Abstract
Background
To assess whether postnatal plasma cholesterol levels are associated with microstructural and macrostructural regional brain development in preterm newborns.
Methods
Sixty preterm newborns (born 24–32 weeks gestational age) were assessed using MRI studies soon after birth and again at term-equivalent age. Blood samples were obtained within 7 days of each MRI scan to analyze for plasma cholesterol and lathosterol (a marker of endogenous cholesterol synthesis) levels. Outcomes were assessed at 3 years using the Bayley Scales of Infant Development, Third Edition.
Results
Early plasma lathosterol levels were associated with increased axial and radial diffusivities and increased volume of the subcortical white matter. Early plasma cholesterol levels were associated with increased volume of the cerebellum. Early plasma lathosterol levels were associated with a 2-point decrease in motor scores at 3 years.
Conclusions
Higher early endogenous cholesterol synthesis is associated with worse microstructural measures and larger volumes in the subcortical white matter that may signify regional edema and worse motor outcomes. Higher early cholesterol is associated with improved cerebellar volumes. Further work is needed to better understand how the balance of cholesterol supply and endogenous synthesis impacts preterm brain development, especially if these may be modifiable factors to improve outcomes.
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Acknowledgments
The authors would like to dedicate this manuscript to late Sheila M. Innis, RD, PhD and thank her for her guidance and mentorship. The authors also thank Roger Dyer for his assistance with analyzing blood samples for cholesterol and lathosterol levels for this study after Dr. Innis’ passing. The authors also thank Kenneth J. Poskitt, MD, FRCPC for his assistance in reviewing MRI scans at the University of British Columbia study site. The authors also thank the families and children who have participated in this study. The study was supported by the Gerber Foundation (Fremont, MI) [EWYT], Canadian Institutes for Health Research (CIHR) CHI 151135 [to S.P.M.], National Institutes of Health (NIH) NIH R01 NS046432 [to A.J.B.], and NIH P01 NS082330 [to D.X.]. The funders had no role in study design, data collection, analysis or interpretation, decision to publish, or preparation of the manuscript.
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Kamino, D., Chau, V., Studholme, C. et al. Plasma cholesterol levels and brain development in preterm newborns. Pediatr Res 85, 299–304 (2019). https://doi.org/10.1038/s41390-018-0260-0
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DOI: https://doi.org/10.1038/s41390-018-0260-0
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