Network based statistics reveals trophic and neuroprotective effect of early high dose erythropoetin on brain connectivity in very preterm infants

Abstract

Periventricular white matter injury is common in very preterm infants and it is associated with long term neurodevelopmental impairments. While evidence supports the protective effects of erythropoetin (EPO) in preventing injury, we currently lack the complete understanding of how EPO affects the emergence and maturation of anatomical brain connectivity and function. In this case-control study, connectomic analysis based on diffusion MRI tractography was applied to evaluate the effect of early high-dose EPO in preterm infants. A whole brain, network-level analysis revealed a sub-network of anatomical brain connections in which connectivity strengths were significantly stronger in the EPO group. This distributed network comprised connections predominantly in the frontal and temporal lobe bilaterally, and the effect of EPO was focused on the peripheral and feeder connections. EPO resulted in a globally increased clustering coefficient and higher local efficiency, while higher strength, efficiency and increased clustering was found for regions in the temporal lobe, supramarginal gyrus, inferior frontal gyrus, in the caudate and cingulate gyri. The connectivity network most affected by the EPO treatment showed a steeper increase in FA with age compared to the placebo group. These results demonstrate a weak but widespread effect of EPO on the structural connectivity network and a possible trophic effect of EPO reflected by increasing network segregation, predominantly in local connections.