Pathogenesis and Prevention of Fetal and Neonatal Brain Injury

Abstract

Recent advances in the clinical management of at-risk pregnancy and care of the newborn have reduced morbidity and mortality among sick neonates, and improved our knowledge of factors that influence the risks of brain injury. In parallel, the refinement of imaging techniques has added to the ability of clinicians to define the etiology, timing and location of pathologic changes with diagnostic and prognostic relevance to the developing fetus and newborn infant. Abnormalities of brain growth, or injury to the developing brain can occur during pregnancy; during labor and delivery, hypoxia, acidosis and ischemia pose major risks to the fetus. Defined practices for the management of pregnancy and delivery, and evidence-based strategies for care in the newborn period are influencing outcome. However, newborn infants, especially those born prematurely, remain at risk from situations that can cause or worsen brain injury. The literature reviewed here explains the mechanisms and timing of injury, and the importance of hypoxia, ischemia, hypotension and infection; describes current diagnostic strategies, neuroimaging technologies and care entities available; and outlines approaches that can be used to prevent or mitigate brain injury. Some show particular promise, and all are relevant to lowering the incidence and severity of brain damage.

Near infrared spectroscopy of the central nervous system: monitoring oxygenation in the neonatal brain and in the spinal cord following traumatic injury

“…13 The brain of a sick newborn is vulnerable to injury from hypoxia and ischemia, regardless of the cause, and, importantly, where an infant has residual effects from prior hypoxic or ischemic stress incurred during a problematic labor or complicated delivery, the effects of a post-natal hypoxic insult are compounded, as the physiologic consequences of both events combine and act synergistically in the context of brain injury. 3 Infants born prematurely are at increased risk of injury because of the immaturity of their neuro-vasculature. The fetal brain undergoes rapid development during the last trimester; 14 so a very premature infant lacks the duplication of blood supply to many parts of the brain that develops as a fetus matures, and which adds an important level of protection against hypoxia and ischemia.…”

“…Mechanisms underlying this form of injury include: variations in cerebral venous pressure, major cerebral vasodilatation or constriction, altered distribution of CBF, systemic fluctuations in circulating blood volume, and significant changes in oxygen or carbon dioxide tension. 3,16 Fetal growth to term also allows other areas of the brain to fully develop rendering the mature brain more resistant to oxygen lack. In immature premature infants the primary brain injury seen on MRI is non-cystic white matter injury; 17 the causal factor for this is the vulnerability of immature oligodendrocyte precursors to hypoxia/ischemia.…”

“…Both required skills to achieve insertion and avoid excessive blood loss which is a problem in premature infants because of their small circulating volume; the radial site was only feasible in larger infants, and all arterial canulae could only be left in situ for a limited period due to associated risks of thrombosis, embolism and infection. 3,27,28 Pulse oximetry was a major advance, but the first instrument developed in 1972 by bioengineers required considerable evolutionary refinement before the technology could enter effective clinical use. Clinicians made it clear that to be an effective adjunct for critical care a simple real-time measure was what was required, and to achieve this scientists had to modify the physics employed, average signals and develop algorithms that delivered the numeric readouts relied on today.…”

“…So, where local vessels are damaged or local perfusion compromised by acute traumatic SCI, multidirectional flow can protect the cord through preferential perfusion achieved by diversion of blood flow from less critical tissue, 50,51 as occurs in the fetal brain in response to partial and prolonged anoxic stress. 3 Cerebral blood flow: Adequate cerebral perfusion pressure is required to provide sufficient cerebral blood flow to meet the high metabolic demands of the brain; importantly this includes adequate provision of both oxygen and glucose and also the maintenance of energy generation pathways within brain cells through stability of the intracellular biochemical milieu; for example, stability of intracellular pH and maintained integrity of cell membranes are essential to the integrity of cellular function. 20 Normally, the cerebral vasculature responds to changes in cerebral perfusion pressure by adapting cerebrovascular resistance (CVR).…”

“…Consequently, NIRS technologies are increasingly relied on as an adjunct to aid CNS monitoring during the intensive care of premature newborn infants and critically ill adults to optimize physiologic function, and in order to guide intraoperative and anesthetic management. [1][2][3][4][5][6][7] Important lessons relevant to the further evolution of NIRS applications in medicine are to be found in how and why the advances that have led to effective monitoring of oxygenation in the CNS came about. The original pioneering work in newborn infants established a role for NIRS as a means of monitoring changes in brain blood volume and oxygenation relevant to their care, but required refinement.…”