Abstract
ObjectivePremature birth is associated with numerous complex abnormalities of white and gray matter and a high incidence of long‐term neurocognitive impairment. An integrated understanding of these abnormalities and their association with clinical events is lacking. The aim of this study was to identify specific patterns of abnormal cerebral development and their antenatal and postnatal antecedents.MethodsIn a prospective cohort of 449 infants (226 male), we performed a multivariate and data‐driven analysis combining multiple imaging modalities. Using canonical correlation analysis, we sought separable multimodal imaging markers associated with specific clinical and environmental factors and correlated to neurodevelopmental outcome at 2 years.ResultsWe found five independent patterns of neuroanatomical variation that related to clinical factors including age, prematurity, sex, intrauterine complications, and postnatal adversity. We also confirmed the association between imaging markers of neuroanatomical abnormality and poor cognitive and motor outcomes at 2 years.InterpretationThis data‐driven approach defined novel and clinically relevant imaging markers of cerebral maldevelopment, which offer new insights into the nature of preterm brain injury. Ann Neurol 2017;82:233–246
Highlights
Separate from these effects, the analysis revealed unexpected patterns of abnormality associated with sex and antenatal and postnatal adversity, a number of which were associated with neurodevelopmental outcome at 2 years corrected age
We have provided interactive multimodal statistical maps to allow researchers to explore these rich data in detail, and here we offer an initial appreciation of the clinical-anatomical correlations
It is well established that brain growth and development during the preterm period is characterized by increases in brain tissue volume and white matter fractional anisotropy (FA), alongside decreasing cortical diffusivity and T2 signal intensity.[7,8,31,32]
Summary
Premature birth is associated with numerous complex abnormalities of white and gray matter and a high incidence of long-term neurocognitive impairment. We sought separable multimodal imaging markers associated with specific clinical and environmental factors and correlated to neurodevelopmental outcome at 2 years. We use data-driven, multivariate methods to test the hypothesis that brain development is altered by multiple environmental factors interacting with early extrauterine exposure following preterm birth. We combined independent component analysis (ICA) and canonical correlation analysis (CCA) to identify associations between a set of clinical/environmental risk factors and brain development in preterm infants defined using T1-weighted (T1w), T2-weighted (T2w), and diffusion MRI. We found a set of novel patterns of brain abnormality associated with specific clinical risk factors and correlated with cognitive and motor outcomes at 2 years
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