Clinical trial NCT02008045: MR Imaging of Perinatal Brain Injury
Official title: Advanced MR Imaging of Perinatal Brain Injury: Correlation with Neurocognitive Outcome
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Perinatal White Matter Brain Injury
Keywords: MRI
Imaging
Neurocognitive
White matter injury
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2013-12-11
Enrollment: 300
Sex: ALL
Minimum age (years): 1
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Participants will be enrolled between birth and 7 years of age.

Brief summary: The purpose of this study is to collect and compare information from cranial ultrasounds, magnetic resonance imaging scans, neurological exam and neuropsychological assessments of children. The investigators hope that the information collected in this study will help with early screening, diagnosis and treatment of brain injury in newborns as well as identify a connection between MR imaging (MRI-magnetic resonance imaging, MRS-magnetic resonance spectroscopy) and neurodevelopmental outcome.

Detailed description: In the last two decades, major advances have been made in the clinical care of premature and term infants, including in the management of sepsis and respiratory compromise that can contribute to neurological disabilities in survivors. The incidence of classic cystic periventricular leukomalacia (PVL) has declined and a more diffuse and non-cystic pattern of cerebral white matter injury is more predominant. Although multiple pathologies occur in premature infants, the principal variety accounting for the predominance of neurodevelopmental disability is PVL. This disability in very low birth weight infants (VLBW) (\< 1500 grams) includes cognitive/behavioral deficits in 25-50% and cerebral palsy in 5-10%. Neuroimaging studies of VLBW survivors suggest that the cerebral palsy is related to the focal necrotic lesions of PVL, whereas the cognitive/behavioral deficits correlate with more diffuse cerebral white matter injury. PVL is defined as damaged immature cerebral white matter with periventricular focal necrosis ("focal" component) in association with diffuse reactive gliosis and microglial activation in the surrounding white matter ("diffuse" component). Of note, PVL occurs in the late preterm infant and the term infant, particularly in cases of congenital heart disease. The pathogenesis of perinatal white matter injury is currently thought to be related to a complex interaction between maternal/fetal infection, cytokines and hypoxia-ischemia which results in both the generation of reactive oxygen specific agents (oxidative stress), apoptotic oligodendrocyte cell death, and axonal injury. In long-term survivors with PVL, neuroimaging studies often demonstrate reduced cerebral white matter volume, impaired myelination, ventriculomegaly and reduced volume in the cerebral cortex, thalamus/basal ganglia and cerebellum. In many of these long-term studies, the preterm children studies had normal cranial ultrasound. Cranial ultrasound, however, is not adequate for assessing non-cystic focal or diffuse white matter injury. To date, there are no longitudinal MR studies of preterm or congenital heart disease infants which correlate advanced neonatal MR imaging techniques with long-term neurodevelopmental outcome or advanced MR techniques performed in the childhood period.

Eligibility criteria: Inclusion Criteria:

* Preterm babies and neonates with congenital heart disease
* Term Neonates

Exclusion Criteria:

* Severe congenital brain malformation
* Significant chromosomal abnormality / syndrome which could confound the neurodevelopmental follow up data
* Preterm birth and congenital heart disease
* Focal neurological abnormality
* Chronic seizures
* Severe congenital brain malformation
* Significant chromosomal abnormality/ syndrome which could confound the neurodevelopmental follow up data
* Major pregnancy complication (diabetes, eclampsia)
* Sepsis
* ECMO
* Significant birth trauma and/or hypoxic ischemic injury

Primary outcomes:
measure: Developmental Assessment
timeFrame: 18 Months
Secondary outcomes:
measure: Assessment of White Matter Injury in Brain
timeFrame: Baseline
measure: Changes in White Matter Injury from Baseline
timeFrame: at 6 Years
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Ashok Panigrahy, MD
role: PRINCIPAL_INVESTIGATOR
References: