Increased risk of neurodevelopmental impairment associated with reduced brain volume at term-equivalent age in preterm infants with germinal matrix hemorrhage

To assess the association of low-grade germinal matrix–intraventricular hemorrhage (GM-IVH) with reduced supratentorial and white matter volumes at term-equivalent age, and to evaluate whether these volumes are related to neurodevelopmental impairment (NDI). This study included preterm infants (gestational age at birth < 37 weeks) who underwent cranial ultrasound within three days of birth and three-dimensional T1-weighted brain magnetic resonance imaging at 34–46 weeks’ postmenstrual age from December 2020 to August 2024. Participants were categorized into the control, GMH (Papile grades 1–2), and punctate white matter lesion (PWML) groups; infants with severe conditions were excluded. A U-Net-based algorithm was used to automatically segment supratentorial and white matter volumes. NDI was defined as a motor score ≤ 85 or cognitive and language scores both ≤ 85 on the Bayley-III. Standardized residuals were calculated to assess volume deviation from the sex-specific reference (control group) and compared according to low-grade GM-IVH and NDI status. A two-way analysis of variance with Tukey’s post hoc test was used for statistical comparison. A total of 171 infants (89 girls; gestational age, 28.32 ± 2.76 weeks; postmenstrual age, 37.81 ± 2.36 weeks) were included, with 119 in the control group, 41 in the GMH group, and 11 in the PWML group. The supratentorial volume-PMA slope was lower in the GMH and PWML groups than in the control group (19.37 cm³/week for control; 12.37 cm³/week for GMH, P = 0.02; 11.49 cm³/week for PWML, P = 0.04). In the GMH group, significant volume differences were observed between the NDI and non-NDI subgroups (standardized residuals: -1.12 ± 0.58 vs. 0.35 ± 0.69 for supratentorial volume; -0.95 ± 0.68 vs. 0.29 ± 0.92 for white matter volume; both P < 0.001), whereas no significant differences were found in the control group. Low-grade GM-IVH with reduced supratentorial or white matter volume is associated with an increased risk of NDI in preterm infants.