Objective: Caffeine improves neurological outcome in very preterm infants, but the mechanisms responsible for this neurological benefit are unknown. The objective of this study was to assess whether caffeine influenced brain macro- or microstructural development in preterm infants.
Methods: Seventy preterm infants <1,251 g birthweight randomly allocated to either caffeine (n = 33) or placebo (n = 37) underwent brain magnetic resonance imaging (MRI) at term-equivalent age; white and gray matter abnormalities were qualitatively scored, global and regional brain volumes were measured, and white matter microstructure was evaluated using diffusion-weighted imaging.
Results: There were no significant differences between the groups in the extent of white matter or gray matter abnormality, or in global or regional brain volumes. In contrast, although only available in 28 children, caffeine exposure was associated with reductions in the apparent diffusion coefficient, and radial and axial diffusivity with the greatest impact in the superior brain regions. The alterations in diffusion measures were not mediated by lowering the rate of lung injury, known as bronchopulmonary dysplasia.
Interpretation: These diffusion changes are consistent with improved white matter microstructural development in preterm infants who received caffeine.