Abstract: Although nucleated red blood cells (nRBCs) are rarely found circulating in older children,1 they are commonly seen in the blood of newborns. They are primarily produced in the fetal bone marrow in response to erythropoietin and are stored in the marrow as precursors to reticulocytes and mature erythrocytes. Many acute and chronic stimuli cause increases in the number of circulating nRBCs from either increased erythropoietic activity or a sudden release from the marrow storage pools. This paper reviews the various pathological processes associated with increased production and release of nRBCs. It emphasises the effects of acute, subacute, and chronic asphyxia on nRBC counts.#### Key message 1 Common causes of increased nucleated red blood cells include prematurity, increased erythropoiesis from chronic hypoxia, anaemia, and maternal diabetes, from acute stress mediated release from the marrow stores, and from postnatal hypoxia. Extreme increases may occasionally be idiopathic. #### Key message 2 When increased nRBC counts are seen with acute and subacute asphyxia, the magnitude of the increase is a function of the severity and duration of the asphyxia. However, there is a large overlap between the nRBC values found after acute, subacute, and chronic asphyxia; asphyxia of any duration does not always cause an increased nRBC count, and extreme increases may be found without asphyxia. Nucleated red blood cells are sometimes called erythroblasts, normoblasts, or normocytes. For this review, the term “normoblasts” will be used to refer to the cells when they are in the bone marrow and “nRBCs” when they are in circulating blood. Clinically it is best to express nRBCs as an absolute number of cells per unit volume, either “nRBCs/mm3” or “nRBCs/l”. However, most clinical laboratories and many research publications report nRBCs relative to 100 white blood cells (WBCs). Unfortunately the extreme variability in the number of leucocytes …

Abstract: Asphyxia remains one of the main causes of later disability in term infants. Despite many publications identifying possible predictors of outcome in this population of interest, little is known of the long-term developmental outcome of asphyxiated term neonates. Observational studies have largely focused on short-term outcomes, with an emphasis on significant neurologic sequelae and intellectual impairments. This article reviews the literature that has described the developmental outcome of asphyxiated term newborns. As part of this review, we have also highlighted the evolution of the definition of asphyxia and delineated appropriate markers that should be used in future research on this population.

Abstract: Background Previous research has found an association between obstetric complications and schizophrenia, but in many studies the sample size was limited, and no assessment of specific exposures was possible. Aims To assess the role of different complications, and in particular to distinguish between disordered foetal development and hypoxia at birth. Method From the Stockholm County In-Patient Register and community registers, we identified 524 cases of schizophrenia and 1043 controls, matched for age, gender, hospital and parish of birth. Data on obstetric complications were obtained from birth records. Results There was a strong association between signs of asphyxia at birth and schizophrenia (OR 4.4; 95% C11.9-10.3) after adjustment for other obstetric complications, maternal history of psychotic illness and social class. Conclusions Signs of asphyxia at birth are associated with an increased risk of schizophrenia in adults.

Abstract: Objective: Twenty-six patients with accidental hypothermia combined with circulatory arrest or severe circulatory failure were rewarmed to normothermia by use of extracorporeal circulation (ECC). The aim of the present study was to evaluate our results. Patients and methods: The treatment of six female and 20 male patients (median age: 26.7 years; range 1.9‐76.3 years) rewarmed in the period 1987‐2000 was evaluated retrospectively. Hypothermia was related to immersion/submersion in cold water (na 17), avalanche (na 1) or prolonged exposure to cold surroundings (na 8). Prior to admission, the trachea was intubated and cardiopulmonary resuscitation (CPR) initiated in all patients with cardiorespiratory arrest (na 22), whereas in those with respiration/circulation (na 4) only oxygen therapy via a facemask was given. Results: Nineteen of the 26 patients were weaned off ECC whereas seven died because of refractory respiratory and/or cardiac failure. Eight of the 19 successfully weaned patients were discharged from hospital after a median of 10 days. One patient died 3 days after circulatory arrest (complete atrioventricular block) resulting in severe cerebral injury. The remaining ten patients died following 1‐2 days due to severe hypoxic brain injury (na 5), cerebral bleeding (na 1) or irreversible cardiopulmonary insufficiency (na 4). Based on the reports from the site of accident, two groups of patients were identified: the asphyxia group (na 15) (submersions (na 14); avalanche accident (na 1)) and the non-asphyxia group (na 11) (patients immersed or exposed to cold environment). Seven intact survivors discharged from hospital belonged to the nonasphyxia group whereas one with a severe neurological deficit was identified within the asphyxia group. Conclusion: Patients with nonasphyxiated deep accidental hypothermia have a reasonable prognosis and should be rewarmed before further therapeutic decisions are made. In contrast, drowned patients with secondary hypothermia have a very poor prognosis. The treatment protocol under such conditions should be the subject for further discussion. q 2001 Elsevier Science B.V. All rights reserved.

Abstract: Objective: To assess the impact of time of birth on infant mortality and early neonatal mortality in full term and preterm births. Design: Analysis of data from the Swedish birth register, 1973-95. Participants: 2 102 324 spontaneous live births of infants without congenital malformation. Outcome measurements: Absolute and relative risk of infant mortality, early neonatal mortality, and early neonatal mortality related to asphyxia. Results: Infant mortality, early neonatal mortality, and early neonatal mortality related to asphyxia were higher in infants who were born during the night (9 pm to 9 am) compared with those born during the day for 1973-9, 1980-9, and 1990-5. The difference was more dramatic for preterm infants. The largest difference was observed during 1990-5, when there was a 30% increase in early neonatal mortality (relative risk 1.31, 95% confidence interval 1.10 to 1.57) and a 70% increase in early neonatal mortality related to asphyxia (1.70, 1.22 to 2.38) in preterm infants born during the night compared with rates for preterm infants born during the day. A detailed analysis over 24 hours revealed two “high risk” periods: between 5 pm and 1 am and around 9 am. Conclusions: Infants born during the night have a greater risk of infant and early neonatal mortality and early neonatal mortality related to asphyxia than those born during the day. There has been no improvement over the past two decades. The problem is more serious for preterm births and was even worse in the 1990s. Shift changes and the hours immediately after such changes are high risk periods for neonatal care. What is already known on this topic Infants born at night have a greater risk of early neonatal mortality and early neonatal mortality related to asphyxia than those born during the day The causes are unclear but may be related to insufficient or less experienced staff or excess workload during the night What this study adds In Sweden the relative risks of infant and early neonatal mortality and mortality related to asphyxia for infants born during the night compared with during the day did not diminish during 1973-95, are greater for preterm infants, and were greater in the 1990s There are two “high risk” periods for early neonatal mortality: 5 pm to 1 am and around 9 am The exact reasons are unclear but better vigilance and an improvement in shift changes may be required to improve neonatal health care further

Abstract: Asphyxia during delivery is considered a main cause of stillbirth in pigs, but piglets suffering from intermittent asphyxia during delivery are also less viable at birth and less prone to adapt to extrauterine life. In an effort to improve pig viability, one attractive solution would be to increase oxygen supply through oxygen inhalation by the newborn pig. The objective of this study was to test effects of oxygen inhalation immediately after birth on various physiological parameters and piglet survival. The experiment was performed on 252 Pietrain x Large White piglets, half of them reoxygenated immediately after birth. They were maintained during 20 min in a chamber where oxygen concentration was monitored at 40% and were then put back with the sow and the control pigs. Oxygen inhalation affected piglet metabolism. Through stimulation of oxidative metabolism (reduction of circulating levels of lactate) and lowering of the level of postnatal hypothermia (particularly for the lightest pigs), oxygen inhalation increased piglet viability and reduced mortality during the 1st d of life by 75% (2 vs 8%). No additional effects were observed during the following days and overall mortality between birth and weaning at 21 d was reduced from 12 to 8%.

Abstract: Objective : To investigate the long-term neuropsychological consequences of perinatal asphyxia (PA). Methods : A group of adolescents were assessed with antecedents of mild ( n = 8) and moderate ( n = 20) PA, and a matched group of 28 healthy adolescents as a control group. Neuropsychological assessment included tests of memory, perceptual-motor skills, and frontal lobe functions, because these are areas of cognitive functioning susceptible to hypoxic conditions. Results : Subjects with moderate PA showed significant differences from the control group on tests related to delayed recall for both verbal and visual information, perceptual-motor speed, and tests assessing attention and executive functions. Conversely, subjects in the mild PA group exhibited scores which were similar to those of the control group in all the assessed variables. Conclusion : The present findings demonstrate that subtle but persistent neuropsychological deficits were observed in adolescents with antecedents of moderate PA, but no...

Abstract: The onset and duration of hypoxic-ischemic (HI) insults rarely can be determined precisely in perinatal asphyxia. The need to establish the timing of HI insults will be critical for the successful application of evolving neuroprotective therapies that may be administered to the asphyxiated newborn. Diffusion-weighted magnetic resonance imaging has emerged as an imaging technique that can be used to identify HI brain injury before the detection of abnormalities by conventional magnetic resonance imaging. This case illustrates the early changes in diffusion-weighted and conventional magnetic resonance imaging studies and in quantitative values of the apparent diffusion coefficient in a unique case of neonatal asphyxia in which the onset and duration of the HI insult were known. Pediatrics 2001;108: 1211-1214; hypoxia-ischemia, newborn brain, perinatal l asphyxia, diffusion-weighted imaging, proton magnetic resonance spectroscopy.

Abstract: The basic mechanisms leading to cell death in birth asphyxia are becoming better known. Some of these are excitotoxicity, inflammation and oxidative stress. In the so-called therapeutic window -between the primary and secondary energy failure - modulation of these processes may be beneficial, reducing apoptosis and perhaps necrosis. In order to reduce oxidative stress, reoxygenation with low oxygen concentrations, even as low as room air, might be beneficial. Increased oxidative stress might have long-term effects on brain growth and development and there is evidence indicating that exposure to 100% oxygen after birth for only a few minutes might have long-term effects. New guidelines for newborn resuscitation have recently been published but more research is needed in this field, especially regarding resuscitation of preterm infants, where few data exist.

Abstract: The purpose of the present study was to determine whether endotoxins (lipopolysaccharides, LPS) affect the fetal cardiovascular system in a way likely to cause brain damage. Thirteen fetal sheep were chronically instrumented at a mean gestational age of 107 ± 1 days. After control measurements of organ blood flow (microsphere method), blood gases, and acid base balance were obtained, seven of 13 fetuses received LPS (53 ± 3 μg/kg fetal weight) intravenously. Sixty minutes later, asphyxia was induced by occlusion of the maternal aorta for 2 minutes. Measurements of organ blood flows were made at −60, −1, +2, +4, +30, and +60 minutes. Unlike in the control group, after LPS infusion there was a significant decrease in arterial oxygen saturation (−46%; P < .001) and pH (P <. 001). In LPS-treated fetuses the portion of combined ventricular output directed to the placenta decreased significantly (−76%; P <. 001), whereas output to the fetal body (+60%; P <. 001), heart (+167%; P <. 05), and adrenals (+229%; P <. 01) increased. Furthermore, during asphyxia circulatory centralization was impaired considerably in LPS-treated fetuses, and there was clear evidence of circulatory decentralization. This decentralization caused a severe decrease in cerebral oxygen delivery by 70%. Wihin 30 minutes after induction of asphyxia five of seven LPS-treated featuses died, whereas all control fetuses recovered completely. Endotoxemia severely impaired fetal cardiovascular control during normoxia and asphyxia, resulting in a considerable decrease in cerebral oxygen delivery. These effects might have important effects in the development of fetal brain damage associated with intrauterine infection.

Abstract: Asphyxia is a name given to different kinds of lesions that can produce similar histologic findings. Thus, because of the varied nature of the different kinds of lesions, as well as the incidence of similar qualitative histologic findings with different causes, the aim of this work was to study special kinds of injuries with particular subsequent impairment. These include some diagnostic problems of sudden death of natural causes, including aspiration, suffocation, drowning, and strangulation. Ranking was made of 167 victims based on the diagnosis as having: aspiration (n = 35), suffocation (n = 88), drowning (n = 27), and strangulation (n = 17). Stepwise discriminant analysis of the resulting data showed that lung necropsies from victims of these four events could be distinguished from one another. Statistical differences among the four groups were observed for eight morphologic parameters. A robust discriminant function permitted an adequate classification of the four groups of disease in 85.03% of the cases. Lung autopsies with congestion, septal hemorrhage, and foreign body showed a specificity of 100% for victims of aspiration, whereas ductal overinsufflation, interstitial edema, and bronchiolar constriction showed a specificity of 81.8% in victims of suffocation. Intraalveolar edema and dilatation of the alveolar spaces with secondary compression of the septal capillaries characterized drowning. Victims of strangulation showed a strong alveolar hemorrhage, with alveolar collapse and overinsufflation, associated with bronchiolar dilatation. It is concluded that semiquantitative analysis of lung autopsies might be a useful supplementary histologic criterion to support the diagnosis of asphyxia.

Abstract: SUMMARY A female infant was delivered at term with complications of severe meconium aspiration and birth asphyxia. Surface cooling was performed in the first 24 hours as part of the management of her birth asphyxia. Woody erythema was noted at 24 hours, followed by the formation of red–purple nodules on the 6th day. Clinical findings in the first 24 hours were suggestive of cold panniculitis. However, clinical and histological findings progressed to be in keeping with the diagnosis of subcutaneous fat necrosis of the newborn (SCFN). Furthermore, the immediate postnatal period was complicated by pain resistant to treatment with opiates. Asymptomatic hypercalcaemia was noted on periodic testing at 7 weeks and treated by rehydration, diuretics, prednisolone, etidronate and a low-calcium and -vitamin D diet. A review of the clinical and histological findings of the relevant panniculitides occurring in the postnatal period is presented, as well as a review of the treatment of hypercalcaemia in SCFN.

Abstract: Overlaying, the accidental death by smothering caused by a larger individual sleeping on top of an infant, is a cause of death that has been documented for centuries. The hazard of death has been reported to be greater in infants less than 5 months of age but may occur in children up to the age of 2 years. When an adult or older child rolls on top of an infant, mechanical asphyxia results. The face may be pressed into the mattress or into the body of the sleeping adult or older child. The infant's air may be expressed, and he or she is unable to cry due to pressure on the thorax and the inability to inhale. Some pathologists and investigators believe that the victims of overlaying have no pertinent physical findings at autopsy and that any injury is indicative of inflicted trauma. Others believe that one may see contusions and abrasions from overlaying in and of itself. Wedging is another form of accidental mechanical asphyxia that may have negative autopsy findings. The prevalence of bruising, contusions, or facial and ocular petechiae is not clear. The author reviewed all pediatric forensic cases referred for autopsy to the Forensic Section of the Medical University of South Carolina/Medical Examiners' Office over the past 15 years, from 1985 to 1999. Of these, all cases of overlaying, cases listed as undetermined sudden infant death syndrome versus overlaying, and wedging were included. The cases were analyzed as to victims' age, sex, race, location/bedding, bed-sharer, and whether the bed-sharer was known to have ingested drugs or alcohol before sleep. Postmortem physical findings were also reviewed, particularly for documentation of contusions, abrasions, or facial or ocular petechiae. By clarifying not only the victim, bed-sharer, and scenario but also the presence or absence of physical findings in cases of overlaying, wedging, and other accidental asphyxia, we can better categorize these cases.

Abstract: The severity of neurologic dysfunction after circulatory arrest depends on cerebral reperfusion during and after resuscitation. The objective of current study was to investigate the temporal and spatial patterns of the cerebral perfusion immediately after resuscitation. Precise control of circulatory arrest was achieved in rats by combination of asphyxia and transient blockage of cardiac-specific beta-adrenergic receptors with esmolol, an ultra-short-acting beta-blocker. Animals were randomized into 3 groups with resuscitation starting 0.5 (sham group, no asphyxia, n = 5), 4 (Group 2, n = 5), or 12 minutes (Group 3, n = 8) later by retrograde intraarterial infusion of donor blood along with a resuscitation mixture. Cerebral perfusion was measured by magnetic resonance imaging (MRI) using arterial spin labeling. The average perfusion before arrest was 163 +/- 27 mL 100 g(-1) min(-1) under isoflurane anesthesia. Resuscitation led to transient perfusion increase, which started from thalamus and hypothalamus and later shifted to the cortex. Severe hypoperfusion to as low as 6% to 20% of the normal level developed in the first 10 to 20 minutes of reperfusion and lasted for at least 2 hours. On the fifth day after circulatory arrest, all animals showed a normal level of perfusion (159 +/- 57 mL 100 g(-1) min(-1) ) and minimal neurologic deficit. Nevertheless, histologic examination revealed extensive changes in the CA1 region of the hippocampus consistent with global ischemia and reperfusion damage. The combination of an improved circulatory arrest model and noninvasive MRI cerebral perfusion measurements provides a powerful tool for investigations of circulatory arrest and resuscitation, allowing for evaluation of therapies aimed at modulating cerebral reperfusion.

Abstract: Inspite of major advances in monitoring technology and knowledge of fetal and perinatal medicine, perinatal asphyxia is one of the significant causes of mortality and long term morbidity. Data from National Neonatal Perinatal Database suggests that perinatal asphyxia contributes to almost 20% of neonatal deaths in India. “Failure to initiate or sustain respiration after birth” has been defined as criteria for the diagnosis of asphyxia by WHO. Perinatal asphyxia results in hypoxic injury to various organs including kindneys, lungs and liver but the most serious effects are seen on the central nervous system. Levene’s classification is a useful clinical tool for grading the severity of hypoxic ischemic encephalopathy. Good supportive care is essential in the first 48 hours after asphyxia to prevent ongoing brain injury in the penumbra region. Strict monitoring and prompt correction is needed for common problems including temperature maintenance, blood sugars, blood pressure and oxygenation. Phenobarbitone is the drug of choice for the treatment of convulsions.

Abstract: Editor,—Seizures in infancy and early childhood responsive to pyridoxine are well recognised but rare. Baxter has recently observed that almost a third of neonatal cases of pyridoxine dependency present with apparent birth asphyxia and/or suspected hypoxic-ischaemic encephalopathy, and recommended that, because of the high proportion of atypical cases, all children with early onset (younger than 3 years old) intractable seizures or status should receive a trial of pyridoxine whatever the suspected cause.1 Following this recommendation can be of …

Abstract: Traditionally, it has been believed that the cardiovascular and hormonal responses to asphyxia in preterm fetuses are immature, and this immaturity contributes to their apparent vulnerability to neura

Abstract: The aim of this study was to investigate the effect of prematurity, neonatal sepsis, respiratory distress syndrome (RDS) and perinatal asphyxia on monocyte HLA-DR expression of neonates using a flow cytometric method based on monocyte negative selection. The subjects were one hundred and thirty-one neonates (59 healthy, 44 septicaemic, 20 with RDS and eight with perinatal asphyxia) and 20 healthy adults. Monocyte HLA-DR expression was measured using one-colour HLA-DR labelling in a gate for monocytes obtained using the combination of CD3-CD19–PE/CD15–FITC MoAbs. In addition, the common dual staining method using MoAbs against two CD14 epitopes (TUK4, MO2) was evaluated. With the one-colour HLA-DR labelling higher purity and recovery values of monocytes were achieved than with the dual labelling method. Healthy neonates had significantly lower percentages of HLA-DR+ monocytes than adults (69 ± 13% versus 91·5 ± 2·5%) and comparable mean fluorescence intensity (MFI) (119 ± 25 versus 131 ± 26). Values did not differ significantly between healthy term and preterm neonates. Preterm neonates with RDS had a significantly lower percentage of HLA-DR+ monocytes than the healthy preterm neonates. In neonates with asphyxia both parameters were comparable to those of the healthy ones. Septicaemic neonates presented significantly lower values of both parameters than the healthy, RDS and asphyxiated neonates. Monocyte negative selection provides a reliable estimation of HLA-DR expression on monocytes. Expression of monocyte HLA-DR is lower in healthy neonates in comparison with adults and is further decreased in neonates with sepsis and RDS, but it is not influenced by prematurity and perinatal asphyxia.

Abstract: We studied 57 low-birth-weight premature neonates, of whom 29 suffered from perinatal asphyxia and/or infection, while the remaining 28 did not and served as controls. We measured peripheral nucleated red blood cell (NRBC) absolute numbers as well as interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)-alpha cytokine serum levels at 24 h postnatally and on days 3 and 7 following birth. Fourteen of the asphyxiated/infected neonates and 12 controls had neurologic assessments at the corrected postnatal age of 18 months. We found NRBC absolute numbers and serum IL-1beta and IL-6 cytokine levels at 24 h postnatally to be significantly higher in neonates with perinatal asphyxia/infection than in the controls (p = 0.022, p = 0.036 and p = 0.037, respectively). TNF-alpha levels did not differ. Neurologic examination at the corrected postnatal age of 18 months showed 8 out of the 14 children who had been asphyxiated/infected as neonates to have abnormal findings, while 12 children who were used as controls during their neonatal period were normal. Abnormal neurologic findings correlated with high NRBC counts and IL-1beta and IL-6 levels at 24 h postnatally. In conclusion, increased NRBC counts and proinflammatory cytokine levels in asphyxiated/infected neonates represent early markers for subsequent neurologic impairment.

Abstract: This study investigated the influence of temperature or glutamate antagonism on the immediate outcome of perinatal asphyxia. Perinatal asphyxia was produced by water immersion of fetus-containing uterus horns removed by cesarean section from ready to deliver rats. The uterus horns were kept in a water bath for different time periods, before the pups were delivered and stimulated to breathe. After delivery, the pups were assessed for behavior and for systemic glutamate, aspartate, lactate and pyruvate levels measured with in vivo microdialysis, or ex vivo for energy-rich phosphates, including adenosine triphosphate (ATP), in brain, heart and kidney. In a series of experiments, asphyxia was initiated in a water bath at 37°C, before the pup-containing uterus horns were moved for different time intervals to a 15°C bath. In another series of experiments, the mothers were treated with N-methyl-D-aspartate (NMDA) antagonist, dizocilpine (MK-801), or α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) antagonist, 2,3-dihydroxy-6-nitro-7-sulfamoyl benzo(f) quinoxaline (NBQX) 1 h before hysterectomy and asphyxia at 37°C. The rate of survival rapidly decreased following exposure to more than 16 min of asphyxia, and no survival could be observed after 22 min of asphyxia. An LD50 was estimated to occur at ~19 min of asphyxia. The outcome was paralleled by a decrease in ATP in kidney, followed by a decrease in heart and brain. A maximal decrease in ATP was observed after 20 min of asphyxia in all tissues. Systemic microdialysis revealed that glutamate, aspartate and pyruvate levels were increased with a peak after 5 min of asphyxia. In contrast, lactate levels increased along with the length of the insult. Survival was increased when the pup-containing uterus horns were moved from a 37°C to a 15°C bath, at 15 min of asphyxia (the LD50 was thus increased to 30 min). If the shift occurred at 10 or 5 min of asphyxia, the LD50 increased to 80 or 110 min, respectively. The effect of glutamate antagonism was minor compared to hypothermia; the best effect (an increase in the LD50 to ~22 min) was observed after combining AMPA and NMDA antagonists.

Abstract: This article summarizes the recent medical literature regarding perinatal asphyxia with respect to timing and mechanisms of injury for neonates who were clinically diagnosed with an encephalopathy in the newborn period. Multiple mechanisms of injury are reviewed, including genetic vulnerability, acquired inflammatory responses, and clotting defects that can lead to ischemic-induced brain damage. Before effective treatments for fetal and neonatal brain disorders can be developed, accurate and timely diagnoses of fetal or neonatal brain injury must be achieved. Specific subsets of children can then benefit from neuroprotective strategies that can target the specific developmental aspects of brain adaptation or plasticity relative to the specific etiology and timing of injury after asphyxia.

Abstract: Aim: A study was undertaken to examine specific circumstances that may lead to accidental asphyxial deaths in infants on sofas. Methods: Coronial files in South Australia (Australia) from 1989 to 1998, and files at the Office of the Medical Examiner in San Diego County (USA) from 1991 to 1998 were searched for all cases of infant deaths occurring on sofas. Results: A total of 10 cases with complete death scene descriptions were found. Four deaths were attributed to sudden infant death syndrome and six deaths to accidental asphyxia, of which four involved shared sleeping with an adult. Lethal circumstances involved infants being overlayed by an adult (n = 2), wedged between an adult and the back of a sofa (n = 1), sleeping with an intoxicated/sedated adult (n = 2), wedged between pillows and the back of a sofa (n = 1), and wedged into the back of a sofa (n = I ). Conclusions: Although shared sleeping of an adult with an infant on a sofa may result in accidental asphyxia, there is also the potential for wedging and accidental asphyxia of infants sleeping alone on a sofa. For this reason the use of sofas for both shared and solitary infant sleeping is discouraged.

Abstract: Stillborn fetuses commonly demonstrate three mechanisms of death: hydrops, asphyxia, or shock. For each mechanism, the autopsy can discover any of multiple etiologies. This paper reviews the etiologies and pathogeneses of fetal death from that perspective.

Abstract: Two tryptophan metabolites, the anti-excitotoxic N-methyl-D-aspartate (NMDA) receptor antagonist kynurenic acid (KYNA) and the free radical generator 3-hydroxykynurenine (3-HK), have been proposed to influence neuronal viability in the mammalian brain. In rats, the brain content of both KYNA and 3-HK decreases immediately after birth, possibly to ensure normal postnatal functioning of NMDA receptors. Because complications of birth asphyxia have been suggested to be associated with anomalous NMDA receptor function, we examined the acute effects of an asphyctic insult on the brain levels of KYNA and 3-HK in neonatal rats. Asphyxia was induced in animals delivered by cesarean section on the last day of gestation, using the procedure introduced by Bjelke et al. (Brain Res 543: 1-9, 1991). KYNA and 3-HK levels were determined in the brain at seven time points between 10 min and 24 h after asphyxia. Up to 6 h, asphyxia caused 160-267% increases in KYNA levels. In the same tissues, 3-HK levels decreased (significantly at five of the seven time points), demonstrating an asphyxia-induced shift in kynurenine pathway metabolism toward the neuroprotectant KYNA. This shift might constitute the brain's attempt to counter the ill effects of birth asphyxia. Furthermore, the transient increase in the brain KYNA/3-HK ratio in these animals might be causally related to the well-documented detrimental long-term effects of asphyxia.