Brain injury is highly associated with preterm birth. Complications of prematurity, including spontaneous or necrotizing enterocolitis (NEC)-associated intestinal perforations, are linked to lifelong neurologic impairment, yet the mechanisms are poorly understood. Early diagnosis of preterm brain injuries remains a significant challenge. Here, we identified subventricular zone echogenicity (SVE) on cranial ultrasound in preterm infants following intestinal perforations. The development of SVE was significantly associated with motor impairment at 2 years. SVE was replicated in a neonatal mouse model of intestinal perforation. Examination of the murine echogenic subventricular zone (SVZ) revealed NLRP3-inflammasome assembly in multiciliated FoxJ1+ ependymal cells and a loss of the ependymal border in this postnatal stem cell niche. These data suggest a mechanism of preterm brain injury localized to the SVZ that has not been adequately considered. Ultrasound detection of SVE may serve as an early biomarker for neurodevelopmental impairment after inflammatory disease in preterm infants. Display omitted •Subventricular zone echogenicity (SVE) is associated with intestinal perforations•SVE predicts motor impairment in preterm infants with intestinal perforation•Modeled intestinal perforation leads to ependymal inflammasome activation in mice•SVE is associated with permanent ependymal cell loss in the mouse subventricular zone Epstein and Janos et al. have identified subventricular zone echogenicity (SVE) in preterm infants with intestinal perforations. SVE was predictive of future motor impairment in affected infants. Using a mouse model, SVE was associated with an inflammatory injury to the ependymal layer that was associated with stem cell niche dysfunction.