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

Objective: To evaluate diffuse white matter abnormality (DWMA) volume at term-equivalent age as an independent predictor of neurodevelopmental outcomes in preterm infants.

Study design: 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.

Results: 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.

Conclusions: 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.