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PubMedDate not supplied

Serial visual evoked potentials and outcome in term birth asphyxia.

Birth asphyxia is a major cause of neonatal mortality and morbidity. It remains difficult to predict accurately neurologic outcome among survivors, particularly infants with moderate hypoxic-ischemic encephalopathy. Visual evoked potential (VEP) is a reproducible measure of cortical function and reflects acute changes in central nervous system status secondary to asphyxial insult. We performed serial VEPs on 36 term infants with documented birth asphyxia to investigate the relationship between VEPs and neurodevelopmental outcome at 18 months of age. Fourteen infants were neurologically intact at subsequent examination; all had normal VEPs during the first week of life. Twenty-two infants had died or were significantly handicapped at 18 months of age; 20 had abnormal VEPs persisting beyond day 7 of life. Abnormal VEPs accurately predicted abnormal outcome (100%) and were both sensitive (91%) and specific (100%). In 20 infants who were classified as moderately asphyxiated according to the criteria of Sarnat and Sarnat, even greater accuracy, sensitivity, and specificity (all 100%) were observed. VEPs demonstrate good correlation with neurodevelopmental outcome in term infants with birth asphyxia and provide accurate prognostic information useful in the clinical management of these infants.

Apgar Score↗
PubMed2006

Does naloxone alone increase resuscitation rate during cardiopulmonary resuscitation in a rat asphyxia model?

Cardiac arrest was induced with asphyxia to identify if naloxone alone increases resuscitation rate during cardiopulmonary resuscitation in a rat asphyxia model. The animals were randomized into either a saline group (Sal-gro, treated with normal saline 1 ml iv, n = 8), a low-dose naloxone group (treated with naloxone 0.5 mg/kg iv, n = 8), or a high-dose naloxone group (HN-gro, treated with naloxone 1 mg/kg iv, n = 8) in a blinded fashion during resuscitation. At the end of 10 minutes of asphyxia, cardiopulmonary resuscitation was started, and each drug was administered at the same time. The rate of restoration of spontaneous circulation was seen in 1 of 8, 3 of 8, and 7 of 8 animals in the Sal-gro, LN-gro, and HN-gro, respectively. The rate of restoration of spontaneous circulation in HN-gro was significantly higher than that in Sal-gro (P < .05). Naloxone (1 mg/kg) alone can increase resuscitation rate following asphyxial cardiac arrest in rats.

Animals↗
PubMed2005

C-section birth per se or followed by acute global asphyxia altered emotional behaviour in neonate and adult rats.

Birth complications such as perinatal asphyxia are considered risk factors for later neurobehavioural disorders. Behavioural analysis of animal models may help to clarify the contribution of particular patterns of early hypoxia and their combination to psychiatric morbidity. Wistar rats underwent caesarean section (c-section) alone or c-section followed by asphyxia, the latter induced by placing pups still in uterus horns into a water bath at 37 degrees C for 20 min. Vaginally delivered pups were used as controls. Frequency of ultrasound emissions was analysed following isolation at a lower temperature than that of the home nest (23+/-0.5 degrees C) and reunion with their mother (3 min) on postnatal day (PND) 13 (maternal potentiation test). A sex-dependent effect of hypoxia was observed, with higher production of ultrasounds in hypoxic males. Caesarean-delivered pups produced significantly more ultrasounds than those vaginally delivered. At adolescence (PND 35) rats underwent a 25 min social interaction test with a conspecific of the same sex and age. Significant alterations in investigative behaviour (inclusive of: nose, anogenital, body sniffing, and following) were evident in caesarean-delivered rats of both sexes, but not in rats experiencing perinatal asphyxia. At adulthood, auditory, and context conditioned responses, analysed in a fear conditioning test, were not markedly affected either by c-section or c-section plus hypoxia. However, hypoxic rats emitted significantly more 22 kHz ultrasounds than c-section or vaginally delivered rats during the training session. In conclusion, differential effects appear to be brought about by c-section and by hypoxia mainly related to emotional/anxious responses.

Animals↗
PubMed2006

Changes in BAER amplitudes after perinatal asphyxia during the neonatal period in term infants.

We recorded serially brainstem auditory evoked response (BAER) during the neonatal period in term infants who suffered perinatal asphyxia. The amplitudes of BAER components was analysed at 40 dB above BAER threshold of each subject who had a threshold<or=25 dB nHL. No apparent changes in the amplitudes of waves I and III during the first 5 days after birth. The two wave amplitudes were slightly reduced thereafter. On day 30, the amplitudes were slightly smaller than in normal controls. No statistical significant differences were found in the two amplitudes between the infants after asphyxia and the controls on any days studied. In contrast, wave V amplitude showed a trend of reduction during the whole neonatal period. The amplitude was reduced slightly on the first day after birth, but reduced further on day 3 (ANOVA, P<0.01). Thereafter, the reduction persisted without any significant change. On day 30, wave V amplitude remained significantly smaller than in the controls (P<0.001). Compared to the controls, V/I amplitude ratio was slightly smaller during the neonatal period, but V/III amplitude ratio was significantly smaller on most of the days studied (P<0.05-0.01). The persistent reduction of wave V amplitude suggests a sustained neuronal damage of the auditory brainstem in infants after perinatal asphyxia.

Acoustic Stimulation↗
PubMed2005

Asphyxia and depolarization increase adenosine levels in perilymph.

Extracellular adenosine has been suggested as a modulator of cochlear function. To date the release of adenosine into the extracellular spaces of the cochlea has not been demonstrated. Therefore, experiments were designed to examine whether adenosine release into perilymph could be detected in response to depolarization by high potassium concentrations or in response to asphyxia. For this purpose, the perilymph compartment of guinea pigs was perfused with an artificial perilymph and the effluent assayed for ATP, ADP, AMP and adenosine. Results indicate that potassium induced a slight, significant increase and asphyxia induced a very large, significant increase in adenosine levels in perilymph effluent. No changes in the levels of the other compounds were measured. It is concluded that depolarization and asphyxia can induce the release of adenosine into perilymph.

Adenosine↗
PubMedDate not supplied

Intrauterine asphyxia: clinical implications for providers of intrapartum care.

Advances in science and technology have allowed researchers to gain a better understanding of the pathophysiology leading to long-term neurologic damage in newborns. Intrapartum events are now known to be an infrequent cause of adverse neurologic outcome. Clinicians caring for women during labor must have an understanding of the pathophysiology of intrauterine asphyxia as well as an awareness of the capabilities and limitations of available intrapartum fetal assessment tools to diagnose intrauterine fetal asphyxia or predict neurologic outcome. This article reviews the physiology of acid-base balance and fetal gas exchange as well as the current scientific understanding of the role of intrauterine asphyxia in the pathophysiology of neonatal encephalopathy and cerebral palsy. Recommendations for care and documentation are included.

Acid-Base Equilibrium↗
PubMed2006

Theophylline for renal function in term neonates with perinatal asphyxia: a randomized, placebo-controlled trial.

OBJECTIVE: To study whether prophylactic theophylline can reduce the incidence and/or severity of renal failure in term infants with perinatal asphyxia. STUDY DESIGN: Term neonates with severe perinatal asphyxia were randomized to receive a single dose of either theophylline (study group, n = 40) or placebo (control group, n = 30) during the first hour of life. Daily weight, output/input ratio, 24-hour fluid intake, and urine volumes were recorded during the first 5 days of life. Those infants with asphyxial renal failure were followed up for 1 year. RESULTS: The incidence of severe renal dysfunction was increased in the control group. Creatinine clearance was higher and excretion of beta 2 microglobulin (beta2M) was lower in the theophylline group. Conversely, the glomerular filtration rate was lower in the control group. In infants with renal failure, serum creatinine and creatinine clearance returned to normal in the neonatal period, and the increased beta2M excretion normalized by age 6 weeks. CONCLUSIONS: A single dose of theophylline within the first hour of birth in term neonates with perinatal asphyxia results in a significant decrease in serum creatinine level and urinary excretion of beta2M, along with an increase in creatinine clearance.

Asphyxia Neonatorum↗
PubMed2004

Prognostic correlative values of the late-infancy MRI pattern in term infants with perinatal asphyxia.

The aim of this study was to define the risk ratios of the late-infancy magnetic resonance imaging pattern for long-term outcome in term infants with perinatal asphyxia. We evaluated 65 term infants with perinatal asphyxia and performed magnetic resonance imaging examinations between 4-12 months of age. Magnetic resonance imaging scans were classified as follows: (1) periventricular leukomalacia in 21 (32%) infants, (2) marked cortical atrophy in 17 (26%) infants, (3) multicystic encephalomalacia in 10 (15%) infants, (4) deep gray matter involvement in 8 (12%) infants, (5) focal cortical involvement in 6 (9%) infants, (6) myelination delay in 3 (5%) infants. The overall outcome was favorable in 19 (29%) of 65 infants. Infants with diffuse cortical involvement (multicystic encephalomalacia and marked cortical atrophy) are four times (odds ratio: 4.4 and 4.1 respectively) more likely to attain the unfavorable outcome than the infants with other patterns of magnetic resonance imaging. Infants with focal cortical involvement had relatively favorable outcome in 60% of the cases. In conclusion, it appears that the overall outcome of infants with perinatal asphyxia correlated well with the magnetic resonance imaging patterns obtained between 4 and 12 months of age.

Asphyxia Neonatorum↗
PubMed2006

Early continuous video-EEG in acute near-total intrauterine asphyxia.

The evolution of electroencephalographic changes after acute hypoxic-ischemic injury is poorly understood, as a clear time of insult is often absent and continuous electroencephalographic monitoring in the first 3 days after such injury has not been previously reported. Infants who suffer sudden profound asphyxia, often termed "acute near-total intrauterine asphyxia", have evidence of damage to the deep gray matter. In these infants it is possible to time the onset and duration of cerebral ischemia. This report describes early continuous video-electroencephalography from 3 hours after birth in an infant with the characteristic clinical and radiologic features of acute near-total intrauterine asphyxia.

Acute Disease↗
PubMed2000

Histologic and biochemical study of the brain, heart, kidney, and liver in asphyxia caused by occlusion of the umbilical cord in near-term fetal lambs.

OBJECTIVE: We sought to determine the relationship between the degree of histologic changes in the brain, heart, kidney, and liver in fetal lambs after severe asphyxia and to analyze the role of oxidative stress in the pathogenesis of fetal multiple organ failure. STUDY DESIGN: Eight chronically instrumented near-term fetal lambs were asphyxiated by partial umbilical cord occlusion for approximately 60 minutes until the fetal arterial pH reached <6.9 and the base excess reached <-20 mEq/L. An additional 6 fetuses were used as sham-asphyxiated controls. Fetal heart rates, blood pressure, fetal breathing movements, and arterial blood gases and acid-base states were serially monitored. The brain, heart, kidney, and liver were collected 72 hours after asphyxia, processed, and histologically examined after hematoxylin and eosin staining. Fetal brain histologic features were classified into 5 grades, with 5 being the most severe damage. The other organs were examined histologically by pathologists who were blinded to the treatment. Each organ was assayed for tissue concentrations of thiobarbituric acid-reactive substances, superoxide dismutase, glutathione, lactate, and glucose. RESULTS: Myocardial changes of necrosis, phagocytosis, and contraction bands occurred in only 2 of the most severely (grade 5) brain-damaged fetuses. The same 2 cases showed fatty changes and congestion in the liver. In the kidney all asphyxiated cases showed tubular necrosis, but glomeruli were generally spared. Of the measures of oxidative stress, only liver tissue levels of thiobarbituric acid-reactive substances and superoxide dismutase were significantly higher in the asphyxiated group than in the control group, but there was no correlation with the degree of damage. Lactate level was higher only in the heart in the asphyxiated fetuses. CONCLUSION: Renal tubular damage was seen with all degrees of asphyxia, despite variable brain damage. Histologic changes in the myocardium and liver were seen only with the most severe brain damage. Oxidative stress appears to play a role in the pathogenesis of liver damage.

Animals↗
PubMed2003

Blockade of D1 dopaminergic transmission alleviates c-fos induction and cleaved caspase-3 expression in the brains of rat pups exposed to prenatal cocaine or perinatal asphyxia.

Hypoxia due to uterine vasoconstriction may be an important cause of the teratogenic consequences of prenatal cocaine exposure. We used immediate-early gene and cleaved caspase-3 expression patterns to monitor fetal brain regions affected by intrauterine hypoxia and prenatal cocaine and pretreatment with the D1 dopamine receptor antagonist SCH 23390 to determine how much of the induction observed was due to dopamine. Both cocaine binge (3 x 15 mg/kg) and perinatal asphyxia on embryonic day 22 (E22) induced c-fos in the striatum as well as in several other brain regions within 3 h after treatment. Maternal administration of a D1 dopamine antagonist, SCH 23390, before either cocaine or asphyxia exposure dramatically reduced the numbers of Fos-immunoreactive cells in the striatum as well as in many other brain regions. Cells immunoreactive for cleaved caspase-3 expression were more numerous after perinatal asphyxia than after prenatal cocaine exposure in most brain regions 24 h after C-section. SCH 23390 decreased caspase-3 expression after both birth insults, indicating that the increased incidence of apoptosis is related to overactivation of dopaminergic pathways.

Animals↗
PubMed1982

The effects of different rates of plasmanate infusions upon brain blood flow after asphyxia and hypotension in newborn piglets.

Brain blood flow was determined in 21 spontaneously breathing, awake, newborn piglets during control, asphyxia, superimposed hypotension, and subsequent volume expansion (15 ml/kg of plasmanate). The piglets were divided into three groups based upon the rate of volume expansion: rapid infusion group-piglets received plasmanate in three minutes; slow infusion group-piglets received plasmanate in 30 minutes: the noninfused group-piglets did not receive plasmanate. The results showed comparable increases in brain blood flow among each group during asphyxia, and similar reduction to preasphyxia values during superimposed hypotension. Although pressure-passive changes occurred, the rate of volume expansion did not influence the magnitude of change in brain blood flow. Significantly lower arterial blood pressure and brain blood flow were observed in those piglets who did not have a plasmanate infusion. Intracranial hemorrhages were not observed at autopsy in any of the study subjects. These data indicate that rapid or slow infusion of plasmanate for volume restoration did not influence the pattern of brain blood flow and that in these relatively mature brains, intracranial bleeding was not observed. Both plasmanate infused groups had higher brain blood flows at study completion (when compared to controls), reflecting compensation for anemia to maintain adequate oxygen delivery. Furthermore, regional differences in blood flow were found during asphyxia and superimposed hypotension (brain-stem greater than cerebellum greater than cerebrum), probably reflecting compensatory protection of vital portions of the central nervous system.

Animals↗
PubMed1994

Gastrointestinal and renal blood flow velocity profile in neonates with birth asphyxia.

Pulsed Doppler ultrasound blood flow profiles were studied, before the initiation of enteral feedings, in 23 neonates with birth asphyxia. We observed a significant direct correlation between the reduction of peak velocity and increased resistance in the renal and superior mesenteric arteries to the severity of asphyxia (r = 0.8; p < 0.05); the changes often persisted up to 3 days of age. Longitudinal evaluation of flow in these vessels might help to time the initiation of enteral nutrition in neonates with asphyxia.

Asphyxia Neonatorum↗
PubMed1998

Prospective validation of a scoring system for predicting neonatal morbidity after acute perinatal asphyxia.

OBJECTIVE: To prospectively validate a previously reported scoring system for identifying the near-term infant at risk for the multiple organ system sequelae of acute perinatal asphyxia. STUDY DESIGN: Prospective observational study. SETTING: Three Denver teaching hospitals, each providing comprehensive obstetric care. SUBJECTS: Newborn infants of 36 weeks or more gestation. INTERVENTION: None. STATISTICAL ANALYSIS: Chi-squared analysis with Fisher's exact test. OUTCOME: Scores consisting of graded abnormalities in fetal heart rate monitoring, umbilical arterial base deficit, and 5-minute Apgar score were calculated by the research nurse after admission of the infant to the nursery (range of possible scores, 0 to 9). A second nurse, blinded to these data, prospectively followed the newborn's hospital course for multiple organ system morbidity. RESULTS: Three thousand two hundred thirty-eight newborns were studied; 366 required neonatal intensive care unit admission. Eleven newborns had a score > or = 6 (mean umbilical artery pH = 6.98, base deficit = 17.1 mEq/L). Morbidities in these 11 newborns included seizures (2), hypoxic-ischemic encephalopathy (5), respiratory distress (9), hypotension (7), renal dysfunction (9), hypoglycemia/hypocalcemia (4), and thrombocytopenia or disseminated intravascular coagulopathy (3). The odds ratio (OR) and 95% confidence interval (CI) for newborns admitted to the neonatal intensive care unit with a score > or = 6 for having multiple organ system morbidity, defined as three or more affected organ systems, was 38.5 (95% CI, 9.2 to 127.8). The scoring system showed a stronger relationship with multiple organ system morbidity than did isolated individual indicators commonly used to identify asphyxia calculated on the same subjects: for those with pH < 7.00, OR 24 (95% CI, 6.4 to 94.1); base deficit > or = 10 mEq/L, OR 4.5 (95% CI, 1.9 to 10.3), and 5-minute Apgar score < or = 3, OR 7.4 (95% CI, 1.3 to 38.1). CONCLUSION: This scoring system, encompassing both immediate intrapartum and postpartum measures and acid-base status proximate to the time of delivery, is useful for rapidly identifying the term and near-term newborn at risk for multiple organ system morbidity after acute perinatal asphyxia.

Acidosis↗
PubMed2000

Energy metabolism in graded perinatal asphyxia of the rat.

Although information on energy metabolism during hypoxemic-ischemic states is abundant, data on perinatal asphyxia (PA) are limited. As results from hypoxia-ischemia cannot be directly extrapolated to PA, a clinical entity characterized by acidosis, hypoxemia and hypercapnia, we decided to use a rat model of graded PA during delivery. Cesarean section was performed at the 21st day of gestation and the pups, still in the uterus horns, were asphyxiated from 0 to 20 minutes. In this model survival decreases with the length of asphyxia. Early changes of energy-rich phosphates in brain, heart and kidney were determined by HPLC. ATP and phosphocreatine gradually decreased with the length of asphyxia, with highest ATP depletion rate occurring in the kidney. ATP: brain 1.39 +/- 0.71 (0 min) to 0.06 microM/g wwt (20 min); heart 4.73 +/- 0.34 (0 min) to 1.08 +/- 0.47 (20 min); kidney 1.62 +/- 0.11 (0 min) to 0.02 +/- 0.02 (20 min). Phosphocreatine: brain 1.65 +/- 0.68 (0 min) to 0.51 +/- 0.45 microM/g (20 min); heart 6.98 +/- 0.38 (0 min) to 6.17 +/- 1.07 (20 min); kidney 8.23 +/- 0.86 (0 min) to 3.76 +/- 0.54 (20 min). We present data on energy derangement in a rat model of PA, closely resembling the clinical situation, showing that energy depletion precedes cell damage and death.

Adenine Nucleotides↗
PubMed2001

Increased kynurenic acid in the brain after neonatal asphyxia.

In the brain, L-kynurenine is an intermediate for the formation of kynurenic acid, a metabolite with neuroprotective activities, and a substrate for the synthesis of 3-hydroxy-kynurenine, a metabolite with neurotoxic properties. In the present study, alterations of L-kynurenine, 3-hydroxy-kynurenine and kynurenic acid levels were examined in the brain of neonatal (10 minutes old) rats after 5, 10, 15 or 20 minutes of asphyxia, and in the brain of the corresponding caesarean-delivered controls, using sensitive high-performance liquid chromatographic methods. Among kynurenines we found a marked time-dependent increase of kynurenic acid levels, a moderately delayed increase of 3-hydroxy-kynurenine, and a trend for a decrease of L-kynurenine content. Thus, the brain reacted rapidly to the oxygen deficit by increasing kynurenic acid levels by 44% already after 5 minutes of asphyxia, and the most prominent elevation of kynurenic acid (302% of control) was found after 20 minutes of asphyxia--the critical time limit of survival.

Animals↗
PubMed1998

mRNA levels of the hypoxia inducible factor (HIF-1) and DNA repair genes in perinatal asphyxia of the rat.

Hypoxia inducible factor 1 (HIF-1) is a transcription factor which is expressed, when mammalian cells are subjected to hypoxia, activating the transcription of genes encoding proteins thought important for maintaining oxygen hemostasis. The aim of the study was to evaluate HIF-1 mRNA levels in a non-invasive model of perinatal asphyxia (PA). Brain was taken for studies on HIF-1 alpha and beta 10 min following the asphyctic period. To rule out influences by the redox status we also determined antioxidant enzyme mRNA levels for superoxide dismutase, catalase, glutathion peroxidase and performed electron spin resonance studies. To study the link to protein phosphorylation as previously proposed, we evaluated mRNA levels for protein kinase C. As DNA breaks were reported to occur in PA, we determined mRNA levels of two genes representing DNA nucleotide excision repair, ERCC2 and ERCC3, and a DNA repair gene involved in the repair of oxidation mediated DNA damage, XRCC1. mRNAs for HIF-1 were not detectable following 5-20 minutes of asphyxia. The antioxidant enzymes did not show any changes during the asphyctic periods either and electron spin resonance failed to detect the presence of the hydroxyl radical. PKC significantly decreased with the length of the asphyctic period. ERCC2 and XRCC1 mRNAs were inducible during the acute phase of asphyxia indicating early repair phenomena. HIF-1 may not be relevant for periods of PA up to 20 minutes, the maximal survival time in our model. Neonatal factors may be responsible for that phenomenon although we cannot rule out that HIF-1 changes may occur at the protein level.

Animals↗
PubMedDate not supplied

Detection of transitory myocardial ischemia secondary to perinatal asphyxia.

Transitory myocardial ischemia (TMI) is seen as a complication of severe asphyxia. Its presentation is variable, ranging from tachypnea to cardiogenic shock, and it is often masked by the predominant disease. The objective of this study was to detect TMI secondary to perinatal asphyxia in a population of asphyxiated newborns (NB) in comparison with asphyxiated NB with no evidence of TMI. From April 1996 to December 1997, 43 asphyxiated (stressed) NB were studied. Three were excluded. Patients were placed into two groups: Group A with TMI (n = 33) and Group B without TMI (n = 7). No significant differences were found in gestational age, birth weight, extrauterine age, Apgar score, or total creatine phosphokinase values between the two groups. Differences were found in CPK-MB levels and in ischemic electrocardiographic changes and blockages, especially for Group A. In this group, only 24 (72.7%) were cardiovascularly symptomatic. We conclude that TMI secondary to perinatal asphyxia is more frequent than has been reported. Thus, it would be useful in all asphyxiated NB to measure CPK-MB isoenzyme activity and patients can then be submitted to an electrocardiogram for detection in order to offer opportune treatment when required.

Asphyxia Neonatorum↗