Altered corpus callosum development and corpus callosum-cerebellar spatial relationships in preterm infants at...

Preterm (PT) birth disrupts critical third-trimester brain maturation, particularly affecting the corpus callosum (CC) and cerebellum. As interconnected components of cerebro-cerebellar networks, their developmental trajectories and spatial relationships remain incompletely understood. This study used serial cranial ultrasonography to characterize these alterations from birth to term-equivalent age (TEA).

This prospective observational study included 117 neonates, comprising 60 term infants and 57 PT infants. A total of 719 cranial ultrasound examinations were analyzed. PT infants underwent serial weekly ultrasonography from birth to 40 weeks' corrected gestational age (CGA), whereas term infants were examined within the same TEA window. CC morphometry, including CC length (CCL), CC curve length (CCCL), height, area, and thickness, CC-fastigium length (CCFL), CC-fastigium angle (CCFA), and vermis morphometry were measured. Developmental trajectories were assessed using nonlinear regression, segmented linear regression, and linear mixed-effects models. Multivariable regression was used to identify factors independently associated with morphometric outcomes.

At TEA, the PT infants had shorter CCL (39.8±2.3 vs. 42.5±3.8 mm, adjusted P=0.015), shorter CCCL (53.7±6.0 vs. 68.5±17.4 mm, adjusted P=0.004), smaller vermis area (400.3±94.6 vs. 455.9±81.1 mm², adjusted P=0.041), shorter CCFL (42.1±10.3 vs. 48.6±3.0 mm, adjusted P<0.001), and larger CCFA (43.1±6.8° vs. 33.6±4.5°, adjusted P<0.001) than the term controls. In the PT infants, segmented regression showed rapid CCL growth before 35 weeks' CGA (1.04 mm/week, P<0.001), followed by no significant linear growth thereafter (P=0.059). CCFL continued to increase after 35 weeks but at a slower rate (0.55 mm/week, P<0.001), whereas CCFA showed an exploratory nonlinear trajectory. In the multivariable analysis, PT birth was independently associated with shorter CCL [β=-2.30, 95% confidence interval (CI): -4.15 to -0.46, P=0.015] and larger CCFA (β=7.04, 95% CI: 3.60-10.48, P<0.001).

PT birth is associated with quantitatively measurable alterations in CC development, cerebellar vermis size, and CC-cerebellar spatial configuration at TEA. Serial cranial ultrasonography captured divergent postnatal growth trajectories, including a late-PT inflection in CC growth and persistent enlargement of CCFA. These findings support ultrasound-based longitudinal morphometric monitoring of postnatal brain development in PT infants.