Neonatal white matter damage and the fetal inflammatory response

In 1962 a long-recognized pathologic abnormality in neonatal brains characterized by multiple telencephalic focal white matter necroses was renamed periventricular leukomalacia (PVL) and the authors inappropriately asserted that their entity was caused by anoxia. They also failed to include three other white matter histologic abnormalities. In this essay, we identify the breadth of white matter pathology, especially in very preterm newborns, and show that none of the four histologic expressions of white matter damage, including focal necrosis, are associated with hypoxemia or correlates as hypotension, but are instead associated with markers of fetal or perinatal inflammation, particularly in preterm babies. We begin with the background needed to evaluate the evidence.