Neonatal Brain Microstructure and Machine-Learning-Based Prediction of Early Language Development in Children Born Very Preterm

Abstract

BackgroundVery-low-birth-weight preterm infants have a higher rate of language impairments compared with children born full term. Early identification of preterm infants at risk for language delay is essential to guide early intervention at the time of optimal neuroplasticity. This study examined near-term structural brain magnetic resonance imaging (MRI) and white matter microstructure assessed on diffusion tensor imaging (DTI) in relation to early language development in children born very preterm. MethodsA total of 102 very-low-birth-weight neonates (birthweight≤1500g, gestational age ≤32-weeks) were recruited to participate from 2010 to 2011. Near-term structural MRI was evaluated for white matter and cerebellar abnormalities. DTI fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were assessed. Language development was assessed with Bayley Scales of Infant-Toddler Development-III at 18 to 22 months adjusted age. Multivariate models with leave-one-out cross-validation and exhaustive feature selection identified three brain regions most predictive of language function. Distinct logistic regression models predicted high-risk infants, defined by language scores >1 S.D. below average. ResultsOf 102 children, 92 returned for neurodevelopmental testing. Composite language score mean ± S.D. was 89.0 ± 16.0; 31 of 92 children scored <85, including 15 of 92 scoring <70, suggesting moderate-to-severe delay. Children with cerebellar asymmetry had lower receptive language subscores (P = 0.016). Infants at high risk for language impairments were predicted based on regional white matter microstructure on DTI with high accuracy (sensitivity, specificity) for composite (89%, 86%), expressive (100%, 90%), and receptive language (100%, 90%). ConclusionsMultivariate models of near-term structural MRI and white matter microstructure on DTI may assist in identification of preterm infants at risk for language impairment, guiding early intervention.