title: Timing of injury in the fetus and neonate.
abstract: OBJECTIVE
  The aim of this article is to assess evidence for the timing of brain injury associated with clinical encephalopathy in the fetus and newborn.
  
  
  RESULTS
  Older studies found strong epidemiological links between antenatal factors, including exposure to infection, and acute encephalopathy and later cerebral palsy. In contrast, recent cohort studies using early magnetic resonance imaging and spectroscopy, near-infrared spectroscopy and electroencephalogram monitoring suggest that the majority of brain injury in infants with evidence of encephalopathy occurs in the immediate perinatal period and conversely that it is relatively uncommon for chronic, antepartum injury to present with symptoms at birth. A key experimental study showed that mild infection can lead to long-lasting sensitization of the brain to subsequent mild hypoxia-ischemia. This provides a plausible mechanistic link between some antenatal complications and acute perinatal injury. Consistent with this, randomized controlled trials have demonstrated that therapeutic hypothermia can significantly improve outcome of neonatal encephalopathy at term. Electroencephalogram monitoring seems to be the most promising modality to identify infants who may benefit from potential neuroprotective treatments, but more research is needed to refine its use.
  
  
  CONCLUSIONS
  There is now strong evidence that brain injury commonly occurs in the immediate perinatal period, and so may be potentially treatable.
authors.affiliation: Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. aj.gunn@aukland.ac.nz
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Gunn
authors.forename: Laura
authors.initials: L
authors.lastname: Bennet
mesh_terms: D001921:Brain / Q000473:pathology; D001925:Brain Damage, Chronic / Q000151:congenital* / Q000175:diagnosis / Q000628:therapy; D002547:Cerebral Palsy / Q000151:congenital / Q000175:diagnosis / Q000628:therapy; D004569:Electroencephalography; D005865:Gestational Age; D006801:Humans; D007035:Hypothermia; D020925:Hypoxia-Ischemia, Brain / Q000151:congenital* / Q000175:diagnosis / Q000628:therapy; D007231:Infant, Newborn; D013997:Time Factors