Markers of perinatal hypoxia–ischaemia and neurological injury: assessing the impact of insult duration

Abstract

Hypoxic–ischaemic insults occurring during or after birth can cause both acute and long‐term neurological impairment. The duration of the insult is a critical factor, but most published reports of duration have important limitations. After the onset of a persistent bradycardia in 125 term born infants, abnormal outcomes occurred in two by 10 minutes, in 12 out of 47 (26%) delivered between 11 and 20 minutes, and in 55 out of 65 (85%) delivered after 20 minutes. Series with unspecified gestation or including infants born preterm give comparable results in over 500 additional cases. Before 20 minutes there was little correlation with severity, while after 20 minutes most were severely impaired. Limited neuroimaging data suggest that damage restricted to the basal ganglia and thalamus may begin to occur after 10 minutes, associated Rolandic damage after 15 minutes, and other cortical involvement after 20 minutes. Associated white matter damage can occur after any duration. There were little data for other patterns of damage. What this paper adds Some term born infants can withstand 20 minutes of fetal bradycardia without acute or chronic damage. Durations in humans are not the same as in animal models.

Neuroimaging of Basal Ganglia in Neurometabolic Diseases in Children

“…Due to preterm birth, the thalamus is suggested to be the most vulnerable deep gray matter structure [33][34][35][36]. Limited neuroimaging data suggest that the damage to the basal ganglia and the thalamus may occur within 10 min following the hypoxic-ischemic insult [35].…”

Fetal hypoxia‐ischaemia: wrong time, wrong place

“…Baxter has explored the question: how much is too much when it comes to perinatal hypoxia? As expected, the answer is complicated and relates to both the depth and duration of the ischemia as well as maternal and fetal factors. Broadly speaking, if the ischemia lasted less than 20 minutes, there was partial correlation with clinical severity—some infants were affected, and some were not—while if presumed ischemia extended beyond 20 minutes, most, but not all, were severely impaired.…”

“…5 However, a safe minimum duration of partial ischemia cannot be defined. 1 Until we understand better the issues that may influence an individual's resistance or susceptibility to a situation in which they may be exposed, it is unlikely that hard lines can be drawn. While magnetic resonance imaging can demonstrate patterns thought to support the timing of an injury again, the rules cannot be applied rigorously in every circumstance.…”

“…Delays in obtaining ACTH and training time for families due to the need for injections rather than oral administration can potentially prolong the time that a child experiences hypsarrhythmia and spasms, thus potentially affecting long-term developmental outcome. 1 Li et al 2 provide a meta-analysis of multiple randomized controlled trials that have compared the various forms of hormonal therapies, namely prednisolone/prednisone and ACTH, evaluating their comparative efficacy in cessation of hypsarrhythmia and spasms, and adverse event profile. While each of these studies was randomized and controlled, the outcomes between different hormonal therapies were not always powered to detect a difference between the various hormonal therapies (notably the United Kingdom Infantile Spasms Study).…”

“…Conversely, outcomes from big data analysis suggest that for some, even an apparently minor insult may lead to an adverse outcome . However, a safe minimum duration of partial ischemia cannot be defined …”