Early brain markers in newborns at risk for cerebral palsy

ENSEMBLE: European Newborn Study: Early Markers for a Better LifE

This project will try a computer model to help doctors predict developmental problems in newborns with MRI-confirmed brain injuries who are at high risk for cerebral palsy.

Quick facts

• Study type: Observational
• Enrollment: 1000 (estimated)
• Ages: 0 Years to 2 Years
• Sex: All
• Sponsor: UMC Utrecht (other)
• Locations: 8 sites (Paris and 7 other locations)
• Trial ID: NCT07189494 on ClinicalTrials.gov

What this trial studies

This observational, multicenter European effort will collect routine clinical data and MRI findings from newborns with brain injuries and store them in a shared database to train machine learning models. No extra tests are required for the child beyond standard clinical care, while parents complete two online questionnaires at 3–4 months and at 2 years corrected age. The study aims to combine imaging, clinical course, and parent-reported experience to identify early markers that predict later developmental outcomes. Findings will be used to develop practical recommendations to support families and guide early follow-up.

Who should consider this trial

Good fit: Infants with MRI-confirmed brain injury at term-equivalent age or within 10 days after birth—such as extensive punctate white matter injury, periventricular hemorrhagic infarction, significant cerebellar injury, cystic periventricular leukomalacia (grade 3–4), severe intraventricular hemorrhage (grade III), marked posthemorrhagic ventricular dilatation, perinatal asphyxia with central gray or watershed injury, or perinatal arterial ischemic stroke—are the intended participants.

Not a fit: Infants without MRI-confirmed brain injury, those with only very mild or unrelated conditions, or families unable to complete the follow-up questionnaires are unlikely to gain direct benefit from this project.

Why it matters

Potential benefit: If successful, the model could help clinicians identify infants at highest risk earlier so they can receive targeted monitoring and earlier supportive interventions.

How similar studies have performed: Similar efforts combining early neuroimaging and clinical data with machine learning have produced promising but still preliminary results, so this work builds on emerging evidence rather than on an established diagnostic tool.

Eligibility criteria

Inclusion Criteria:

* All infants with confirmed brain injury on MRI at high risk for CP.

Particularly, infants with the following brain injuries at risk for CP will be considered on MRI at term equivalent age or within 10 days after birth or sentinel event:

* Extensive punctate white matter injury.
* Periventricular hemorrhagic infarction (any location).
* Cerebellar injury (ischemic and/or hemorrhages) involving the vermis or involving more than 1/3 of the cerebellar hemisphere and/or lesions involving the cerebellar vermis (Meijler \& Steggerda, 2019).
* Cystic periventricular leukomalacia (grade 3 \& 4).
* intraventricular hemorrhages grade III.
* Posthemorrhagic ventricular dilatation exceeding the 97°percentile + 4mm for the ventricular index (Cizmeci et al., 2020).
* Perinatal asphyxia with hypoxic ischemic injury of the central gray matter and/or perirolandic area.
* Perinatal asphyxia with hypoxic ischemic injury in the watershed areas.
* Perinatal ischemic arterial stroke at high risk for CP, thus with involvement of the corticospinal tracts, cortex, white matter and basal ganglia (Wagenaar et al., 2018).
* Presence of other brain injuries with expected adverse motor outcome (i.e. big subdural and parenchymal bleedings with/without midline shift, bilirubin induced brain injury) in preterm infants, term infants with neonatal encephalopathy with/without neonatal seizures.

  * Written informed parental consent (Dutch, English, French, German, Italian, Spanish).

Exclusion Criteria:

* Infants not matching the inclusion criteria.
* Any proven or suspected severe congenital anomaly, genetic or metabolic disorder.
* Presence of an infection of the central nervous system.
* Parents \< 18 years old.
* Not being able to read one of the six Informed Consent languages.

Where this trial is running

Paris and 7 other locations

• Assistance Publique Hôpitaux de Paris — Paris, France (RECRUITING)
• University Hospital Essen — Essen, Germany (RECRUITING)
• Ospedale Pediatrico Meyer Firenze — Florence, Italy (RECRUITING)
• Istituto Giannina Gaslini — Genova, Italy (NOT_YET_RECRUITING)
• Ospedale Maggiore di Milano — Milan, Italy (RECRUITING)
• Fondazione Stella Maris — Pisa, Italy (RECRUITING)
• UMC Utrecht — Utrecht, Netherlands (RECRUITING)
• University Hospital La Paz — Madrid, Spain (RECRUITING)

Conditions: Cerebral Palsy, cerebral palsy, machine learning, diagostic tool