Neuroimaging of Babies During Natural Sleep to Assess Typical Development and Cerebral Palsy

Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age2-11
SponsorDanish Research Centre for Magnetic Resonance

About this trial

Background: Early diagnosis of cerebral palsy (CP) is crucial, enabling intervention when neuroplasticity is at its highest. Magnetic resonance imaging (MRI) plays a vital role in CP diagnosis. Currently, diagnostic MRI of newborns and infants with suspected brain damage relies heavily on structural MR images. The current study aims to i) establish procedures for clinical infant and toddler MRI during natural sleep, ii) use advanced MRI sequences, such as advanced diffusion-weighted imaging (DWI), that may be more sensitive in detecting early brain damage, and iii) map relationships between early brain development, and motor function and development.

Methods: The NIBS-CP study will enroll approximately 200 infants either at risk for CP or typically developing. Infants will be followed longitudinally (for three waves) between 3 months and 2 years of age with cerebral MRI at 3 Tesla and comprehensive assessments of motor and cognitive functioning. The MRI protocol includes advanced diffusion-weighted imaging, high-resolution structural MRI, and MR spectroscopy. The motor and cognitive assessments include Hand Assessment in Infants, Alberta Infant Motor Scales, Hammersmith Infant Neurological Examination, Peabody Developmental Motor Scales, Bayley Scales of Infant Development, and Ages and Stages Questionnaires. NIBS-CP aims to establish normative material on early brain development of Danish children and conduct normative modeling of typical and atypical development to identify deviations in brain development at the level of the single child.

Discussion: Identifying predictive brain structural features of motor function and motor development is key to the future use of early MRI in the clinical work-up, as this promotes early diagnosis and (clinical) intervention strategies tailored to the individual child.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Preterm birth with gestational age below 32 weeks

Birth weight below 1500 g

Moderate to severe brain injury (A label of moderate to severe brain injury was considered if there was Papile grade three to four intraventricular haemorrhage, cystic periventricular leukomalacia, neonatal stroke, term hypoxic-ischaemic encephalopathy (≥35 weeks gestation at birth) or other significant neurological condition)

History (e.g., neonatal seizures, ECMO, meningitis, kernicterus, severe hypoglycemia) or neurological risk factors (malformations in CNS, increased tone)

Disqualifiers

Infants have any MRI contraindications, e.g., pacemaker or other implanted electronic devices.

Families do not speak or understand Danish.

Families do not wish to be informed about incidental findings on the MRI, or scores within the clinical range in the neurological, motor, or cognitive assessments.

Trial population

Infants at risk of cerebral palsy: 160 infants with a high risk of CP will be enrolled in CP-EDIT (ClinicalTrials.gov ID NCT05835674). At least 2/3 are expected to be from the 'new-born detectable risk pathway' and less than 1/3 from the 'infant-detectable pathway'. At inclusion, infants will mainly be 3-6 months of age, though the age range between 2-11 months is accepted. It is expected that at least 50-60 of the high-risk infants will participate in the NIBS-CP study, with an upper limit of 100 infants. Typically developing infants: To establish a Danish normative sample of early brain development and a control group to the CP-EDIT cohort, approx. 140-150 typically developing infants will be recruited to NIBS-CP (approx. 200 infants when combining the high-risk and typically developing groups). The age range and mean age of the typically developing infants will be matched to that of the high-risk infants.

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

  • No intervention, observational

    Other intervention

    No intervention, observational

Treatment groups

200 Participants
are divided into 2 treatment groups
Group A: Typically developing infants1 intervention
Group B: High Risk for Cerebral Palsy1 intervention

Trial outcomes

Primary outcomes

1

Diffusion-weighted magnetic resonance imaging

Microstructural measures obtained from fixel-based and tensor-based analysis.

Time frame
Baseline, 12 months, 24 months
2

Brain volumetric measures

Total brain volume, cortex volume, and white matter volume, as well as regional grey matter volume of cortical parcels and subcortical grey matter structures measured in mm3

Time frame
Baseline, 12 months, 24 months
3

Cortical thickness

Global and regional measures of apparent cortical thickness measured in mm

Time frame
Baseline, 12 months, 24 months
4

Brain connectivity measures

Brain connectivity measures obtained from structural covariance and tractography-based connectivity analyses

Time frame
Baseline, 12 months, 24 months

Secondary outcomes

1

Hand assessment for infants (HAI)

The HAI measures the degree and quality of goal-directed actions performed with each hand separately as well as with both hands together. The HAI is scored on 17 items (12 unimanual and 5 bimanual)

Time frame
Baseline, 12 months
2

Alberta Infant Motor Scale (AIMS)

The AIMS is an observational assessment scale that measures gross motor maturation in infants from birth through independent walking. The scale consists of 58 items organized into four positions: prone, supine, sitting, and standing. Each item describes three aspects of motor performance - weight-bearing, posture, and antigravity movements.

Time frame
Baseline, 12 months
3

Peabody Developmental Motor Scales (PDMS-2)

PDMS-2 is an in-depth assessment of gross and fine motor skills of children from birth through 5 years.

Time frame
24 months
4

Bayley Scales of Infant and Toddler Development, Fourth Edition (BSID-4)

BSID-4 is a standardized and norm-referenced assessment that measures the cognitive, motor, language, and social-emotional development of infants and toddlers aged 0-3 years.

Time frame
24 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Danish Research Centre for Magnetic Resonance

Lead sponsor

Hvidovre University Hospital

Collaborator

Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Denmark

Collaborator