Plasma cholesterol levels and brain development in preterm newborns

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.

Figure 1.. Diffusion tensor imaging and regions of interest.

The anisotropy color maps of an infant born at 26-6/7 weeks gestational age and scanned at 29-3/7 weeks postmenstrual age are presented in two axial planes to demonstrate the regions of interest. Regions of interest in the (1) anterior, (2) central, and (3) posterior cortical white matter were averaged for analysis of cortical white matter. Regions of interest in the (4) basal ganglia and (6) thalamus were averaged for analysis of deep grey matter. Other regions of interest included the (5) posterior limb of the internal capsul and the (7) optic radiations. Colors display the predominant diffusion directions, with red representing right-left, green representing anterior-posterior, and blue presenting superior-inferior directions.