A Controversial Medicolegal Issue: Timing the Onset of Perinatal Hypoxic-Ischemic Brain Injury

Abstract

Perinatal hypoxic-ischemic brain injury, as a result of chronic, subacute, and acute insults, represents the pathological consequence of fetal distress and birth or perinatal asphyxia, that is, “nonreassuring fetal status.” Hypoxic-ischemic injury (HII) is typically characterized by an early phase of damage, followed by a delayed inflammatory local response, in an apoptosis-necrosis continuum. In the early phase, the cytotoxic edema and eventual acute lysis take place; with reperfusion, additional damage should be assigned to excitotoxicity and oxidative stress. Finally, a later phase involves all the inflammatory activity and long-term neural tissue repairing and remodeling. In this model mechanism, loss of mitochondrial function is supposed to be the hallmark of secondary injury progression, and autophagy which is lysosome-mediated play a role in enhancing brain injury. Early-induced molecules driven by hypoxia, as chaperonins HSPs and ORP150, besides common markers for inflammatory responses, have predictive value in timing the onset of neonatal HII; on the other hand, clinical biomarkers for HII diagnosis, as CK-BB, LDH, S-100beta, and NSE, could be useful to predict outcomes.

Risk factors for cerebral palsy in neonates due to placental abruption

“…10 In the last two decades, medicolegal claims arising from perinatal brain injury have continued growing. 11 In Japan, obstetrics-related lawsuits filed between 2004 and 2008 accounted for approximately 10-15% of the overall total across all specialties. However, since the institution of this system, obstetrics-related lawsuits have started to fall to approximately 7% of the total.…”

Combination of Constraint-Induced Movement Therapy with Electroacupuncture Improves Functional Recovery following Neonatal Hypoxic-Ischemic Brain Injury in Rats

“…HI brain injury is associated with approximately 25% of neonatal deaths globally [ 34 , 35 ]. In cases of survival, HI injury causes severe, long-term neurological disorders in infants and children, including cerebral palsy and motor and cognitive deficits [ 3 , 4 ]. Oxidative stress might be an important contributing factor in perinatal HI brain injury [ 4 ], causing an inflammatory response, apoptosis, and necrosis in the neural environment.…”

“…HI injury is characterized by sequential occurrences, with damage in the early phase involving cytotoxic edema, acute lysis, and oxidative stress. Later phases of HI response include inflammatory activity, apoptosis, necrosis, and long-term neural tissue repairing or remodeling [ 3 , 4 ]. It was reported that 10 to 50% of patients who survived neonatal HI usually lost motor function, and 20 to 50% have lost sensory function or cognitive function [ 2 , 5 ].…”

Journey to the Center of the Fetal Brain: Environmental Exposures and Autophagy

“…Consequently, it is desirable to have insight into the opportune time to perform a measurement so as to capture autophagy activity when it is occurring. For example, Fineschi suggested a model of hypoxia that first uses chaperone proteins such as heat shock proteins (HSPs) and oxygen-regulated protein (ORP150) to detect the onset of the inflammatory response to hypoxia (Fineschi et al, 2017 ).…”