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.