Preterm birth is a major public-health issue because of its increasing incidence combined with the frequent occurrence of subsequent behavioral, neurological, and psychiatric challenges faced by surviving infants. Approximately 10-15% of very preterm children (born <30 weeks gestational age) develop cerebral palsy, and 30 - 60% of very preterm children experience cognitive impairments. These impairments include visual-motor problems, attentional difficulties, impaired memory, delayed acquisition of language, executive dysfunction, learning disabilities, poor social skills, and higher rates of social withdrawal, anxiety and depression. In addition, an increased prevalence of developmental disorders such as attention deficit/hyperactivity disorder, autism and schizophrenia, has been described in the preterm population. These adverse outcomes are related to white matter (WM) and grey matter (GM) injury sustained during the neonatal period and its effects on subsequent brain development. We seek to develop imaging biomarkers, measurable during infancy, that provide sensitivity and specificity in identifying infants at risk for poor neurodevelopmental outcome. The biomarkers will consist of the following magnetic resonance (MR) imaging measures: 1) conventional T1- and T2-weighted images, 2) volumetry (volumes for cortical GM, deep nuclear GM, myelinated WM, unmyelinated WM, and cerebrospinal fluid), 3) diffusion tensor imaging (apparent diffusion coefficient, relative anisotropy, axial and radial diffusivity), and 4) surface-based morphometry (integrated folding index, average sulcal depth, cortical surface area, percentage of buried cortex). The main cohort of this study will consist of 120 very preterm infants born <30 weeks gestational age. They will undergo MR studies soon after birth, at 30 weeks postmenstrual age (PMA), 34 weeks PMA, and term equivalent. Infants enrolled during Year 1 (n = 30) will also be imaged at age 4 years. The MR indices listed above will be compared with MR data from healthy control subjects and clinical outcome data obtained at term equivalent and 2 and 4 years of age. The proposed studies are designed to engender a deeper understanding of the nature and timing of cerebral injury, laying the groundwork for the development of neuroprotective strategies and improving clinical practices. The longitudinal design will allow us to study both structural abnormalities and compensatory changes in response to injury. Identification during the newborn period of infants at high risk for poor developmental outcome will allow early targeting of therapy services to these infants. If successful, the proposed studies will lead to improved outcomes for prematurely-born infants. Project Narrative: This study is designed to use magnetic resonance imaging to improve our understanding of the brain injury sustained by prematurely-born infants. This understanding has the potential to improve clinical practices and assist with the development of medications to reduce injury in these babies, ultimately reducing disabilities. It will also help identify those infants who are at high risk for developing cerebral palsy or mental retardation so they can be provided early access to therapy services.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD057098-05
Application #
8245159
Study Section
Developmental Brain Disorders Study Section (DBD)
Program Officer
Raju, Tonse N
Project Start
2008-04-01
Project End
2013-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
5
Fiscal Year
2012
Total Cost
$573,612
Indirect Cost
$174,736
Name
Washington University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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Engelhardt, Erin; Inder, Terrie E; Alexopoulos, Dimitrios et al. (2015) Regional impairments of cortical folding in premature infants. Ann Neurol 77:154-62

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