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.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Study Section
Developmental Brain Disorders Study Section (DBD)
Program Officer
Raju, Tonse N
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Washington University
Schools of Medicine
Saint Louis
United States
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Vesoulis, Zachary A; Rhoades, Janine; Muniyandi, Pournika et al. (2017) Delayed cord clamping and inotrope use in preterm infants. J Matern Fetal Neonatal Med :1-8
Ryckman, Justin; Hilton, Claudia; Rogers, Cynthia et al. (2017) Sensory processing disorder in preterm infants during early childhood and relationships to early neurobehavior. Early Hum Dev 113:18-22
Rogers, Cynthia E; Sylvester, Chad M; Mintz, Carrie et al. (2017) Neonatal Amygdala Functional Connectivity at Rest in Healthy and Preterm Infants and Early Internalizing Symptoms. J Am Acad Child Adolesc Psychiatry 56:157-166
Sylvester, Chad M; Smyser, Christopher D; Smyser, Tara et al. (2017) Cortical Functional Connectivity Evident After Birth and Behavioral Inhibition at Age 2. Am J Psychiatry :appiajp201717010018
Smyser, Christopher D; Snyder, Abraham Z; Shimony, Joshua S et al. (2016) Resting-State Network Complexity and Magnitude Are Reduced in Prematurely Born Infants. Cereb Cortex 26:322-333
Shimony, Joshua S; Smyser, Christopher D; Wideman, Graham et al. (2016) Comparison of cortical folding measures for evaluation of developing human brain. Neuroimage 125:780-790
Rogers, Cynthia E; Smyser, Tara; Smyser, Christopher D et al. (2016) Regional white matter development in very preterm infants: perinatal predictors and early developmental outcomes. Pediatr Res 79:87-95
Dunsirn, Sonya; Smyser, Christopher; Liao, Steve et al. (2016) Defining the nature and implications of head turn preference in the preterm infant. Early Hum Dev 96:53-60
Pineda, Roberta G; Reynolds, Lauren C; Seefeldt, Kristin et al. (2016) Head Lag in Infancy: What Is It Telling Us? Am J Occup Ther 70:7001220010p1-8
Smyser, Christopher D; Dosenbach, Nico U F; Smyser, Tara A et al. (2016) Prediction of brain maturity in infants using machine-learning algorithms. Neuroimage 136:1-9

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