Objective To determine associations between body composition and concurrent measures of brain development including (1) Tissue-specific brain volumes and (2) White matter microstructure, among very preterm infants at term equivalent age.

Design Prospective observational study.

Setting Single-centre academic level III neonatal intensive care unit.

Patients We studied 85 infants born <33 weeks’ gestation.

Methods At term equivalent age, infants underwent air displacement plethysmography to determine body composition, and brain MRI from which we quantified tissue-specific brain volumes and fractional anisotropy (FA) of white matter tracts. We estimated associations of fat and lean mass Z-scores with each brain outcome, using linear mixed models adjusted for intrafamilial correlation among twins and potential confounding variables.

Results Median gestational age was 29 weeks (range 23.4–32.9). One unit greater lean mass Z-score was associated with larger total brain volume (10.5 cc, 95% CI 3.8 to 17.2); larger volumes of the cerebellum (1.2 cc, 95% CI 0.5 to 1.9) and white matter (4.5 cc, 95% CI 0.7 to 8.3); and greater FA in the left cingulum (0.3%, 95% CI 0.1% to 0.6%), right uncinate fasciculus (0.2%, 95% CI 0.0% to 0.5%), and right posterior limb of the internal capsule (0.3%, 95% CI 0.03% to 0.6%). Fat Z-scores were not associated with any outcome.

Conclusions Lean mass—but not fat—at term was associated with larger brain volume and white matter microstructure differences that suggest improved maturation. Lean mass accrual may index brain growth and development.