Abstract
We aimed to evaluate diffusion tensor imaging (DTI) in infants born extremely preterm, to determine the effect of erythropoietin (Epo) on DTI, and to correlate DTI with neurodevelopmental outcomes at 2 years of age for infants in the Preterm Erythropoietin Neuroprotection (PENUT) Trial. Infants who underwent MRI with DTI at 36 weeks postmenstrual age were included. Neurodevelopmental outcomes were evaluated by Bayley Scales of Infant and Toddler Development (BSID-III). Generalized linear models were used to assess the association between DTI parameters and treatment group, and then with neurodevelopmental outcomes. A total of 101 placebo- and 93 Epo-treated infants underwent MRI. DTI white matter mean diffusivity (MD) was lower in placebo- compared to Epo-treated infants in the cingulate and occipital regions, and occipital white matter fractional isotropy (FA) was lower in infants born at 24–25 weeks vs. 26–27 weeks. These values were not associated with lower BSID-III scores. Certain decreases in clustering coefficients tended to have lower BSID-III scores. Consistent with the PENUT Trial findings, there was no effect on long-term neurodevelopment in Epo-treated infants even in the presence of microstructural changes identified by DTI.
Highlights
Advances in neonatology have led to unprecedented improvements in neonatal survival such that infants born at 22-0/7 to 25-6/7 weeks’ gestation have a 70% survival rate [1]
Diffusion tensor imaging (DTI) is an magnetic resonance imaging (MRI) technique that aims to clarify the microstructure of the brain by measuring the directionality and rate of water diffusion within the structures of an MRI voxel [13]
Of the 741 infants enrolled in the Preterm Erythropoietin Neuroprotection (PENUT) Trial, 469 infants were enrolled across eight designated MRI sites (229 placebo-treated and 240 Epo-treated), with approximately equal stratification within each group for 24–25 week and 26–27 week gestational age (GA)
Summary
Advances in neonatology have led to unprecedented improvements in neonatal survival such that infants born at 22-0/7 to 25-6/7 weeks’ gestation have a 70% survival rate [1]. Neurodevelopmental outcomes for extremely preterm (EP) infants have not improved at the same rate. At least 50% of infants born prematurely have qualitative evidence of cerebral white matter injury on magnetic resonance imaging (MRI) at term-equivalent age [6,7]. These gross white matter findings are correlated with increased risk of neurodevelopmental impairment (NDI), but they are limited in their ability to describe the exact structural and functional alterations responsible for these outcomes [8,9,10,11,12]. FA in grey matter decreases during the last trimester as does MD, reflecting an increase in cellular and synaptic complexity and density [16]
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