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Title: Diffusion tensor MRI of white matter of healthy full-term newborns: Relationship to neurodevelopmental outcomes

Author
item FENG, KAIYANG - University Arkansas For Medical Sciences (UAMS)
item ROWELL, AMY - University Arkansas For Medical Sciences (UAMS)
item ANDRES, ALINE - University Arkansas For Medical Sciences (UAMS)
item BELLANDO, BETTY JAYNE - University Arkansas For Medical Sciences (UAMS)
item LOU, XIANGYANG - University Arkansas For Medical Sciences (UAMS)
item GLASIER, CHARLE - University Arkansas For Medical Sciences (UAMS)
item RAMAKRISHNAIAH, RAGHU - University Arkansas For Medical Sciences (UAMS)
item Badger, Thomas
item OU, XIAWEI - University Arkansas For Medical Sciences (UAMS)

Submitted to: Radiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/9/2019
Publication Date: 6/4/2019
Citation: Feng, K., Rowell, A.C., Andres, A., Bellando, B., Lou, X., Glasier, C.M., Ramakrishnaiah, R.H., Badger, T.M., Ou, X. 2019. Diffusion tensor MRI of white matter of healthy full-term newborns: Relationship to neurodevelopmental outcomes. Radiology. https://doi.org/10.1148/radiol.2019182564.
DOI: https://doi.org/10.1148/radiol.2019182564

Interpretive Summary: It is well-known that early brain white matter injury can lead to issues in later neurodevelopment in children. However, it is not clear whether white matter developmental variations in healthy newborns are also associated with changes in neurodevelopmental outcomes. White matter (composed largely of myelinated neurons) refers to areas of the brain that, through tracts (axons), connect important regions involved in learning and other functions. Studies at ACNC have identified small changes in white matter in healthy newborns associated with maternal obesitybut more knowledge is needed to understand the implications of these small changes in the newborn brain to long-term cognitive outcomes in children. In this study, we used magnetic resonance imaging (MRI) to measure brain white matter development in newborns, and then used Bayley Scales of Infant Development to test neurodevelopmental outcome at ~2 years of age. We found that white matter integrity in several regions of the newborn brain (e.g., in the corpus callosum which connects left and right brain, and in the projection fibers which connect deep brain to brain cortex) significantly correlated with cognitive, language, and motor ability at age 2 years. These findings indicate that brain white matter developmental status at the newborn stage is very important for later neurodevelopment and cognitive outcomes. This is despite the rapid growth of brain during infancy and many factors after birth that may also affect brain development. Thus, early-life factors that impact white matter growth and development during infancy may have long-term consequences for brain function in healthy young children.

Technical Abstract: It is well known that white matter injuries observed at birth are associated with adverse neurodevelopmental outcomes later in life. Whether or not white matter developmental variations in healthy newborns are also associated with changes in neurodevelopmental outcomes remains to be established. In this prospective study, 38 healthy full-term newborns underwent an MRI examination of the brain including diffusion tensor imaging (DTI) at age ~2 weeks, and a Bayley Scales of Infant Development (BSID) test at age ~2 years. Voxel-wise correlation analyses of DTI measured fractional anisotropy (FA, a reflection of white matter integrity) and BSID measured neurodevelopmental test scores were performed using tract-based spatial statistics (TBSS), followed by region-of-interest (ROI) analyses of correlations between mean FA in selected white matter ROIs and each BSID subscale score (cognitive, language, motor, socioemotional and adaptive behavior). TBSS analyses showed widespread clusters in major white matter tracts with positive correlations (P < 0.05, corrected for the voxel-wise multiple comparisons) between FA at age 2 weeks and multiple BSID subscale scores at age 2 years. These correlations were independent to a number of demographic parameters of the infants (and their mothers) as well as family environment. Gestational age at birth appeared to be a true confounding factor for these correlations; however, after controlling for it, ROI analyses still showed positive correlations (P < 0.05) between mean FA in many white matter ROIs and BSID cognitive, language, and motor scores. Despite brain plasticity in growth and many potential postnatal influences during infancy, newborn's brain white matter developmental status may still be a strong indicator of later neurodevelopmental outcomes, even for the healthy infant population.