Is Periventricular Leucomalacia aResult of Hypoxic-Ischaemic Injury?

Abstract

Decrease in the arterial partial pressure of carbon dioxide (PaCO₂) causes a reduction in cerebral blood flow in humans and in most animal species; in adults as well as in newborns and even in fetal life. Severely decreased PaCO₂ increases cerebral lactate production, modifies spontaneous electric brain activity, and may decrease the metabolic rate of oxygen. A relation between very low PaCO₂ and brain injury, however, has not been shown in adult humans or full-term newborn infants, nor in perinatal animals. In contrast, an association between low PaCO₂ and cerebral palsy and white matter injury in preterm infants has been reported repeatedly. A cause-and-effect relation is suggested by data from the immature rat: brain damage induced by ligation of a carotid artery can be reduced by adding CO₂ to the inspired gas and hence avoiding the consequences of spontaneous hyperventilation. This may be relevant for the clinical care of preterm infants, since PaCO₂ to a large extent is a function of respiratory management. The questions to be addressed are whether hypocapnia sensitises the brain to hypoxaemia, and also whether the escape mechanisms are less effective in the preterm human brain.

Cortical structural abnormalities in very preterm children at 7years of age

“…The mechanism responsible for this alteration in cingulate sulcal structure remains unknown, but if cortical folding is driven by mechanical tension along long-distance axons (Van Essen, 1997), folding abnormalities may reflect altered patterns of connectivity in VPT children. This is consistent with the observation that hypoxia-ischemia, a known risk factor for brain injury in preterm infants (Dammann and leviton, 1997 and Greisen and Vannucci, 2001), produces an increased number of apoptotic cingulate neurons in piglets (Mehmet et al, 1994). The asymmetry of sulcal abnormalities in our findings are consistent with previous reports of anatomical asymmetries in medial cortical regions (Paus et al 1996; Thompson et al, 2010).…”

Blood protein concentrations in the first two postnatal weeks associated with early postnatal blood gas derangements among infants born before the 28th week of gestation. The ELGAN Study

“…Preterm newborns who experience hypocapnia are at increased risk of cerebral white matter damage [30–33]. We sought, but found only minimal evidence in support of the hypothesis that inflammation is an intermediary.…”

Early postnatal illness severity scores predict neurodevelopmental impairments at 10 years of age in children born extremely preterm

“…Accordingly, SNAP-II could be viewed as a marker or indicator for such risk. While both hypoxemia and hypotension, examples of physiologic instability, have been invoked to account for brain damage in very preterm newborns,(32-39) sufficient support for these claims has yet to be provided. (40-44) Further, despite efforts to improve physiologic stability,(41, 45-52) the rate of neurodevelopmental derangements among extremely preterm infants remains high in numerous studies.…”