Novel Diffuse White Matter Abnormality Biomarker at Term-Equivalent Age Enhances Prediction of Long-term Motor Development in Children Born Very Preterm

ABSTRACT Our objective was to evaluate the independent prognostic value of a novel MRI biomarker – objectively diagnosed diffuse white matter abnormality volume (DWMA; diffuse excessive high signal intensity) – for prediction of motor outcomes in very preterm infants. We prospectively enrolled a geographically-based cohort of very preterm infants without severe brain injury and born before 32 weeks gestational age. Structural brain MRI was obtained at term-equivalent age and DWMA volume was objectively quantified using a published validated algorithm. These results were compared with visually classified DWMA. We used multivariable linear regression to assess the value of DWMA volume, independent of known predictors, to predict motor development as assessed using the Bayley Scales of Infant & Toddler Development, Third Edition at 3 years of age. The mean (SD) gestational age of the cohort was 28.3 (2.4) weeks. In multivariable analyses, controlling for gestational age, sex, and abnormality on structural MRI,DWMA volume was an independent prognostic biomarker of Bayley Motor scores ( β = –12.59 [95% CI: –18.70, –6.48] R 2 =0.41). Conversely, visually classified DWMA was not predictive of motor development. In conclusion, objectively quantified DWMA is an independent prognostic biomarker of long-term motor development in very preterm infants and warrants further study.