Interleukin-6 and tumor necrosis factor-alpha levels in plasma and cerebrospinal fluid of term newborn infants with hypoxic-ischemic encephalopathy

OBJECTIVES: To determine plasma and cerebrospinal fluid (CSF) levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: A controlled, prospective study of 20 control neonates, 19 term newborn infants presenting with sepsis and no meningitis, and 19 asphyxiated term newborn infants. Blood and CSF samples were collected within 48 hours of birth for IL-6 and TNF-alpha determinations. RESULTS: Median plasma IL-6 was similar in sepsis and asphyxia but significantly higher than in control neonates. Median plasma TNF-alpha was similar in asphyxia and control neonates but significantly lower than in sepsis. In asphyxiated newborn infants, median CSF IL-6 and TNF-alpha were significantly higher than in sepsis and control neonates. Median CSF IL-6 was significantly higher in sepsis than in control neonates. Median CSF TNF-alpha was similar in newborn infants with sepsis and control neonates. IL-6 and TNF-alpha CSF/plasma ratios were similar in newborn infants with sepsis and control neonates but lower than in asphyxiated newborn infants. CONCLUSIONS: Term newborn infants with HIE have elevated CSF IL-6 and TNF-alpha levels. Plasma IL-6 is increased in asphyxia and sepsis. Plasma TNF-alpha is increased only in sepsis. High IL-6 and TNF-alpha CSF/plasma ratios in asphyxia suggest that these cytokines are produced in the brain of term newborn infants with HIE.     

New insights into the pathogenesis of perinatal hypoxic‐ischemic brain injury

Background: Pathogenesis of perinatal hypoxic‐ischemic brain injury (HIE) is complex. In this study, we examined the role of neuroinflammation, oxidative stress and growth factors in perinatal hypoxic‐ischemic brain damage. Methods: Ninety neonates (>32 weeks' gestation) with perinatal HIE were enrolled prospectively. Perinatal HIE was categorized into three stages according to the Sarnat and Sarnat clinical scoring system and changes seen on amplitude integrated electroencephalography. Cerebrospinal fluid (CSF) for interleukin‐6 (IL‐6) and glutathione peroxidase analysis was taken in the first 48 h of life and subsequent CSF for neuron‐specific enolase (NSE) and vascular endothelial growth factor (VEGF) analysis 72 h after birth. Neurodevelopmental outcome was assessed at 12 months of corrected gestational age using the Denver Developmental Screening Test. Results: Concentrations of NSE in CSF correlated with severity of HIE (P < 0.0001) and corresponded well with subsequent neurodevelopmental outcome. Concentrations of IL‐6 in CSF were markedly increased in neonates with severe HIE (P < 0.0001) and those with subsequent neurological sequels, but were normal in the majority of neonates with mild and moderate HIE. Glutathione peroxidase activity in CSF was significant with the stage of HIE (P < 0.0001) and gestational age (P < 0.0001) and corresponded well with subsequent neurodevelopmental outcome. Advanced stage of HIE was associated with increased concentrations of VEGF in CSF (P < 0.0001). Neurological outcomes at 12 months of age correlated best with CSF level of NSE (P < 0.001) and IL‐6 (P < 0.001). Conclusion: Our results suggest that neuroinflammation plays a principal role in perinatal hypoxic‐ischemic brain damage and we postulate that oxidative stress and upregulation of VEGF might be important contributing factors in the pathogenesis of hypoxic‐ischemic brain injury, particularly in preterm neonates.     

Cerebrospinal fluid prostaglandins, interleukin 1 beta, and tumor necrosis factor in bacterial meningitis. Clinical and laboratory correlations in placebo-treated and dexamethasone-treated patients

Prostaglandins (PGs), interleukin 1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF alpha) are likely mediators of local inflammatory reactions. We measured PGE2, PGI2, IL-1 beta, and TNF concentrations in paired cerebrospinal fluid (CSF) samples (on admission, CSF1, and 18 to 30 hours later, CSF2) from 80 infants and children with bacterial meningitis. Forty patients received dexamethasone sodium (0.6 mg/kg per day in four intravenous doses) and 40 received an intravenous saline placebo. In CSF1, PGE2, PGI2, IL-1 beta, and TNF were detected in 90%, 56%, 98%, and 71% of specimens with mean (+/- SEM) concentrations of 462 +/- 65, 377 +/- 62, 1266 +/- 242, and 799 +/- 227 pg/mL, respectively. Concentrations of PGE2 correlated significantly with PGI2, IL-1 beta, TNF, and lactate and inversely correlated with glucose concentrations in the first CSF specimens. The PGE2, PGI2, IL-1 beta, and TNF were still detected in 40%, 18%, 97%, and 60%, respectively, of second CSF specimens obtained from placebo-treated patients. Compared with patients who had detectable PGI2 or TNF alpha concentrations in CSF2 specimens, those placebo-treated patients with no detectable PGI2 or TNF alpha activity in CSF2 had a lower incidence of neurological sequelae. Dexamethasone-treated patients had significantly lower PGE2, IL-1 beta, and lactate concentrations and higher glucose concentrations in CSF 18 to 30 hours later, shorter duration of fever, and a lower incidence of neurological sequelae than did placebo-treated patients.     

振幅整合脑电图在足月儿缺氧缺血性脑病早期诊断和预后评估的意义

目的对足月新生儿缺氧缺血性脑病（HIE）生后6h内振幅整合脑电图（aEEG）的变化及其在HIE早期诊断和神经学预后评估的价值进行初步探讨。方法对2003年5月至2005年2月间在我院新生儿病房住院的33例足月HIE患儿在生后6h内进行aEEG描记,并将aEEG监测结果与HIE患儿临床分度及18个月时的神经学预后进行相关性分析,分析其在HIE早期诊断和神经学预后预测中的价值。结果33例HIE患儿中,aEEG正常20例（60．6％）,轻度异常5例（15．2％）,重度异常8例（24．2％）。33例HIE患儿中,轻度HIE 17例（51．5％）,中度HIE 9例（27．3％）,重度HIE 7例（21．2％）。25例进行神经预后分析,其中19例神经学预后正常,1例伤残（智力缺陷）,5例死亡。aEEG分类结果与HIE临床分度及其神经学预后均相关性强。aEEG异常预测新生儿中重度HIE的敏感性为100％,特异性为81．3％,阳性预测值为85．0％,阴性预测值为100％;预测HIE异常神经学预后的敏感性为100％、特异性为90．9％、阳性预测值为93．3％和阴性预测值为100％。结论对足月HIE新生儿生后6h内aEEG监测能早期预测HIE病情轻重程度并预测其神经学预后。     

新生儿缺氧缺血性脑病脑脊液环磷酸腺苷变化及其临床意义

目的 探讨新生儿缺血缺氧性脑病(HIE)脑脊液(CSF)环磷酸腺苷(cAMP)变化及其临床意义。方法 采用法国:Immunotech公司提供的125I-cAMP放免药盒对86例HIE患儿进行脑脊液cAMP。结果 中、重度HIE组CSI-cAMP值较非HIE组明显降低,有显著差异(P<0.05);重度HIE患儿CSI-cAMP值较轻、中度患儿降低,差异具有显著性(P<0.05);恢复期较急性期CSF-cAMP值都有所升高,但无显著差异。结论 HIE时CSF-cAMP降低,病情愈重,降低愈明显。CSF-cAMP测定可作为HIE患儿判断病情的辅助指标。     

Denver developmental screening test II for early identification of the infants who will develop major neurological deficit as a sequalea of hypoxic-ischemic encephalopathy

BACKGROUND: The primary aim of this study was to find widely available, inexpensive, and non-invasive parameters for early identification or prediction of the infants with hypoxic-ischemic encephalopathy (HIE) who will have a severe adverse outcome (classified as death or a major neurological deficit). METHODS: Fifty-seven full-term or near-term newborn infants with a diagnosis of HIE were consecutively admitted to the neonatal intensive care unit and studied. Occurrence of seizures during the first 24 h, cranial ultrasonography (US) findings within the first 5 days of life, and Denver developmental screening test II (DDST II) at 6 months of age, were analyzed in relation to mortality and neurological status at 2 years of age. RESULTS: Of the 57 infants, 10 were lost to follow-up. Twenty of the remaining 47 infants had a severe adverse outcome. Among the predictors of severe adverse outcome, occurrence of seizures was found to have a poor predictive accuracy. Cranial US had 100% sensitivity, however with a rather low specificity (55%). However, DDST II at 6 months of age, yielded a very high predictive accuracy (sensitivity=100%, specificity=95%). CONCLUSION: We conclude that DDST II at 6 months of age could be used in predicting severe neurological outcome in infants with HIE.     

Interleukin-6 in the cerebrospinal fluid after perinatal asphyxia is related to early and late neurological manifestations

OBJECTIVES: To investigate if the concentration of interleukin-6 (IL-6) in the cerebrospinal fluid (CSF) is affected by perinatal asphyxia, and to examine the relation of IL-6 levels in the CSF to the severity of hypoxic-ischemic encephalopathy (HIE), to brain damage, and to the neurological outcome. METHODS: Asphyxiated term neonates were included. Cerebrospinal fluid IL-6 was measured by a sensitive enzyme-linked immunosorbent assay. RESULTS: Twenty neonates were studied: 3 had no HIE, 5 had stage 1, 6 had stage 2, and 6 had stage 3. CSF IL-6 levels (8 to 90 hours of life) were higher in neonates with HIE stage 3 (range, 65 to 2250 pg/mL) when compared with neonates with HIE stage 0 to 2 (<2 pg/mL in 12 neonates, 10 pg/mL in 1). According to neuroimaging techniques and/or pathological examination, 14 neonates were normal, and 5 showed signs of brain damage; 1 was not classified. CSF IL-6 levels were significantly higher in neonates with signs of brain damage. Finally, 5 neonates had adverse outcomes (4 died, 1 had cerebral palsy), 2 had mild motor impairment, and 13 had normal outcomes. CSF IL-6 levels were higher in neonates with adverse outcomes (range, 65 to 2250 pg/mL) compared with neonates with favorable outcomes. CONCLUSION: The magnitude of IL-6 response in the CSF after perinatal asphyxia is related to the severity of neonatal HIE, to brain damage, and to the neurological outcome. Our results suggest that IL-6 might play a role in neonatal hypoxic-ischemic brain damage.     

Evaluation of interleukin-6, tumour necrosis factor-α and interleukin-1β for early diagnosis of neonatal sepsis

The objective of this study was to assess the contribution of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) to an early diagnosis of early-onset neonatal sepsis. A cohort of 117 newborn infants delivered during a 1-y period had IL-6, TNF-alpha and IL-1beta, blood and cerebrospinal fluid (CSF) cultures, leucocyte and platelet count collected on the initial evaluation of possible early-onset sepsis. They were divided into four groups: I, positive blood and/or CSF cultures; II, probably infected with clinical sepsis but negative cultures; III, same as group II but mother received antibiotic antepartum; and IV, newborn infants that did not receive any antibiotic therapy. There were no differences among the four groups with respect to mean gestational ages and birthweights, median Apgar scores, type of delivery, or number of newborn infants with leucocyte count <5000 mm(-3) or >25000 mm(-3), platelet count <100000 mm(-3), immature/total neutrophil ratio >0.2, absolute neutrophil count <1000mm(-3) and median IL-1beta levels. Median IL-6 and TNF-alpha levels were significantly higher in groups with patients with a diagnosis of clinical sepsis than in controls. The optimal cut-off point was 32 pg ml(-1) for IL-6 and 12 pg ml(-1) for TNF-alpha. The combination of both provided a sensitivity of 98.5%. In conclusion, the combination of IL-6 and TNF-alpha is a highly sensitive marker of sepsis in the immediate postnatal period.     

Effects of hypothermia on NSE and S-100 protein levels in CSF in neonates following hypoxic/ischaemic brain damage

Aim: The aim of the study was to evaluate the effects of hypothermia on neuron‐specific enolase (NSE) and S‐100 protein levels in cerebrospinal fluid (CSF) in neonates with hypoxic/ischaemic encephalopathy (HIE). Methods: Fifty‐one enrolled neonates with HIE were divided into two groups: hypothermia (n = 23) and control (n = 28). NSE and S‐100 protein were measured with immunoradiometric assays. Amino acid neurotransmitters were also measured by reversed‐phase high‐performance liquid chromatography. Neurodevelopmental assessments were performed at 3 and 12 months of age. Results: Neuron‐specific enolase and S‐100 levels were lower, and neurodevelopment outcome was better in the hypothermia group compared with the control group. Among the infants who received hypothermia, CSF NSE and S‐100 were significantly higher in those who developed severe neurological impairment (mental development index or physical development index <70). There were no significant differences between the two groups in amino acid neurotransmitters. Conclusion: These results indicated that hypothermia was associated with decreased CSF NSE and S‐100 level and correlated with neurodevelopmental outcome in infants with HIE.     

Prediction of neurological outcome after birth asphyxia from early continuous two-channel electroencephalography.

OBJECTIVE: To determine whether two-channel continuous electroencephalography (EEG) applied within 12 h of birth can predict the severity of neurological complications and neurodevelopmental outcome following birth asphyxia. METHODS: A continuous two-channel EEG was performed within 12 h of birth in 22 infants suspected of having suffered birth asphyxia and 11 healthy control infants (22 infants at a general and 11 at a specialist paediatric unit). Criteria to categorise normal and abnormal EEG records were defined and compared with the severity of hypoxic/ischaemic encephalopathy (HIE) and with neurodevelopmental outcome, assessed at or after 12 months of age. RESULTS: EEG recordings were commenced at a median (range) of 2 h 50 min (1 h 45 min to 12 h) after birth. Technically satisfactory recordings were obtained in all but one infant. All control infants remained asymptomatic and had a normal EEG with discernible sleep/awake periods. 12 h after birth the EEG was normal in all 12 infants suspected of asphyxia who remained well or developed grade 1 HIE and was abnormal in six of nine infants with grade II or III HIE. Fifteen of 16 infants suspected of asphyxia with a normal neurodevelopmental outcome had a normal EEG at 12 h; transient abnormalities lasting not more than 8 h had been detected in three of these infants. All five infants who died or developed neurodevelopmental abnormalities had an abnormal EEG. At 12 h of age the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and likelihood ratio for predicting severe (grade II or III) HIE were: 67, 100, 100, 80% and infinity and for subsequent death or neurodevelopmental impairments: 100, 94, 83, 100 and 16%, respectively. Assessment of the EEG before 12 h of age altered prognostic accuracy: 4 h after birth the sensitivity, specificity, positive and negative predictive values and the likelihood ratio for poor neurodevelopmental outcome were 100, 71, 33%, 100 and 3.7%, respectively (16 infants). CONCLUSION: Continuous two-channel EEG is an accurate tool for assessing the severity of neurological insult soon after birth asphyxia.     

Inflammatory markers in intrauterine and fetal blood and cerebrospinal fluid compartments are associated with adverse pulmonary and neurologic outcomes in preterm infants

Recent evidence strongly implicates the inflammatory response to intrauterine infection in the pathogenesis of neonatal brain and lung injury. We hypothesized that lung and brain injury in preterm infants occurs during a common developmental window of vulnerability as the result of an inflammatory response in different compartments. To determine whether inflammatory markers in these compartments are associated with bronchopulmonary dysplasia (BPD) or cranial ultrasound (CUS) abnormalities in infants <33 wk gestation age (GA) and <1501 g birth weight, we analyzed placental pathology and serum and cerebrospinal fluid (CSF) IL-6, IL-1beta, and tumor necrosis factor-alpha (TNF-alpha) concentrations in 276 infants. Logistic regressions were performed stratified by GA. Histologic chorioamnionitis was significantly associated with BPD in infants /=17 pg/mL was associated with an abnormal CUS in infants >28 wk GA (OR 3.36, p = 0.023) but not /=6.5 pg/mL and TNF-alpha >/=3 pg/mL were associated with abnormal CUS in infants /=28 wk GA. These data suggest that in infants 相似文献   

Cerebrospinal fluid levels of cytokines and soluble tumour necrosis factor receptor in acute disseminated encephalomyelitis

We determined the concentrations of interleukin-1beta (IL-1beta, IL-6, IL-10, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), and soluble TNF receptor 1 (sTNFR1) in CSF from 18 patients with acute disseminated encephalomyelitis (ADEM) to investigate the role of cytokines in the pathogenesis of the disease in the acute stage. Cytokines and sTNFR1 were measured by ELISA. The CSF IL-6, IL-10, TNF-alpha, and sTNFR1 concentrations were elevated in 16, 13, 3, and 11 of the 18 patients with ADEM, respectively. CSF concentrations of IL-10 and sTNFRI correlated positively with each other in the patients (P<0.01). Myelin basic protein levels in CSF of the patients with elevated CSF sTNFR1 levels were significantly higher than those in CSF of the patients with normal CSF sTNFR1 levels (P<0.05). IL-1beta and IFN-gamma were not elevated in CSF. Our results suggest that IL-6 and TNF-alpha mediate inflammation in the central nervous systems in ADEM. We speculated that TNF-alpha is related to demyelination and that IL-10 is induced to modulate TNF-alpha-induced inflammation in ADEM. CONCLUSION: these findings suggest that cytokines such as tumour necrosis factor-alpha, soluble tumour necrosis factor receptor 1, interleukin-6, and interleukin-10 are related to the pathogenesis of acute disseminated encephalomyelitis in the acute stage.     

一氧化氮和内皮素-1在新生儿缺氧缺血性脑病中的作用

目的　研究新生儿缺氧缺血性脑病(HIE)患儿脑脊液一氧化氮(NO)和内皮素-1(ET-1)水平变化,探讨NO 和ET-1在HIE中的作用及相互关系。方法　检测24 例HIE患儿脑脊液NO和ET-1 水平,并与8 例对照组比较。结果　HIE组患儿脑脊液NO 和ET-1 水平明显高于对照组(P< 0.05),中、重度HIE组患儿脑脊液NO 和ET-1水平明显高于轻度HIE组(P< 0.05),头颅CT异常HIE患儿脑脊液ET-1 水平明显高于CT正常者(P< 0.01)。结论　NO和ET-1 参与新生儿HIE的病理生理过程,脑脊液NO和ET-1 是反映脑实质损伤的重要指标     

Cardiac troponin I concentrations in neonates with hypoxic-ischaemic encephalopathy

Aim: Myocardial dysfunction is a frequent sequel of perinatal asphyxia. Cardiac troponin I (cTnI) is a marker of myocardial injury and a surrogate marker of myocardial dysfunction in adults, but there are few data in neonates. Our aim was to compare serum cTnI concentrations with clinical severity of encephalopathy and with duration of inotropic support in asphyxiated neonates. Methods: Retrospective study of 60 neonates admitted with hypoxic‐ischaemic encephalopathy (HIE). cTnI concentrations measured within 36 h of birth were compared with clinical grade of HIE (Sarnat‐Sarnat classification) and with duration of inotropic support. Results: Serum cTnI concentrations and duration of inotropic support were significantly greater with increasing severity of HIE. Median (95% CI) cTnI concentrations were 0.04 μg/L (0.02–0.07 μg/L) in grade 1 HIE, 0.12 μg/L (0.08–0.20 μg/L) in grade 2 HIE and 0.67 μg/L (0.41–1.35 μg/L) in grade 3 HIE. Median (95% CI) duration of inotropic support required was 0 h (0–24 h) in grade 1 HIE, 28 h (0–118 h) in grade 2 HIE and 48 h (0–140 h) in grade 3 HIE. Conclusion: In asphyxiated neonates, cTnI concentrations within 36 h of birth correlate strongly with clinical grade of HIE and with duration of inotropic support. Early cTnI concentrations may provide a useful proxy marker for the anticipated severity of myocardial dysfunction.     

内皮素和一氧化氮与新生儿缺氧缺血性脑病的研究

目的 探讨血浆与脑脊液中内皮素,一氧化氮在新生儿缺氧缺血性脑病中的作用及其相互关系。方法 对３５例ＨＩＥ患儿分别采用放射免疫法测定血浆和ＣＳＦ中ＥＴ－１,硝酸根不原酶法测定血浆和ＣＳＦ中ＮＯ＾－２／ＮＯ＾－３值ＮＯ水平,并观察其急性期,恢复期的动态变化。     

Cytokine response in cerebrospinal fluid from preterm infants with posthaemorrhagic ventricular dilatation

Aim: Posthaemorrhagic ventricular dilatation (PHVD) is closely associated with white matter damage and neurological disability in the preterm infant. Proinflammatory cytokines have been implicated in the pathogenesis of white matter injury and subsequent cerebral palsy. The aim of this study was to determine the levels of proinflammatory cytokines in cerebrospinal fluid (CSF) from preterm infants with PHVD and to correlate the levels to white matter damage and neurodevelopmental outcome. Methods: CSF samples were obtained from 24 preterm infants with expanding PHVD and 19 preterm infants with normal ultrasound. Tumour necrosis factor-3 (TNF-3), interleukin-13 (IL-13), interleukin-8 (IL-8) and interferon-3 (IFN-3) in CSF were measured by enzyme-linked immunosorbent assay, and IL-6 was measured by bioassay. Results: The concentrations of TNF-3, IL-13, IL-6 and IL-8 were significantly elevated in CSF from infants with PHVD. TNF-3 was detected in 43% of PHVD infants and 11% of controls ( p = 0.04). IL-13 was detected in 67% of PHVD infants and 0% of controls (p 3 0.0001). The concentrations of IL-6 were 368 (145-460) pg ml 31 in the PHVD group and 30 (25-41) pg ml 31 in the control group (p 3 0.0001), and those of IL-8 were 3000 (1620-3400) pg ml 31 in the PHVD group and 35 (0-230) pg ml 31 in the control group (p 3 0.0001). Cytokine concentrations did not correlate with white matter lesions on ultrasound, shunt dependence or neurological outcome within the PHVD group. Conclusion: There was an intense and prolonged inflammatory reaction in CSF from preterm infants with PHVD and a high risk for subsequent white matter injury and permanent neurological impairment.     

Neuron specific enolase in asphyxiated newborns: association with encephalopathy and cerebral function monitor trace.

Neuron specific enolase (NSE) in serum and cerebrospinal fluid (CSF) and glutamate in CSF were investigated in the immediate postasphyctic period in 22 term newborn infants. The cerebral function monitor (CFM) pattern was also assessed and hypoxic-ischaemic encephalopathy (HIE) was graded. NSE was significantly increased in the CSF of infants with HIE (median value 25.4 micrograms/l) compared with control infants (10.0 micrograms/l). Infants with the highest concentrations died. NSE in CSF correlated with the degree of asphyxial damage. Glutamate and NSE in CSF did not correlate, presumably due to the different time factors of the release after the insult. NSE in CSF corresponded well with the type of CFM pattern, which was also highly predictive of outcome.     

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目的 观察脑苷肌肽注射液(国产神经节苷脂GM1)治疗新生儿缺氧缺血性脑病(HIE)的疗效.方法 2004年8月至2006年4月北京朝阳医院儿科对MCU收治的70例新生儿HIE患儿随机分为两组,治疗组(n=36)使用脑苷肌肽治疗,与对照组(n=34)使用胞二磷胆碱或1,6-二磷酸果糖治疗,通过比较两组患儿临床神经症状恢复时间及新生儿行为神经评分(NBNA)来判断药物的疗效.结果 脑苷肌肽与胞二磷胆碱或1,6-二磷酸果糖治疗新生儿HIE的疗效差异无显著性意义(P＞0.05),均能在7～10 d使神经症状恢复正常,在生后2周NBNA评分绝大多数在正常范围内.结论 早期应用脑苷肌肽治疗新生儿HIE有良好疗效.     

Alterations in antioxidant enzyme activities in cerebrospinal fluid related with severity of hypoxic ischemic encephalopathy in newborns

BACKGROUND: The antioxidant status of the tissue affected by ischemia-reperfusion is of great importance for the primary endogenous defense against the free-radical-induced injury. OBJECTIVE: In this study, we aimed to evaluate the relationship between the activities of antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT)] in cerebrospinal fluid (CSF) and severity of hypoxic-ischemic encephalopathy (HIE) in newborns. METHODS: Thirty full-term asphyxiated infants (gestational age >37 weeks) and 11 full-term infants (none of whom showed any signs of asphyxia) were included in this study. Activities of SOD, GPX, and CAT in CSF were measured within the first 72 h of life in infants with HIE and controls. RESULTS: Activity of SOD in CSF was significantly higher in infants with HIE compared with controls (p<0.05). GPX and CAT activities were higher in infants with HIE than they were in controls; however, the differences were not statistically significant (p > 0.05). The activities of GPX and CAT were significantly increased in severe HIE as compared with mild HIE and controls (p < 0.05). CONCLUSION: Both the duration of the hypoxic-ischemic insult and the severity of HIE modulate elevations of enzymatic activity as an adaptive response to excessive free radical production in CSF in newborn infants with HIE. The activities of antioxidant enzyme alterations in CSF correspond highly to the severity of HIE, and these patterns may be useful for diagnostic and prognostic purposes.     

One-year neurodevelopmental outcome after moderate newborn hypoxic ischaemic encephalopathy

OBJECTIVES: To define the 1-year neurodevelopmental outcome for survivors of moderate (Sarnat stage 2) neonatal hypoxic-ischaemic encephalopathy (HIE) to facilitate appropriate parental counselling. METHODS: Hospital-based retrospective review of admissions to a tertiary newborn intensive care unit between 1988 and 2000. All babies admitted for seizures were reviewed and those in whom the probable diagnosis was moderate HIE were identified from chart review. Perinatal variables, number of anticonvulsants, duration of hospital stay and 1-year neurodevelopmental outcome was recorded in survivors. RESULTS: Fifty-three babies who survived probable moderate HIE were identified. Forty-two of these were seen at 1 year of age. Of these, 22 (52%) had normal development and neurological examination and four (9.5%) had mild developmental delay with normal neurological examination. Thirteen babies (31%) had cerebral palsy, 11 of whom also had developmental delay. Two infants (5%) who had been severely impaired at 6 months died before 1 year of age. Overall, 36% of survivors of the neonatal period had significant disability and or had died by 1 year of age. Duration of anticonvulsant treatment and length of hospital stay were significantly related to adverse outcome. CONCLUSIONS: These data suggest morbidity rates after moderate HIE in the upper end of the range previously described in the literature. Systematic longer-term follow up of this high-risk group of infants is needed.