Abnormal brain maturation in preterm neonates associated with adverse developmental outcomes

Objective: Our objective was to determine the association of early brain maturation with neurodevelopmental outcome in premature neonates. Methods: Neonates born between 24 and 32 weeks' gestation (April 2006 to August 2010) were prospectively studied with MRI early in life and again at term-equivalent age. Using diffusion tensor imaging and magnetic resonance spectroscopic imaging, fractional anisotropy (FA) (microstructure) and N-acetylaspartate (NAA)/choline (metabolism) were measured from the basal nuclei, white matter tracts, and superior white matter. Brain maturation is characterized by increasing FA and NAA/choline from early in life to term-equivalent age. In premature neonates, systemic illness and critical care therapies have been linked to abnormalities of these measures. Of the 177 neonates in this cohort, 5 died and 157 (91% of survivors) were assessed at 18 months' corrected age (adjusted for prematurity) using the Bayley Scales of Infant and Toddler Development III motor, cognitive, and language composite scores (mean = 100, SD = 15). Results: Among these 157 infants, white matter injury was seen in 48 (30%). Severe white matter injury, in 10 neonates (6%), was associated with a decrease in motor (-18 points; p < 0.001) and cognitive (-8 points; p = 0.085) scores. With greater severity of adverse neurodevelopmental outcomes, slower increases in FA and NAA/choline were observed in the basal nuclei and brain white matter regions as neonates matured to term-equivalent age, independent of the presence of white matter injury. Conclusions: In the preterm neonate, abnormal brain maturation evolves through the period of neonatal intensive care and is associated with adverse neurodevelopmental outcomes.