Abstract: A neonatal lamb model has been developed to examine the regulation of cerebral blood flow (CBF) and oxygen metabolism during the critical period after an asphyxial insult. Nine newborn lambs had control measurements and timed measurements after asphyxia of CBF (radioactive microsphere technique), arterial and cerebral venous (sagittal sinus) blood gases and oxygen contents performed. Immediately after resuscitation from asphyxia, there was a marked increase in CBF compared to control (239 +/- 22 versus 82 +/- 7 ml X 100 g-1 X min-1, mean +/- SEM; p less than 0.01). Cerebral oxygen delivery (CBF X arterial O2 content) increased from 12.87 +/- 1.20 to 37.40 +/- 3.40 ml X 100 g-1 X min-1 (p less than 0.01), while cerebral O2 consumption was significantly decreased compared to control (4.75 +/- 0.42 to 3.42 +/- 0.46 ml X 100 g-1 X min-1, p less than 0.05). Cerebral fractional O2 extraction, the relationship between oxygen uptake and delivery fell from 0.38 +/- 0.03 to 0.09 +/- 0.02; p less than 0.01. This reactive hyperemia was followed in all animals by a period of hypoperfusion. CBF (52 +/- 4 ml X 100 g-1 X min-1), O2 delivery (7.94 +/- 0.50 ml X 100 g-1 X min-1), and cerebral O2 consumption (3.34 +/- 0.24 ml X 100 g-1 X min-1) were all significantly depressed when compared to control. These data demonstrate important changes in CBF and O2 metabolism after neonatal asphyxia that may be important to the pathogenesis of brain injury.

Abstract: The serum activity of SGOT and SGPT is one of the more specific parameters of liver cell injury both in adults and in the pediatric age-group. The determination of serum transaminase activity could offer a routine and rapid laboratory test for establishing the presence of hepatic cellular damage following intrauterine or perinatal asphyxia. In fact, it appears that there is a correlation between hypoxia and the increase in serum activity of transaminases in full-term and premature asphyxiated newborns. However, this increase is reversible up to the 30th day of life. The behavior of transaminase enzymatic activity in premature asphyxiated newborns compared to full-term asphyxiated newborns suggests a higher resistance of membranes to hypoxic-ischemic injuries and a lower enzymatic pool of cellular metabolism in premature newborns. Therefore, knowledge of the behavior of SGOT and SGPT activity may have important implications in the diagnosis and early treatment of perinatal asphyxia.

Abstract: Asphyxia, with its attendant hypotension, is by far the most common cause of neonatal cerebral infarction and frequently results in lesions of the parieto-occipital white matter. This study examines the effects of hypotension on regional cerebral blood flow (CBF), local cerebral glucose utilization (LCGU), and serum prostaglandin levels in newborn beagle pups. The animals (24 to 96 hours old) were anesthetized, tracheotomized, and paralyzed. Pups were randomly divided into two groups: one was subjected to hemorrhagic hypotension and the other received no insult. Hypotension was induced by slow venous hemorrhage to maintain a mean arterial blood pressure of 20 to 30 mm Hg. Autoradiographic determinations of LCGU using carbon-14 (14C)-2-deoxyglucose were performed 45 minutes after randomization to groups. Autoradiographic determinations of CBF were performed using 14C-iodoantipyrine on a second group of pups 15 minutes after randomization. Prostaglandins were measured immediately before and 15 minutes after insult or control manipulation. There were no significant differences in the values for thromboxane B2 or 6-keto-prostaglandin F1 alpha, the stable breakdown products of thromboxane A2, and prostacyclin. Prostaglandin E2 levels significantly increased in response to hemorrhagic hypotensive insult. In addition, although regional CBF was maintained in cortical and central gray matter structures during hypotension, CBF to the periventricular temporal and parietal white matter zones significantly decreased, and LCGU was increased in these same regions during hypotensive insult. The uncoupling of CBF and metabolism in these periventricular white matter regions may be responsible for the neuropathological sequelae of perinatal asphyxia.

Abstract: An analysis of antepartum, intrapartum, and postpartum variables was performed in a retrospective controlled study of 34 normally formed term infants who had perinatal asphyxia and subsequently displayed generalised seizures within 48 hours of birth. The aim was to identify any association, firstly between these variables and seizures, and secondly between these variables and subsequent morbidity and mortality among the seizure group. Maternal age greater than 35 years, duration of labour, meconium stained liquor, abnormal intrapartum fetal heart rate trace, and operative delivery were associated with seizures. A low Apgar score at five minutes, and intermittent positive pressure ventilation at birth of longer than 10 minutes were associated with subsequent morbidity and mortality. A striking relation between poor intrauterine growth and either death or handicap in the asphyxia group emphasised the value of growth measurements as a predictor of outcome. The overall incidence of seizures was 1.6 per 1000 term deliveries. There was a significant correlation between the seizure incidence and the intrapartum mortality rate. The incidence of seizures secondary to asphyxia in term infants, occurring less than 48 hours after delivery, may be a valuable index of the quality of perinatal care.

Abstract: Cerebrovascular volume and transmural pressure loads accompanying acute increases in cerebral blood flow are implicated in the pathogenesis of periventricular-intraventricular hemorrhage in preterm infants. An acute increase in cerebral blood flow would be expected during acute recovery from asphyxia. Therefore, cerebrovascular hemodynamics, including flow (microspheres), were studied during and after acute recovery from asphyxia in seven newborn dogs in order to study the determinants of these volume and pressure loads. During the acute recovery phase, cerebral hemispheric blood flow was 69.6 ± 10 ml/100 g/min (mean ± SEM) representing a 250% increase from baseline values of 19.9 ± 1.8 ml/100 g/min (p < 0.005), while combined cerebellar-brainstem flow was 204.3 ± 19.3 ml/100 g/min representing a 536% increase from baseline values of 32.0 ± 1.5 ml/100 g/min (p < 0.005). Blood flow to both areas had returned to baseline levels 20 min after the onset of recovery. Associated with this cerebral hyperemia was an acute increase in mean arterial pressure from 21.3 ± 4.5 mm Hg at end asphyxia to 69.5 ± 6.0 mm Hg at peak recovery (p < 0.01), and parallel acute increases in sagittal sinus pressure (from 4.0 ± 0.4 to 14.6 ± 1.9 mm Hg, p ±.01) and cerebrospinal fluid pressure (from 3.8 ± 0.4 to 14.3 ± mm Hg, p <1). Central venous pressure fell from 4.3 ± 6 mm Hg at end asphyxia to 1.6 ± 0.5 mm Hg, and thus is not a determinant of the elevation in sagittal sinus pressure. AH of these pressure changes were attained within 20–30 s of the onset of recovery. Assuming that acute changes in cerebrospinal fluid pressure reflect acute changes in cerebrovascular volume via the cranial compliance (volume/pressure) relationship, then the acute (<30s) elevation of cerebrospinal fluid pressure reflects an acute cerebrovascular volume load. Also, the elevated cerebrospinal fluid pressure considerably modifies both the cerebral arterial and venous transmural pressures. The cranial compliance relationship thus plays a key role in determining both volume and transmural pressure loads. We propose that the combination of a high cranial compliance and frequent acute cerebral flow/volume loads may be involved in the pathogenesis of periventricular-intraventricular hemorrhage in premature newborn infants.

Abstract: Thirty four consecutive neonates with birth asphyxia or respiratory problems were examined in the first week of life to clarify the relation between neonatal myoglobinuria and acute renal failure. Investigations included determination of creatinine clearance, fractional sodium excretion, and N-acetyl-beta-D glucosaminidase index as an indicator of tubular injury. The infants' gestational ages ranged from 29 to 41 weeks (mean 36 weeks). Fifteen infants did not have myoglobinuria on the first day of life (group A); myoglobinuria was mild in eight infants (group B) and severe in eleven (group C). Two infants in group B and seven in group C developed acute renal failure (47%). Ten infants in group C (91%) had severe asphyxia, five of whom (45%) also suffered neonatal seizures and intracranial haemorrhage. We suggest that myoglobin derived from muscle breakdown in asphyxiated infants may lead to acute renal failure secondary to a reduction in renal blood flow, or to tubular damage.

Abstract: Previous studies have shown that severe neonatal asphyxia and hypoxia lead to a redistribution of cerebral blood flow (CBF) with a preferential perfusion of the brain stem.

Abstract: Levels of ascorbic acid (AA) in the plasma, brain, and adrenal gland of rats were determined after 15 min of hypoxia (PaO2 less than 25 mm Hg) and following asphyxia. In rabbits, AA plasma levels were followed up to 75 min of reoxygenation following 15 min of hypoxia of the same severity. A significant increase (approximately 70%) in AA levels was found in plasma of rats and rabbits after hypoxia and asphyxia. This increase was found to be transient, with a return to normal levels within 1 h after resumption of normal oxygenation. Pretreatment with dexamethasone reduced the increase in AA level in both rabbits and rats. Adrenalectomy in rats, performed 24 h before the experiment, abolished the response to hypoxia. Ascorbate levels in the cerebral cortex, hypothalamus, and adrenal gland of awake rats subjected to hypoxia or asphyxia were found to be the same as in normoxic rats. Our results suggest that the observed changes in plasma AA levels are probably mediated through adrenocorticotropic hormone and that the adrenal gland is the major source of ascorbate efflux into the circulation during oxygen deprivation.

Abstract: Cardio-respiratory responses to asphyxia produced by decreased uterine perfusion were studied in 15 sheep fetuses. In chronic (spinal-anesthetized) and acute (inhalation-anesthetized) preparations, we measured fetal PO2, PCO2, pH, heart rate, arterial and umbilical venous pressures at rest and 5 min after controlled reductions of maternal aortic blood flow. Umbilical blood flow was determined by electromagnetic flow transducer on the fetal descending aorta with the iliac arteries ligated, in conjunction with radionuclide-labelled microspheres. In contrast to previous studies in which fetal hypoxaemia was produced by decreased maternally inspired O2 concentrations, decreasing degrees of uterine perfusion were associated with increasing degrees of hypercapnea and acidemia, as well as hypoxaemia. In chronic experiments, heart rate and umbilical blood flow fell significantly in response to decreased uterine perfusion with all degrees of hypoxaemia studied. In acute experiments, during the control period, PO2 values were similar to those of chronic experiments while values for pH and umbilical blood flow were lower and those for umbilical vascular resistance were higher. In the acute experiments, hypoxic stresses identical to those in the chronic studies failed to produce significant hemodynamic changes, except for bradycardia in response to severe hypoxaemia. These differences were apparently due to the pharmacologic effects of halothane and the operative stresses.

Abstract: Cord blood gas determinations were made on arterial and venous blood from 78 babies weighing less than 2000 gm at birth, including 52 weighing 1500 gm or less Correlations were made with Apgar scores and intrapartum events as well as with birthweight (BW) and gestational age (GA) Significant differences were seen between mean BW, GA, and Apgar scores for survivors versus nonsurvivors but only BW and GA were found to affect mortality The incidence of low Apgar scores, which was high, was inversely related to BW and GA Correlations between cord blood gases and Apgar scores were poor, most newborns showing normal gases irrespective of Apgar scores The authors conclude that the term "asphyxia" is an overused explanation for low Apgar scores among very low birthweight babies; they believe it should be reserved for those depressed states proved to be associated with disturbed respiratory physiology

Abstract: The brain damage which results from a combination of systemic hypoxia and reduced cerebral blood flow (ischemia) in the fetus and newborn infant remains a major cause of chronic neurological disability. Hypoxia denotes a partial lack of oxygen with or without concurrent accumulation of carbon dioxide. Asphyxia is that state in which pulmonary or placental gas exchange ceases, resulting in progressive hypoxemia or anoxemia combined with hypercapnia. Ischemia is a reduction in or cessation of blood flow. It rarely occurs during the perinatal period without antecedent hypoxia or asphyxia.

Abstract: This study was undertaken to investigate the effects of neonatal asphyxia on brain development, with special reference to the kinetics of neuronal proliferation by using autoradiography. For 30 minutes, two-day-old suckling mice, Jcl:ICR strain, were put into a chamber which was constantly flushed with 100% CO/sub 2/ gas. After the exposure to asphyxia, 29% of the mice survived. Cell cycle studies were carried out at two days and at seven days on the external matrix cells, the precursor of the granule cells, at the external granular layer of the cerebellum from CO/sub 2/-exposed and control mice by /sup 3/H-thymidine autoradiography. At two days the generation time of the control mice was about 15 hours, whereas that of the asphyxiated mice was about 17 hours. The prolongation of the generation time in the asphyxiated mice was caused mainly by a delay in the G2 phase. This prolongation was apparent for about five days and thereafter growth caught up. These results suggest that neonatal asphyxia has an adverse effect on cerebellar neuronal proliferation that may revert to normal spontaneously in older animals.

Abstract: There are conflicting opinions about the significance of 5 perinatal findings felt to be indicators of asphyxia (meconium staining of the amniotic fluid, abnormal fetal heart rate patterns, acidotic fetal scalp blood gases, low Apgar scores, and acidotic cord blood gases). A review of the literature was undertaken to determine the strength of association of each of these findings with adverse outcomes. Although all studies contained methodological problems, these indicators were found to have strong associations with one or more adverse outcomes such as perinatal death, low Apgar scores or cerebral palsy. The strength of the association (relative risk) was found to vary inversely with the prevalence of the outcome.

Abstract: To evaluate the effect of chronic beta 1-adrenoceptor blockade on physiological adaptation to asphyxia a study was done on exteriorized sheep fetuses of 127-142 days gestational age. Eleven pregnant ewes were infused with metoprolol for 5 days prior to experiment. Another 10 ewes were infused with saline and served as controls. Asphyxia was induced by intermittent complete obstruction of maternal placental blood flow. Fetal electro-cardiogram, heart rate, cardiac output, myocardial contractility and cerebral blood flow were measured together with blood pH, lactate and hypoxanthine. Neurophysiological responses were evaluated by changes in somatosensory evoked electroencephalogram. The beta 1-blocked fetuses showed less responsiveness in myocardial contractility and heart rate during reoxygenation. This curtailed reaction resulted in accelerated lactic acidosis, increased break-down of intracellular energy rich substances and impaired cerebral function. Nine of the ten controls survived the experiment and 8 of them regained their somatosensory evoked EEG potentials, whereas 7 of the 11 beta-blocked fetuses survived and only 3 regained original somatosensory evoked EEG potentials. It is concluded that beta 1-adrenoceptor blockade impairs the adaptive responses to asphyxia in the ovine fetus and decreases its ability to survive severe asphyxia.

Abstract: It has been reported that approximately 45-55% of all premature infants born weighing less than 1,500gm were found to have periventricular-intraventricular or intracerebral hemorrhage (PVH/IVH). A relatively prominent blood supply, tenuous integrity, impaired autoregulation of the capillaries in the germinal matrix and the environmental factors have been proposed as the major pathogenesis of the hemorrhage. A real time sector scanner (ATL, Mark Ⅲ) with portable equipment was used for evaluating intracranial lesions of 92 premature infants in Changhua Christian Hospital in the period May to September 1983. These babies had the gestational age ranged from 26 to 36 weeks (mean 30.78±2.41 week) and with birth weight ranged from 700gm to 2,490gm (mean 1,583±514 gm). Fifty-one of them developed PVH/IVH. The mean gestational age, mean birth weight and Apgar scores were lower in those infants with hemorrhage and resuscitation during birth was usually needed, too. During the five-month period, the infants with birth weight of 1,500gm or less and with a gestational age of less than 32 weeks were routinely surveyed. The other group of preterms weighing from 1,500 gm to 2,500 gm were also scanned whenever hemorrhage was supsected. We found that 58.33% of the infants with gestational age of 32 weeks or less and 56% of babies weighing under 1,500gm suffered a PVH/IVH. The incidence of hemorrhage decreased dramatically with gestational Period more than 32 weeks and birth weight above 1,500 gm infants. Besides, certain identifiable risk factors, such as: prematurity, asphyxia, need for resuscitation, postnatal transfer, RDS, mechanical ventilation, hypercapnia acidosis, hypothermia, hypotension were analyzed in relation to the development of PVH/IVH. Meanwhile, sonographic grading of intracerebral hemorrhage can be used as an important prognostic indicator of these infants.

Abstract: The effects of anaesthetic agents, per se, on the asphyxiated foetus are difficult to quantitate clinically. Anaesthesia is often necessary in foetal distress, however, to effect a rapid delivery. To investigate the effect of general anaesthetic agents commonly used for Caesarean section we administered these agents to 18 chronically prepared pregnant ewes with asphyxiated foetuses in utero. The foetuses were asphyxiated by partial occlusion of the umbilical cord until foetal arterial pH had decreased from 7.30 to a range of 7.08–7.13. The animals were divided into three groups: Group A which received no anaesthesia and thus served as a control, Group B which received thiopentone (3 mg·kg-1) intravenously followed by 50 per cent nitrous oxide and 0.5 per cent halothane in oxygen for 15 minutes, and Group C which received thiopentone (3 mg·kg-1 ) followed by one per cent halothane in oxygen for 15 minutes. Foetal cerebral, myocardial, and renal blood flows were measured by injection of radioactive microspheres after production of asphyxia and after 5 and 15 minutes of anaesthesia. General anaesthesia in both groups B and C abolished the hypertension and bradycardia produced by foetal asphyxia secondary to umbilical cord occlusion. There were no significant differences between Groups B and C in foetal pH, PCO2, or PO2. Two foetuses in the nitrous oxide group died after ten minutes of anaesthesia, but the aetiology of the sudden demise is unclear. We conclude that general anaesthesia abolishes the foetal response to umbilical cord occlusion and does not improve foetal oxygenation or acid-base status.

Abstract: An animal model for studying the relationship between perinatal asphyxia and hyaline membrane disease (HMD) is described. The HMD developed in these Macaca mulatta (rhesus) and M. arctoides (stump tail) monkeys was clinically, physiologically, and histologically similar to that seen in human infants. The monkeys were delivered by cesarean section at a gestational age of 85-91% of term when surfactant, though present, was less than mature levels. Asphyxia at birth proved to be an important factor in disease development. Five minutes of asphyxia immediately before the first breath greatly increased the incidence and severity of HMD when compared to nonasphyxiated controls of a similar gestational age. Amniotic fluid L/S ratios did not differ significantly in the asphyxiated and control groups but data based on static pressure-volume studies of the excised lungs indicated that the surfactant activity of the asphyxiated group was significantly less. Lung maturity with regard to surfactant production appears to be a critical factor. The data from these experiments, together with data cited in the literature, strongly suggest that the lung and its surfactant system is most vulnerable to hypoxia and/or acidosis during the early stages of surfactant production. The asphyxiated non-human primate model used here should prove valuable for studying the pathogenesis of HMD and especially for further clarifying the relationship between perinatal asphyxia and HMD.

Abstract: Umbilical cord haematoma is an infrequent condition associated with high perinatal and fetal mortality and morbidity. This report describes a rare case of umbilical cord haematoma associated with loss of fetal beat to beat variation during labour. The infant exhibited mild asphyxia only. Previous publications are reviewed and fetal heart rate changes associated with umbilical cord haematoma are discussed.

Abstract: Twenty newborn infants with birth asphyxia were alternately assigned to ventilation with either the Samson or the Laerdal infant resuscitator During resuscitation significantly greater percentage changes in pH (1,1% v 0,2%; P less than 0,05), hydrogen ion concentration (-15,6% v -2,1%; P less than 0,05) and partial arterial carbon dioxide pressure (-24,5% v -11,9%; P less than 0,02) were seen in the Laerdal group There was also a tendency towards improved oxygenation and lung compliance and quicker establishment of spontaneous respiration in the Laerdal group We therefore conclude that the Laerdal resuscitator is superior to the Samson one in the management of infants with birth asphyxia