Neuroimaging in former preterm children who received erythropoiesis stimulating agents

Abstract

BackgroundIn premature children, erythropoiesis-stimulating agents (ESAs) may improve developmental outcome. It is not clear which of the several potential mechanisms are responsible for this improvement. High-resolution MRI and diffusion tensor imaging characterize brain structure and white matter organization, offering possible insight into the long-term effect of ESAs on brain development.MethodsMRI scans were performed at 3.5-4 years of age on former preterm infants treated with ESAs or placebo, and on healthy term controls. Mean cortical thickness, surface area, and fractional anisotropy (FA) were compared across study groups, and were correlated with general IQ measures.ResultsUnivariate analysis found no significant effect of ESAs on cortical thickness (P=0.366), surface area (P=0.940), or FA (P=0.150); however, there was a greater increase in FA among ESA-treated girls. Group analysis found significant correlations between FA and Full-Scale IQ (P=0.044) and Verbal IQ (P=0.036), although there was no significant relationship between Full-Scale IQ and FA among just the preterm children.ConclusionESA treatment may have a preferential effect on white matter development in girls, although factors other than just whole-brain FA are involved in mediating cognitive outcome.

Figure 1. ESA Treatment Effect On Fractional Anisotropy By Gender

Interaction of gender and group (Placebo, Treated) on global fractional anisotropy of white matter tracts. Fractional anisotropy principal component is expressed as a T score (mean for entire sample, including term, was 50, SD =10).

Figure 2. Fiber Tracts Most Affected By ESA Treatment In Girls

The four fiber tracts most affected by ESA treatment in girls were cingulum, anterior corona radiata, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus. Mean FA was calculated over each of these tracts as identified above.