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Prognostic Value of Clinical Tests in Neonates With Hypoxic-Ischemic Encephalopathy Treated With Therapeutic Hypothermia: A Systematic Review and Meta-Analysis.

ABSTRACT: Background and Objective: There remains an unmet clinical need for markers that predict outcomes in the hypothermia-treated (HT) infants with HIE. The aim of this meta-analysis was to investigate the prognostic accuracy of currently available clinical tests performed in the immediate post-natal period for predicting neurological outcomes between 18 months and 3 years of age in HT near-term and term infants with perinatal asphyxia and HIE. Methods: A comprehensive review of the Embase, Cochrane library, and PubMed databases was performed to identify studies that evaluated the prognostic value of clinical tests for neurological outcomes in HT near-term and term infants with perinatal asphyxia and hypoxic-ischemic encephalopathy. Pooled sensitivity and specificity with corresponding 95% confidence intervals and area under the receiver operating characteristic (ROC) curve (AUC) were calculated. Results: Of the 1,144 relevant studies, 26 studies describing four clinical tests conducted in 1458 HT near-term or term infants were included. For predicting an unfavorable neurological outcome, of the imaging techniques, MRI within 2 weeks of birth performed best on sensitivity 0.85 (95% CI 0.79-0.89), specificity 0.72 (95% CI 0.66-0.77), and AUC 0.88; among the neurophysiological tests, multichannel EEG (Electroencephalogram) demonstrated the sensitivity 0.63 (95% CI 0.49-0.76), specificity 0.82 (95% CI 0.70-0.91), and AUC 0.88, and for aEEG (amplitude-integrated electroencephalography) background pattern pooled sensitivity, specificity and AUC were 0.90 (95% CI 0.86-0.94), 0.46 (95% CI 0.42-0.51), and 0.78 whereas for SEPs (Somatosensory evoked potentials), pooled sensitivity and specificity were 0.52 (95% CI 0.34-0.69), 0.76 (95% CI 0.63-0.87), and AUC 0.84, respectively. Conclusions: In the wake of the era of TH, MRI and neurophysiological tests (aEEG or EEG) were promising predictors of adverse outcomes, while SEPs need high-quality studies to confirm the findings. Continued follow-up of the children and well-designed large prospective studies are essential to determine whether these benefits are maintained in later childhood.

SUBMITTER: Liu W

PROVIDER: S-EPMC7052385 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Prognostic Value of Clinical Tests in Neonates With Hypoxic-Ischemic Encephalopathy Treated With Therapeutic Hypothermia: A Systematic Review and Meta-Analysis.

Liu Weiqin W Yang Qifen Q Wei Hong H Dong Wenhui W Fan Ying Y Hua Ziyu Z

Frontiers in neurology 20200225

<b>Background and Objective:</b> There remains an unmet clinical need for markers that predict outcomes in the hypothermia-treated (HT) infants with HIE. The aim of this meta-analysis was to investigate the prognostic accuracy of currently available clinical tests performed in the immediate post-natal period for predicting neurological outcomes between 18 months and 3 years of age in HT near-term and term infants with perinatal asphyxia and HIE. <b>Methods:</b> A comprehensive review of the Emba ...[more]

PMID: 32161566

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Project description:ImportanceNeonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH) frequently experience seizures, which are associated with adverse outcomes. Efforts to rapidly identify seizures and reduce seizure burden may positively change neurologic and neurodevelopmental outcomes.ObjectiveTo describe the onset, treatment, and evolution of seizures in a large cohort of newborns with HIE during TH assisted by a telehealth model and remote neuromonitoring approach.Design, setting, and participantsThis was a prospective, observational, multicenter cohort study performed between July 2017 and December 2021 in 32 hospitals in Brazil. Participants were newborns with HIE meeting eligibility criteria and receiving TH. Data were analyzed from November 2022 to April 2023.ExposureInfants with HIE receiving TH were remotely monitored with 3-channel amplitude-integrated electroencephalography (aEEG) including raw tracing and video imaging, and bedside clinicians received assistance from trained neonatologists and neurologists.Main outcomes and measuresData on modified Sarnat examination, presence, timing and seizure type, aEEG background activity, sleep-wake cycling, and antiepileptic drugs used were collected. Descriptive statistical analysis was used with independent t test, χ2, Mann-Whitney test, and post hoc analyses applied for associations.ResultsA total of 872 cooled newborns were enrolled; the median (IQR) gestational age was 39 (38-40) weeks, 518 (59.4%) were male, and 59 (6.8%) were classified as having mild encephalopathy by modified Sarnat examination, 504 (57.8%) as moderate, and 180 (20.6%) as severe. Electrographic seizures were identified in 296 newborns (33.9%), being only electrographic in 213 (71.9%) and clinical followed by electroclinical uncoupling in 50 (16.9%). Early abnormal background activity had a significant association with seizures. Infants with flat trace had the highest rate of seizures (58 infants [68.2%]) and the greatest association with the incidence of seizures (odds ratio [OR], 12.90; 95% CI, 7.57-22.22) compared with continuous normal voltage. The absence of sleep-wake cycling was also associated with a higher occurrence of seizures (OR, 2.22; 95% CI, 1.67-2.96). Seizure onset was most frequent between 6 and 24 hours of life (181 infants [61.1%]); however, seizure occurred in 34 infants (11.5%) during rewarming. A single antiepileptic drug controlled seizures in 192 infants (64.9%). The first line antiepileptic drug was phenobarbital in 294 (99.3%).Conclusions and relevanceIn this cohort study of newborns with HIE treated with TH, electrographic seizure activity occurred in 296 infants (33.9%) and was predominantly electrographic. Seizure control was obtained with a single antiepileptic drug in 192 infants (64.9%). These findings suggest neonatal neurocritical care can be delivered at remote limited resource hospitals due to innovations in technology and telehealth.

Project description:Despite progresses in neonatal care, the mortality and the incidence of neuro-motor disability after perinatal asphyxia have failed to show substantial improvements. In countries with a high level of perinatal care, the incidence of asphyxia responsible for moderate or severe encephalopathy is still 2-3 per 1000 term newborns. Recent trials have demonstrated that moderate hypothermia, started within 6 hours after birth and protracted for 72 hours, can significantly improve survival and reduce neurologic impairment in neonates with hypoxic-ischemic encephalopathy. It is not currently known whether neuroprotective drugs can further improve the beneficial effects of hypothermia. Topiramate has been proven to reduce brain injury in animal models of neonatal hypoxic ischemic encephalopathy. However, the association of mild hypothermia and topiramate treatment has never been studied in human newborns. The objective of this research project is to evaluate, through a multicenter randomized controlled trial, whether the efficacy of moderate hypothermia can be increased by concomitant topiramate treatment.Term newborns (gestational age ? 36 weeks and birth weight ? 1800 g) with precocious metabolic, clinical and electroencephalographic (EEG) signs of hypoxic-ischemic encephalopathy will be randomized, according to their EEG pattern, to receive topiramate added to standard treatment with moderate hypothermia or standard treatment alone. Topiramate will be administered at 10 mg/kg once a day for the first 3 days of life. Topiramate concentrations will be measured on serial dried blood spots. 64 participants will be recruited in the study. To evaluate the safety of topiramate administration, cardiac and respiratory parameters will be continuously monitored. Blood samplings will be performed to check renal, liver and metabolic balance. To evaluate the efficacy of topiramate, the neurologic outcome of enrolled newborns will be evaluated by serial neurologic and neuroradiologic examinations. Visual function will be evaluated by means of behavioural standardized tests.This pilot study will explore the possible therapeutic role of topiramate in combination with moderate hypothermia. Any favourable results of this research might open new perspectives about the reduction of cerebral damage in asphyxiated newborns.

Project description:Diastolic dysfunction often complicates myocardial ischemia with increased mortality rates. However, less is known about diastolic function after perinatal asphyxia in neonates with hypoxic-ischemic encephalopathy (HIE) during therapeutic hypothermia (TH) and rewarming.AimThe aim of this study was to assess diastolic function with tissue Doppler imaging (TDI) in neonates with moderate-severe HIE during TH and rewarming.MethodNewborns at >36 weeks' gestation with moderate-severe HIE treated with TH were evaluated with targeted neonatal echocardiography (TNE), including TDI, within 24 h of TH initiation (T1), at 48-72 h of treatment (T2), and after rewarming (T3). These retrospective data were collected and compared with a control group of healthy babies at >36 weeks' gestation that was prospectively evaluated following the same protocol.ResultsA total of 21 patients with HIE + TH and 15 controls were included in the study. Myocardial relaxation before the onset of biventricular filling was prolonged in the HIE + TH group during TH with significantly longer isovolumic relaxation time (IVRT') in the left ventricle (LV), the septum, and the right ventricle (RV). This was associated with slower RV early diastolic velocity (e') and prolonged filling on T1. Total isovolumic time (t-IVT; isovolumic contraction time [IVCT'] + IVRT') and myocardial performance index (MPI') were globally increased in asphyxiated neonates. All these differences persisted after correction for heart rate (HR) and normalized after rewarming. TDI parameters assessing late diastole (a' velocity or e'/a' and E/e' ratios) did not differ between groups.ConclusionTDI evaluation in our study demonstrated a pattern of early diastolic dysfunction during TH that normalized after rewarming, whereas late diastole seemed to be preserved. Our data also suggest a possible involvement of impaired twist/untwist motion and dyssynchrony. More studies are needed to investigate the impact and therapeutic implication of diastolic dysfunction in these babies, as well as to clarify the role of TH in these findings.

Dataset Information

Prognostic Value of Clinical Tests in Neonates With Hypoxic-Ischemic Encephalopathy Treated With Therapeutic Hypothermia: A Systematic Review and Meta-Analysis.

Publications

Prognostic Value of Clinical Tests in Neonates With Hypoxic-Ischemic Encephalopathy Treated With Therapeutic Hypothermia: A Systematic Review and Meta-Analysis.

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