Grant: CIHR Clinician Scientist - Phase 2

Neurodevelopmental impairments are common in newborns delivered prior to term age and result in a large burden of long-term disability. White matter injury, abnormal brain development and systemic illness are interrelated abnormalities that commonly follow preterm birth and may lead to adverse neurodevelopment. Focal non-cystic white matter injury is the characteristic pattern of brain injury in premature newborns. Though focal non-cystic white matter injury is associated with diffuse abnormalities of motor and cognitive function, how this happens is unknown. Systemic illness, such as infection, and therapy, such as postnatal corticosteroids, may also be associated with diffuse abnormalities of motor and cognitive function. The mechanisms by which these conditions cause abnormal outcome are largely unknown. Preliminary data suggest that white matter injury and specific systemic conditions, such as infection, diffusely impair brain development. The overall hypothesis of this prospective cohort study is that delayed brain development, due to systemic illness and white matter injury, results in abnormal motor and cognitive outcome. We will quantify brain development and injury in premature newborns using advanced magnetic resonance (MR) techniques shortly after birth and again at term-equivalent age: deformation tensor morphometry for anatomic brain structure, diffusion tensor imaging for brain connectivity and MR spectroscopic imaging for brain metabolism. A better understanding of the clinical factors that impact brain development and white matter injury will allow us to directly improve the neurodevelopmental outcome of premature newborns.