Abstract
Skeletal muscle is a plastic tissue that undergoes structural changes during childhood. Previous studies assumed a simple linear muscle growth function with respect to age, but longitudinal data are needed to check this assumption, and to develop both parameter- and muscle-specific growth trajectories. Both muscle quantity and quality are related to muscle function, indicating the importance of normal muscle development to participate in daily life activities. In children with altered muscle growth, such as those with neurological or neuromuscular disorders, norm-reference data are crucial to improve understanding of abnormal muscle development in relation to age and to optimize age-specific therapeutic interventions. The overall aim of the current prospective study was to create an extensive longitudinal normative database on muscle morphology and composition of the medial gastrocnemius and semitendinosus muscle in typically developing (TD) children, aged 4 months to 12 years old, hereby developing muscle- and parameter-specific norm-reference trajectories. Muscle morphology, that is, muscle belly length (ML), tendon length (TL), muscle-tendon unit length (MTUL), muscle volume (MV) and cross-sectional area (CSA), and muscle composition, that is, echo-intensity (EI), were assessed using three-dimensional freehand ultrasound. Muscle morphology was also normalized to body height, body weight or the product of body height and weight. It was hypothesized that absolute morphological parameters increase gradually with increasing age, following a simple straight linear growth pattern, while normalized morphological parameters were expected to remain stable over time. Mixed-effect models were fitted to estimate muscle- and parameter-specific trajectories with respect to age. Linear mixed-effect models (LMM) and non-linear mixed-effect models (non-LMM) were compared using the Akaike information criterion, with a lower value indicating a better model fit. Data were collected from 59 TD children (median age [interquartile range]: 5.92 [1.33-8.97] years; boys/girls: 29/30; 3-8 repeated measurements) for the medial gastrocnemius, totaling 230 measurements, and from 55 TD children (median age [interquartile range]: 5.95 [1.57-8.63] years; boys/girls: 26/29; 3-7 repeated measurements) for the semitendinosus, totaling 207 measurements. The current results revealed that for the absolute morphological parameters of the medial gastrocnemius, the longitudinal trajectory of MTUL showed a piecewise trajectory with a significant breakpoint (p < 0.0001) at the age of 2.16 years influenced by ML growth, and another at the age of 6.91 years influenced by TL growth. CSA and MV showed comparable trajectories, with trajectory changes around ages 2 and 10 years. For the semitendinosus, TL and CSA increased linearly with age, whereas ML was best fitted by an LMM with a quadratic function, with an inflection point around the age of 7 years. MV displayed a piecewise trajectory with a significant breakpoint (p < 0.0001) at 4.53 years. The normalized parameters of both muscles showed a more complex pattern than the expected straight horizontal trajectory. Non-LMM with one significant breakpoint (p < 0.0001) showed the best fit for EI of both muscles, but only small changes in relation to age were seen. Our results demonstrated that changes in muscle parameters according to age cannot be explained by merely a simple straight linear trajectory and highlighted the importance of muscle- and parameter-specific models.