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IntroductionPerinatal management and prognostic value of clinical evaluation and diagnostic tools have changed with the generalization of therapeutic hypothermia (TH) in infants with hypoxic-ischemic encephalopathy (HIE)Aimto ascertain the prognostic value of amplitude integrated electroencephalogram (aEEG) in neonates with HIE considering hours of life and treatment with TH.MethodsA systematic review was performed. Inclusion criteria were studies including data of neonates with HIE, treated or not with TH, monitored with aEEG and with neurodevelopmental follow-up of at least 12 months. The period of bibliographic search was until February 2016. No language restrictions were initially applied. Consulted databases were MEDLINE, Scopus, CINHAL and the Spanish language databases GuiaSalud and Bravo. Article selection was performed by two independent reviewers. Quality for each individual paper selected was evaluated using QUADAS-2. Review Manager (RevMan) version 5.3 software was used. Forest plots were constructed to graphically show sensitivity and specificity for all included studies, separating patients treated or not with hypothermia. Summary statistics were estimated using bivariate models and random effects approaches with the R package MADA from summary ROC curves. Meta-regression was used to estimate heterogeneity and trends.Resultsfrom the 403 articles initially identified, 17 were finally included and critically reviewed. In infants not treated with hypothermia the maximum reliability of an abnormal aEEG background to predict death or moderate/severe disability was at 36 hours of life, when a positive post-test probability of 97.90% was achieved (95%CI 88.40 to 99.40%). Positive likelihood ratio (+LR) at these hours of life was 26.60 (95%CI 4.40 to 94.90) and negative likelihood ratio (-LR) was 0.23 (95%CI 0.10 to 0.44). A high predictive value was already present at 6 hours of life in this group of patients, with a positive post-test probability of 88.20% (95%CI 79.80 to 93%) and a +LR of 4.34 (95%CI 2.31 to 7.73). In patients treated with TH the maximum predictive eliability was achieved at 72 hours of life (post-test probability of 95.70%, 95%CI 84.40 to 98.50%). +LR at this age was 24.30 (95%CI 5.89 to 71.30) and–LR was 0.40 (95%CI 0.25 to 0.57). Predictive value of aEEG at 6 hours of life was low in these patients (59.10%, 95%CI 55.70 to 63%).ConclusionThis study confirms that aEEG´s background activity, as recorded during the first 72 hours after birth, has a strong predictive value in infants with HIE treated or not with TH. Predictive values of traces throughout the following 72 hours are a helpful guide when considering and counselling parents about the foreseeable long-term neurological outcome

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Therapeutic hypothermia (TH) initiated within 6 h from birth is the most effective therapeutic approach for moderate to severe hypoxic-ischemic encephalopathy (HIE). However, underlying mechanisms and effects on the human metabolism are not yet fully understood. This work aims at studying the evolution of several energy related key metabolites in newborns with HIE undergoing TH employing gas chromatography – mass spectrometry. The method was validated following stringent FDA requirements and applied to 194 samples from a subgroup of newborns with HIE (N = 61) enrolled in a multicenter clinical trial (HYPOTOP) for the determination of lactate, pyruvate, ketone bodies and several Krebs cycle metabolites at different sampling time points. The analysis of plasma samples from newborns with HIE revealed a decrease of lactate, pyruvate and β-hydroxybutyrate concentrations, whereas rising malate concentrations were observed. In healthy control newborns (N = 19) significantly lower levels of pyruvate and lactate were found in comparison to age-matched newborns with HIE undergoing TH, whereas acetoacetate and β-hydroxybutyrate levels were clearly increased. Access to a validated analytical method and a controlled cohort of newborns with HIE undergoing hypothermia treatment for the first time allowed the in-depth study of the evolution of key metabolites of metabolic junctions in this special population.

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