Diffuse white matter abnormality is independently predictive of neurodevelopmental outcomes in preterm infants

To evaluate diffuse white matter abnormality (DWMA) volume at term-equivalent age as an independent predictor of neurodevelopmental outcomes in preterm infants. In this multicentre prospective cohort study, 392 preterm infants (≤32 weeks' gestation) underwent term-equivalent MRI with automated DWMA quantification. The primary outcome was cognitive function at 3 years corrected age using the Differential Ability Scales-II General Conceptual Ability (GCA) score. Secondary outcomes included motor function (Bayley-III) and cerebral palsy (CP) at 2 years. Multivariable regression analysed DWMA's prognostic value. Follow-up was available for 89% (GCA) and 87% (Bayley-III/CP) of participants (mean gestational age 29 (SD: 2.5 weeks). Mean GCA was 94 (20.2); Bayley motor composite was 93 (14.5). CP was diagnosed in 12% of children (28 Gross Motor Function Classification System level I, six level II and III and five level IV and V). Higher DWMA volume independently predicted lower cognitive (β=-1.9; 95% CI -3.7 to -0.1), though only marginally over existing predictors (p=0.04), and motor scores (β=-2.0; 95% CI -3.3 to -0.7; p=0.003) and increased CP risk (adjusted OR=1.7; 95% CI 1.2 to 2.4; p=0.003) after controlling for clinical and socioeconomic factors. Socioeconomic disadvantages have amplified DWMA's adverse effects. This first external validation study demonstrates that objective DWMA quantification independently predicts multiple developmental outcomes through age 3 in preterm infants. The findings validate DWMA's pathological significance and support its utility as an early biomarker for risk stratification and targeted intervention.