Prognostic Tests in Term Neonates With Hypoxic-Ischemic Encephalopathy: A Systematic Review

Department of Neonatology, and.
PEDIATRICS (Impact Factor: 5.47). 12/2012; 131(1). DOI: 10.1542/peds.2012-1297
Source: PubMed


Background and Aims Hypoxic Ischemic Encephalopathy (HIE) following perinatal asphyxia in term neonates is associated with long term neurological sequelae or demise. The aim of this systematic review was to investigate the prognostic value of currently used clinical tests in neonatal patients with HIE.
Methods MEDLINE, EMBASE, Central and CINAHL were searched until November 2011. Studies were included if they: (1) concerned infants with a gestational age ≥ 36 weeks suffering perinatal asphyxia and HIE; (2) evaluated prognostic tests in either cooled or non-cooled patients; (3) reported on neurodevelopmental outcome results at a follow up age ≥ 18 months. Study selection, assessment of methodological quality, and data extraction was performed by three independent reviewers. Pooled sensitivities and specificities of investigated tests were calculated when possible.
Results Included in the analysis were 29 studies describing 13 different prognostic tests conducted 1631 times in 1306 term neonates. Investigated tests comprised a range of imaging modalities, neurophysiological tests and clinical neurological exams. Most promising neurophysiology tests (first week of life) were: aEEG (sens. 0.93, [95%CI 0.78–0.98]; spec. 0.90 [0.60–0.98]); EEG (sens. 0.92 [0.66–0.99]; spec. 0.83 [0.64–0.93]) and VEP (sens. 0.90 [0.74–0.97]; spec. 0.92 [0.68–0.98]).
Conclusions The available evidence suggests an important role for aEEG, EEG, and VEP. Given the heterogeneity of the tests’ performance and outcomes studied, accurate predictions of long term outcomes in these critically ill neonates await the results of well designed large prospective studies that evaluate the best possible combination and timing of diagnostic tests.

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    • "HIE occurring in fetuses and neonates is a major cause of acute mortality and chronic neurological disability in surviving individuals (16). An increasing number of studies have indicated that there is a complicated correlation between HIE and the immune system (17,18). "
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    ABSTRACT: The present study aimed to investigate the potential roles of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and high-sensitivity C-reactive protein (Hs-CRP) in the progression and prognosis of neonatal hypoxic-ischemic encephalopathy (HIE). The observation group comprised 74 neonates with HIE and the control group comprised 74 healthy neonates. The serum levels of IL-6, TNF-α and Hs-CRP were measured in the patients with HIE and the normal control infants. The correlations between the variances in the levels of these inflammatory cytokines and the different clinical gradings and prognoses of the disease were analyzed. The data revealed significant upregulation of the serum levels of IL-6, TNF-α and Hs-CRP in patients with HIE. The increase in the levels of these inflammatory mediators correlated with the severity of the disease and also had a positive correlation with the prognosis of the disease. In conclusion, high levels of IL-6, TNF-α and Hs-CRP were observed in neonatal patients with HIE. Thus, these inflammatory mediators may play a role in the progression and prognosis of the disease.
    Experimental and therapeutic medicine 10/2014; 8(4):1259-1262. DOI:10.3892/etm.2014.1869 · 1.27 Impact Factor
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    • "It is a significant complication of neonatal asphyxia. HIE is also a leading cause of neonatal fatality and disability in children; therefore, it remains the focus for investigation in numerous studies (1). The pathogenesis of HIE remains unclear although, based on related studies, it has been considered as a multi-mechanism combination of anoxia- and ischaemia-induced energy exhaustion, reperfusion and oxidative stress, the toxic effects of excitatory amino acids (EAAs), inflammatory injury (2) and cell apoptosis (3). "
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    ABSTRACT: It remains unclear whether mild hypothermia affects energy metabolism in the brain tissue of newborns with hypoxic-ischaemic encephalopathy (HIE). The current study aimed to investigate the effect of mild hypothermia on energy metabolism in neonatal HIE and assess brain energy metabolism using position emission tomography/computed tomography (PET/CT) scanning. The mean standardised uptake values of (18)F-fluorodeoxyglucose ((18)F-FDG) were used to determine the glucose metabolic rate in various brain anatomical regions, including the thalamus, basal ganglia and the frontal, parietal and occipital lobes. The rate of glucose metabolism significantly improved following treatment with mild hypothermia therapy and conventional therapy (P<0.001). Prior to the treatment, no significant differences were identified between the groups (P>0.05). Following treatment, the rate of glucose metabolism was significantly improved in the mild hypothermia therapy group compared with that in the conventional therapy group (P<0.001). Thus, these results indicate that mild hypothermia therapy effectively promotes the recovery of patients with neonatal HIE. (18)F-FDG PET/CT scanning may be used to provide reference values for the assessment of energetic metabolism in patients with neonatal HIE.
    Experimental and therapeutic medicine 10/2014; 8(4):1219-1224. DOI:10.3892/etm.2014.1884 · 1.27 Impact Factor
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    • "Neonatal HIE is one of the most important causes of moderate and severe neurological disabilities in children. Furthermore, long-term evaluations have found that there are manifestations of subtle cognitive deficits and behavioral alterations even in cases of mild neonatal HIE [7,8]. However, clinical and pathological features of human perinatal brain lesions display striking variations according to the gestational ages [9]. "
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    ABSTRACT: In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE) in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND) 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions.
    PLoS ONE 12/2013; 8(12):e82502. DOI:10.1371/journal.pone.0082502 · 3.23 Impact Factor
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