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

NCT06396520 | Recruiting

• 1 other identifier: NIBS-CP
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cerebral Palsy; Development, Infant; Infant Development

Keywords

MRI; Brain development; Diffusion MRI; Motor development; Cognitive development; Normative modelling; Hand assessment for infants; Alberta Infant Motor scale; Motor functioning; Cerebral Palsy; Typically developing; Infants; Toddlers; Children; Peabody Developmental Motor Scales; Corticospinal tract; Motor system

Outcome Measures

Primary Outcomes (7)

• Diffusion-weighted magnetic resonance imaging

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

  Baseline, 12 months, 24 months

• 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

  Baseline, 12 months, 24 months

• Cortical thickness

  Global and regional measures of apparent cortical thickness measured in mm

  Baseline, 12 months, 24 months

• Brain connectivity measures

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

  Baseline, 12 months, 24 months

• Indices of myelination

  T1/T2 contrast in grey and white matter regions

  Baseline, 12 months, 24 months

• MR-spectroscopy measures

  Brain metabolic measures (metabolites: NAA, choline, creatine, myoinositol, lactate) obtained from voxels containing the basal ganglia and thalamus in the left and right hemispheres.

  Baseline, 12 months, 24 months

• Surface area

  Global and regional surface area measured in mm2

  Baseline, 12 months, 24 months

Secondary Outcomes (6)

• Hand assessment for infants (HAI)

  Baseline, 12 months

• Alberta Infant Motor Scale (AIMS)

  Baseline, 12 months

• Peabody Developmental Motor Scales (PDMS-2)

  24 months

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

  24 months

• Ages & Stages (ASQ)

  12 months, 24 months

Study Arms (2)

Typically developing infants

Born after gestational week 37, Uneventful birth, No known history of brain injury, No known neurological disorders

Other: No intervention, observational

High Risk for Cerebral Palsy

Recruitment through CP-EDIT (Clinical trials.gov ID: NCT05835674), inclusion criteria. 'Newborn-detectable risk-pathway'. Preterm birth with gestational age below 32 or birth weight below 1500 g and clinical concern, Moderate to severe brain injury (Papile grade 3 to 4 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, Extra Corporal Membrane Oxygenation, meningitis, kernicterus, severe hypoglycemia) or neurological risk factors (brain malformation, increased tone), Parental concern and one of the factors above 'Infant detectable risk-pathway'. Inability to sit independently by age 9 months, Hand function asymmetry or crawl asymmetry, Inability to take weight through the plantar surface of the feet, History (as above) or neurological risk factors, Parental concern and one of the factors above.

Other: No intervention, observational

Interventions

No intervention, observational OTHER

No intervention, observational

High Risk for Cerebral Palsy; Typically developing infants

Eligibility Criteria

• Age: 2 Months - 11 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study 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.

You may qualify if:

• Group: 'Newborn-detectable risk-pathway'
• 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)
• Group: 'Infant detectable risk-pathway'
• Inability to sit independently by age 9 months
• Hand function asymmetry or crawl asymmetry
• Inability to take weight through the plantar surface of the feet
• History (e.g., as above) or neurological risk factors
• \- Consent to health-relevant information on clinical findings being passed on to the medical doctors in CP-EDIT and/or their primary care physician.
• Born \>37 weeks
• Uneventful birth
• No known history of brain injury
• No neurological condition

You may not qualify if:

• 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.

Sponsors & Collaborators

• Danish Research Centre for Magnetic Resonance: lead
• Hvidovre University Hospital: collaborator
• Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Denmark: collaborator

Study Sites (1)

Danish Research Centre for Magnetic Resonance

Hvidovre, Capital Region, 2650, Denmark

RECRUITING

Related Publications (4)

• Wagenaar N, Verhage CH, de Vries LS, van Gasselt BPL, Koopman C, Leemans A, Groenendaal F, Benders MJNL, van der Aa NE. Early prediction of unilateral cerebral palsy in infants at risk: MRI versus the hand assessment for infants. Pediatr Res. 2020 Apr;87(5):932-939. doi: 10.1038/s41390-019-0664-5. Epub 2019 Nov 13.

  PMID: 31722367 BACKGROUND

• Korom M, Camacho MC, Filippi CA, Licandro R, Moore LA, Dufford A, Zollei L, Graham AM, Spann M, Howell B; FIT'NG; Shultz S, Scheinost D. Dear reviewers: Responses to common reviewer critiques about infant neuroimaging studies. Dev Cogn Neurosci. 2022 Feb;53:101055. doi: 10.1016/j.dcn.2021.101055. Epub 2021 Dec 27.

  PMID: 34974250 BACKGROUND

• Rutherford S, Barkema P, Tso IF, Sripada C, Beckmann CF, Ruhe HG, Marquand AF. Evidence for embracing normative modeling. Elife. 2023 Mar 13;12:e85082. doi: 10.7554/eLife.85082.

  PMID: 36912775 BACKGROUND

• Rutherford S, Kia SM, Wolfers T, Fraza C, Zabihi M, Dinga R, Berthet P, Worker A, Verdi S, Ruhe HG, Beckmann CF, Marquand AF. The normative modeling framework for computational psychiatry. Nat Protoc. 2022 Jul;17(7):1711-1734. doi: 10.1038/s41596-022-00696-5. Epub 2022 Jun 1.

  PMID: 35650452 BACKGROUND

MeSH Terms

Conditions

Cerebral Palsy

Condition Hierarchy (Ancestors)

Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Kathrine Skak Madsen, PhD

  Senior Researcher

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Line K Johnsen, PhD

CONTACT

+4561145571; linekj@drcmr.dk

Kathrine Skak Madsen, PhD

CONTACT

+45 38623323; kathrine@drcmr.dk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2024
• First Posted: May 2, 2024
• Study Start: June 1, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 28, 2026

Record last verified: 2026-01

Locations

DK (1)