Clinical trial NCT06111898: Neuro-biomechanical Determinants for Motor Behavior in High-risk Infants
Official title: Neuro-biomechanical Aspects Determining the Motor Behavior in Infants With High-risk of Neuromotor Impairments
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Premature Birth
Cerebral Palsy
Neurodevelopmental Disorders
Brain Injuries
Nervous System Diseases
Keywords: Brain Imaging
General Movements
3D freehand ultrasound
Muscle Morphology
Electromyography
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
First posted: 2023-11-01
Enrollment: 348
Sex: ALL
Minimum age (years): 35
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Preterm or a term born Infants with detectable risk factors for neurodevelopmental impairments will be enrolled

Brief summary: This project focuses on motor development, muscle growth and muscle activity. Using advanced, instrumented tests such as , the link between muscles and the movement characteristics will be studied. In addition, the evolution of these neuro-biomechanical determinants during the first year of life will be investigated. The examinations are planned for a group of high-risk infants (e.g. premature birth, cases of asphyxia, etc.) compared with a group of infants with typical development.

Detailed description: Background and rationale:

Prematurity and the associated causes of perinatal brain damage, as well as neonatal stroke and birth asphyxia, are major risk factors for neurodevelopmental disorders appearing from birth. In addition, these neuromotor disorders resulting from impaired brain development appear progressively over the course of the first year, affecting early movement and muscle growth. Therefore, early diagnosis and motor therapy are essential to improve long-term neurodevelopmental outcomes. However, in order to provide adequate strategies for these high-risk infants, it is crucial to identify the determinants of potential neuromotor deficits and their consequences on early motor behavior and developmental trajectory during the first year of life. A multimodal tool is needed to reveal the early neuro-biomechanical determinants of motor behavior in infants at high risk of neurodevelopmental disorders.

Objective(s):

* Establishing a comprehensive multimodal tool for the assessment of neuro-biomechanical determinants of motor behavior in the first year of life in high-risk infants for neurodevelopmental impairments, further referred to as "advanced muscle and movement analysis (AMMA)"
* Revealing early neuro-biomechanical determinants in high-risk infants covering the first year of life, including the time points in the neonatal period, at term age, at 3 months of (corrected) age, at 6 months of (corrected) age and at 12 months of (corrected) age, by using the AMMA

Outcome(s):

* Using valid and reliable assessments within the protocol
* Differences in neuro-biomechanical determinants between typically developing infants and high-risk infants at each time point.
* Associations between the neuro-biomechanical determinants of motor behaviour in high-risk infants at each time point
* Changes over time and interaction in the neuro-biomechanical determinants, and comparisons of these evolutions in high-risk infants with typical development.

Methodology

The current study is a national, single center (Geneva University Hospitals), observational study. This observational research will perform both cross-sectional and longitudinal data collection for cohorts of live-born infants.

The study population for this study will include children, i.e., neonates and infants between the age of 35-36 weeks of gestational age to 12 months of (corrected) age. Further, two main groups of children will be included, (a) typically developing (TD) children and (b) children at high-risk for neurodevelopmental impairments. The TD children will be used as a control group.

Procedure

Multiple study visits are planned for longitudinal data collection within the first year of life, i.e. a time of term age, at 3 months, at 6 months and 12 months of age. For the preterms, the investigators also plan to perform an assessment in the neonatal period, i.e. 35-36 weeks of gestation.

The duration of each visit session will be around 90 minutes per participant, providing also time for feeding moments and adaptation of the infant to the new environment. The visit in the neonatal period will be organized at the Neonatology Unit at HUG (Geneva University Hospitals). All visits from the term (equivalent) age will be organized in the Kinesiology Laboratory at the HUG.

In general, clinical data such as birth information, structural brain MRI and developmental assessments will be derived from the medical records.

The main procedures during each research visit are:

1. Muscle assessment: using 3D freehand ultrasound technique, measuring the lower legs muscles, assessing muscle volume and length.
2. Neuromotor development: using standardized scales, measuring the gross motor development and motor repertoire, assessing age-appropriate neuromotor development.
3. Motor behavior: using surface electromyography and motion capture system, measuring spontaneous movements, assessing the movement quality and quantity

Eligibility criteria: Inclusion \& exclusion criteria for group of high-risk infants:

* Infants born before or at 28 weeks of gestation
* Infants born after 28 weeks of gestation and with brain injury.
* A term birth with the clinical diagnosis of asphyxia (ischemic event with hypothermia) or neonatal stroke
* Exclusion in case of genetic syndrome, or lower limb pathology (e.g. spina bifida)

Inclusion \& exclusion criteria for group of typically developing children:

* Born at a gestational age above 37 weeks
* Birth weight between P10 and P90
* Head circumference between P10 and P90
* Ph \>7.1
* Exclusion in case of genetic syndrome, lower limb pathology and/or brain malformations

Primary outcomes:
measure: General Movement Assessment
timeFrame: 35-36 weeks of gestation; term equivalent age, 3 months (corrected) age
measure: Hammersmith Neonatal/Infant Neurological Examination
timeFrame: 35-36 weeks of gestation; term equivalent age, 3 months (corrected) age, 6 months (corrected) age and 12 months (corrected) age.
measure: Change in muscle morphology size
timeFrame: 35-36 weeks of gestation; term equivalent age, 3 months (corrected) age, 6 months (corrected) age and 12 months (corrected) age.
measure: Change in muscle morphology length
timeFrame: 35-36 weeks of gestation; term equivalent age, 3 months (corrected) age, 6 months (corrected) age and 12 months (corrected) age.
measure: Change in muscle activity
timeFrame: 35-36 weeks of gestation; term equivalent age, 3 months (corrected) age, 6 months (corrected) age and 12 months (corrected) age.
measure: Change in motor behaviour
timeFrame: 35-36 weeks of gestation; term equivalent age, 3 months (corrected) age, 6 months (corrected) age and 12 months (corrected) age.
Secondary outcomes:
measure: Bayley Scales of Infant and Toddler Development - Version III
timeFrame: 3 months (corrected) age, 6 months (corrected) age and 12 months (corrected) age.
measure: Alberta Infant Motor Scale (AIMS)
timeFrame: 3 months (corrected) age, 6 months (corrected) age and 12 months (corrected) age.
measure: Magnetic resonance imaging of the brain: classification
timeFrame: up to 4 weeks post-term age
measure: Magnetic resonance imaging of the brain: quantification
timeFrame: up to 4 weeks post-term age
Other outcomes:
Locations:
city: Geneva
country: Switzerland
facility: University Hospitals Geneva
Study officials:
References:
citation: Pascal A, Govaert P, Oostra A, Naulaers G, Ortibus E, Van den Broeck C. Neurodevelopmental outcome in very preterm and very-low-birthweight infants born over the past decade: a meta-analytic review. Dev Med Child Neurol. 2018 Apr;60(4):342-355. doi: 10.1111/dmcn.13675. Epub 2018 Jan 19.
citation: Rosenbaum P, Paneth N, Leviton A, Goldstein M, Bax M, Damiano D, Dan B, Jacobsson B. A report: the definition and classification of cerebral palsy April 2006. Dev Med Child Neurol Suppl. 2007 Feb;109:8-14.
citation: Gough M, Shortland AP. Could muscle deformity in children with spastic cerebral palsy be related to an impairment of muscle growth and altered adaptation? Dev Med Child Neurol. 2012 Jun;54(6):495-9. doi: 10.1111/j.1469-8749.2012.04229.x. Epub 2012 Feb 27.
citation: De Beukelaer N, Vandekerckhove I, Huyghe E, Molenberghs G, Peeters N, Hanssen B, Ortibus E, Van Campenhout A, Desloovere K. Morphological Medial Gastrocnemius Muscle Growth in Ambulant Children with Spastic Cerebral Palsy: A Prospective Longitudinal Study. J Clin Med. 2023 Feb 16;12(4):1564. doi: 10.3390/jcm12041564.
citation: Willerslev-Olsen M, Choe Lund M, Lorentzen J, Barber L, Kofoed-Hansen M, Nielsen JB. Impaired muscle growth precedes development of increased stiffness of the triceps surae musculotendinous unit in children with cerebral palsy. Dev Med Child Neurol. 2018 Jul;60(7):672-679. doi: 10.1111/dmcn.13729. Epub 2018 Mar 24.