Moderate and late preterm infants exhibit widespread brain white matter microstructure alterations at term-equivalent age relative to term-born controls
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Despite the many studies documenting cerebral white matter microstructural alterations associated with very preterm birth (<32 weeks’ gestation), there is a dearth of similar research in moderate and late preterm infants (born 32–36 weeks’ gestation), who experience higher rates of neurodevelopmental delays than infants born at term (≥37 weeks’ gestation). We therefore aimed to determine whether whole brain white matter microstructure differs between moderate and late preterm infants and term-born controls at term-equivalent age, as well as to identify potential perinatal risk factors for white matter microstructural alterations in moderate and late preterm infants. Whole brain white matter microstructure was studied in 193 moderate and late preterm infants and 83 controls at term-equivalent age by performing Tract-Based Spatial Statistics analysis of diffusion tensor imaging data. Moderate and late preterm infants had lower fractional anisotropy and higher mean, axial and radial diffusivities compared with controls in nearly 70 % of the brain’s major white matter fiber tracts. In the moderate and late preterm group, being born small for gestational age and male sex were associated with lower fractional anisotropy, largely within the optic radiation, corpus callosum and corona radiata. In conclusion, moderate and late preterm infants exhibit widespread brain white matter microstructural alterations compared with controls at term-equivalent age, in patterns consistent with delayed or disrupted white matter microstructural development. These findings may underpin some of the neurodevelopmental delays observed in moderate and late preterm children.
KeywordsMagnetic resonance imaging Diffusion tensor imaging Tract-based spatial statistics Preterm birth Late preterm Neonate
We thank our research coordinator Emma McInnes, our research nurses, and the families for their willingness to participate in this study. We also acknowledge the expertise and efforts of the MRI technologists at the Melbourne Children’s MRI Centre, Royal Children’s Hospital, Melbourne.
This study was supported by the Australian National Health and Medical Research Council (Project Grant ID 1028822; Centre of Clinical Research Excellence Grant ID 546519; Centre of Research Excellence Grant ID 1060733; Senior Research Fellowship ID 1081288 to P.J.A.; Early Career Fellowship ID 1053787 to J.L.Y.C., ID 1053767 to A.J.S., ID 1012236 to D.K.T.), Murdoch Childrens Research Institute, Clinical Sciences Theme Grant, the Victorian Government Operational Infrastructure Support Program, and The Royal Children’s Hospital Foundation. The research of A.L. is supported by VIDI Grant 639.072.411 from The Netherlands Organisation for Scientific Research (NWO).
Conflict of interest
Claire E Kelly, Jeanie LY Cheong, Lillian Gabra Fam, Alexander Leemans, Marc L Seal, Lex W Doyle, Peter J Anderson, Alicia J Spittle and Deanne K Thompson declare that they have no conflict of interest.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, and the applicable revisions at the time of the investigation. Informed consent was obtained from all patients for being included in the study.
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