Pathogenesis of Preterm Intraventricular Haemorrhage

Intraventricular haemorrhage (IVH) is the primary neuropathology in infants born very preterm. IVH describes bleeding into the ventricular space of the newborn brain, originating from the germinal matrix, termed germinal matrix haemorrhage. IVH is diagnosed at a rate of 1 in 5 infants born very preterm (less than 32 weeks' gestation), but the incidence increases with earlier gestation at birth. IVH is graded in severity (I to IV), and the neurological sequelae of IVH in infants born very preterm are significant, with more than 1 in 4 infants with any grade of IVH subsequently diagnosed with a moderate to severe neurodevelopmental deficit, increasing to more than half of infants diagnosed with severe IVH (grade III/IV).

The high susceptibility to IVH in infants born at less than 32 weeks' arises in part to the presence of the germinal matrix. The germinal matrix is a transient brain region that produces neural stem and progenitor cells. The germinal matrix region is rich in angiogenic blood vessels that have a low density of pericyte and astrocyte coverage to provide structural stability, and it is a border zone for vascular endpoints that are highly fragile to haemodynamic instability. In addition to immaturity, antenatal complications may also adversely impact cerebrovascular development, pericyte and astrocyte coverage, and subsequently the structural integrity of the blood-brain barrier that might increase the risk for IVH.

Here, we will report the maturational profile of cerebrovascular development in the extremely preterm neonate, and implications for susceptibility to IVH, the complications that may contribute to the risk of haemorrhage, and neurodevelopmental deficits that primarily arise from IVH. We aimed to elucidate the cellular foundations of IVH to provide insight into neuroprotective targets.