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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.

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.., Competing Interests: None declared., (Thieme. All rights reserved.)

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., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

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., (© The Author(s) [2024]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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)., (© 2024. The Author(s).)

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., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Our aim was to investigate the relationship between persistent pulmonary hypertension of the newborn (PPHN), short-term brain injury or death, and clinical parameters in infants with moderate to severe hypoxic ischemic encephalopathy (HIE)., Methods: Retrospective single-center cohort study of 274 HIE infants, 230 underwent Therapeutic Hypothermia (TH). Primary outcome was severe HIE brain injury on MRI and/or death within the first month of life in relation to presence and severity of PPHN (clinical or echocardiographic). Secondary outcomes were HIE brain injury pattern, abnormal electroencephalogram (EEG), seizures, clinical, and laboratory differences. A logistic regression model was performed to evaluate PPHN presence and severity as risk factor for brain injury or death., Results: The combined outcome of severe brain injury or death was higher in the clinical PPHN group vs non-PPHN (32.6 vs 22.8%, p = 0.014). There was no difference in brain injury, seizure burden or EEG abnormalities associated with PPHN, despite those with PPHN being sicker with higher ventilation needs and worse laboratory values than those without. Mortality had a strong correlation with echocardiographic PPHN with the highest incidence in severe (36%) vs moderate (7.7%) vs mild PPHN (10%, p = 0.002). Highest mortality had those with 'early exit' who did not complete 72 hours of TH (71.4%)., Conclusions: In infants with HIE, PPHN was not associated with increased risk of brain injury as evident on MRI, nor seizure burden, despite being sicker with worse laboratory values. However, mortality rates were higher the worse the PPHN, especially with early exit from TH.

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., (© 2023. The Author(s).)

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., (© 2021 New York Academy of Sciences.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Competing interests: CG has received support from Chiesi Pharmaceuticals to attend an educational conference; in the past 5 years he has been an investigator on received research grants from Medical Research Council, National Institute for Health Research, Canadian Institutes of Health Research, Department of Health in England, Mason Medical Research Foundation, Westminster Medical School Research Trust and Chiesi Pharmaceuticals, and has been an unremunerated member of the Neonatal Data Analysis Unit Board, which oversees the NNRD., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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 6 hours. 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 25 years, 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., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

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., Competing Interests: The authors have declared that no competing interests exist.

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., (© 2020 American Academy of Neurology.)

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.

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., Competing Interests: The authors have nothing to disclose.

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.

Background: Hypoxic-ischaemic encephalopathy (HIE) is a leading cause of mortality and long-term neurological sequelae, affecting thousands of children worldwide. Current therapies to treat HIE are limited to cooling. Stem cell-based therapies offer a potential therapeutic approach to repair or regenerate injured brain tissue. These preclinical findings have now culminated in ongoing human neonatal trials., Objectives: To determine the efficacy and safety of stem cell-based interventions for the treatment of hypoxic-ischaemic encephalopathy (HIE) in newborn infants., Search Methods: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 5), MEDLINE via PubMed (1966 to 8 June 2020), Embase (1980 to 8 June 2020), and CINAHL (1982 to 8 June 2020). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials., Selection Criteria: Randomised controlled trials, quasi-randomised controlled trials and cluster trials comparing 1) stem cell-based interventions (any type) compared to control (placebo or no treatment); 2) use of mesenchymal stem/stromal cells (MSCs) of type (e.g. number of doses or passages) or source (e.g. autologous versus allogeneic, or bone marrow versus cord) versus MSCs of other type or source; 3) use of stem cell-based interventions other than MSCs of type (e.g. mononuclear cells, oligodendrocyte progenitor cells, neural stem cells, hematopoietic stem cells, and inducible pluripotent stem cells) or source (e.g. autologous versus allogeneic, or bone marrow versus cord) versus stem cell-based interventions other than MSCs of other type or source; or 4) MSCs versus stem cell-based interventions other than MSCs., Data Collection and Analysis: For each of the included trials, two authors independently planned to extract data (e.g. number of participants, birth weight, gestational age, type and source of MSCs or other stem cell-based interventions) and assess the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow-up). The primary outcomes considered in this review are all-cause neonatal mortality, major neurodevelopmental disability, death or major neurodevelopmental disability assessed at 18 to 24 months of age. We planned to use the GRADE approach to assess the quality of evidence., Main Results: Our search strategy yielded 616 references. Two review authors independently assessed all references for inclusion. We did not find any completed studies for inclusion. Fifteen RCTs are currently registered and ongoing. We describe the three studies we excluded., Authors' Conclusions: There is currently no evidence from randomised trials that assesses the benefit or harms of stem cell-based interventions for the prevention of morbidity and mortality following hypoxic-ischaemic encephalopathy in newborn infants., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objective: Drowning is a leading cause of unintentional injury-related death in low- and middle-income countries (LMICs). This study was undertaken to know the epidemiology, intensive care needs and predictors of outcome of children with drowning., Methods: Records of children below 12 years admitted with drowning to the emergency room and/or paediatric intensive care unit (PICU) of a tertiary care hospital in North India were retrospectively analysed. 'Favourable outcome' was defined as normal neurological status at discharge (normal cognition and no motor deficits) and 'unfavourable outcome' as death or abnormal neurological status at discharge. Multivariable analysis was done for predictors of unfavourable outcome., Results: Twenty-seven children were analyzed, 14 (51.8%) were boys. Median (IQR) age was 18 months (12-30). The median (IQR) duration of submersion was 4 min (3-9). Six children (22.2%) presented in pulseless arrest, and 7 (43.7%) had both hypoxaemia (saturation <94% on room air) and encephalopathy (GCS <13) at admission. Ten children (37%) were transferred to PICU; principal indications being hypoxic ischaemic encephalopathy (HIE) (n = 6) and ventilation (n = 4). One child died, four survived with sequalae. Predictors of unfavourable outcome on univariable analysis were hypoxaemia, or pulseless arrest at admission, HIE and need for mechanical ventilation; none of these could predict outcome on multivariable analysis., Conclusion: Hypoxaemia or pulseless arrest at admission, HIE and need for ventilation predict unfavourable outcome. Appropriate on-site resuscitation and early stabilization may improve outcome in children with drowning in LMIC., (© The Author(s) [2019]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: This study aimed to describe the experience with a protocol of therapeutic hypothermia (TH) in southern Brazil., Study Design: Newborns with gestational age > 35 weeks with evidence of perinatal asphyxia plus moderate or severe encephalopathy were recruited between March 2011 and November 2017. Whole-body hypothermia for 72 hours, starting within the first 6 hours of life was used. Survivors underwent magnetic resonance imaging (MRI) and electroencephalogram (EEG). The primary outcome was death during hospitalization and neurodevelopment assessed using the Bayley Scales of Infant Development III (BSID III) at 12 months of age., Results: A total of 72 newborns were treated (41 with moderate encephalopathy and 31 with severe encephalopathy), of whom 16 died. MRI was performed in 56 patients, and 24 presented some alterations. Fifty-three patients had an EEG: 11 normal, 20 mildly altered, 12 moderately altered, and 10 severely altered. Forty patients were evaluated through BSID III: 45% presented with some delay in neurodevelopment, 8 (20%) had motor retardation, 15 (37.5%) had language delay, and 13 (32.5%) had a delay in cognitive development., Conclusion: Mortality and adverse events were similar to those described in large randomized controlled trials. TH is a safe and an effective method of neurologic protection in asphyxiated newborns in a developing country when performed adequately., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Hypoxic ischaemic encephalopathy may lead to death or severe long-term morbidity. Therapeutic hypothermia (TH) increases survival without impairments in childhood, but prognostic uncertainty may remain for years after birth. Clear and accurate communication is imperative but challenging. This article explores the predictive value of routinely performed assessments during TH, as well as the qualitative research relating to parental experience. This article will benefit paediatric trainees, consultants and nurse practitioners in providing: (1) the background information needed for initiating a conversation with parents regarding outcome and (2) optimising their communication with parents in translating jargon, prognosis and uncertainty., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hypoxic ischemic encephalopathy (HIE) is brain injury caused by different reasons and the most common diagnosed is neonatal HIE. Most of the existing treatments have their own shortcomings or there are still some unexplained mechanisms in it. Topiramate (TPM) is a new drug for the treatment for seizures in neonates with HIE, but is currently used off-label. Our protocol aims to access the efficiency and safety of TPM for HIE., Methods and Analysis: Eight databases will be searched by 2 independent researchers for the article on the topic of using TPM as treatment for HIE, including PubMed, the Cochrane Central Register of Controlled Trials (Cochrane Library), Embase, and Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Wang Fang Database and Chinese Science and Technology Periodical database (VIP). The included papers are those published from the established date of the databases to 2019. The therapeutic effects based on the grade of neonatal behavioral neurological assessment will be regarded as the primary outcomes. RevMan V5.3 will be used to compute the data synthesis and carry out meta-analysis. The risk of bias will be appraised by the Cochrane risk of bias tool. Rare ratio for dichotomous outcomes and mean different for continuous data will be expressed with 95% confidence intervals (CI) for analysis. A random effects model or a fixed effects model will be employed, when heterogeneity is found or not. Subgroup analysis and sensitivity analysis will be applied if the heterogeneity is obvious., Results: This study will provide the recent evidence of TPM for HIE from reducing seizure acticity., Conclusion: The conclusion of this study will provide proof to evaluate if TPM is effective and safe in the treatment of HIE.PROSPERO registration number: PROSPERO CRD42018117981.

Background: The objective of this study was to evaluate the prognostic role of postnatal acute kidney injury (AKI) on neurodevelopmental outcome in infants with hypoxic-ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH)., Methods: This is a prospective observational study including all neonates with HIE receiving TH between 2009 and 2016 at a single center. AKI was classified according to the Kidney Disease: Improving Global Outcomes definition modified for neonatal age. Child development was assessed using the Griffiths Mental Development Scales (GMDS). Study outcome was defined as unfavorable outcome (including death or disability according to GMDS) or favorable otherwise, at 12 and 24 months., Results: One-hundred and one neonates (median gestational age 39 weeks) were included. AKI was diagnosed in 10 neonates (10%). Seven patients died within the first year, 35 patients had disability at 12 months, and 45 patients at 24 months. AKI was associated with increased likelihood of unfavorable outcome at 24 months (100% vs. 59% in neonates without AKI; p = 0.01). AKI showed good positive predictive value (1.00, 95% CI 0.71-1.00) and specificity (1.00, 95% CI 0.88-1.00), but poor negative predictive value (0.41, 95% CI 0.30-0.52) and sensitivity (0.19, 95% CI 0.11-0.32) at 24 months., Conclusions: AKI might be a reliable indicator of death or long-term disability in infants with HIE receiving TH, but the absence of AKI does not guarantee a favorable long-term outcome.

Objective: To investigate the impact of hypoxic-ischemic brain injury (HIBI) on brain development in neonatal rats of different sexes. Methods: From January 1 to December 31, 2018, 60 7-day-old SD rats were randomly divided into HIBI-F group (20 rats), HIBI-M group (20 rats), and control group (20 rats, 10 females and 10 males). The animal model of HIBI was established with Rice-Vannucci method, with the rats' left common carotid artery double-ligated and severed. The rats were then placed in an incubator and exposed to a hypoxic gas mixture (8% O(2), 92% N(2)) for 90 minutes. No intervention was given to the control group. Two weeks after HIBI, the motor development was evaluated by footprint analysis, the residual brain volume was measured by brain magnetic resonance imaging (MRI), and the damage of synaptic ultra structure was analyzed by transmission electron microscope. One-way ANOVA or χ(2) test was used for inter-group statistical analysis, and paired sample t test was used to compare the bilateral step length and toe distance of rats in the same group. Results: The mortality rate of HIBI-F was significantly higher than that of HIBI-M (20%(4/20) vs. 10%(2/20), χ(2)=40.000, P =0.001). The right step length and toe distance in HIBI-M group and HIBI-F group were significantly shorter than those in control group ((7.5±0.3) cm and (7.9±0.5) cm vs. (8.2±0.5) cm, F= 9.605, P< 0.01, (0.9±0.1) cm and (1.0±0.0) cm vs. (1.1±0.1) cm, F= 71.437, P< 0.01). Besides, according to above data, the right step length and toe distance in HIBI-M group were significantly shorter than those in the HIBI-F group (both P< 0.01). Furthermore, the right step length was significantly shorter than the left step length ((8.3±0.4) and (8.3±0.5) cm, t= 5.289 and 10.580, P= 0.001 and 0.010, respectively) and toe distance ((1.1±0.1) and (1.1±0.1) cm, t= 7.953 and 6.435, respectively, both P <0.01) in both HIBI-M group and HIBI-F group. Similarly, the synaptic gap of the left precentral gyrus neurons was longer in HIBI-M group and HIBI-F group than that in control group ((23.4±1.3) and (19.7±1.6) nm vs. (18.9±0.6) nm, F= 71.719, P <0.01), and also longer in HIBI-M group than that in HIBI-F group ( t= 7.645, P <0.01). Likewise, the residual brain volume in HIBI-M group and HIBI-F group was significantly less than that in control group ((67±4)% and (75±5)% vs. 100%, F= 406.122, P <0.01), and the residual brain volume in HIBI-M group was significantly less than that in HIBI-F group ( t= -5.281, P <0.01). Conclusions: Male neonatal rats are more vulnerable to HIBI and have severer subsequent brain injury and hemiplegia. Different treatment strategies for HIBI patients of different sexes should be developed.

Background: Birth asphyxia in term neonates remains a serious condition that causes significant mortality and long-term neurodevelopmental sequelae despite hypothermia treatment. The objective of this study was to review therapeutic hypothermia practices in a large population of neonates with hypoxic-ischemic encephalopathy (HIE) across Canada and to identify determinants of adverse outcome., Methods: Our retrospective observational cohort study examined neonates≥36 weeks, admitted to the Canadian Neonatal Network NICUs between 2010 and 2014, diagnosed with HIE, and treated with hypothermia. Adverse outcome was defined as death and/or brain injury. Maternal, birth, and postnatal characteristics were compared between neonates with adverse outcome and those without. The association between the variables which were significantly different (p < 0.05) between the two groups and adverse outcome were further tested, while adjusting for gestational age, birth weight, gender, and initial severity of encephalopathy., Results: A total of 2187 neonates were admitted for HIE; 52% were treated with hypothermia and 40% developed adverse outcome. Initial severity of encephalopathy (moderate, p = 0.006; severe, p < 0.0001), hypotension treated with inotropes (p = 0.001), and renal failure (p = 0.007) were significantly associated with an increased risk of death and/or brain injury., Conclusions: In asphyxiated neonates treated with hypothermia, not only their initial severity of encephalopathy on admission, but also their cardiac and renal complications during the first days after birth were significantly associated with risk of death and/or brain injury. Careful monitoring and cautious management of these complications is warranted.

Objective: Apgar scores of zero at 10 min strongly predict mortality and morbidity in infants. However, recent data reported improved outcomes among infants with Apgar scores of zero at 10 min. We aimed to review the mortality rate and neurodevelopmental outcomes of infants with Apgar scores of zero at 10 min in Japan., Design: Observational study., Patients: Twenty-eight of 768 infants registered in the Baby Cooling Registry of Japan between 2012 and 2016, at >34 weeks' gestation, with Apgar scores of zero at 10 min who were treated with therapeutic hypothermia., Interventions: We investigated the time of first heartbeat detection in infants with favourable outcomes and who had neurodevelopmental impairments or died., Main Outcome Measures: Clinical characteristics, mortality rate and neurodevelopmental outcomes at 18-22 months of age were evaluated., Results: Nine (32%) of the 28 infants died before 18 months of age; 16 (57%) survived, but with severe disabilities and 3 (11%) survived without moderate-to-severe disabilities. At 20 min after birth, 14 of 27 infants (52%) did not have a first heartbeat, 13 of them died or had severe disabilities and one infant, who had the first heartbeat at 20 min, survived without disability., Conclusion: Our study adds to the recent evidence that neurodevelopmental outcomes among infants with Apgar scores of zero at 10 min may not be uniformly poor. However, in our study, all infants with their first heartbeat after 20 min of age died or had severe disabilities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine the neurodevelopment outcomes after therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy (HIE) and identify the neonatal magnetic resonance imaging (MRI) findings associated with neurological outcome in a middle-income country., Study Design: All infants born after 35 completed weeks' gestation with signs of moderate to severe encephalopathy and evidence of perinatal asphyxia before 6 hours of life were submitted to whole-body hypothermia and were imaged at 18 ± 8.4 days of life (range 7-33 days) after birth. Surviving infants had the neurodevelopment outcome assessed at 12 to 18 months of age by trained professional masked to MRI findings., Results: Forty-eight infants included, MRI scans were obtained from 34 infants; 14 (29.1%) patients died during hospitalization before MRI was performed. Nine (64.3%) of 14 patients were classified as severe encephalopathy presented Posterior Limb Internal Capsule (PLIC) sign at the MRI, 10 (71.4%) thalamus and basal ganglia (TBG) lesion, 9 (64.3%) white matter (WM) lesion, and 7 (50.0%) cortical lesion. Severe encephalopathy was associated with the motor delay at 12-18 months by Bayley III, Alberta Infant Motor Scale (AIMS), and Gross Motor Function Classification System (GMFCS) scores (p = .020, p = .048, p = .033, respectively), but not for the cognitive (p = .167) or language skills (p = .309). Lower BSID-III motor, cognitive, and language composite scores were associated with PLIC sign (p = .047; p = .006 and p = .003, respectively). TBG lesion (p = .051) and cortical lesion (p = .030) were associated with lower language composite score. Motor delay by AIMS and the presence of PLIC sign, TBG lesion, WM lesion, and Cortical lesion on MRI were observed (p < .001; p = .002; p = .001 and p = .027, respectively); as well as higher GMFCS score were associated with the presence of PLIC sign, TBG lesion, WM lesion, and Cortical lesion on MRI (p < .001; p = .001; p = .001, and p = .011, respectively)., Conclusions: Brain MRI in neonates with HIE after therapeutic hypothermia is a valuable tool for diagnosis of encephalopathy cerebral abnormalities and is an early predictor of outcome in infants treated with whole body hypothermia for HIE in the Brazilian experience.

Objective: To investigate the potential value of uterine artery pulsatility index (UtA-PI) and serum levels of the angiogenic placental growth factor (PlGF) and the antiangiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1) in the prediction of adverse perinatal outcome in small-for-gestational-age (SGA) and non-SGA neonates at 35-37 weeks' gestation., Methods: This was a prospective observational study of 19 209 singleton pregnancies attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, sonographic estimation of fetal weight, color Doppler ultrasound for measurement of mean UtA-PI, and measurement of serum concentrations of PlGF and sFlt-1. Multivariable logistic regression analysis was carried out to determine which of the factors from maternal or pregnancy characteristics and measurements of UtA-PI, PlGF and sFlt-1 provided a significant contribution in the prediction of each of four adverse outcome measures: first, stillbirth; second, Cesarean delivery for suspected fetal compromise in labor; third, neonatal death or hypoxic ischemic encephalopathy Grade 2 or 3; and, fourth, admission to the neonatal unit (NNU) for ≥ 48 h. Predicted probabilities from logistic regression analysis were used to construct receiver-operating characteristics curves to assess the performance of screening for these adverse outcomes., Results: First, 83% of stillbirths, 82% of Cesarean sections for presumed fetal compromise in labor, 91% of cases of neonatal death or hypoxic ischemic encephalopathy and 86% of NNU admissions for ≥ 48 h occurred in pregnancies with a non-SGA neonate. Second, UtA-PI > 95 th percentile, sFlt-1 > 95 th percentile and PlGF < 5 th percentile were associated with increased risk of Cesarean delivery for suspected fetal compromise in labor and NNU admission for ≥ 48 h; the number of stillbirths and cases of neonatal death or hypoxic ischemic encephalopathy was too small to demonstrate significance in the observed differences from cases without these adverse outcomes. Third, multivariable logistic regression analysis demonstrated that, in the prediction of Cesarean delivery for suspected fetal compromise in labor, there was no significant contribution from biomarkers; the prediction of NNU admission for ≥ 48 h by maternal demographic characteristics and medical history was only marginally improved by the addition of sFlt-1 or PlGF. Fourth, for each biomarker, the detection rate of adverse outcome was higher in SGA than in non-SGA neonates, but this increase was accompanied by an increase in false-positive rate. Fifth, the relative risk of UtA-PI > 95 th , sFlt-1 > 95 th and PlGF < 5 th percentiles for most adverse outcomes was < 2.5 in both SGA and non-SGA neonates., Conclusions: In pregnancies undergoing routine antenatal assessment at 35-37 weeks' gestation, measurements of UtA-PI, sFlt-1 or PlGF provide poor prediction of adverse perinatal outcome in both SGA and non-SGA fetuses. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)

Background: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia., Methods: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age ≥ 36 weeks and a birth weight ≥ 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion., Discussion: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia., Trial Registration: NCT03162653, www.ClinicalTrials.gov , May 22, 2017.

We aimed to correlate amplitude-integrated EEG (aEEG) in neonatal hypoxic ischemic encephalopathy (HIE) with early magnetic resonance imaging (MRI). In this retrospective study, 32 neonates over 35 weeks' gestation with moderate/severe HIE who were treated with hypothermia were included. Early MRI scans and daily aEEG background were categorized to mild/normal, moderate, and severely abnormal. Time to sleep cycling was noted on aEEG. Mantel-Haenszel test for trends was used to explore associations between aEEG and MRI and outcome. LOESS regression was used for exploring the association of cycling with MRI scores. MRI was normal/mildly abnormal in 20 (63%) infants; in 9 (28%), moderately abnormal; and in 3 (9%), severely abnormal. Twenty-seven (84%) infants s urvived. MRI severity score was significantly associated with aEEG background score on the third and fourth days of life (p < 0.01). An increase in the MRI severity score was noted if sleep cycling appeared after the fifth day of life.Conclusions: Depressed aEEG at the third and fourth days of life and appearance of cycling beyond the fifth day of life are associated with cerebral MRI abnormalities and may be associated with increased risk of abnormal outcome. What is known: • Since therapeutic hypothermia has been shown to change long-term outcome, amplitude-integrated EEG in infants with hypoxic ischemic neonatal encephalopathy soon after birth have a limited predictive power for long-term outcome in treated infants. • Brain MRI after therapeutic hypothermia in the above infants has a significant predictive value for long-term outcome What is new: • Background amplitude-integrated EEG activity depression at the age of 3 and 4 days and delay of appearance of cycling activity are associated with worse MRI scores and may be predictive of worse long-term outcome.

Background Erythropoietin (EPO) appears to confer neuroprotection to the injured brain. Randomized clinical trials (RCTs) have demonstrated its safety in neonates with hypoxic-ischemic encephalopathy (HIE); however, the evidence is unclear. The objective of this study was to examine the role of EPO in perinatal HIE by a systematic review and meta-analysis. Methods Database search included Embase, MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Central Register of Controlled Trials (CENTRAL). RCTs reporting a death, neurodevelopmental outcomes or brain injury were included. Two authors extracted the data independently from included studies and assessed the level of evidence (LOE). Results Six RCTs (EPO=5 and darbepoetin α=1) involving 454 neonates were included. A trend toward a lower risk of death was identified in infants treated with EPO [EPO with or without hypothermia: five RCTs, 368 participants, relative risk (RR) 0.74, 95% confidence interval (CI) 0.47-1.19, LOE-low; EPO without hypothermia: four RCTs, 318 participants, RR 0.89, 95% CI 0.49-1.32, LOE-low]. EPO treatment without hypothermia compared to placebo resulted in a reduced risk of cerebral palsy (two RCTs, 230 participants, RR 0.47, 95% CI 0.27-0.80, LOE-moderate) and moderate to severe cognitive impairment (two RCTs, 226 participants, RR 0.49, 95% CI 0.28-0.85, LOE-moderate). A reduced risk of brain injury was identified in EPO treated infants (EPO with or without hypothermia, two RCTs, 148 participants, RR 0.70, 95% CI 0.53-0.92, LOE-moderate). Conclusion EPO administration in neonates with perinatal HIE reduces the risk of brain injury, cerebral palsy and cognitive impairment. The evidence is limited to suggest its role as an adjuvant to hypothermia. Larger powered trials are underway to overcome this limitation.

Importance: Guidelines for declaration of brain death in children were revised in 2011 by the Society of Critical Care Medicine, American Academy of Pediatrics, and Child Neurology Society. Despite widespread medical, legal, and ethical acceptance, ongoing controversies exist with regard to the concept of brain death and the procedures for its determination., Objectives: To determine the epidemiology and clinical characteristics of pediatric patients declared brain dead in the United States., Design, Setting, and Participants: This study involved the abstraction of all patient deaths from the Virtual Pediatric Systems national multicenter database between January 1, 2012, and June 30, 2017. All patients who died in pediatric intensive care units (PICUs) were included., Main Outcomes and Measures: Patient demographics, preillness developmental status, severity of illness, cause of death, PICU medical and physical length of stay, and organ donation status, as well as comparison between patients who were declared brain dead vs those who sustained cardiovascular or cardiopulmonary death., Results: Of the 15 344 patients who died, 3170 (20.7%) were declared brain dead; 1861 of these patients (58.7%) were male, and 1401 (44.2%) were between 2 and 12 years of age. There was a linear association between PICU size and number of patients declared brain dead per year, with an increase of 4.27 patients (95% CI, 3.46-5.08) per 1000-patient increase in discharges (P < .001). The median (interquartile range) of patients declared brain dead per year ranged from 1 (0-3) in smaller PICUs (defined as those with <500 discharges per year) to 10 (7-15) for larger PICUs (those with 2000-4000 discharges per year). The most common causative mechanisms of brain death were hypoxic-ischemic injury owing to cardiac arrest (1672 of 3170 [52.7%]), shock and/or respiratory arrest without cardiac arrest (399 of 3170 [12.6%]), and traumatic brain injury (634 of 3170 [20.0%]). Most patients declared brain dead (681 of 807 [84.4%]) did not have preexisting neurological dysfunction. Patients who were organ donors (1568 of 3144 [49.9%]) remained in the PICU longer after declaration of brain death compared with those who were not donors (median [interquartile range], 29 [6-41] hours vs 4 [1-8] hours; P < .001)., Conclusions and Relevance: Brain death occurred in one-fifth of PICU deaths. Most children declared brain dead had no preexisting neurological dysfunction and had an acute hypoxic-ischemic or traumatic brain injury. Brain death determinations are infrequent, even in large PICUs, emphasizing the importance of ongoing education for medical professionals and standardization of protocols to ensure diagnostic accuracy and consistency.

Objective: To determine in-hospital outcomes of neonates with hypoxic ischemic encephalopathy (HIE) requiring extracorporeal membrane oxygenation (ECMO)., Study Design: Single-center retrospective study from 2005 to 2016 of neonates ≥35 weeks gestation with moderate/severe HIE, requiring ECMO for persistent pulmonary hypertension of newborn (PPHN)., Results: Our cohort (n = 20) received therapeutic hypothermia for moderate (n = 12), severe (n = 5), or undocumented severity (n = 3) of HIE. During ECMO, 30% (n = 6) infants developed intracranial hemorrhage at a median (IQR) duration of 24 (20) hours. Sixteen (80%) infants survived to discharge, among which 15 had MRI performed; 47% (n = 7) had normal MRI, 20% (n = 3) had intracranial hemorrhage and 13% (n = 2), 13% (n = 2) and 7% (n = 1) had NICHD stage 1, 2, and 3 pattern of brain injury respectively., Conclusions: In this high-risk population of neonates, use of ECMO was safe and efficacious as demonstrated by survival and outcomes.

Objective: To determine the short-term outcomes (abnormal brain magnetic resonance imaging [MRI]/death) in infants born with a 10-minute Apgar score of 0 who received therapeutic hypothermia and compare them with infants with higher scores., Study Design: This is a retrospective review of 293 neonates (gestational age ≥ 35 weeks) born between November 2006 and October 2015 admitted with hypoxic-ischemic encephalopathy who received therapeutic hypothermia. Results of brain MRIs were assessed by the basal ganglia/watershed scoring system. Short-term outcomes were compared between infants with Apgar scores of 0, 1 to 4, and ≥5 at 10 minutes., Results: Eight of 17 infants (47%) with an Apgar of 0 at 10 minutes survived, having 4 (24%) without abnormalities on the brain MRI and 7 (41%) without severe abnormalities. There was no significant difference in the combined outcomes of "death/abnormal MRI" and "death/severe abnormalities on the MRI" between infants with Apgar scores of 0 and 1 to 4. Follow-up data were available for six of eight surviving infants, and none had moderate or severe neurodevelopmental impairment., Conclusion: In the cooling era, 47% of infants with no audible heart rate at 10 minutes and who were admitted to the neonatal intensive care unit survived; 24% without abnormalities on the brain MRI and 41% without severe abnormalities., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Preterm birth is one of the main country health indicators. It is associated with high mortality and significant morbidity in preterm newborns with cerebral palsy and potential long-term neurodevelopmental disabilities like cognitive and learning problems. The main lesions could be: a) white matter injuries, generally associated with cortical and other regions of grey matter neuronal-axonal disturbances; b) intracranial hemorrhage that includes germinal matrix, intraventricular and parenchymal, c) cerebellum injuries. The white matter lesions include cystic and non-cystic (with microscopic focal necrosis) periventricular leukomalacia and non-necrotic diffuse white matter injury. Multiple etiologic factors are associated with these injuries. Anatomical and physiological characteristics of periventricular vascular structures predispose white matter to cerebral ischemia and, interacting with infection/inflammation factors, activate microglia, generating oxidative stress (mediated by free oxygen and nitrogen radicals), pro-inflammatory cytokine and glutamate toxicity, energetic failure and vascular integrity disturbances. All these factors lead to a particular vulnerability of pre-oligodendrocytes that will affect myelination. Hypoxia-ischemia also may produce selective neuronal necrosis in different cerebral regions. Germinal matrix is a highly vascularized zone beneath ependymal or periventricular region that constitutes a capillary bed with a particular structural fragility that predispose it to hemorrhage.

It is well-documented in the literature that infants who suffer from hypoxic ischemic encephalopathy are at high risk for neurologic sequelae or even death. With the addition of therapeutic hypothermia into the treatment regimen for neonatal hypoxic ischemic encephalopathy, newborns afflicted with hypoxic ischemic encephalopathy were given the opportunity for a better outcome. Questions linger as to the most optimal treatment strategy of therapeutic hypothermia for these newborns. The goal of this article is to discuss current management strategies, as well as future trends, for infants with hypoxic ischemic encephalopathy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aim: To assess the electrocardiography and echocardiography changes during therapeutic hypothermia and rewarming period in encephalopathic infants with long-term adverse neurological outcome., Methods: Prospective multicentre longitudinal study. We included 64 consecutive infants with moderate or severe hypoxic ischaemic encephalopathy undergoing therapeutic hypothermia who had 18-24 month-outcome data. We analysed electrocardiography and heart rate changes before, during and after therapeutic hypothermia. Superior vena cava flow, left ventricular cardiac output and stroke volume were studied using echocardiography during and immediately after therapeutic hypothermia. An abnormal outcome was defined as death or moderate/severe disability at 18-24 months., Results: Neonates with higher superior vena cava flow pre-rewarming had significantly higher odds of documented long-term adverse outcome when compared to newborns with good outcome (OR 1.57; 95%CI, 1.1-1.78; p = 0.01 after adjustment). QTc and RR intervals were significantly longer at 12, 24, 36 and 48 h in infants with good outcome compared with those with adverse outcome (p < 0.001). During therapeutic hypothermia, infants with poor outcome had a higher heart rate at 12, 24, 36, 48, 60 h after birth compared with those with good outcome (p < 0.001). From 36 h on, heart rate gradually increased and RR and QTc intervals progressively shortened with values back to normal after rewarming., Conclusions: Infants with hypoxic ischaemic encephalopathy who have adverse neurological outcome show a preferential cerebral blood flow redistribution during therapeutic hypothermia. Infants with poor outcome have higher heart rate and shorter RR and QTc intervals during therapeutic hypothermia., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Hypoxic-ischaemic encephalopathy (HIE) is a serious birth complication affecting term and late preterm newborns. Although therapeutic hypothermia (cooling) has been shown to be an effective therapy for neonatal HIE, many cooled infants have poor long-term neurodevelopmental outcomes. In animal models of neonatal encephalopathy, inhaled xenon combined with cooling has been shown to offer better neuroprotection than cooling alone., Objectives: To determine the effects of xenon as an adjuvant to therapeutic hypothermia on mortality and neurodevelopmental morbidity, and to ascertain clinically important side effects of xenon plus therapeutic hypothermia in newborn infants with HIE. To assess early predictors of adverse outcomes and potential side effects of xenon., Search Methods: We used the standard strategy of the Cochrane Neonatal Review Group to search the Cochrane Library (2017, Issue 8), MEDLINE (from 1966), Embase (from 1966), and PubMed (from 1966) for randomised controlled and quasi-randomised trials. We also searched conference proceedings and the reference lists of cited articles. We conducted our most recent search in August 2017., Selection Criteria: We included all trials allocating term or late preterm encephalopathic newborns to cooling plus xenon or cooling alone, irrespective of timing (starting age and duration) and concentrations used for xenon administration., Data Collection and Analysis: Two review authors independently assessed results of searches against predetermined criteria for inclusion, assessed risk of bias, and extracted data. We performed meta-analyses using risk ratios (RRs), risk differences (RDs), and number needed to treat for an additional beneficial outcome (NNTB) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences (MDs) for continuous data., Main Results: A single randomised controlled trial enrolling 92 participants was eligible for this review. Researchers have not reported long-term neurodevelopmental outcomes, including the primary outcome of this review - death or long-term major neurodevelopmental disability in infancy (18 months to three years of age). Cooling plus xenon was not associated with reduced mortality at latest follow-up, based upon low quality evidence. Investigators noted no substantial differences between groups for other secondary outcomes of this review, such as biomarkers of brain damage assessed with magnetic resonance imaging and occurrence of seizures during primary hospitalisation. Available data do not show an increased adverse event rate in the cooling plus xenon group compared with the cooling alone group., Authors' Conclusions: Current evidence from one small randomised controlled pilot trial is inadequate to show whether cooling plus xenon is safe or effective in near-term and term newborns with HIE. Further trials reporting long-term neurodevelopmental outcomes are needed.

Objective: To evaluate the association between sedation-analgesia (SA) during initial 72 h and death/disability at 18 months of age in neonatal hypoxic-ischemic encephalopathy (HIE)., Design: This was a secondary analysis of the NICHD therapeutic hypothermia (TH) randomized controlled trial in moderate or severe HIE. Receipt of SA and anticonvulsant medications at five time points were considered: prior to and at baseline, 24, 48, and 72 h of TH or normothermia. Disability was defined as mental developmental index <85, cerebral palsy, blindness, hearing impairment, or Gross Motor Function Classification System 2-5., Results: Of the 208 RCT participants, 38 (18%) infants had no exposure to SA or anticonvulsants at any of the five time points, 20 (10%) received SA agents only, 81 (39%) received anticonvulsants only, and 69 (33%) received both SA and anticonvulsants. SA category drugs were not administered in 57% of infants while 18% received SA at ≥3 time points; 72% infants received anticonvulsants during 72 h of intervention. At 18 months of age, disability among survivors and death/disability was more frequent in the groups receiving anticonvulsants, with (48 and 65%) or without (37 and 58%) SA, compared to groups with no exposure (14 and 34%) or SA (13 and 32%) alone. Severe HIE (aOR 3.60; 1.59-8.13), anticonvulsant receipt (aOR 2.48; 1.05-5.88), and mechanical ventilation (aOR 7.36; 3.15-17.20) were independently associated with 18-month death/disability, whereas TH (aOR 0.28; 0.13-0.60) was protective. SA exposure showed no association with outcome., Conclusions: The risk benefits of SA in HIE need further investigation.

Objective: To find out the effect of melatonin as adjunct therapy on outcome of admitted newborns presenting with hypoxic ischaemic encephalopathy., Methods: This randomized controlled trial was conducted at King Edward Medical University, Lahore, Pakistan, from October 2016 to March 2017, and comprised newborns with gestational age of 34 weeks or higher who fulfilled the definition of hypoxic ischaemic encephalopathy and presented within 12 hours of birth. The severity of hypoxic ischaemic encephalopathy was assessed by Thompson score. The subjects were randomised into standard treatment group and intervention group which received melatonin 10mg orally via nasogastric tube at admission. Newborns were followed for 28 days to see the effect of melatonin in terms of survival rate. Data was analyzed using SPSS 20., Results: There were 80 newborns with overall mean gestational age of 36.81±1.7 weeks and mean birth weight of 2578.75±536 grams. Each of the two groups had 40(50%) subjects. In the intervention group, 35(87%) subjects and 26(65%) cases in the standard treatment group survived (p=0.03)., Conclusions: Administration of melatonin as an adjunct therapy in the management of newborns with hypoxic ischaemic encephalopathy led to improved survival rate.

Neonatal hypoxic-ischemic encephalopathy remains associated with considerable death and disability. In multiple randomized controlled trials, therapeutic hypothermia for neonatal moderate or severe hypoxic-ischemic encephalopathy among term infants has been shown to be safe and effective in reducing death and disability in survivors. In this article, the current status of infant and childhood outcomes following this therapy is reviewed. The clinical approaches that may help to optimize this innovative neuroprotective therapy are presented., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Perinatal brain injury may lead to long-term morbidity and neurodevelopmental impairment. Improvements in perinatal care have resulted in the survival of more infants with perinatal brain injury. The effects of hypoxia-ischemia, inflammation, and infection during critical periods of development can lead to a common pathway of perinatal brain injury marked by neuronal excitotoxicity, cellular apoptosis, and microglial activation. Various interventions can prevent or improve the outcomes of different types of perinatal brain injury. The objective of this article is to review the mechanisms of perinatal brain injury, approaches to prevention, and outcomes among children with perinatal brain injury., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aim: To describe the cerebral blood flow velocity pattern and investigate cerebral autoregulation using transcranial Doppler ultrasonography (TCD) following a global hypoxic-ischaemic (HI) event in children., Methods: This was a prospective, observational study in a quaternary-level paediatric intensive care unit. Intubated children, newborn to 17 years admitted to the PICU following HI injury (asphyxia, drowning, cardiac arrest) were eligible for inclusion. TCD was performed daily until post-injury day 8, discharge, or death, whichever occurred earliest., Results: Twenty-six patients were enrolled. Median age was 3 years (0.33, 11.75), initial pH 6.95, and initial lactate 5.4. Median post-resuscitation Glasgow Coma Score was 3T. Across the entire cohort, cerebral blood flow velocity (CBFV) was near normal on day 1. Flow velocity increased to a maximum median value of 1.4 standard deviations above normal on day 3 and slowly downtrended back to baseline by the end of the study period. Median Paediatric Extended Version of the Glasgow Outcome Score was 4 at three months. No patient in the favourable outcome group had extreme CBFV on day one, and only one patient in the favourable group had extreme CBFV on PID 2. In contrast, 38% of patients in the unfavourable group had extreme CBFV on PID 1 (p=.039 compared to frequency in favourable group), and 55% had extreme CBFV on PID 2 (p = .023 compared to frequency in favourable group). No patient had consistently intact cerebral autoregulation throughout the study period., Conclusions: Following a HI event, patients with favourable neurologic outcomes had flow velocity near normal whereas unfavourable outcomes had more extreme flow velocity. Intermittently intact cerebral autoregulation was more frequently seen in those with favourable neurologic outcomes though return to the autoregulatory baseline appears delayed., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Perinatal asphyxia is an event affecting around four million newborns worldwide. The 0.5 to 2 per 1000 of full term asphyxiated newborns suffer from hypoxic-ischemic encephalopathy (HIE), which is a frequent cause of death or severe disability and, as consequence, the most common birth injury claim for obstetrics, gynaecologists, and paediatricians. Perinatal asphyxia results from a compromised gas exchange that leads to hypoxemia, hypercapnia, and metabolic acidosis. In this work, we applied a metabolomics approach to investigate the metabolic profiles of urine samples collected from full term asphyxiated newborns with HIE undergoing therapeutic hypothermia (TH), with the aim of identifying a pattern of metabolites associated with HIE and to follow their modifications over time. Urine samples were collected from 10 HIE newborns at birth, during hypothermia (48 hours), at the end of the therapeutic treatment (72 hours), at 1 month of life, and compared with a matched control population of 16 healthy full term newborns. The metabolic profiles were investigated by 1H NMR spectroscopy coupled with multivariate statistical methods such as principal component analysis and orthogonal partial least square discriminant analysis. Multivariate analysis indicated significant differences between the urine samples of HIE and healthy newborns at birth. The altered metabolic patterns, mainly originated from the depletion of cellular energy and homeostasis, seem to constitute a characteristic of perinatal asphyxia. The HIE urine metabolome changes over time reflected either the effects of TH and the physiological growth of the newborns. Of interest, the urine metabolic profiles of the HIE non-surviving babies, characterized by the increased excretion of lactate, resulted significantly different from the rest of HIE population.

Background: Adult patients with hypoxic-ischemic encephalopathy (HIE) often incur large costs, but their outcomes are poor. Currently, there is lack of a comprehensive quantitative approach to predict patient prognoses., Methods: A total of 73 adult patients with HIE participated in this prospective, observational study. Clinical assessments, laboratory tests, and electrophysiological examinations were conducted within 3 days after HIE occurred. Logistic regression model was used to identify independent factors associated with patient outcomes., Results: After a 6-month follow-up, 44 (61.1%) patients survived, 28 (38.9%) patients died, and one patient was lost to follow-up. The level of blood calcium and lactate, the presence of electroencephalography reactivity, and Glasgow Coma Scale (GCS) score were significantly associated with the patient's outcome. Based on the regression coefficients from logistic regression analysis, we constructed a scoring system (CEGL; C: calcium, E: EEG reactivity, G: GCS, L: lactate) to predict the possibility of a patient's death. The area under the receiver operating characteristic curve was 0.91 (P < 0.001, 95% CI [0.87-0.95]) with a specificity of 97.7% and a positive predictive value of 97.4%., Conclusion: CEGL score can provide clinicians useful information for assessment of patient prognosis within 6 months after HIE.

Data on the incidence of hypoxic-ischemic encephalopathy (HIE) in the first 6 hours of life together with the implementation of therapeutic hypothermia (TH) are relevant to delineate actions to achieve the lowest rates of neonatal mortality, morbidity, and long-term impact on health associated with HIE. This is population-based national survey study, including newborns ≥35 weeks of gestation with moderate-to-severe HIE from all level III neonatal care units, to provide the incidence of HIE for the period 2012-2013, and the implementation of TH up to June 2015 in Spain. Incidence rate was 0.77 per 1000 live births (95% confidence interval 0.72-0.83). By June 2015, 63% (57/90) of the units had implemented TH; 95% of them performed servo-controlled whole-body TH. For the 2-year period, 86% of the newborns diagnosed with moderate-to-severe HIE received TH. Active TH increased in use from 78% in 2012 to 85% in 2013 (p = 0.01). The main reasons for not cooling were a delay in the diagnosis (31/682) and the fact that the treatment was not offered (20/682). Interhospital patient transfer was performed using passive hypothermia, by appropriately trained personnel in 61% of centers. Eighteen percent of newborns with moderate or severe HIE died, without significant differences between the 2 years. Up-to-date knowledge of the national coverage of neonatal care of infants with HIE in developed countries is a prerequisite to reducing the load of HIE in this area and to facilitating coordinated, eliminate investigation.

Objective:  The objective of this study was to compare complications and mortality in neonates with hypoxic ischemic encephalopathy (HIE) on extracorporeal membrane oxygenation (ECMO) who did and did not receive therapeutic hypothermia (TH)., Study Design:  The Extracorporeal Life Support Organization registry was queried from 2005 to 2013 to identified infants with HIE. Infants ≤30 days of age with HIE on respiratory ECMO were included. Fisher's exact test and the Wilcoxon's rank-sum test were used to compare neonates with and without TH. Logistic regression was used to examine the association of TH with complications and mortality., Results:  There were no difference between neonates with HIE who did ( n  = 78) and did not ( n  = 109) receive TH in demographics, severity of illness, complications, and mortality ( p  = 0.21)., Conclusion:  No differences in complications or mortality in neonates with HIE and respiratory ECMO were observed between those who did and did not receive TH. We suggest that for neonates requiring respiratory ECMO who also have HIE, TH is not contraindicated., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)