RESUMO
Hypoxic-ischaemic encephalopathy (HIE) is a major cause of mortality and neurodevelopmental disability, especially in low-income countries. While therapeutic hypothermia has been shown to reduce morbidity and mortality in infants with HIE, some clinical trials in low-income countries have reported an increase in the risk of mortality. We conducted a systematic review and meta-analysis of all randomized and quasi-randomized controlled trials conducted in low-income and lower-middle-income countries that compared cooling therapy with standard care for HIE. Our primary outcome was composite of neonatal mortality and neurodevelopmental disability at 6 months or beyond. The review was registered with PROSPERO (CRD42022352728). Our review included 11 randomized controlled trials with 1324 infants with HIE. The composite of death or disability at 6 months or beyond was lower in therapeutic hypothermia group (RR 0.78, 95% CI 0.66-0.92, I2 = 85%). Neonatal mortality rate did not differ significantly between cooling therapy and standard care (RR 0.92, 95% CI 0.76-1.13, I2 = 61%). Additionally, the cooled group exhibited significantly lower rates of neurodevelopmental disability at or beyond 6 months (RR 0.34, 95%CI 0.22-0.52, I2 = 0%). Our analysis found that neonatal mortality rate did not differ between cooled and noncooled infants in low- and lower-middle-income countries. Cooling may have a beneficial effect on neurodevelopmental disability and the composite of death or disability at 6 months or beyond.
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Países em Desenvolvimento , Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Humanos , Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/terapia , Hipóxia-Isquemia Encefálica/mortalidade , Recém-Nascido , Resultado do Tratamento , Lactente , Mortalidade Infantil , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: To determine the effectiveness of phase-change-material mattress (PCM) during transportation of newborns with hypoxic ischemic encephalopathy (HIE). STUDY DESIGN: Randomized controlled trial of newborns with HIE from June 2016 to December 2019. Patients were randomized to transport with PCM or without PCM (control) when transferred to a cooling center in northern Vietnam. Primary outcome measure was mortality rate, secondary outcomes including temperature control and adverse effects. RESULT: Fifty-Two patients in PCM-group and 61 in control group. Median rectal temperature upon arrival was 34.5 °C (IQR 33.5-34.8) in PCM-group and 35.1 °C (IQR 34.5-35.9) in control group (p = 0.023). Median time from birth to reach target temperature was 5.0 ± 1.4 h and 5.5 ± 1.2 h in the respective groups (p = 0.065). 81% of those transported with PCM versus 62% of infants transported without (p = 0.049) had reached target temperature within the 6-h timeframe. There was no record of overcooling (< 32 °C) in any of the groups. The was no difference in mortality rate between the two groups (33% and 34% respectively (p > 0.05)). CONCLUSION: Phase-change-material can be used as a safe and effective cooling method during transportation of newborns with HIE in low-resource settings. TRIAL REGISTRATION: The study was retro-prospectively registered in Clinical Trials (04/05/2022, NCT05361473).
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Leitos , Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Transporte de Pacientes , Humanos , Hipóxia-Isquemia Encefálica/terapia , Hipóxia-Isquemia Encefálica/mortalidade , Recém-Nascido , Vietnã , Hipotermia Induzida/métodos , Feminino , Transporte de Pacientes/métodos , Masculino , Temperatura CorporalRESUMO
Purpose To develop a deep learning algorithm to predict 2-year neurodevelopmental outcomes in neonates with hypoxic-ischemic encephalopathy using MRI and basic clinical data. Materials and Methods In this study, MRI data of term neonates with encephalopathy in the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial (ClinicalTrials.gov: NCT02811263), who were enrolled from 17 institutions between January 25, 2017, and October 9, 2019, were retrospectively analyzed. The harmonized MRI protocol included T1-weighted, T2-weighted, and diffusion tensor imaging. Deep learning classifiers were trained to predict the primary outcome of the HEAL trial (death or any neurodevelopmental impairment at 2 years) using multisequence MRI and basic clinical variables, including sex and gestational age at birth. Model performance was evaluated on test sets comprising 10% of cases from 15 institutions (in-distribution test set, n = 41) and 10% of cases from two institutions (out-of-distribution test set, n = 41). Model performance in predicting additional secondary outcomes, including death alone, was also assessed. Results For the 414 neonates (mean gestational age, 39 weeks ± 1.4 [SD]; 232 male, 182 female), in the study cohort, 198 (48%) died or had any neurodevelopmental impairment at 2 years. The deep learning model achieved an area under the receiver operating characteristic curve (AUC) of 0.74 (95% CI: 0.60, 0.86) and 63% accuracy in the in-distribution test set and an AUC of 0.77 (95% CI: 0.63, 0.90) and 78% accuracy in the out-of-distribution test set. Performance was similar or better for predicting secondary outcomes. Conclusion Deep learning analysis of neonatal brain MRI yielded high performance for predicting 2-year neurodevelopmental outcomes. Keywords: Convolutional Neural Network (CNN), Prognosis, Pediatrics, Brain, Brain Stem Clinical trial registration no. NCT02811263 Supplemental material is available for this article. © RSNA, 2024 See also commentary by Rafful and Reis Teixeira in this issue.
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Aprendizado Profundo , Hipóxia-Isquemia Encefálica , Imageamento por Ressonância Magnética , Humanos , Recém-Nascido , Feminino , Masculino , Hipóxia-Isquemia Encefálica/diagnóstico por imagem , Hipóxia-Isquemia Encefálica/diagnóstico , Hipóxia-Isquemia Encefálica/mortalidade , Estudos Retrospectivos , Inteligência Artificial , Valor Preditivo dos TestesRESUMO
Introduction. Therapeutic hypothermia (TH) reduces the risk of death or disability in children with moderate to severe hypoxic ischemic encephalopathy (HIE). Objective. To describe a population of patients with HIE that required TH and their course until discharge. Population and methods. Retrospective, descriptive, cohort study. All patients admitted to TH between 2013 and 2022 were studied. Epidemiological, clinical, monitoring, and treatment data were assessed, together with supplementary tests and condition at discharge. Risk factors were compared between deceased patients and survivors; and, among the latter, those requiring special healthcare needs (SHCN) at discharge. Results. A total of 247 patients were included. Mortality: 11%. Most common sentinel event: prolonged second stage of labor (39%). Treatment initiation: median of 5 hours of life. Seizures: 57%. Intravenous erythropoietin: 66.7%. Abnormal pattern in brain function monitoring: 52%. Normalization of monitoring: median of 24 hours. Pathological magnetic resonance imaging: 42%. Predictor variables of mortality: severe Sarnat and Sarnat staging and pathological ultrasound upon admission. Conclusion. The overall mortality rate was 11%. Referrals increased more markedly since 2018. The time of TH initiation was later than in previous reports. Severe neurological signs as per the Sarnat and Sarnat staging and a pathological baseline cranial ultrasound were independent predictors of mortality at discharge. Patients with SHCN at discharge showed a normalized tracing in the amplitude-integrated electroencephalography performed later. The most common finding in the magnetic resonance imaging was basal ganglia involvement. No statistically significant differences were observed in terms of clinical characteristics or complications among patients who received erythropoietin.
Introducción. La hipotermia terapéutica (HT) reduce el riesgo de muerte o discapacidad en niños con encefalopatía hipóxico-isquémica (EHI) moderada-grave. Objetivo. Describir una población de pacientes con EHI que requirió HT y su evolución hasta el alta hospitalaria. Población y métodos. Estudio descriptivo de cohorte retrospectivo. Se analizaron todos los pacientes que ingresaron a HT entre 2013 y 2022. Se evaluaron datos epidemiológicos, clínicos, de monitoreo, tratamiento, estudios complementarios y condición al alta. Se compararon los factores de riesgo entre pacientes fallecidos y sobrevivientes, y de estos, los que requirieron necesidades especiales al alta (NEAS). Resultados. Se incluyeron 247 pacientes. Mortalidad: 11 %. Evento centinela más frecuente: período expulsivo prolongado (39 %). Inicio del tratamiento: mediana 5 horas de vida. Convulsiones: 57 %. Eritropoyetina intravenosa: 66,7 %. Patrón anormal de monitoreo de función cerebral: 52 %. Normalización del monitoreo: mediana 24 horas. Resonancia magnética patológica: 42 %. Variables predictoras de mortalidad: Sarnat y Sarnat grave, y ecografía patológica al ingreso. Conclusión. La mortalidad global fue del 11 %. Las derivaciones aumentaron en forma más evidente a partir del año 2018. El horario de inicio de HT fue más tardío que en reportes anteriores. Los signos neurológicos de gravedad según la escala de Sarnat y Sarnat y la ecografía cerebral basal patológica fueron predictores independientes de mortalidad al alta. Los pacientes con NEAS presentaron normalización del trazado del electroencefalograma de amplitud integrada más tardío. El hallazgo más frecuente en la resonancia fue la afectación de los ganglios basales. No se encontraron diferencias clínicas ni de complicaciones estadísticamente significativas entre los pacientes que recibieron eritropoyetina.
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Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Humanos , Estudos Retrospectivos , Feminino , Masculino , Estudos de Coortes , Hipóxia-Isquemia Encefálica/terapia , Hipóxia-Isquemia Encefálica/mortalidade , Recém-Nascido , Hipotermia Induzida/métodos , Hospitais Públicos , Lactente , Fatores de Risco , Centros de Atenção Terciária , Fatores de Tempo , Pré-EscolarRESUMO
OBJECTIVE: To determine the safety and effectiveness of sodium bicarbonate administration in the management of metabolic acidemia and short-term outcomes in neonates with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: Retrospective cohort study of neonates born at ≥35 weeks of gestation and receiving therapeutic hypothermia. Demographics, pH, lactate, base deficit, treatment, MRI findings, seizure incidence, death prior to discharge were collected. RESULTS: There was higher mortality (p = 0.010) and injury on MRI (p = 0.008)-primarily deep gray matter (p < 0.001) and cortical injury (p = 0.003)-in the bicarbonate group compared to controls in univariate analysis. The combined outcome of death or abnormal MRI was not significantly associated (OR 1.97, 95% CI 0.80-4.87, p = 0.141) with bicarbonate administration when adjusting for sex, 5-minute Apgar, and initial base deficit. CONCLUSION: This study demonstrated association between bicarbonate use after HIE and negative short-term outcomes. Future prospective trials could overcome the treatment bias limitation demonstrated in this retrospective study.
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Acidose , Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Imageamento por Ressonância Magnética , Bicarbonato de Sódio , Humanos , Recém-Nascido , Hipóxia-Isquemia Encefálica/terapia , Hipóxia-Isquemia Encefálica/mortalidade , Estudos Retrospectivos , Feminino , Masculino , Bicarbonato de Sódio/uso terapêutico , Bicarbonato de Sódio/administração & dosagem , Acidose/etiologia , Resultado do TratamentoRESUMO
BACKGROUND: Neonates with hypoxic ischemic encephalopathy receiving therapeutic hypothermia (HIE + TH) are at risk for acute kidney injury (AKI). The standardized Kidney Disease Improving Global Outcomes (KDIGO) criteria identifies AKI based on a rise in serum creatinine (SCr) or reduced urine output. This definition is challenging to apply in neonates given the physiologic decline in SCr during the first week of life. Gupta et al. proposed alternative neonatal criteria centered on rate of SCr decline. This study aimed to compare the rate of AKI based on KDIGO and Gupta in neonates with HIE and to examine associations with mortality and morbidity. METHODS: A retrospective review was performed of neonates with moderate to severe HIE + TH from 2008 to 2020 at a single center. AKI was assessed in the first 7 days after birth by KDIGO and Gupta criteria. Mortality, brain MRI severity of injury, length of stay, and duration of respiratory support were compared between AKI groups. RESULTS: Among 225 neonates, 64 (28%) met KDIGO, 69 (31%) neonates met Gupta but not KDIGO, and 92 (41%) did not meet either definition. Both KDIGO-AKI and GuptaOnly-AKI groups had an increased risk of the composite mortality and/or moderate/severe brain MRI injury along with longer length of stay and prolonged duration of respiratory support compared to those without AKI. CONCLUSIONS: AKI in neonates with HIE + TH was common and varied by definition. The Gupta definition based on rate of SCr decline identified additional neonates not captured by KDIGO criteria who are at increased risk for adverse outcomes. Incorporating the rate of SCr decline into the neonatal AKI definition may increase identification of clinically relevant kidney injury in neonates with HIE + TH.
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Injúria Renal Aguda , Creatinina , Hipóxia-Isquemia Encefálica , Humanos , Injúria Renal Aguda/sangue , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/terapia , Recém-Nascido , Hipóxia-Isquemia Encefálica/diagnóstico , Hipóxia-Isquemia Encefálica/sangue , Hipóxia-Isquemia Encefálica/terapia , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/mortalidade , Estudos Retrospectivos , Creatinina/sangue , Feminino , Masculino , Hipotermia Induzida , Índice de Gravidade de Doença , Imageamento por Ressonância Magnética , Tempo de Internação/estatística & dados numéricosRESUMO
OBJECTIVE: Hypoxic-ischemic encephalopathy (HIE) is a leading cause of morbidity and mortality in neonates. Therapeutic hypothermia (TH) has improved outcomes and mortality in infants with >36 weeks' gestational age (GA) with moderate-to-severe HIE. There are limited data on the safety and efficacy of TH in preterm infants with HIE. This study describes our experience and examines the safety of TH in neonates with <36 weeks' GA. STUDY DESIGN: A single-center, retrospective study of preterm neonates born at <36 weeks' GA with moderate-to-severe HIE and treated with TH, compared to a cohort of term neonates with HIE (≥37 weeks' GA), was conducted. The term cohort was matched for degree of background abnormality on electroencephalogram, sex, inborn versus outborn status, and birth year. Medical records were reviewed for pregnancy and delivery complications, need for transfusion, sedation and antiseizure medications, electroencephalography and imaging findings, and in-hospital mortality. RESULTS: Forty-two neonates born at <36 weeks' GA with HIE received TH between 2005 and 2022. Data from 42 term neonates were analyzed for comparison. The average GA of the preterm cohort was 34.6 weeks and 39.3 weeks for the term cohort. Apgar scores, degree of acidosis, and need for blood product transfusions were similar between groups. Preterm infants were more likely to require inotropic support (55 vs. 29%, p = 0.026) and hydrocortisone (36 vs. 12%, p = 0.019) for hypotension. The proportion of infants without evidence of injury on magnetic resonance imaging was similar in both groups: 43 versus 50% in preterm and term infants, respectively. No significant difference was found in mortality between groups. CONCLUSION: In this single-center cohort, TH in preterm infants appears to be as safe as in term infants, with no significant increase in intracranial bleeds or mortality. Preterm infants more frequently required inotropes and steroids for hypotension. Further research is needed to determine efficacy of TH in preterm infants. KEY POINTS: · TH is used off-protocol in preterm infants.. · Preterm and term infants have similar mortality.. · Preterm cohort required more inotropic support..
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Idade Gestacional , Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Recém-Nascido Prematuro , Humanos , Hipóxia-Isquemia Encefálica/terapia , Hipóxia-Isquemia Encefálica/mortalidade , Hipotermia Induzida/métodos , Recém-Nascido , Estudos Retrospectivos , Feminino , Masculino , Eletroencefalografia , Mortalidade HospitalarRESUMO
BACKGROUND: In randomized clinical trials, therapeutic hypothermia (TH) has been shown to reduce death and/or moderate-to-severe disability in neonates with hypoxic ischemic encephalopathy (HIE) in high-income countries, while this has not consistently been the case in low-and middle-income countries (LMICs). Many studies reporting on outcomes of neonates with HIE managed with TH are those conducted under controlled study conditions, and few reporting in settings where this intervention is offered as part of standard of care, especially from LMICs. In this study we report on short-term outcomes of neonates with moderate-to-severe HIE where TH was offered as part of standard of care. OBJECTIVE: To determine characteristics and mortality rate at hospital discharge in neonates with moderate-to-severe HIE. METHODS: Hospital records of neonates with intrapartum asphyxia were reviewed for clinical findings, management with TH (cooled or non-cooled) and mortality at hospital discharge. Inclusion criteria were birthweight ≥ 1800 g, gestational age ≥ 36 weeks and moderate-to-severe HIE. Comparisons were made between survivors and non-survivors in cooled and/or non-cooled neonates. RESULTS: Intrapartum asphyxia was diagnosed in 856 neonates, with three having no recorded HIE status; 30% (258/853) had mild HIE, and 595/853 (69%) with moderate-to-severe HIE. The overall incidence of intrapartum asphyxia was 8.8/1000 live births. Of the 595 with moderate-to-severe HIE, three had no records on cooling and 67% (399/592) were cooled. Amongst 193 non-cooled neonates, 126 (67%) had documented reasons for not being cooled with common reasons being a moribund neonate (54.0%), equipment unavailability (11.1%), pulmonary hypertension (9.5%), postnatal age > 6 h on admission (8.7%), and improvement in severity of encephalopathy (8.7%). Overall mortality was 29.0%, being 17.0% and 53.4% in cooled and non-cooled infants respectively. On multivariate analysis, the only factor associated with mortality was severe encephalopathy. CONCLUSION: Overall mortality in neonates with moderate-to-severe HIE was 29.0% and 17.0% in those who were cooled. Cooling was not offered to all neonates mainly because of severe clinical illness, equipment unavailability and delayed presentation, making it difficult to assess overall impact of this intervention. Prospective clinical studies need to be conducted in LMIC to further assess effect of TH in short and long-term outcomes.
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Asfixia Neonatal , Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Humanos , Lactente , Recém-Nascido , Asfixia , Asfixia Neonatal/terapia , Hipóxia-Isquemia Encefálica/mortalidade , Hipóxia-Isquemia Encefálica/terapia , Estudos Prospectivos , África do Sul/epidemiologia , Centros de Atenção TerciáriaRESUMO
OBJECTIVE: Therapeutic hypothermia (TH) for neonatal hypoxic-ischaemic encephalopathy (HIE), delivered mainly in tertiary cooling centres (CCs), reduces mortality and neurodisability. It is unknown if birth in a non-cooling centre (non-CC), without active TH, impacts short-term outcomes. DESIGN: Retrospective cohort study using National Neonatal Research Database and propensity score-matching. SETTING: UK neonatal units. PATIENTS: Infants ≥36 weeks gestational age with moderate or severe HIE admitted 2011-2016. INTERVENTIONS: Birth in non-CC compared with CC. MAIN OUTCOME MEASURES: Primary outcome was survival to discharge without recorded seizures. Secondary outcomes were recorded seizures, mortality and temperature on arrival at CCs following transfer. RESULTS: 5059 infants were included with 2364 (46.7%) born in non-CCs. Birth in a CC was associated with improved survival without seizures (35.1% vs 31.8%; OR 1.15, 95% CI 1.02 to 1.31; p=0.02), fewer seizures (60.7% vs 64.6%; OR 0.84, 95% CI 0.75 to 0.95, p=0.007) and similar mortality (15.8% vs 14.4%; OR 1.11, 95% CI 0.93 to 1.31, p=0.20) compared with birth in a non-CC. Matched infants from level 2 centres only had similar results, and birth in CCs was associated with greater seizure-free survival compared with non-CCs. Following transfer from a non-CC to a CC (n=2027), 1362 (67.1%) infants arrived with a recorded optimal therapeutic temperature but only 259 (12.7%) of these arrived within 6 hours of birth. CONCLUSIONS: Almost half of UK infants with HIE were born in a non-CC, which was associated with suboptimal hypothermic treatment and reduced seizure-free survival. Provision of active TH in non-CC hospitals prior to upward transfer warrants consideration.
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Hospitais/normas , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/terapia , Idade Gestacional , Humanos , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/mortalidade , Recém-Nascido , Unidades de Terapia Intensiva Neonatal/normas , Análise por Pareamento , Transferência de Pacientes , Pontuação de Propensão , Estudos Retrospectivos , Convulsões/etiologia , Análise de Sobrevida , Resultado do Tratamento , Reino Unido/epidemiologiaRESUMO
The outcome after out-of-hospital cardiac arrest has historically been grim at best. The current overall survival rate of patients admitted to a hospital is approximately 10%, making cardiac arrest one of the leading causes of death in the United States. The situation is improving with the incorporation of therapeutic temperature modulation, aggressive prevention of secondary brain injury, and improved access to advanced cardiovascular support, all of which have decreased mortality and allowed for better outcomes. Mortality after cardiac arrest is often the direct result of active withdrawal of life-sustaining therapy based on the perception that neurological recovery is not possible. This reality highlights the importance of providing accurate estimates of neurological prognosis to decision makers when discussing goals of care. The current standard of care for assessing neurological status in patients with hypoxic-ischemic encephalopathy emphasizes a multimodal approach that includes five elements: (1) neurological examination off sedation, (2) continuous electroencephalography, (3) serum neuron-specific enolase levels, (4) magnetic resonance brain imaging, and (5) somatosensory-evoked potential testing. Sophisticated decision support systems that can integrate these clinical, imaging, and biomarker and neurophysiologic data and translate it into meaningful projections of neurological outcome are urgently needed.
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Lesões Encefálicas , Eletroencefalografia , Potenciais Somatossensoriais Evocados , Parada Cardíaca , Hipóxia-Isquemia Encefálica , Lesões Encefálicas/etiologia , Lesões Encefálicas/mortalidade , Lesões Encefálicas/fisiopatologia , Lesões Encefálicas/terapia , Intervalo Livre de Doença , Parada Cardíaca/complicações , Parada Cardíaca/mortalidade , Parada Cardíaca/fisiopatologia , Parada Cardíaca/terapia , Humanos , Hipóxia-Isquemia Encefálica/etiologia , Hipóxia-Isquemia Encefálica/mortalidade , Hipóxia-Isquemia Encefálica/fisiopatologia , Hipóxia-Isquemia Encefálica/terapia , Imageamento por Ressonância Magnética , Taxa de SobrevidaRESUMO
BACKGROUND: : Discovery of evidence of acute brain ischemia or hypoxia and its differentiation from agonal hypoxia represents a task of interest but extremely difficult in forensic neuropathology. Generally, more than 50% of forensic autopsies indicate evidence of brain induced functional arrest of the organ system, which can be the result of a hypoxic/ischemic brain event. Even if the brain is the target organ of hypoxic/ischemic damage, at present, there are no specific neuropathological (macroscopic and histological) findings of hypoxic damage (such as in drowning, hanging, intoxication with carbon monoxide) or acute ischemia. In fact, the first histological signs appear after at least 4 to 6âhours. Numerous authors have pointed out how an immunohistochemical analysis could help diagnose acute cerebral hypoxia/ischemia.Data sources: This review was based on articles published in PubMed and Scopus databases in the past 25âyears, with the following keywords "immunohistochemical markers," "acute cerebral ischemia," "ischemic or hypoxic brain damage," and "acute cerebral hypoxia". OBJECTIVES: : Original articles and reviews on this topic were selected. The purpose of this review is to analyze and summarize the markers studied so far and to consider the limits of immunohistochemistry that exist to date in this specific field of forensic pathology. RESULTS: : We identified 13 markers that had been examined (in previous studies) for this purpose. In our opinion, it is difficult to identify reliable and confirmed biomarkers from multiple studies in order to support a postmortem diagnosis of acute cerebral hypoxia/ischemia. Microtubule-associated protein 2 (MAP2) is the most researched marker in the literature and the results obtained have proven to be quite useful. CONCLUSION: Immunohistochemistry has provided interesting and promising results, but further studies are needed in order to confirm and apply them in standard forensic practice.
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Autopsia/métodos , Encéfalo/patologia , Hipóxia-Isquemia Encefálica/diagnóstico , Imuno-Histoquímica , Doença Aguda , Animais , Biomarcadores/análise , Encéfalo/irrigação sanguínea , Modelos Animais de Doenças , Humanos , Hipóxia-Isquemia Encefálica/mortalidade , Hipóxia-Isquemia Encefálica/patologia , Proteínas Associadas aos Microtúbulos/análise , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
BACKGROUND: Multiple clinical trials have demonstrated the safety and efficacy of erythropoietin in improving neurodevelopmental outcomes in infants with hypoxic-ischemic encephalopathy (HIE). It is undoubtedly urgent to include only randomized controlled trials (RCTs) for more standardized systematic reviews and meta-analyses. The purpose of this study is to examine whether erythropoietin reduces the risk of death and improve neurodevelopmental disorders in infants with HIE. METHODS: The electronic databases of Cochrane Library, EMBASE, PubMed, and Web of Science were searched from the inception to June 2021 using the following key terms: "erythropoietin," "hypoxic-ischemic encephalopathy," and "prospective," for all relevant RCTs. Only English publications were included. The primary outcome was mortality rate. Secondary outcomes included neurodevelopmental disorders, brain injury, and cognitive impairment. The Cochrane risk of bias tool was independently used to evaluate the risk of bias of included RCTs by 2 reviewers. RESULTS: We hypothesized that group with erythropoietin would provide better therapeutic benefits compared with control group. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/FERUS.
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Eritropoetina/uso terapêutico , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Metanálise como Assunto , Revisões Sistemáticas como Assunto , Protocolos Clínicos , Disfunção Cognitiva/prevenção & controle , Eritropoetina/efeitos adversos , Humanos , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/mortalidade , Lactente , Transtornos do Neurodesenvolvimento/prevenção & controle , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Globally, approximately 9 million neonates develop perinatal asphyxia annually of which about 1.2 million die. Majority of the morbidity and mortality occur in Low and middle-income countries. However, little is known about the current trend in incidence, and the factors affecting mortality from hypoxic ischaemic encephalopathy (HIE), in Nigeria. OBJECTIVE: We assessed the trends in incidence and fatality rates and evaluated the predictors of mortality among babies admitted with HIE over five years at the Lagos University Teaching Hospital. METHODS: A temporal trend analysis and retrospective cohort study of HIE affected babies admitted to the neonatal unit of a Nigerian Teaching Hospital was conducted. The socio-demographic and clinical characteristics of the babies and their mothers were extracted from the neonatal unit records. Kaplan-Meir plots and Multivariable Cox proportional hazard ratio was used to evaluate the survival experienced using Stata version 16 (StataCorp USA) statistical software. RESULTS: The median age of the newborns at admission was 26.5 (10-53.5) hours and the male to female ratio was 2.1:1. About one-fifth (20.8%) and nearly half (47.8%) were admitted within 6 hours and 24 hours of life respectively, while majority (84%) of the infants were out-born. The prevalence and fatality rate of HIE in our study was 7.1% and 25.3% respectively. The annual incidence of HIE among the hospital admissions declined by 1.4% per annum while the annual fatality rate increased by 10.3% per annum from 2015 to 2019. About 15.7% died within 24 hours of admission. The hazard of death was related to the severity of HIE (p = 0.001), antenatal booking status of the mother (p = 0.01) and place of delivery (p = 0.03). CONCLUSION: The case fatality rate of HIE is high and increasing at our centre and mainly driven by the pattern of admission of HIE cases among outborn babies. Thus, community level interventions including skilled birth attendants at delivery, newborn resuscitation trainings for healthcare personnel and capacity building for specialized care should be intensified to reduce the burden of HIE.
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Mortalidade Hospitalar/tendências , Hipóxia-Isquemia Encefálica/mortalidade , Adulto , Feminino , Idade Gestacional , Humanos , Hipóxia-Isquemia Encefálica/epidemiologia , Hipóxia-Isquemia Encefálica/patologia , Incidência , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Idade Materna , Nigéria/epidemiologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Índice de Gravidade de Doença , Centros de Atenção Terciária , Adulto JovemRESUMO
This study aimed to identify hospital neonatal mortality rate (NMR) and the causes of neonatal deaths, and to understand risk factors associated with neonatal mortality in a national tertiary hospital in Cambodia. The study included all newborn infants, aged 0-28 days old, hospitalized in the Pediatrics department of Khmer-Soviet Friendship Hospital between January 2016 and December 2017. In total, 925 infants were included in the study. The mean gestational age was 35.9 weeks (range, 24-42 weeks). Preterm infants and low birth weight accounted for 47.5% and 56.7%, respectively. With respect to payment methods, the government (53.5%) and non-governmental organizations (NGO) (13.7%) paid the fees as the families were not in a financial position to do so. The hospital NMR at the Pediatrics department was 9.3%. Respiratory distress syndrome (37.2%) was the main cause of deaths followed by hypoxic-ischemic encephalopathy (31.4%) and neonatal infection (21.0%). Factors associated with neonatal mortality were Apgar score at 5th minute <7 (adjusted odds ratio (AOR) = 3.57), payment by the government or NGO (AOR = 11.32), admission due to respiratory distress (AOR = 11.94), and hypothermia on admission (AOR = 9.41). The hospital NMR in the Pediatrics department was 9.3% (95% confidence interval 7.50-11.35) at Khmer-Soviet Friendship Hospital; prematurity and respiratory distress syndrome were the major causes of neonatal mortality. Introducing continuous positive airway pressure machine for respiratory distress syndrome and creating neonatal resuscitation guidelines and preventing hypothermia in delivery rooms are required to reduce the high NMR.
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Hipóxia-Isquemia Encefálica/mortalidade , Infecções/mortalidade , Nascimento Prematuro/mortalidade , Síndrome do Desconforto Respiratório do Recém-Nascido/mortalidade , Centros de Atenção Terciária/estatística & dados numéricos , Índice de Apgar , Camboja/epidemiologia , Feminino , Financiamento Governamental , Idade Gestacional , Humanos , Hipotermia/epidemiologia , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Organizações/economia , Fatores de RiscoRESUMO
OBJECTIVE: Hypoxic-ischaemic encephalopathy (HIE) remains a leading cause of neonatal mortality and neurodisability. We aimed to determine the incidence of HIE and management patterns against national guidelines. DESIGN: Retrospective cohort study using the National Neonatal Research Database. SETTING: Neonatal units in England and Wales. PATIENTS: Infants 34-42 weeks gestational age (GA) with a recorded diagnosis of HIE. MAIN OUTCOMES: Incidence of HIE, mortality and treatment with therapeutic hypothermia (TH) were the main outcomes. Temporal changes were compared across two epochs (2011-2013 and 2014-2016). RESULTS: Among 407 462 infants admitted for neonatal care, 12 195 were diagnosed with HIE. 8166 infants ≥36 weeks GA had moderate/severe HIE, 62.1% (n=5069) underwent TH and mortality was 9.3% (n=762). Of infants with mild HIE (n=3394), 30.3% (n=1027) underwent TH and 6 died. In late preterm infants (34-35 weeks GA) with HIE (n=635, 5.2%), 33.1% (n=210) received TH and 13.1% (n=83) died. Between epochs (2011-2013 vs 2014-2016), mortality decreased for infants ≥36 weeks GA with moderate/severe HIE (17.5% vs 12.3%; OR 0.69, 95% CI 0.59 to 0.81, p<0.001). Treatment with TH increased significantly between epochs in infants with mild HIE (24.9% vs 35.8%, p<0.001) and those born late preterm (34.3% vs 46.6%, p=0.002). CONCLUSIONS: Mortality of infants ≥36 weeks GA with moderate/severe HIE has reduced over time, although many infants diagnosed with moderate/severe HIE do not undergo TH. Increasingly, mild HIE and late preterm infants with HIE are undergoing TH, where the evidence base is lacking, highlighting the need for prospective studies to evaluate safety and efficacy in these populations.
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Hipóxia-Isquemia Encefálica/epidemiologia , Hipóxia-Isquemia Encefálica/terapia , Doenças do Prematuro/epidemiologia , Doenças do Prematuro/terapia , Inglaterra/epidemiologia , Idade Gestacional , Humanos , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/mortalidade , Incidência , Lactente , Recém-Nascido , Doenças do Prematuro/mortalidade , Estudos Retrospectivos , Índice de Gravidade de Doença , País de Gales/epidemiologiaRESUMO
INTRODUCTION: Hypoxic ischemic encephalopathy is a neurological condition occurring immediately after birth following a perinatal asphytic episode. Therapeutic hypothermia is a safe and effective intervention to reduce mortality and major disability in survivors. In Latin America, perinatal asphyxia is a major problem, but no data are available characterizing its current situation in the region or the impact of hypoxic ischemic encephalopathy on its management. OBJECTIVE: Understand the prevalence, mortality and use of therapeutic hypothermia in newborns at ≥36 weeks gestational age with hypoxic ischemic encephalopathy admitted to neonatal units reporting to the Ibero-American Society of Neonatology Network. METHODS: The Ibero-American Society of Neonatology Network groups various neonatology centers in Latin America that share information and collaborate on research and medical care. We evaluated data on newborns with ≥36 weeks gestational age reported during 2019. Each unit received a guide with definitions and questions based on the Society's 7th Clinical Consensus. Evaluated were encephalopathy frequency and severity, Apgar score, need for resuscitation at birth, use of therapeutic hypothermia and clinical evolution at discharge. Our analysis includes descriptive statistics and comparisons made using the chi-square test. RESULTS: We examined reports of 2876 newborns from 33 units and 6 countries. In 2849 newborns with available data, hypoxic encephalopathy prevalence was 5.1% (146 newborns): 27 (19%) mild, 36 (25%) moderate, 43 (29%) severe, and 40 (27%) of unknown intensity. In those with moderate and severe encephalopathy, frequencies of Apgar scores ≤3 at the first minute (p = 0.001), Apgar scores ≤3 at the fifth minute (p ⟨0.001) and advanced resuscitation (p = 0.007) were higher. Therapeutic hypothermia was performed in only 13% of newborns (19). Neonatal mortality from encephalopathy was 42% (61). CONCLUSIONS: Hypoxic ischemic encephalopathy is a neonatal condition that results in high mortality and severe neurological sequelae. In this study, the overall prevalence was 5.1% with a mortality rate of 42%. Although encephalopathy was moderate or severe in 54% of reported cases, treatment with hypothermia was not performed in 87% of newborns. These data reflect a regional situation that requires urgent action.
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Asfixia Neonatal/epidemiologia , Asfixia Neonatal/mortalidade , Hipóxia-Isquemia Encefálica/epidemiologia , Hipóxia-Isquemia Encefálica/mortalidade , Neonatologia , Asfixia Neonatal/complicações , Asfixia Neonatal/terapia , Cuba/epidemiologia , Humanos , Hipóxia-Isquemia Encefálica/terapia , Recém-Nascido , Prevalência , Estados UnidosRESUMO
Predicting long-term outcome in infants with hypoxic-ischemic encephalopathy (HIE) remains an ongoing clinical challenge. We investigated plasma biomarkers and their association with 6-month outcomes in a nonhuman primate model of HIE with or without therapeutic hypothermia (TH) and erythropoietin (Epo). Twenty-nine Macaca nemestrina were randomized to control cesarean section (n = 7) or 20 min of umbilical cord occlusion (UCO, n = 22) with either no treatment (n = 11) or TH/Epo (n = 11). Initial injury severity was scored using 30-min arterial pH, base deficit, and 10-min Apgar score. Twenty-four plasma cytokines, chemokines, and growth factors were measured 3, 6, 24, 72, and 96 h after UCO. Interleukin 17 (IL-17) and macrophage-derived chemokine (MDC) differentiated the normal/mild from moderate/severe injury groups. Treatment with TH/Epo was associated with increased monocyte chemotactic protein-4 (MCP-4) at 3 h-6h, and significantly lower MCP-4 and MDC at 24 h-72h, respectively. IL-12p40 was lower at 24 h-72h in animals with death/cerebral palsy (CP) compared to survivors without CP. Baseline injury severity was the single best predictor of death/CP, and predictions did not improve with the addition of biomarker data. Circulating chemokines associated with the peripheral monocyte cell lineage are associated with severity of injury and response to therapy, but do not improve ability to predict outcomes.
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Quimiocinas/sangue , Citocinas/sangue , Eritropoetina/uso terapêutico , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/terapia , Animais , Animais Recém-Nascidos , Área Sob a Curva , Biomarcadores/sangue , Modelos Animais de Doenças , Feminino , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Hipóxia-Isquemia Encefálica/mortalidade , Hipóxia-Isquemia Encefálica/patologia , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Macaca nemestrina , Proteínas Quimioatraentes de Monócitos/sangue , Gravidez , Curva ROC , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Neonatal hypoxic-ischemic encephalopathy (HIE) in term infants, is a major cause of neonatal mortality and severe neurologic disability. OBJECTIVES: To identify in labor fetal monitoring characteristic patterns and perinatal factors associated with neonatal HIE. STUDY DESIGN: Single-center retrospective case-control study between 2010 and 2017. Cases clinically diagnosed with neonatal HIE treated by therapeutic hypothermia according to strict criteria (HIE-TH) were compared to a group of neonates born in the same period, gestational age-matched diagnosed with fetal distress according to fetal monitoring interpretation that was followed by prompt delivery, without subsequent HIE or therapeutic hypothermia (No-HIE). The primary outcome of the study was the electronic fetal monitoring (EFM) pattern during 60 min prior to delivery; the secondary outcome was the identification of perinatal associated factors. RESULTS: 54 neonates with HIE were treated by therapeutic hypothermia. EFM parameters most predictive of HIE-TH were indeterminate baseline heart rate OR = 47.297, 95% (8.17-273.76) p < 0.001, bradycardia OR = 15.997 95% (4.18-61.18) p < 0.001, low variability OR = 10.224, 95% (2.71-38.45) p < 0.001, higher baseline of the fetal heart rate calculated for each increment of 1 BPM OR = 1.0547, 95% (1.001-1.116) p = 0.047. Rupture of a previous uterine cesarean scar and placental abruption were characteristic of the HIE-TH group 14.8% vs. 1% p < 0.05; and 16.7% vs. 6% p < 0.05, respectively. Adverse neonatal outcomes also differed significantly: HIE-TH had a higher rate of neonatal seizures 46.2% vs. 0% p < 0.001 and mortality 7.7% vs. 0% p < 0.001. CONCLUSIONS: Characteristic fetal monitoring pattern prior to delivery together with acute obstetric emergency events are associated with neonatal HIE, neurological morbidity, and mortality.
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Sofrimento Fetal/diagnóstico , Monitorização Fetal/métodos , Frequência Cardíaca Fetal/fisiologia , Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/etiologia , Estudos de Casos e Controles , Feminino , Sofrimento Fetal/mortalidade , Idade Gestacional , Humanos , Hipóxia-Isquemia Encefálica/mortalidade , Hipóxia-Isquemia Encefálica/terapia , Lactente , Mortalidade Infantil , Recém-Nascido , Doenças do Recém-Nascido , Gravidez , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To determine the association between the extent of diffusion restriction and T2/fluid-attenuated inversion recovery (FLAIR) injury on brain MRI and outcomes after pediatric out-of-hospital cardiac arrest (OHCA). METHODS: Diffusion restriction and T2/FLAIR injury were described according to the pediatric MRI modification of the Alberta Stroke Program Early Computed Tomography Score (modsASPECTS) for children from 2005 to 2013 who had an MRI within 14 days of OHCA. The primary outcome was unfavorable neurologic outcome defined as ≥1 change in Pediatric Cerebral Performance Category (PCPC) from baseline resulting in a hospital discharge PCPC score 3, 4, 5, or 6. Patients with unfavorable outcomes were further categorized into alive with PCPC 3-5, dead due to withdrawal of life-sustaining therapies for poor neurologic prognosis (WLST-neuro), or dead by neurologic criteria. RESULTS: We evaluated MRI scans from 77 patients (median age 2.21 [interquartile range 0.44, 13.07] years) performed 4 (2, 6) days postarrest. Patients with unfavorable outcomes had more extensive diffusion restriction (median 7 [4, 10.3] vs 0 [0, 0] regions, p < 0.001) and T2/FLAIR injury (5.5 [2.3, 8.2] vs 0 [0, 0.75] regions, p < 0.001) compared to patients with favorable outcomes. Area under the receiver operating characteristic curve for the extent of diffusion restriction and unfavorable outcome was 0.96 (95% confidence interval [CI] 0.91, 0.99) and 0.92 (95% CI 0.85, 0.97) for T2/FLAIR injury. There was no difference in extent of diffusion restriction between patients who were alive with an unfavorable outcome and patients who died from WLST-neuro (p = 0.11). CONCLUSIONS: More extensive diffusion restriction and T2/FLAIR injury on the modsASPECTS score within the first 14 days after pediatric cardiac arrest was associated with unfavorable outcomes at hospital discharge.