Asphyxia Group Research Articles

Cytokine response in cerebrospinal fluid after birth asphyxia.

Experimental studies suggest that cytokine-mediated inflammatory reactions are important in the cascade leading to hypoxic-ischemic brain injury. The purpose was to study the content of pro- and antiinflammatory cytokines in cerebrospinal fluid (CSF) of asphyxiated and control infants. Samples of CSF were obtained from 20 infants who fulfilled the criteria of birth asphyxia and from seven newborn control subjects. The concentrations of IL-1beta, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, and granulocyte/monocyte colony-stimulating factor (GM-CSF) were determined with ELISA and of IL-6 using a bioassay. The concentration of IL-6 (pg/mL) was higher in asphyxiated (250, 35-543; median, interquartile range) than in control (0, 0-18) infants (p = 0.001). There was also a significant relationship between IL-6 and the degree of HIE, and between IL-6 and outcome. In addition, the content of IL-8 (pg/mL) was higher (p = 0.009) in the asphyxia group (170, 70-1440), than in the the control group (10, 0-30) and there was an association between IL-8 and degree of HIE. The levels of IL-10, TNF-alpha, GM-CSF, and IL-1beta did not differ between groups. In conclusion, the proinflammatory cytokines IL-6 and IL-8 were markedly elevated in CSF of asphyxiated infants, and the intrathecal levels of these cytokines corresponded to the degree of HIE.

Effect of allopurinol on NMDA receptor modification following recurrent asphyxia in newborn piglets

The present study tests the hypothesis that repeated episodes of asphyxia will lead to alterations in the characteristics of the N-methyl- d-aspartate (NMDA) receptor in the brain cell membrane of newborn piglets and that pre-treatment with allopurinol, a xanthine oxidase inhibitor, will prevent these modifications. Eighteen newborn piglets were studied. Six untreated and six allopurinol treated animals were subjected to eight asphyxial episodes and compared to six normoxic, normocapneic controls. Brain cell membrane Na +,K +-ATPase activity was determined to assess membrane function. Na +,K +-ATPase activity was decreased from control following asphyxia in both the untreated and treated animals (47.7±3.2 vs. 43.0±2.2 and 41.0±5.3 μmol Pi/mg protein/h, p<0.05, respectively). 3H-MK-801 binding studies were performed to measure NMDA receptor binding characteristics. The receptor density ( B max) in the untreated asphyxia group was decreased compared to control animals (0.80±0.11 vs. 1.13±0.33, p<0.05); furthermore, the dissociation constant ( K d) was also decreased (3.8±0.7 vs. 9.2±2.2, p<0.05), indicating an increase in receptor affinity. In contrast, B max in the allopurinol treated asphyxia group was similar to control (1.06±0.37); and K d was higher (lower affinity) than in the untreated group (6.5±1.4, p<0.05). The data indicate that recurrent asphyxial episodes lead to alterations in NMDA receptor characteristics; and that despite cell membrane dysfunction as seen by a decrease in Na +,K +-ATPase activity, allopurinol prevents modification of NMDA receptor–ion channel binding characteristics induced by repeated episodes of asphyxia.

Maturation of peripheral and brainstem auditory function in the first year following perinatal asphyxia: a longitudinal study.

Maturation of peripheral hearing and auditory brainstem following perinatal asphyxia was investigated by longitudinal recording of brainstem auditory evoked potentials (BAEP) during the first year of life in affected infants. The general maturational course of the BAEP following asphyxia was similar to that in a control group of infants with normal births, although there were some abnormalities in the BAEP Response threshold elevation seen in a few asphyxiated infants improved significantly during the first 3 months. The interpeak intervals in the asphyxiated infants did not differ significantly from that of the control-group infants except in the first month, when the I-V and III-V intervals were significantly prolonged in the severe asphyxia group. In contrast, wave V amplitude and V/I ratio were always smaller when compared to that of the control-group infants. Amplitude reduction of wave V was more sustained than the prolonged I-V interval. Persistent hearing loss and brainstem auditory impairment were seen in 6.8% and 14.6% of the asphyxiated infants, respectively. These findings suggest that asphyxia does not interfere significantly with the maturation of the auditory system in most asphyxiated infants and that sustained peripheral hearing loss and brainstem impairment occur only in a small proportion of affected infants.

Effect of asphyxia on urinary epidermal growth factor levels in newborns.

Urinary epidermal growth factor (EGF) excretion in normal newborn as well as neonates with asphyxia was investigated by using radioimmunoassay, and serum creatinine (Scr) levels determined at the same time. The results showed that in severe asphyxia group the ratio of urinary EGF to urinary creatinine (Cr) (EGF/Cr), an index reflecting EGF excretion, was decreased on the first day (P < 0.05) and reached the lowest level on the third day (P < 0.01). However, EGF/Cr values were decreased only on the third day in neonates with mild asphyxia (P < 0.05). On the seventh day, EGF/Cr values of neonates with asphyxia rose to normal. There were a negative correlation between urinary EGF/Cr and Scr. It is suggested that EGF may play a role in the repair of acute renal injury after asphyxia and the detection of urinary EGF concentration is useful in the judgment of severity of renal injury and in the evaluation of the recovery of renal tubule after injury.

Cerebrospinal fluid of newborn infants contains a deglycosylated form of the intermediate filament nestin.

Nestin is an intermediate filament protein found in CNS progenitor cells. Nestin reappears in CNS tumor cells and reactive astrocytes after CNS injury. In this study we investigated whether nestin could be detected in the cerebrospinal fluid (CSF) of newborn infants and whether expression levels change with gestational age (GA) and/or brain injury. Using Western blot analysis, we examined the expression of nestin in the CSF of newborn infants (GA 25-42 wk) with asphyxia (n = 14), periventricular leukomalacia and peri(intra)ventricular hemorrhage (n = 7), and in a control group (n = 11). Protein extract from the periventricular brain tissue of a 1-wk-old infant was also analyzed. Nestin was detected in all the CSF samples and in the protein extract from the periventricular brain tissue. Although the CSF levels of nestin expression did not change with increasing GA, the asphyxia group had significantly lower levels of nestin in the CSF. An unexpected finding was that brain-derived nestin had an apparent molecular mass of approximately 240 kD, whereas all analyzed CSF samples contained two nestin-immunoreactive proteins at 200 and 220 kD. Experimental deglycosylation of the 240-kD form reduced the molecular mass to 220 kD, indicating that nestin undergoes a specific deglycosylation upon release into the CSF.

Neuropsychological consequences of very low birth weight and asphyxia at term: follow-up until school-age.

This prospective, longitudinal study examined neuropsychological consequences of different conditions associated with risks of perinatal asphyxia. Four groups of children, 5 to 9 years of age, were studied: (1) very low birth weight (VLBW) children born small for gestational age (SGA) (n = 34); (2) VLBW children born appropriate for gestational age (AGA) (n = 43); (3) children with signs of birth asphyxia at term (birth asphyxia) (n = 36), and (4) control children (n = 45). Moderately and severely disabled children were excluded. The WISC-R and the NEPSY, a new neuropsychological assessment consisting of attention, language, motor, sensory, visuospatial, and memory subtests, were administered. The VLBW-SGA group had the poorest test results. The VLBW-AGA group was somewhat less impaired, whereas the birth asphyxia group performed at the control group level. Impairment, when present, tended to be diffuse in all groups, affecting psychometric intelligence, naming, visuo-motor performance, tactile finger discrimination, attention, and phonological analysis.

Neonatal urinary uric acid/creatinine [correction of ceratinine] ratio as an additional marker of perinatal asphyxia.

The diagnosis and evaluation of perinatal asphyxia can be problematic and objective means of assessing its severity are lacking. To study the validity of urinary uric acid as a marker of the degree of perinatal asphyxia, the ratio of urinary uric acid to creatinine (UA/Cr) in urine specimens obtained after birth was measured in two groups of infants. Eighteen term infants with Apgar scores < or = 5 at 5 min and/or an umbilical cord blood pH < or = 7.2, and a base deficit > or = 12 meq/l were compared to 50 healthy controls. The severity of the perinatal asphyxia was determined by using an ASPHYXIA SCORE. The UA/Cr was higher in the asphyxiated group when compared to controls. (2.06 +/- 1.12, vs. 0.64 +/- 0.48; P < 0.001). Within the perinatal asphyxia group, a significant correlation was found between the UA/Cr ratio and the asphyxia score. (r = 0.86, P < 0.01). Infants with perinatal asphyxia have a significantly higher urinary UA/Cr ratio. This may be used as an indicator of the severity of perinatal asphyxia.

Birth asphyxia: incidence, clinical course and outcome in a Swedish population.

A total of 42,203 live infants were born in Göteborg in 1985-1991, and 292 term infants had Apgar scores < 7 at 5 min. Infants with congenital malformations, infections and opioid-induced respiratory depression were excluded and thus 227 infants were included in the birth asphyxia group, which formed the basis of this retrospective study. Clinical signs of mild, moderate or severe hypoxic-ischemic encephalopathy (HIE) were present in 65 infants, and in another 10 infants, sedated and on controlled ventilation, HIE was assumed but grading was not possible. The incidences of Apgar scores < 7 at 5 min, birth asphyxia and birth asphyxia with HIE were 6.9, 5.4 and 1.8 per 1,000 live born infants: 95% of infants resuscitated with bag and mask ventilation only, did well, compared with 1 of 11 in whom resuscitation included adrenaline. Seizures occurred in 27 of 227 infants, beginning in 18 infants within 12 h of birth. Small-for-gestational-age (SGA) infants were overrepresented in the birth asphyxia group but not in the birth asphyxia-HIE group. All infants with severe HIE died or developed neurological damage. Half of the infants with moderate, and all of the infants with mild, HIE were reported to be normal at 18 months of age. A total of 0.3 per 1,000 live born infants died and 0.2 per 1,000 developed a neurological disability related to birth asphyxia. The disabilities were dyskinetic (4), tetraplegic (2), spastic diplegic (2), cerebral palsy and mild neuromotor dysfunction (1). The relatively low incidences of birth asphyxia and HIE were probably due to effective antenatal care.

Newborn complications after intrapartum asphyxia with metabolic acidosis in the preterm fetus

OBJECTIVE: Our purpose was to determine the nature of the complications in preterm newborns after intrapartum fetal asphyxia with metabolic acidosis at delivery. STUDY DESIGN: Thirty-seven preterm fetuses with metabolic acidosis were matched with 37 preterm fetuses with normal blood gas measurements at delivery. A complication score expressed the magnitude of newborn complications during the 10 days after delivery. RESULTS: The mean complication score for the preterm newborns at 32 to 36 weeks in the asphyxia group, 9,6, was significantly greater than that for the control group, 3.1. Fetal asphyxia was associated with severe complications in all systems. The complication scores for the preterm newborns <32 weeks in the asphyxia group were of the same order as the control group. This may be related in part of a short duration of the asphyxial insult. The Apgar score at 1 minute was a valuable predictor of newborn complications in both the asphyxia and control groups. CONCLUSIONS: Intrapartum fetal asphyxia with metabolic acidosis at delivery is an important factor in the occurrence of severe complications, particularly in the central nervous system, respiratory system, and kidney, of preterm newborns.

Cerebral blood flow velocity in term newborns following intrapartum fetal asphyxia

Twenty-six term newborns with intrapartum fetal asphyxia, determined biochemically (umbilical artery base deficit > 12 mmol/l), were compared with 59 normal newborns to determine the effect of intrapartum fetal asphyxia on newborn blood pressure and cerebral blood flow velocity following delivery. Cerebral blood flow velocity observations with concurrent measures of blood pressure and heart rate were obtained during the 24 h after delivery and after 24 h. After delivery, diastolic blood pressure in the newborns of the asphyxia group was significantly greater than that of the newborns of the normal group and this difference persisted after 24 h. Cerebral blood flow velocity in the newborns of the asphyxia group was of the same order as that of the newborns of the normal group during the 24 h after delivery. However, there was a significant increase in both peak systolic and end-diastolic blood flow velocity after 24 h. The duration of metabolic acidosis may be a factor in the occurrence of this delayed cerebral blood flow velocity response. Observations of cerebral blood flow velocity should be continued for more than 24 h following delivery to determine the effect of intrapartum fetal asphyxia.

259 SERUM URIC ACID CONCENTRATION AS AN INDEX FOR SEVERE PERINATAL ASPHYXIA

Recently, purine degradation products, especially hypoxanthine, have been studied in relation to perinatal asphyxia. However the final degradation product, uric acid (UA) received little attention. We previously showed a correlation between cord UA levels and Apgar scores in a low risk population. Here we report on serum UA concentrations in relation to perinatal asphyxia. During a period of half a year serum UA and creatinine (CREA) concentrations were measured in blood samples taken from 275 newborns admitted to the NICU in Leuven. In 67 patients, UA and CREA were also measured in a urine sample on the first day of life. A negative correlation was found between the 1 min Apgar score and both the maximal serum UA concentration in the first 24h (r= -0.23, p< 0.025) and the corrected excretion of UA = (urineUA × serumCREA)/urineCREA (r= -0.45, p<0.005). All newborns were classified as normal, moderate or severe with respect to perinatal asphyxia. Newborns with severe asphyxia (n = 14) needed to have obvious neurological and cerebral ultrasound abnormalities at discharge. No significant differences were found in serum UA levels between the groups on the day of birth and the day thereafter due to the large variation in the normal group (303±71 and 351 ± 172 μmol/l). However, on each of the days 2 to 10, serum UA levels were significantly (p<0.05) higher in the severe asphyxia group compared to the other groups. Moreover, all 13 newborns with severe asphyxia who had serum UA measured on day 2 or later had values higher than the normal range (defined as mean + 2SD of the normal group: 357, 297 and 172 μmol/l on days 2,3 and 4). We conclude that newborns with severe perinatal asphyxia have increased levels of serum UA between days 2 and 10 of life.

신생아가사에서 청성뇌간유발반응의 변화

Birth asphyxia is an insult to the fetus or newborn due to lack of oxygen and/or inadequate perfusion to the various organ, especially to the brain. The most important and serious complication of the asphyxia is the hypoxic ischemic encephalopathy. It has been postulated that the auditory brainstem responses(ABR) might be helpful to evaluate the severity of the brainstem lesions by the birth asphyxia. In this study ABR were performed in the 67 full term neonates who had birth asphyxia with Apgar scores 5 or less and 26 normal control neonates. And the latencies,inter-peak latencies, and amplitudes were compared. The results were as follows: There were no statistically significant difference in ABR latencies at 90 dB HL between the neonates with the birth asphyxia and the control group(p&gt;0.05). The latencies of wave V at 30, 45, 60 and 90 dB HL were tended to delay in the asphyxia group compare to the control group although there was no statistical significance (p&gt;0.05). There were statistically significant dimunution of amplitudes of wave V at 30, 45, 60, 90 dB HL and the amplitude of wave I at 90 dB HL in the asphyxia group(p&gt;0.05).

The possible risk of bilirubin encephalopathy as predicted by plasma parameters in neonates with previous severe asphyxia.

The study group consisted of nine mature newborn infants with a previous history of severe asphyxia and a control group of 18 mature, healthy newborns with the same postnatal age and sex. The object of the investigation was to compare the possible risk of development of bilirubin encephalopathy between the two groups as estimated by plasma parameters. The asphyxia group had a significantly lower reserve albumin concentrations for binding of monoacetyldiaminodiphenyl sulphone (P = 0.008), a measure of binding of unconjugated bilirubin, and significantly lower total albumin concentrations (P = 0.02). No significant difference was observed in unconjugated bilirubin concentration. It is suggested that mature newborns with previous severe asphyxia are at a slightly increased risk of developing bilirubin encephalopathy over and above the well-known risk associated with increased permeability of the blood brain barrier.

Complement fragment C3a in plasma of asphyxiated neonates.

Recent clinical studies with adult polytrauma patients indicate that elevated plasma levels of anaphylatoxin C3a correlate with the subsequent development of the adult respiratory distress syndrome (ARDS). However, there are no parameters which allow a reliable diagnosis of ARDS in neonates. As the most predisposing condition for ARDS seems to be shock, plasma C3a was determined in 30 ventilated premature infants and neonates with respiratory distress syndrome (birth weights 660-3350 g) within the first 24 h post partum or 6-24 h after acute asphyxia or shock during the neonatal period. The range of C3a, measured by ELISA, was between 57 and 1000 ng/ml. In the asphyxia group (n = 15) peak levels of C3a in plasma (mean 388 ng/ml) were significantly higher (P less than 0.001) than in the control group (mean 153 ng/ml). In some neonates with suspected ARDS, additional samples were taken. A rise in C3a between days 2 and 8 was associated with a fatal outcome of the disease. As in adults, C3a might be a useful indicator for ARDS in neonates.

Death scene characteristics in 118 fatal cases of autoerotic asphyxia compared with suicidal asphyxia

AbstractA series of 118 autoerotic asphyxial deaths, recorded by the Coroners or Medical Examiners from the Canadian provinces of Ontario and Alberta, were compared with the same number of asphyxial suicides matched by province, year of death (within 3 years) and method of asphyxiation. Comparison of the death scenes revealed major differences between the two groups, with nudity of the body, evidence of a wide range of sexual activity at the time of death, and absence of verbal or written indication of suicidal intent being characteristic of the autoerotic asphyxia group. The data indicate that autoerotic asphyxia and suicidal asphyxia can usually be readily distinguished by death scene features.

Birth asphyxia and the intrapartum cardiotocograph

The intrapartum cardiotocographs (CTGs) of 38 severely asphyxiated, term infants, born during a 17-month period, and those of 120 healthy term infants acting as controls were independently reviewed by three investigators who were unaware of the clinical outcome. Inter-observer agreement was good (Kappa statistic = 0.74, P less than 0.0001). The investigators found that cardiotocographic abnormalities were present in 33 of the asphyxiated infants (87%) and in 35 of the controls (29%) and predicted that the abnormalities were severe enough to lead to significant fetal metabolic acidosis at delivery in 23 asphyxiated infants (61%) and in 11 controls (9%). The differences between the two groups were highly significant (P less than 0.001). Using the traditional diagnostic criteria for fetal distress, the investigators found that fetal blood sampling was indicated in 58% of cases in the asphyxia group and in 20% of controls but was only performed in 16% of asphyxiated infants and in 8% of controls. Furthermore, the median response times of delivery suite staff for abnormal fetal heart rate patterns were similar whether the FHR changes, classified using Krebs' CTG scoring system, were moderate or severe: 80 min and 90 min, respectively. These findings suggest that interpretation of the intrapartum CTG continues to pose major problems for practising obstetricians.

Lumbar CSF eicosanoids in neonates

Lumbar CSF eicosanoids were measured in 11 neonates with perinatal asphyxia and 12 neonates with suspected sepsis. In the asphyxia group low levels of thromboxane B 2 and prostaglandin F 2α were detected in five neonates, all of which had had a lumbar puncture prior to 4 hours of age. In the group with suspected sepsis two infants had positive blood cultures and one had strep meningitis. CSF eicosanoids were nondetectable in all patients in this second group with the exception of the infant with meningitis. With meningitis CSF eicosanoids were markedly elevated. These findings suggest that lumbar CSF eicosanoids do not appear to be a clinically useful tool. The data further suggest that eicosanoids are involved in the inflammatory response to meningitis.

Hypoxia-induced acute changes in capillary and fiber density and capillary red cell distribution in the rat heart.

The influence of acute hypoxia (respiration gas 12%, 10%, and 8% O2 and asphyxia, respectively) on 1) the density of perfused capillaries and muscle fibers, and 2) the capillary red cell distribution was investigated in the left heart of anesthetized rats. To observe capillaries and fibers, fluorescein isothiocyanate-labeled (FITC)-gamma-globulin and lissamine-rhodamine-B200-labeled (RB200) myoglobin were injected intravenously as labels of the perfused intravasal and the extracellular space, respectively. The hypoxic conditions were induced subsequently and maintained for 3 minutes. After this period the heart was rapidly frozen for histological demonstration of the dyes. Ventilation with 12% or 10% O2 did not induce any changes in the density of perfused capillaries; however, 8% O2 in respiration gas did lead to a significant increase (capillaries/mm2: subepicardium, 4,180, controls, 3,620; subendocardium, 3,930, controls, 3,240). A similar increase was found in the asphyxia group (capillaries/mm2: subepicardium, 4,170; subendocardium, 3,700). The increases in the density of perfused capillaries were paralleled by rises in fiber density. This leads to the conclusion that the changes in capillary counts were caused by fiber elongation with a resultant decrease in intercapillary distances. This assumption was supported by observations that there were no signs of changes in ventricular segment length during respiration of 12% or 10% O2 but that an increase did occur with 8% oxygen and with asphyxia. Densities of perfused capillaries exactly coincided with anatomical densities (demonstrated by additional labeling of capillary basement membranes with isolectin B4) in normoxic and asphyctic hearts. The distribution of red cells in the capillaries, determined in histological sections, did not differ appreciably under hypoxia due to reduced O2 in respiration air (12%) or asphyxia. The results obtained indicate that 1) extreme hypoxic states cause the capillaries to move closer to each other due to elongation of myocardial fibers and 2) red cell distribution is not altered during these conditions.

Prediction of perinatal brain damage by cord plasma vasopressin, erythropoietin, and hypoxanthine values

For an assessment of whether cord plasma arginine vasopressin, erythropoietin, and hypoxanthine concentrations are predictors of perinatal brain damage, these concentrations were measured in 62 infants born after preeclampsia of pregnancy, 31 acutely asphyxiated infants, and 38 control infants. Follow-up at 2 years included neurologic examination and the determination of a Bayley mental score. Clear abnormality (death, cerebral palsy, or developmental delay) was found in four infants in the preeclampsia group and five in the asphyxia group; slight abnormality was found in 12 and 6 infants, respectively; and no abnormality was found in the remainder. Neither arginine vasopressin values nor hypoxanthine values predicted adverse outcome in either study group. A high erythropoietin level was found in infants born after preeclampsia regardless of outcome: normal outcome (geometric mean (GM), 102; 95% confidence interval [CI], 69 to 153 mU/ml), slightly abnormal outcome (GM, 100; 95% CI, 37 to 270 mU/ml) or clearly abnormal outcome (GM, 84; 95% CI, 19 to 378 mU/ml). However, asphyxiated infants with clearly abnormal outcome had higher erythropoietin values (GM, 67; 95% CI, 33 to 137 mU/ml; p less than 0.05) than the normal infants (GM, 37; 95% CI, 23 to 59 mU/ml). We conclude that a high erythropoietin level after normal pregnancy, but not after preeclampsia, indicates an increased risk for cerebral palsy or death.

Cord Plasma Vasopressin, Erythropoietin, and Hypoxanthine as Indices of Asphyxia at Birth

To assess the value of cord plasma arginine vasopressin (AVP), erythropoietin (EP), and hypoxanthine (HX) as indices of asphyxia, we studied 62 infants of mothers with preeclampsia, 34 acutely asphyxiated infants, with 5-min Apgar score less than or equal to 6 and/or umbilical arterial pH less than or equal to 7.05, and 38 control infants. Umbilical arterial AVP in the asphyxia group (geometric mean; 95% confidence interval: 180; 92-350 pg/ml) was higher than in the control group (23; 8-66, p = 0.002) and correlated with umbilical arterial pH (r = -0.447, p = 0.028). AVP levels in the preeclampsia group did not differ from controls. Cord venous EP was higher in infants delivered by elective cesarean section from women with severe preeclampsia (115; 75-177 mU/ml, p less than 0.001) than in control infants (23; 18-27); in the whole group EP correlated with pH (r = -0.493, p less than 0.001). EP in the asphyxia group was similar (46; 35-65) to controls (40; 33-47) and did not correlate with pH. Cord arterial HX in the preeclampsia group was similar to controls (12.3; 9.5-16.0 mumol/liter), but elevated in the asphyxia group (23.7; 17.6-31.8, p = 0.001), in which HX correlated with pH (r = 0.558, p = 0.008) and AVP (r = 0.588, p = 0.005). EP did not correlate with AVP or HX in any group, nor did any of the variables correlate with the Apgar score. We conclude that cord plasma AVP and HX reflect acute asphyxia, whereas EP is elevated after more prolonged hypoxia.