Prognostic Tests in Term Neonates With Hypoxic-Ischemic Encephalopathy: A Systematic Review.
ABSTRACT BACKGROUND AND OBJECTIVE:Hypoxic-ischemic encephalopathy (HIE) after perinatal asphyxia in term neonates causes long-term neurologic sequelae or death. A reliable evidence-based prognosis is essential. The study goal was to investigate the prognostic value of currently used clinical tests in neonatal patients with perinatal asphyxia and HIE.METHODS:Searches were made on MEDLINE, Embase, Central, and CINAHL for studies occurring between January 1980 and November 2011. Studies were included if they (1) evaluated outcome in term infants with perinatal asphyxia and HIE, (2) evaluated prognostic tests, and (3) reported outcome at a minimal follow-up age of 18 months. Study selection, assessment of methodologic quality, and data extraction were performed by 3 independent reviewers. Pooled sensitivities and specificities of investigated tests were calculated when possible.RESULTS:Of the 259 relevant studies, 29 were included describing 13 prognostic tests conducted 1631 times in 1306 term neonates. A considerable heterogeneity was noted in test performance, cut-off values, and outcome measures. The most promising tests were amplitude-integrated electroencephalography (sensitivity 0.93, [95% confidence interval 0.78-0.98]; specificity 0.90 [0.60-0.98]), EEG (sensitivity 0.92 [0.66-0.99]; specificity 0.83 [0.64-0.93]), and visual evoked potentials (sensitivity 0.90 [0.74-0.97]; specificity 0.92 [0.68-0.98]). In imaging, diffusion weighted MRI performed best on specificity (0.89 [0.62-0.98]) and T1/T2-weighted MRI performed best on sensitivity (0.98 [0.80-1.00]). Magnetic resonance spectroscopy demonstrated a sensitivity of 0.75 (0.26-0.96) with poor specificity (0.58 [0.23-0.87]).CONCLUSIONS:This evidence suggests an important role for amplitude-integrated electroencephalography, EEG, visual evoked potentials, and diffusion weighted and conventional MRI. Given the heterogeneity in the tests' performance and outcomes studied, well-designed large prospective studies are needed.
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ABSTRACT: This paper reviews the opportunities and challenges for early diagnosis and early intervention in cerebral palsy (CP). CP describes a group of disorders of the development of movement and posture, causing activity limitation that is attributed to disturbances that occurred in the fetal or infant brain. Therefore, the paper starts with a summary of relevant information from developmental neuroscience. Most lesions underlying CP occur in the second half of gestation, when developmental activity in the brain reaches its summit. Variations in timing of the damage not only result in different lesions but also in different neuroplastic reactions and different associated neuropathologies. This turns CP into a heterogeneous entity. This may mean that the best early diagnostics and the best intervention methods may differ for various subgroups of children with CP. Next, the paper addresses possibilities for early diagnosis. It discusses the predictive value of neuromotor and neurological exams, neuroimaging techniques, and neurophysiological assessments. Prediction is best when complementary techniques are used in longitudinal series. Possibilities for early prediction of CP differ for infants admitted to neonatal intensive care and other infants. In the former group, best prediction is achieved with the combination of neuroimaging and the assessment of general movements, in the latter group, best prediction is based on carefully documented milestones and neurological assessment. The last part reviews early intervention in infants developing CP. Most knowledge on early intervention is based on studies in high-risk infants without CP. In these infants, early intervention programs promote cognitive development until preschool age; motor development profits less. The few studies on early intervention in infants developing CP suggest that programs that stimulate all aspects of infant development by means of family coaching are most promising. More research is urgently needed.Frontiers in Neurology 09/2014; 5:185.
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ABSTRACT: A study-level meta-analysis has shown that proton magnetic resonance spectroscopy is a promising prognostic marker in neonatal hypoxic-ischemic encephalopathy. An individual patient data meta-analysis could yield a prognostic tool with improved accuracy enabling well-founded clinical decisions. Our request to share patient data remained unanswered by five out of 18 research groups. Another four declined collaboration for various reasons, including own reanalysis of the data, and lack of parental consent. With less than 40% of the individual patient data available, we refrained from pursuing the proposed study. As future patients may benefit from it, policies mandating data sharing should be introduced.Systematic reviews. 09/2014; 3(1):97.
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ABSTRACT: We examined two potential biomarkers of brain damage in hypoxic-ischemic encephalopathy (HIE) neonates: glial fibrillary acidic protein (GFAP; a marker of gliosis) and ubiquitin C-terminal hydrolase L1 (UCH-L1; a marker of neuronal injury). We hypothesized that the biomarkers would be measurable in cord blood of healthy neonates and could serve as a normative reference for brain injury in HIE infants. We further hypothesized that higher levels would be detected in serum samples of HIE neonates and would correlate with brain damage on magnetic resonance imaging (MRI) and later developmental outcomes.? Serum UCH-L1 and GFAP concentrations from HIE neonates (n = 16) were compared to controls (n = 11). The relationship between biomarker concentrations of HIE neonates and brain damage (MRI) and developmental outcomes (Bayley-III) was examined using Pearson correlation coefficients and a mixed model design. Both biomarkers were detectable in cord blood from control subjects. UCH-L1 concentrations were higher in HIE neonates (p < 0.001), and associated with cortical injury (p < 0.055) and later motor and cognitive developmental outcomes (p < 0.05). The temporal change in GFAP concentrations during (from birth to 96 h of age) predicted motor developmental outcomes (p < 0.05) and injury to the basal ganglia and white matter. Ubiquitin C-terminal hydrolase L1 and GFAP should be explored further as promising serum biomarkers of brain damage and later neurodevelopmental outcomes in neonates with HIE.Frontiers in Neurology 12/2014; 5:273.