Abstract: Although room air is adequate for resuscitating asphyxiated newborn infants, guidelines recommend using 100% oxygen. Hyperoxemia, as has been noted in animal studies, could cause delayed breathing, increased oxygen consumption, and disordered cerebral circulation. In addition, 100% oxygen has caused prolonged oxidation of blood glutathione in neonates. In this study, 51 asphyxiated neonates born at term were randomly assigned to resuscitation with room air (RAR) and 55 to resuscitation with 100% oxygen (OxR). The goal was to learn whether using oxygen for resuscitation triggers oxidative stress. Critical criteria were the Apgar score, the time of the first cry, and sustained respiration. Signs of asphyxia included hypotonia, apnea, a lack of response to external stimuli, pallor, bradycardia, and acidosis. Cesarean delivery was more than twice as frequent in asphyxiated infants than in control subjects, and 1- and 5-minute Apgar scores were reduced. Infants in both experimental groups took significantly longer to the first cry, but the RAR group needed less time of ventilation for resuscitation time than the OxR group (5.3 vs. 6.8 minutes). Hyperoxemia was associated with oxygen resuscitation but not with the use of room air (PO 2 of 126 and 72 mm Hg, respectively). Whole blood levels of reduced glutathione were decreased in both asphyxiated groups; and oxidized glutathione, glutathione cycle enzymes, and superoxide dismutase activity were increased. These changes were, however, significantly greater in the OxR group than in RAR infants. Follow up after the first week of lite and at age 4 weeks showed no differences between the experimental groups. These findings show that asphyxia of newborn infants causes oxidative stress, and that resuscitating them with 100% oxygen causes hyperoxemia and increases oxidative stress. The investigators conclude that room air might be preferable for resuscitating these infants.

Abstract: White matter injury is the most frequently observed brain lesion in preterm infants. The etiology remains unclear, however, both cerebral hypoperfusion and intrauterine infections have been suggested as risk factors. We compared the neuropathological outcome, including the effect on oligodendrocytes, astrocytes, and microglia, following either systemic asphyxia or endotoxemia in fetal sheep at midgestation. Fetal sheep were subjected to either 25 minutes of umbilical cord occlusion or systemic endotoxemia by administration of Escherichia coli lipopolysaccharide (LPS O111:B4, 100 ng/kg, IV). Periventricular white matter lesions were observed in 2 of 6 asphyxiated fetuses, whereas the remaining animals showed diffuse injury throughout the subcortical white matter and neuronal necrosis in subcortical regions, including the striatum and hippocampus. LPS-treatment resulted in focal inflammatory infiltrates and cystic lesions in periventricular white matter in 2 of 5 animals, but with no neuron specific injury. Both experimental paradigms resulted in microglia activation in the white matter, damaged astrocytes, and loss of oligodendrocytes. These results show that the white matter at midgestation is sensitive to injury following both systemic asphyxia and endotoxemia. Asphyxia induced lesions in both white and subcortical grey matter in association with microglia activation, and endotoxemia resulted in selective white matter damage and inflammation.

Abstract: Background and Purpose— The fetus is well known to be able to survive prolonged exposure to asphyxia with minimal injury compared with older animals. We and others have observed a rapid suppression of EEG intensity with the onset of asphyxia, suggesting active inhibition that may be a major neuroprotective adaptation to asphyxia. Adenosine is a key regulator of cerebral metabolism in the fetus. Methods— We therefore tested the hypothesis that infusion of the specific adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), given before 10 minutes of profound asphyxia in near-term fetal sheep, would prevent neural inhibition and lead to increased brain damage. Results— DPCPX treatment was associated with a transient rise and delayed fall in EEG activity in response to cord occlusion (n=8) in contrast with a rapid and sustained suppression of EEG activity in controls (n=8). DPCPX was also associated with an earlier and greater increase in cortical impedance, reflecting earlier onset of p...

Abstract: Brain-specific proteins have been used to detect cerebral injury after birth asphyxia. Previous investigations suggest that serum protein S-100β, brain-specific creatine kinase (CK-BB), and neuron-specific enolase (NSE) are capable of identifying patients with a risk of developing hypoxic-ischemic encephalopathy. Whether detection of elevated serum concentrations of these proteins reflects long-term neurodevelopmental impairment remains to be investigated. We examined serum protein S-100β, NSE, and CK-BB at 2, 6, 12, and 24 h after birth in 29 asphyxiated infants and 20 control infants. Neurodevelopmental follow-up examinations were performed at 20 mo of age using the German revision of the Griffiths scales for developmental assessment. Elevated concentrations of serum protein S-100β, NSE, and CK-BB within 24 h after asphyxia did not correlate with long-term neurodevelopmental delay. We conclude that serum protein S-100β, NSE, and CK-BB, sampled on the first day of life, is of limited value in predicting severe brain damage after birth asphyxia.

Abstract: Objective: To study prospectively the effects of prematurity and perinatal events on the coagulation status of premature infants Patients and main outcome measures: Blood samples from premature infants born before 37 gestational weeks were taken for analysis of coagulation factors II, V, VII, and X and platelet count Results: A total of 125 premature infants, 71 boys, were studied at the median postnatal age of 40 minutes (range 12–100) The lowest median activities of coagulation factors II, V, VII, and X and the platelet count were observed, as expected, in infants (n = 21) born at 24–27 weeks gestation Twin B (n = 14) had lower median activities of coagulation factors II, V, VII, and X than twin A Infants with evidence of mild asphyxia (Apgar score at 5 minutes < 7 or cord pH < 726) had significantly (p < 005) lower levels of coagulation factors II, V, VII, and X and platelet counts than infants without asphyxia Infants who were small for gestational age (SGA) had significantly (p < 005) lower levels of coagulation factors V and VII and platelet counts than infants of appropriate size for gestational age Other prenatal and perinatal variables examined (sex, maternal hypertension and/or pre-eclampsia, antenatal steroid use, mode of delivery, Apgar scores) did not show any significant associations with coagulation status, which may be explained by the small number of infants studied Conclusions: The data strongly suggest that there are distinct differences in specific coagulation tests in different patient populations, which could assist in the identification of extremely preterm, SGA, or asphyxiated preterm infants who may be susceptible to haemorrhagic problems perinatally

Abstract: Positional asphyxia, a fatal condition arising because of the adoption of particular body positions, causing mechanical interference with pulmonary ventilation, can occur in various circumstances that are likely to come under the observation of the specialist in legal medicine (work, car accidents, torture, kidnapping, etc.). It is difficult to diagnose the cause of death in such cases because they generally present with an aspecific anatomopathologic picture. In some situations, positional asphyxia can be hard to distinguish from asphyxia because of chest compression. The main difference is in the way the event occurred: whether the particular position causing the asphyxia had been adopted by choice or by compulsion or necessity when an extrinsic mechanical action would result in traumatic asphyxia. The diagnosis of positional asphyxia is essentially based on 3 criteria: the body position must obstruct normal gas exchange, it must be impossible to move to another position, and other causes of natural or violent death must be excluded. To illustrate the main physiopathologic and diagnostic causes of positional asphyxia, the authors report 2 cases taken from the records of events that came under the observation of the Medico-Legal Sector of Bari University Hospital throughout the last 10 years.

Abstract: Dynamic changes in electrophysiology of brainstem auditory neurons during the first month after birth were studied in 51 term infants after perinatal asphyxia using maximum length sequence brainstem auditory evoked responses. The responses were recorded on d 1, 3, 5, 7, 10, 15, and 30 after birth. On d 1, wave III and V latencies and all interpeak intervals increased significantly at all repetition rates of clicks used (91-910/s), especially the higher rates (ANOVA, p < 0.05-0.0001). On d 3, all these latencies and intervals increased further and differed more significantly from the normal control subjects. Thereafter, the latencies and intervals decreased progressively. On d 7, wave V latency and all intervals still differed significantly from the control subjects. These dynamic changes were more significant at higher rates of clicks than at lower rates. On d 10 and 15, all intervals decreased significantly. On d 30, all wave latencies decreased to the values in the normal control subjects on the same day. The intervals also approached normal values, although the III-V and I-V intervals still increased slightly. These results indicate that hypoxic-ischemic brain damage persists during the first week, with a peak on d 3, and recovers progressively thereafter. By 1 mo, the damage has largely returned to normal. Maximum length sequence brainstem auditory evoked responses results correlated well with the stage of hypoxic-ischemic encephalopathy during the first week. The present study revealed a general time course of brainstem pathophysiology after asphyxia, although there were individual variations. Our findings can be used as a reference to monitor cerebral function and help judge the value of neuroprotective or therapeutic interventions. The first week, particularly the first 3 d, is a critical period of hypoxic-ischemic brain damage, and early intervention may prevent or reduce deterioration of the damage.

Abstract: Birth asphyxia is a perinatal occurrence that, in serious cases, may lead to permanent adverse consequences or death. This retrospective case-control study of term neonates with birth asphyxia, defined as a 5-minute Apgarscore less than 7, had as its goal to explore risk factors for birth asphyxia itself, related hypoxic-ischemic encephalopathy (HIE), and asphyxia-related disability and death. Infants who died of nonasphyxial causes, such as infection or maternal sedation, were not included. Among more than 42,000 live births reviewed for the years 1985 through 1991 in an urban Swedish population were 225 cases of birth asphyxia that were matched with nonasphyxial control cases. The study group included 75 infants with both asphyxia and HIE. Surviving infants were followed for 18 months or longer, and those viewed as neurologically disabled were followed for 1.5 to 3 years longer. Twenty-two infants in the asphyxia group died or developed asphyxia-related neurological disability. Rates of birth asphyxia, pure birth asphyxia, and asphyxia-related HIE during the 7-year review period were, respectively, 6.9, 5.4, and 1.9 per 1000 live births. The asphyxia-related mortality rate was 0.26 per 1000 live births, and the rate of neurological impairment at the 18-month follow-up was 0.2 per 1000. Factors associated with birth asphyxia included single marital status (odds ratio [OR] = 7.1), intrauterine meconium release (OR = 4.1), operative delivery (OR = 8.7), breech delivery (OR = 20.3), and oxytocin augmentation (OR = 2.9). Other associated parameters were cord complications (OR = 15.8) and external compression to aid delivery (OR = 6.2). Significant cardiotocographic (CTG) correlates included repeated late decelerations (OR = 29.4), occasional late or variable decelerations (OR = 2.2), and a lack of accelerations (OR = 5.2). All groups of infants with asphyxia were delivered operatively or instrumentally more often than were the matched control infants. No association was evident between asphyxia and maternal age, smoking, illnesses, time of delivery (day vs. night or seasonal), or previous cesarean delivery. Independent risk factors for HIE included intrauterine meconium release, CTG score, and operative delivery. This is one of the few population-based studies of risk factors for asphyxia and perhaps the first to separately examine risk factors for pure asphyxia, HIE, and asphyxia-related death and disability. Asphyxia was strongly associated with CTG abnormalities, particularly the absence of baseline variability. CTG monitoring definitely is indicated for women given oxytocin augmentation, one of the factors associated with asphyxia in this study.

Abstract: Objective : This study was undertaken to analyze indications, complications, outcome and the factors influencing neonatal mechanical ventilation.Methods : Prospective observational study conducted on 102 consecutive newborns, who required mechanical ventilation in a medical college tertiary neonatal care setting.Results : The commonest indication was birth asphyxia (37.3%), followed by hyaline membrane disease (HMD) (31.4%), meconium aspiration syndrome (MAS) (21.2%), septicemia (14.7%) and apnea of prematurity (5.9%). The overall survival rate in our study was 51 %. Babies weighing less than 1.5 kg and less than 32 weeks of gestation had survival rates of 30% and 25% respectively. The best outcome among various indications was observed in babies with MAS (63.6%) followed by pneumonia (62.5%) and HMD (53.1%). Babies with birth asphyxia and septicemia had a low survival rate of only 42% and 40% respectively. The overall complication rate in the study was 58.8%. Common complications encountered were septicemia (42%), tube block (36%) and air leak (15%).Conclusion : About half (51%) of newborns requiring mechanical ventilations for various indications survived and more than half (58.8%) developed complications. The study also reconfirms that survival rate increases with birth weight and gestational age irrespective of indication.

Abstract: There is only limited morphologic information on long-term alterations and neurotransmitter changes after perinatal asphyxia, and no long-term study showing neurodegeneration has been reported so far. We used an animal model for perinatal asphyxia well documented in the rat to investigate the guinea pig as a species highly mature at birth. Cesarean section was performed on full-term pregnant guinea pigs, and pups, still in membranes, were placed into a water bath at 37 degrees C for asphyxia periods from 2 to 4 min. Thereafter pups were given to surrogate mothers and examined at 3 mo of age. We studied brain areas reported to be hypoxia-sensitive. Neurodegeneration was evaluated by fluoro-jade, neuronal loss by Nissl, reactive gliosis by glial fibrillary acidic protein staining, and differentiation by neuroendocrine-specific protein C immunoreactivity. We tested tyrosine hydroxylase, the vesicular monoamine transporter, and dopamine beta-hydroxylase, representing the monoaminergic system; the vesicular acetylcholine transporter; and the excitatory amino acid carrier 1. Neurodegeneration was evident in cerebellum, hippocampal area CA1, and hypothalamus, and neuronal loss could be observed in cerebellum and hypothalamus; gliosis was observed in cerebellum, hippocampus, hypothalamus, and parietal cortex; dedifferentiation was found in hypothalamus and striatum; and monoaminergic, cholinergic, and amino acidergic deficits were shown in several brain regions. The major finding of the present study was that neurodegeneration and dedifferentiation evolved in the guinea pig, a species highly mature at birth. The relevance of this contribution is that a simple animal model of perinatal asphyxia resembling the clinical situation of intrauterine hypoxia-ischemia and presenting with neurodegeneration was characterized.

Abstract: Background: Perinatal asphyxia may lead to multiorgan damage as well as brain injury. Posthypoxic hypothermia (HT) may protect other organs in addition to the brain. The aim of this

Abstract: Background. There have been few studies comparing the response to asphyxia and the effectiveness of typical cardiopulmonary resuscitation (CPR) using exogenous epinephrine administration and manual closed-chest compression between total intravenous anaesthesia (TIVA) and inhalational anaesthesia. Methods. Twenty pigs were randomly assigned to two study groups anaesthetized using either 2% end-tidal isoflurane (n=10) or propofol (12 mg kg−1 h−1)–fentanyl (50 μg kg−1) (n=10). Asphyxia was induced by clamping the tracheal tube until the mean arterial pressure (MAP) decreased to 40% of the baseline value (40% MAP time). The tracheal tube was declamped at that point, and CPR was performed. Haemodynamic parameters and blood samples were obtained before the induction of asphyxia, at 1-min intervals during asphyxia, and 1, 2, 3, 5, 10, 30 and 60 min after asphyxia. Results. TIVA maintained the MAP against hypoxia–hypercapnia stress significantly longer than isoflurane anaesthesia (mean ( sd ) 40% MAP time 498 (95) and 378 (104) s respectively). In all animals in the isoflurane group, spontaneous circulation returned within 1 min of the start of CPR. In six of the TIVA animals, spontaneous circulation returned for 220 (121) s; spontaneous circulation did not return within 5 min in the remaining four animals. Conclusions. Although TIVA is less prone than isoflurane anaesthesia to primary cardiovascular depression leading to asphyxia, TIVA is associated with reduced effectiveness of CPR in which resuscitation because of asphyxic haemodynamic depression occurs.

Abstract: OBJECTIVE: The present study was undertaken to examine specific features of unintentional traumatic asphyxial deaths in childhood. METHODS: Coronial files and records at the Forensic Science Centre in Adelaide, South Australia, were examined over a 35-year period from 1966 to 2000 for all cases of traumatic asphyxial death occurring in children under the age of 17 years. RESULTS: Six cases of unintentional fatal traumatic asphyxia were identified. All of the victims were boys with an age range of 2-15 years (mean 6.8 years) and all were found dead at the scene. Fatal traumatic asphyxia resulted from entrapment beneath a chest of drawers, beneath a table tennis table, between a pile of wooden pallets and a metal fence, between a conveyor belt and its frame, and under a motor vehicle (in two cases). CONCLUSIONS: Fatal traumatic asphyxia in childhood is a rare event, with younger children commonly being trapped by furniture or by industrial equipment while playing, and older children being trapped under motor vehicles in similar circumstances to adult traumatic asphyxial deaths. Unsupervised play of young children around heavy and potentially unstable pieces of furniture may be dangerous, particularly if more than one child is present. Unsupervised play of young children in industrial yards should be avoided. Language: en

Abstract: The formation of oxygen-derived free radicals in hypoxic and ischemic/reperfused brains has been proposed as an important step that links brain injury to neuronal death. Previously, we have demonstrated that reactive oxygen species (ROS) production was significantly increased in rat neostriatum during acute perinatal asphyxia (PA) in pups. In this article, we have studied the time course of ROS production in the neostriatum and neocortex of adult rats subjected to PA using electron spin resonance spectrometry (ESR) in order to record ROS production. Further more, we analyzed the actions of hypothermia on ROS release in pups and adult rats. We used for this study 6-month-old rats that suffered sub-severe and severe PA when they were pups. The most significant production of ROS was detected either in the neostriatum or neocortex at 19 and 20 min of PA. Hypothermia during 20 and 100 min at 15 degrees C prevented ROS formation either in pups and adult rats. These data further support the concept that free radicals may contribute to the brain injury alterations and that hypothermia can prevent long-term sequelae induced by PA.

Abstract: Necrotizing enterocolitis (NEC) is the most common acquired gastrointestinal emergency in neonates. We have developed an animal model of NEC in asphyxiated newborn pigs and investigated the effects of asphyxia on blood flow in superior mesenteric artery and abdominal aorta, cardiovascular data, arterial acid-base and blood gas parameters, and endothelial cytoskeletal structure in mesenteric microvasculature. Anesthetized, mechanically ventilated newborn pigs were included in two groups: piglets underwent severe asphyxia, and sham-operated control animals. A cardiovascular and metabolic failure developed in asphyxiated piglets approximately 1 h after the induction: severe hypotension and bradyarrhythmia were seen and significant reductions of the blood flow were measured in the superior mesenteric artery and abdominal aorta during the critical phase. Rearrangement of cytoskeletal actin structure corresponding to enhanced vascular permeability was seen with bodipy phallacidin in mesenterial endothelium of asphyxiated piglets after a 24-h recovery period. In conclusion, severe vasomotor changes during asphyxia may result in mesenteric endothelial dysfunction implicated in increased vascular permeability, edema formation, and development of NEC in asphyxiated piglets.

Abstract: The purpose of this study was to determine the number of deaths which were caused by choking in a 10 year period in the Irish psychiatric in-patient population and the factors associated with such deaths.

Abstract: The effect of asphyxia on iron metabolism and lipid peroxidation in newborn infants with hypoxic-ischemic encephalopathy (HIE) was investigated. Non-protein-bound iron (NPBI) and lipid peroxidation (thiobarbituric-acid-reactive species; TBARS) in plasma and hematological iron indices were measured in 15 healthy newborn infants (mean gestational age 39 04 weeks, SD 1); 15 asphyxiated infants without neurological abnormalities (AS-HIE; mean gestational age 38.8 weeks, SD 0.9); and 15 asphyxiated infants with neurological abnormalities (AS+HIE; mean gestational age 39.75 weeks, SD 1.4). Follow-up was performed at the age of 5 months. It was found that the detectable rates of NPBI in 10 of 15 of the AS-HIE group and 13 of 15 of the AS+HIE group were significantly higher than that of the control group (5 of 15; both p < 0.01). Plasma levels of TBARS in the control (9.20 micromol/L, SD 1.9) and AS-HIE infants (10.13 micromol/L, SD 2.7) were significantly lower than those of the AS+HIE group (13.42 micromol/L, SD 2.8). Serum iron, total iron binding capacity, and transferrin saturation in the AS+HIE group was higher than the corresponding values of the control and AS-HIE groups, although no statistical difference was found among them. At 5 months of age, all control and AS-HIE infants were neurologically normal, whether or not their NPBI was detectable. Of the 12 AS+HIE infants, four (all of whom had detectable NPBI) were neurologically impaired. The average Gross Development Quotient of AS+HIE infants was significantly lower than that of the control or AS-HIE groups (p < 0.01). Results showed that asphyxia could affect iron metabolism and lead to a significant increase in NPBI and lipid peroxidation in newborn infants with HIE, indicating that iron delocalization induced by asphyxia plays a role in the brain injury of asphyxiated infants.

Abstract: Neonatal asphyxia results in hypoxic-ischaemic encephalopathy. Previous studies have demonstrated that brain hypoxia and ischaemia lead to the production of proinflammatory cytokines, including tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and IL-6. Transcription factor NF-kappaB is essential for the expression of these cytokines. We examined whether or not NF-kappaB is activated in peripheral mononuclear cells (PBMC) in neonatal asphyxia by flow cytometry. In addition, we examined the relationship between NF-kappaB activation in PBMC and the neurological prognosis. Flow cytometry analysis demonstrated that the level of NF-kappaB activation in CD14+ monocytes/macrophages of the patients with asphyxia who had neurological sequelae was significantly higher than in the controls, and in the patients with asphyxia who survived (31.7 +/- 7.2%versus 2.5 +/- 0.9%, P = 0.008, and versus 1.6 +/- 1.4%, P = 0.014, respectively). Our findings suggest that NF-kappaB activation in peripheral blood CD14+ monocytes/macrophages in neonatal asphyxia is important for predicting the subsequent neurological sequelae.

Abstract: Background: Early detection and quantification of brain damage in neonatal asphyxia is important. In adults, S100 protein in blood is associated with damage to the central nervous system. Objective: To determine whether S100 protein can be detected in arterial and venous cord blood of healthy newborns and to relate S100 protein concentrations in cord blood to mode of delivery. Method: S100 protein levels in umbilical cord blood of 81 healthy infants were determined. Results: S100 protein was present in arterial (median concentration 1.62 μg/l) and venous (median concentration 1.36 μg/l) cord blood. Levels were significantly higher in vaginal births (median arterial concentration 1.72 μg/l; median venous concentration 1.48 μg/l) than births by caesarean section (1.51 μg/l and 1.26 μg/l respectively). Conclusion: More research is necessary to determine whether S100 protein is a useful marker in neonatal asphyxia.

Abstract: In asphyxiated newborn infants, cholestasis often leads to extensive investigations and a cause can rarely be found.