The objective of this chapter is to trace the evolution of intraventricular hemorrhage in the premature infant highlighting the importance of the germinal matrix, a critical role for cerebral blood ...flow changes in the genesis of hemorrhage, clinical factors that increase the bleeding risk, and potential preventative strategies. In 1976, neuropathological studies demonstrated capillary rupture within the germinal matrix as the precursor of hemorrhage. In 1980, introduction of cranial ultrasound facilitated diagnosis of intraventricular hemorrhage. In 1979, loss of cerebral autoregulation in sick newborn infants was demonstrated. In the 1980’s, studies demonstrated the importance of intravascular factors in provoking hemorrhage. In 1983, the association of cerebral blood flow velocity fluctuations and subsequent hemorrhage was demonstrated. In 1994, antenatal steroids use to accelerate lung development was recommended. This was associated with an unanticipated reduction in hemorrhage. In the mid 1990’s early indomethacin administration was associated with a reduction of severe hemorrhage.
Pathophysiology of Birth Asphyxia Rainaldi, Matthew A; Perlman, Jeffrey M
Clinics in perinatology,
09/2016, Letnik:
43, Številka:
3
Journal Article
Recenzirano
The pathophysiology of asphyxia generally results from interruption of placental blood flow with resultant fetal hypoxia, hypercarbia, and acidosis. Circulatory and noncirculatory adaptive mechanisms ...exist that allow the fetus to cope with asphyxia and preserve vital organ function. With severe and/or prolonged insults, these compensatory mechanisms fail, resulting in hypoxic ischemic injury, leading to cell death via necrosis and apoptosis. Permanent brain injury is the most severe long-term consequence of perinatal asphyxia. The severity and location of injury is influenced by the mechanisms of injury, including degree and duration, as well as the developmental maturity of the brain.
The fetal inflammatory response syndrome (FIRS) is characterized by umbilical cord inflammation and elevated fetal pro-inflammatory cytokines. Surviving neonates, especially very preterm infants, ...have increased rates of neonatal morbidity including neurodevelopmental impairment. The mechanism of brain injury in FIRS is complex and may involve “multiple hits.” Exposure to in utero inflammation initiates a cascade of the fetal immune response, where pro-inflammatory cytokines can cause direct injury to oligodendrocytes and neurons. Activation of microglia results in further injury to vulnerable pre-myelinating oligodendrocytes and influences the integrity of the fetal and newborn's blood-brain barrier, resulting in further exposure of the brain to developmental insults. Newborns exposed to FIRS are frequently exposed to additional perinatal and postnatal insults that can result in further brain injury. Future directions should include evaluations for new therapeutic interventions aimed at reducing brain injury by dampening FIRS, inhibition of microglial activation, and regeneration of immature oligodendrocytes.
Early initiation of basic resuscitation interventions within 60 s in apneic newborn infants is thought to be essential in preventing progression to circulatory collapse based on experimental ...cardio-respiratory responses to asphyxia. The objectives were to describe normal transitional respiratory adaption at birth and to assess the importance of initiating basic resuscitation within the first minutes after birth as it relates to neonatal outcome.
This is an observational study of neonatal respiratory adaptation at birth in a rural hospital in Tanzania. Research assistants (n=14) monitored every newborn infant delivery and the response of birth attendants to a depressed baby. Time to initiation of spontaneous respirations or time to onset of breathing following stimulation/suctioning, or face mask ventilation (FMV) in apneic infants, and duration of FMV were recorded.
5845 infants were born; 5689 were liveborn, among these 4769(84%) initiated spontaneous respirations; 93% in ≤30 s and 99% in ≤60 s. Basic resuscitation (stimulation, suction, and/or FMV) was attempted in 920/5689(16.0%); of these 459(49.9%) received FMV. Outcomes included normal n=5613(96.0%), neonatal deaths n=56(1.0%), admitted neonatal area n=20(0.3%), and stillbirths n=156(2.7%). The risk for death or prolonged admission increases 16% for every 30 s delay in initiating FMV up to six minutes (p=0.045) and 6% for every minute of applied FMV (p=0.001).
The majority of lifeless babies were in primary apnea and responded to stimulation/suctioning and/or FMV. Infants who required FMV were more likely to die particularly when ventilation was delayed or prolonged.
Accumulating evidence points to an evolving process of brain injury after intrapartum hypoxia-ischemia that initiates in utero and extends into a recovery period. It is during this recovery period ...that the potential for neuroprotection exists.
This discussion briefly reviews the cellular characteristics of hypoxic-ischemic cerebral injury and the current and future therapeutic strategies aimed at ameliorating ongoing brain injury after intrapartum hypoxia-ischemia.
As part of the Newborn Drug Development Initiative, the National Institute of Child Health and Human Development and the US Food and Drug Administration cosponsored a workshop held March 29 and 30, 2004, in Baltimore, Maryland. Information for this article was gathered during that workshop. Literature searches of MEDLINE (Ovid) and EMBASE (1996–2005) were also conducted; search terms included
newborn, infant, hypoxia-ischemia, hypoxic-ischemic encepbalopatby, asphyxia, pathogenesis, treatment, reperfusion injury, and
mechanisms, as well as numerous interventions (ie,
therapeutic bypotbermia, magnesium, and
barbiturates).
The acute brain injury results from the combined effects of cellular energy failure, acidosis, glutamate release, intracellular calcium accumulation, lipid peroxidation, and nitric oxide neurotoxicity that serve to disrupt essential components of the cell, resulting in death. Many factors, including the duration or severity of the insult, influence the progression of cellular injury after hypoxia-ischemia. A secondary cerebral energy failure occurs from 6 to 48 hours after the primary event and may involve mitochondrial dysfunction secondary to extended reactions from primary insults (eg, calcium influx, excitatory neurotoxicity, oxygen free radicals, or nitric oxide formation). Some evidence suggests that circulatory and endogenous inflammatory cells/mediators also contribute to ongoing brain injury. The goals of management of a newborn infant who has sustained a hypoxic-ischemic insult and is at risk for injury should include early identification of the infant at highest risk for evolving injury, supportive care to facilitate adequate perfusion and nutrients to the brain, attempts to maintain glucose homeostasis, and consideration of interventions to ameliorate the processes of ongoing brain injury. Recent evidence suggests a potential role for modest hypothermia (ie, a reduction in core body temperature to −34°C) administered to high-risk term infants within 6 hours of birth. Either selective (head) or systemic (body) cooling reduces the incidence of death and/or moderate to severe disability at 18-month follow-up. Additional strategies—including the use of oxygen free radical inhibitors and scavengers, excitatory amino acid antagonists, and growth factors; prevention of nitric oxide formation; and blockage of apoptotic pathways—have been evaluated experimentally but have not been replicated in a systematic manner in the human neonate. Other avenues of potential neuroprotection that have been studied in immature animals include platelet-activating factor antagonists, adenosinergic agents, monosialoganglioside GM1, insulin-like growth factor-1, and erythropoietin.
Much progress has been made toward understanding the mechanisms contributing to ongoing brain injury after intrapartum hypoxiaischemia. This should facilitate more specific pharmacologic intervention strategies that might provide neuroprotection during the reperfusion phase of injury.
Maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can present with or without symptoms at the time of birth. Symptomatic mothers are more likely be associated with ...preterm births. Population studies demonstrate a consistent association of SARS-CoV-2 infection and a reduction in preterm birth rate. Newborns with positive SARS-CoV-2 test results appear to have minimal burden of illness that is directly associated with a viral infection. Neonatal mortality directly related to SARS-CoV-2 is extremely rare. Maternal vaccination in pregnant women leads to maternal antibody production, and this can occur as early as 5 days after the first vaccination dose.
Abstract Hyperthermia at the time of or following a hypoxic-ischemic insult has been associated with adverse neurodevelopmental outcome. Moreover, an elevation in temperature during labor has been ...associated with a variety of other adverse neurologic sequelae such as neonatal seizures, encephalopathy, stroke, and cerebral palsy. These outcomes may be secondary to a number of deleterious effects of hyperthermia including an increase in cellular metabolic rate and cerebral blood flow alteration, release of excitotoxic products such as free radicals and glutamate, and hemostatic changes. There is also an association between chorioamnionitis at the time of delivery and cerebral palsy, which is thought to be secondary to cytokine-mediated injury. We review experimental and human studies demonstrating a link between hyperthermia and perinatal brain injury.
Hypoxic-ischemic cerebral injury that occurs during the perinatal period is one of the most commonly recognized causes of severe, long-term neurologic deficits in children; it is often referred to as ...cerebral palsy. Despite improvements in perinatal practice during the past several decades, the incidence of cerebral palsy attributed to intrapartum asphyxia has remained essentially unchanged, primarily because management strategies were supportive and not targeted toward the processes of ongoing injury. Two processes of neuronal injury can be demonstrated after hypoxia-ischemia: neuronal necrosis and apoptosis. Because the mechanisms of these processes likely differ, strategies to minimize brain damage in an affected infant after hypoxia-ischemia likely will have to include interventions that target both processes. The goals of management of a newborn infant who has sustained a hypoxic-ischemic insult and is at risk for evolving injury should include (1) early identification of the infant at highest risk for evolving to the syndrome of hypoxic-ischemic encephalopathy, (2) supportive care to facilitate adequate perfusion and nutrients to the brain, and (3) consideration of interventions to ameliorate the processes of ongoing brain injury. Although the neurology group was unable to develop a definitive framework for the study of neuroprotective strategies for neonatal encephalopathy, it (1) listed key questions to be addressed before exploring possible study designs for managing hypoxic-ischemic encephalopathy in neonates, (2) identified important study-design issues, (3) determined general principles and key elements for neuroprotective-treatment strategies, (4) identified potential treatment strategies, (5) proposed a clinical-trial framework, and (6) identified key elements for a potential clinical-trial framework comparing hypothermia with hypothermia "plus" for moderate-to-severe encephalopathy.
Approximately 40,000 newborns die each year in Tanzania. Regional differences in outcome are common. Reviewing current local data, as well as defining potential causal pathways leading to death are ...urgently needed, before targeted interventions can be implemented.
To describe the clinical characteristics and potential causal pathways contributing to newborn death and determine the presumed causes of newborn mortality within seven days, in a rural hospital setting.
Prospective observational study of admitted newborns born October 2014-July 2017. Information about labour/delivery and newborn management/care were recorded on data collection forms. Causes of deaths were predominantly based on clinical diagnosis.
671 were admitted to a neonatal area. Reasons included prematurity n = 213 (32%), respiratory issues n = 209 (31%), meconium stained amniotic fluid with respiratory issues n = 115 (17%) and observation for < 24 hours n = 97 (14%). Death occurred in 124 infants. Presumed causes were birth asphyxia (BA) n = 59 (48%), prematurity n = 19 (15%), presumed sepsis n = 19 (15%), meconium aspiration syndrome (MAS) n = 13 (10%) and congenital abnormalities n = 14 (11%). More newborns who died versus survivors had oxygen saturation <60% on admission (37/113 vs 32/258; p≤0.001) respectively. Moderate hypothermia on admission was common i.e. deaths 35.1 (34.6-36.0) vs survivors 35.5 (35.0-36.0)°C (p≤0.001). Term newborns who died versus survivors were fourfold more likely to have received positive pressure ventilation after birth i.e. 4.57 (1.22-17.03) (p<0.02).
Intrapartum-related complications (BA, MAS), prematurity, and presumed sepsis were the leading causes of death. Intrapartum hypoxia, prematurity and attendant complications and presumed sepsis, are major pathways leading to death. Severe hypoxia and hypothermia upon admission are additional contributing factors. Strategies to identify fetuses at risk during labour e.g. improved fetal heart rate monitoring, coupled with timely interventions, and implementation of WHO interventions for preterm newborns, may reduce mortality in this low resource setting.
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