Intraventricular haemorrhage and posthaemorrhagic hydrocephalus: pathogenesis, prevention and future interventions

Intraventricular haemorrhage (IVH) is still a major complication of preterm birth with serious disability resulting. The fragile blood vessels in the germinal matrix below the ventricular lining and the instability of blood flow to this highly vascular area are the main mechanisms behind IVH. There is good evidence that corticosteroid therapy before preterm delivery reduces mortality and IVH substantially with a trend towards a reduction in disability. There is good evidence that postnatal indomethacin reduces IVH but no evidence that mortality or disability is reduced. There is evidence that stabilizing cerebral blood flow with pancuronium in infants with respiratory distress reduces IVH in the minority of infants with marked fluctuations. There is limited evidence that postnatal vitamin E and ethamsylate reduce IVH but insufficient evidence of reduced mortality or disability. Hydrocephalus following IVH results initially from multiple small blood clots throughout the CSF channels impeding circulation and re-absorption. Transforming growth factor beta is released into the CSF and there is mounting evidence that this cytokine stimulates the laying down of extracellular matrix proteins such as laminin and fibronectin which produce permanent obstruction to the CSF pathways. Interventions such as early lumbar punctures, diuretic drugs to reduce CSF production and intraventricular fibrinolytic therapy have been tested and, not only fail to prevent shunt dependence, death or disability, but have significant adverse effects. Surgical interventions such as subcutaneous reservoir and external drain have not been subject to controlled trial. Ventriculoperitoneal shunt is not feasible in the early phase after IVH but, despite the problems with blockages and infections, remains the only option for infants with excessive head expansion over periods of weeks. New treatment approaches aimed at preventing hydrocephalus are needed.