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Tract-based spatial statistics to assess the neuroprotective effect of early erythropoietin on white matter
Ruth L O'Gorman1, Hans U Bucher2, Ulrike Held3
11 MR Research Centre, Children's University Hospital of Zurich, Switzerland.
Insights
Early erythropoietin (EPO) treatment improved white matter development in preterm infants. This neuroprotective cytokine shows promise for preventing neurodevelopmental impairment in vulnerable newborns.
Area of Science:
- Neonatal Neurology
- Neuroimaging
- Developmental Neuroscience
Background:
- Preterm infants face significant risks of neurodevelopmental impairment despite improved survival rates.
- Current clinical practices lack effective neuroprotective therapies for preterm infants.
- Erythropoietin (EPO), a cytokine for anemia, exhibits potential neuroprotective and neuroregenerative properties in preclinical models.
Purpose of the Study:
- To evaluate the impact of recombinant human erythropoietin (rhEPO) on the microstructural development of cerebral white matter in preterm infants.
- To assess white matter integrity using advanced neuroimaging techniques at term equivalent age.
Main Methods:
- A randomized, double-blind, placebo-controlled multicenter study involving 58 preterm infants.
- Administration of rhEPO (3000 IU) or placebo intravenously within 42 hours of birth.
- High-resolution diffusion tensor imaging (DTI) at term equivalent age, analyzed with tract-based spatial statistics (TBSS).
Main Results:
- Infants receiving rhEPO showed significantly increased fractional anisotropy (FA) in key white matter tracts, including the corpus callosum and internal capsule.
- TBSS analysis revealed widespread improvements in white matter microstructure in the rhEPO group compared to placebo.
- Mean FA was significantly higher in the rhEPO-treated group (P < 0.001).
Conclusions:
- Early administration of recombinant human erythropoietin enhances white matter development in preterm infants.
- DTI and TBSS confirm the positive effects of rhEPO on cerebral white matter microstructure.
- This study suggests rhEPO as a potential therapeutic agent for improving neurodevelopmental outcomes in preterm infants.
Abstract:
Despite improved survival, many preterm infants undergo subsequent neurodevelopmental impairment. To date, no neuroprotective therapies have been implemented into clinical practice. Erythropoietin, a haematopoietic cytokine used for treatment of anaemia of prematurity, has been shown to have neuroprotective and neuroregenerative effects on the brain in many experimental studies. The aim of the study was to assess the effect of recombinant human erythropoietin on the microstructural development of the cerebral white matter using tract-based spatial statistics performed at term equivalent age. A randomized, double-blind placebo-controlled, prospective multicentre study applying recombinant human erythropoietin in the first 42 h after preterm birth entitled 'Does erythropoietin improve outcome in preterm infant' was conducted in Switzerland (NCT00413946). Preterm infants were given recombinant human erythropoietin (3000 IU) or an equivalent volume of placebo (NaCl 0.9%) intravenously before 3 h of age after birth, at 12-18 h and at 36-42 h after birth. High resolution diffusion tensor imaging was obtained at 3 T in 58 preterm infants with mean (standard deviation) gestational age at birth 29.75 (1.44) weeks, and at scanning at 41.1 (2.09) weeks. Imaging was performed at a single centre. Voxel-wise statistical analysis of the fractional anisotropy data was carried out using tract-based spatial statistics to test for differences in fractional anisotropy between infants treated with recombinant human erythropoietin and placebo using a general linear model, covarying for the gestational age at birth and the corrected gestational age at the time of the scan. Preterm infants treated with recombinant human erythropoietin demonstrated increased fractional anisotropy in the genu and splenium of the corpus callosum, the anterior and posterior limbs of the internal capsule, and the corticospinal tract bilaterally. Mean fractional anisotropy was significantly higher in preterm infants treated with recombinant human erythropoietin than in those treated with placebo (P < 0.001). We conclude that early recombinant human erythropoietin administration improves white matter development in preterm infants assessed by diffusion tensor imaging and tract-based spatial statistics.
