Brain Volumes at Term-Equivalent Age in Preterm Infants: Imaging Biomarkers for Neurodevelopmental Outcome through Early School Age

Keunen, Kristin, Išgum, Ivana, van Kooij, Britt J M, Anbeek, Petronella, van Haastert, Ingrid C, Koopman-Esseboom, Corine, van Stam, Petronella C, Nievelstein, Rutger A J, Viergever, Max A, de Vries, Linda S, Groenendaal, Floris, Benders, Manon J N L


Journal of Pediatrics 172 p. 88-95


OBJECTIVE: To evaluate the relationship between brain volumes at term and neurodevelopmental outcome through early school age in preterm infants.

STUDY DESIGN: One hundred twelve preterm infants (born mean gestational age 28.6 ± 1.7 weeks) were studied prospectively with magnetic resonance imaging (imaged at mean 41.6 ± 1.0 weeks). T2- and T1-weighted images were automatically segmented, and volumes of 6 tissue types were related to neurodevelopmental outcome assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (cognitive, fine, and gross motor scores) at 24 months corrected age (n = 112), Griffiths Mental Development Scales (developmental quotient) at age 3.5 years (n = 98), Movement Assessment Battery for Children, Second Edition (n = 85), and Wechsler Preschool and Primary Scale of Intelligence, Third Edition at age 5.5 years (n = 44). Corrections were made for intracranial volume, maternal education, and severe brain lesions.

RESULTS: Ventricular volumes were negatively related to neurodevelopmental outcome at age 24 months and 3.5 years, as well as processing speed at age 5.5 years. Unmyelinated white matter (UWM) volume was positively associated with motor outcome at 24 months and with processing speed at age 5.5 years. Cortical gray matter (CGM) volume demonstrated a negative association with motor performance and cognition at 24 months and with developmental quotient at age 3.5 years. Cerebellar volume was positively related to cognition at these time points. Adjustment for brain lesions attenuated the relations between cerebellar and CGM volumes and cognition.

CONCLUSIONS: Brain volumes of ventricles, UWM, CGM, and cerebellum may serve as biomarkers for neurodevelopmental outcome in preterm infants. The relationship between larger CGM volumes and adverse neurodevelopment may reflect disturbances in neuronal and/or axonal migration at the UWM-CGM boundary and warrants further investigation.