Premium
Hypoxia–ischemia is not an antecedent of most preterm brain damage: the illusion of validity
Author(s) -
Gilles Floyd,
Gressens Pierre,
Dammann Olaf,
Leviton Alan
Publication year - 2018
Publication title -
developmental medicine and child neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.658
H-Index - 143
eISSN - 1469-8749
pISSN - 0012-1622
DOI - 10.1111/dmcn.13483
Subject(s) - hypoxia (environmental) , ischemia , neuropathology , encephalopathy , hypoxemia , hypoxic ischemic encephalopathy , etiology , medicine , asphyxia , neuroscience , brain damage , neonatal encephalopathy , psychology , disease , physiology , intensive care medicine , bioinformatics , pathology , anesthesia , biology , chemistry , organic chemistry , oxygen
Brain injury in preterm newborn infants is often attributed to hypoxia–ischemia even when neither hypoxia nor ischemia is documented, and many causative speculations are based on the same assumption. We review human and animal study contributions with their strengths and limitations, and conclude that – despite all the work done in human fetal neuropathology and developmental models in animals – the evidence remains unconvincing that hypoxemia, in the fetus or newborn infant, contributes appreciably to any encephalopathy of prematurity. Giving an inappropriate causal name to a disorder potentially limits the options for change, should our understanding of the etiologies advance. The only observationally‐based title we think appropriate is ‘encephalopathy of prematurity’. Future pathophysiological research should probably include appropriately designed epidemiology studies, highly active developmental processes, infection and other inflammatory stimuli, the immature immune system, long chain fatty acids and their transporters, and growth (neurotrophic) factors. What this paper adds Fetal hypoxemia is rarely documented in brain injury studies. Animal studies fail to consider human–animal fetal anatomical differences. Putative treatments from animal models have not found clinical use. Observational studies constitute the only approach to etiological understanding. No convincing evidence yet that hypoxemia injures preterm brain. Encephalopathy of prematurity is preferable to hypoxia‐ischemia as a term for this disorder. Encephalopathy of prematurity is preferable to hypoxia‐ischemia as a term for this disorder.