Introduction

Neurodevelopmental disability in prematurely born infants remains a very significant problem worldwide, for which there is no specific treatment. While there have been significant improvements in the survival of preterm infants, this has not been matched by improvements in morbidity; indeed there is some evidence that disability has increased, with a moderate rise in the childhood prevalence of cerebral palsy. The high incidence of neurological morbidity within this group of babies poses a considerable burden on families and the health system. We need to considerably increase our understanding of when and how this injury occurs to develop effective ways of alleviating the burden.

Traditionally, brain injury in preterm infants has been thought to reflect a fundamental vulnerability of the developing periventricular white matter to damage. However, recent evidence suggests a much more complex picture. In the present review, we will critically dissect the neuropathology of hypoxic preterm brain injury, including the underappreciated importance of acute gray-matter as well as white-matter damage, and the timing and mechanisms of injury, and highlight key unresolved issues.

The long-term problem: neurodevelopmental handicap

Children born preterm (<37 weeks) have high rates of disability including visual damage, mental retardation, epileptic seizures, and cerebral palsy. The incidence of these deficits increases steeply with decreasing gestational age and birthweight.