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Title: Gestational age at birth and brain white matter development in term-born infants and children

Author
item OU, XIAWEI - Arkansas Children'S Nutrition Research Center (ACNC)
item GLASIER, CHARLES - University Arkansas For Medical Sciences (UAMS)
item RAMAKRISHNAIAH, RAGHU - Arkansas Children'S Nutrition Research Center (ACNC)
item KANIF, ALISA - Arkansas Children'S Nutrition Research Center (ACNC)
item ROWELL, A - Arkansas Children'S Hospital
item PIVIK, R - Arkansas Children'S Nutrition Research Center (ACNC)
item ANDRES, ALINE - Arkansas Children'S Nutrition Research Center (ACNC)
item CLEVES, M - Arkansas Children'S Nutrition Research Center (ACNC)
item Badger, Thomas

Submitted to: American Journal of Neuroradiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/22/2017
Publication Date: 12/1/2017
Citation: Ou, X., Glasier, C.M., Ramakrishnaiah, R.H., Kanif, A., Rowell, A.C., Pivik, R.T., Andres, A., Cleves, M.A., Badger, T.M. 2017. Gestational age at birth and brain white matter development in term-born infants and children. American Journal of Neuroradiology. 38(12):2373-2379. http://doi.org/10.3174/ajnr.A5408.
DOI: https://doi.org/10.3174/ajnr.A5408

Interpretive Summary: The length of gestational age (the length of time a baby is in the womb prior to birth) is critical to brain development, and may influence how factors such as maternal obesity, metabolic health, and postnatal diet impact long-term brain function of children. Brain white matter differences are reported in healthy adolescents who were born prematurely compared to those who were born full-term (defined as 37-41 weeks of completed gestation). Conventionally, there has been no concern for children's later growth and development once the gestation at birth reaches term (>=37 weeks). However, recently there is an emergence of literature to show that length of gestation for term-born (37-41 weeks of completed gestation) children may also have effects on their neurodevelopment and cognitive performance. Few studies have directly looked into the effects of gestation time for term-born children using advanced neuroimaging methods. In this study, we used diffusion tensor imaging (a magnetic resonance imaging method which is very sensitive to brain white matter abundance) to study term-born, healthy 2-week-old infants and 8-year-old children to determine if there are associations between gestational age at birth and white matter structures. We found that longer gestational length during the normal term period positively correlated with greater white matter integrity in the 2-week-old term infants but not in the 8-year-old term-born children. Our results suggested that longer gestation (even for those regarded as born full-term) may benefit infant brain white matter development. This benefit is not apparent by the time children reach age 8 years, presumably because of catch-up effects or influences of other factors after birth. Future studies intend to further investigate how gestation length in normal term birth affects brain grey matter (another component of the brain that contains mainly neuronal cell bodies and processes neural signals). These studies highlight that interpretations related to the effects of maternal obesity, health and nutrition, or a child's postnatal diet on brain development must also take into consideration the important role of gestation time.

Technical Abstract: Studies on infants and children born preterm have shown that adequate gestational length is critical for brain white matter development. Less is known regarding how variations in gestational age at birth in term infants and children affect white matter development, which was evaluated in this study. Using DTI tract-based spatial statistics methods, we evaluated white matter microstructures in 2 groups of term-born (>=37 weeks of gestation) healthy subjects: 2-week-old infants (n = 44) and 8-year-old children (n = 63). DTI parameters including fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were calculated by voxelwise and ROI methods and were correlated with gestational age at birth, with potential confounding factors such as postnatal age and sex controlled. Fractional anisotropy values, which are markers for white matter microstructural integrity, positively correlated (P < .05, corrected) with gestational age at birth in most major white matter tracts/regions for the term infants. Mean diffusivity values, which are measures of water diffusivities in the brain, and axial and radial diffusivity values, which are markers for axonal growth and myelination, respectively, negatively correlated (P < .05, corrected) with gestational age at birth in all major white matter tracts/regions excluding the body and splenium of the corpus callosum for the term infants. No significant correlations with gestational age were observed for any tracts/regions for the term-born 8-year-old children. Our results indicate that longer gestation during the normal term period is associated with significantly greater infant white matter development (as reflected by higher fractional anisotropy and lower mean diffusivity, axial diffusivity, and radial diffusivity values); however, similar associations were not observable in later childhood.