact of treatment timing on swallowing. We retrospectively evaluated swallowing biomechanics and function among infants who received a disease modifying treatment and a swallow study as part of routine clinical care at 13 international children's hospitals. Swallow studies were prospectively analyzed for measures of biomechanics using BabyVFSSImP© and Swallowtail, with chart reviews used to evaluate measures of function including oral intake status and secretion management. Data was reported with descriptive statistics, with differences in swallowing outcomes compared between infants who received pre-symptomatic and symptomatic treatment using non-parametric t-tests.

69 infants meeting eligibility criteria were included. The majority received treatment after symptom onset (N = 52, 75%) and had two copies of survival motor neuron 2 (SMN2) (pre-symptomatic N = 17, 100%; symptomatic N = 48, 92%). Median age of infants at the time of their last videofluoroscopic swallow study was 7.92 months (IQR 4.83). While profound impairments in swallowing biomechanics were rare among infants who received pre-symptomatic treatment, they were common among infants treated after symptom onset, with significantly worse (higher) scores in four BabyVFSSImP© domains (ts > 3.25, ps ≤ 0.01, δ > 0.42): Palatal-Pharyngeal Approximation, Airway Invasion/Laryngeal Closure, Aspiration, and Pharyngeal Transport and Clearance. Although all pre-symptomatic treated infants were managing secretions without suctioning and nearly all were consuming full age-appropriate nutrition (N = 15, 88%), similar to biomechanics, select pre-symptomatic treated infants did exhibit profound functional impairments.

Infants who receive pre-symptomatic treatment for spinal muscular atrophy typically have good swallowing outcomes, without profound impairments in biomechanics, reliance on suctioning for secretion management, and reliance on alternative nutrition care. Pharyngeal biomechanical deficits are substantially more common among those infants that receive treatment after symptom onset, and likely are associated with subclinical neural degradation at the time treatment is administered.

The online version contains supplementary material available at 10.1186/s13023-025-04049-9.