Correlation analysis between the amniotic fluid contamination and clinical grading of neonatal hypoxic-ischemic encephalopathy and biomarkers of brain damage.

BACKGROUND: Amniotic fluid contamination (AFC) is a risk factor for neonatal hypoxic ischemic encephalopathy (HIE); however, the correlation between AFC level and the incidence and clinical grading of HIE, in addition to relevant biomarkers of brain damage, have not been assessed. METHODS: This single-center observational study included 75 neonates with moderate-to-severe HIE. The neonates with HIE were divided into four subgroups according to the AFC level: normal amniotic fluid with HIE group (NAF-HIE), I°AFC with HIE group (I°AFC-HIE), II°AFC with HIE group (II°AFC-HIE), and III°AFC with HIE group (III°AFC-HIE). The control groups consisted of 35 healthy neonates. The clinical grading of neonatal HIE was performed according to the criteria of Sarnat and Sarnat. Serum tau protein and S100B were detected by enzyme-linked immunosorbent assay kits. Correlations of serum tau protein and S100B were evaluated using the Pearson correlation analysis. RESULTS: (1) The incidence of neonatal HIE in the NAF-HIE group was 20 cases (26. 7%), I°AFC-HIE was 13 cases (17.3%), II°AFC-HIE was 10 cases (13.3%), and III°AFC-HIE was 32 cases (42. 7%). The incidence of moderate-to-severe HIE in the I°-III°AFC-HIE groups was 73.3% (55/75). (2) In 44 cases with severe HIE, 26 cases (59.1%) occurred in the III°AFC-HIE group, which had a significantly higher incidence of severe HIE than moderate HIE (p < 0.05). In NAF-HIE and I°AFC-HIE groups, the incidence of moderate HIE was 45.2% and 29.0%, respectively, which was higher than that of severe HIE (X2 = 9.2425, p < 0.05; X2 = 5.0472, p < 0.05, respectively). (3) Serum tau protein and S100B levels in the HIE groups were significantly higher than in the control group (all p < 0.05), and were significantly higher in the III°AFC-HIE group than in the NAF-HIE and I°AFC-HIE groups (all p < 0.05). (4) Serum tau protein and S100B levels in the severe HIE group were significantly higher in the moderate HIE group (all p < 0.05). (5) Serum tau protein and S100B levels were significantly positively correlated (r = 0.7703, p < 0.0001). CONCLUSION: Among children with severe HIE, the incidence of III°AFC was higher, and the levels of serum tau protein and S100B were increased. AFC level might be associated with HIE grading.

Nutrition of Newborns with Hypoxic-Ischaemic Encephalopathy during Therapeutic Hypothermia - A Survey of Practice in Polish Neonatal Care Units.

BACKGROUND: The nutritional practice for newborns with hypoxic-ischaemic encephalopathy during therapeutic hypothermia differs among Polish neonatal care units, as no guidelines are provided. We assessed the prevailing procedures. MATERIAL AND METHODS: Data was collected through an anonymous, web-based questionnaire. We surveyed aspects of the current nutritional practices and the reasoning behind the choice of the feeding strategy. RESULTS: Thirty-one responses were obtained (31/33, 94%). Based on participants' estimations, 342 newborns are diagnosed with hypoxic-ischaemic encephalopathy and qualified for therapeutic hypothermia annually. Among them, almost ⅓ is fed exclusively parenterally, while 71% both ways-parenterally and enterally. In the vast majority of units, the introduction of enteral nutrition takes place during the first 48 hours of therapeutic hypothermia, and breast milk is primarily provided, although with substantial first feeding volume differentiation (an average of 2,9 ml/kg (0,3 - 10ml/kg)). Adverse events, such as necrotising enterocolitis, sepsis, and glycemia level disturbances that derive from the initiation of enteral nutrition, are difficult to estimate as no official statistics are provided. CONCLUSIONS: The majority of newborns after hypoxic-ischaemic encephalopathy treated with therapeutic hypothermia are fed both parenterally and enterally during the procedure, predominantly with expressed or donor breast milk. However, due to the lack of nutritional guidelines, significant variability of nutritional strategies concerning initiation time, type and volume of enteral feeds given is noted. Therefore, further studies are required to clarify feeding recommendations.

Sudden death due to butane abuse - An overview.

Volatile Solvents Abuse (VSA) poses major health risks, especially for young people and those living in precarious socio-economic conditions. Such substances can in fact bring about psychoactive effects such as euphoria, and even lead to sudden death from cardiac arrhythmias, respiratory depression, myocardial infarction, laryngospasm, encephalopathy, and rhabdomyolysis. The present case report is centered around a 23-year-old man who died in prison due to inhalation of a cooker gas mixture (n-butane, propane, and isobutane) inside a plastic bag. External examination and autopsy showed non-specific signs of asphyxia associated with edema and brain swelling. Histological signs of early myocardial damage and hypoxic-ischemic injury (HII) were highlighted in the brain and cerebellum, as well as activated macrophages and anthracotic-like material in the lungs. Toxicological investigations revealed the presence of propane, isobutane and n-butane in liquids and biological samples. Besides the cardiotoxic effect, there was an asphyctic component due to the plastic bag that may have facilitated death. The assessment of cerebral HII and cardiopulmonary damage in acute cases is very important to prove death by butane inhalation. In the forensic field, it may be useful to shed more light on intoxications, deaths, and butane encephalopathies, as the latter can be mistaken for a hypoxic-ischemic encephalopathy.

Blood-brain barrier permeability for the first 24 hours in hypoxic-ischemic brain injury following cardiac arrest.

BACKGROUND: This study aimed to explore the changes in blood-brain barrier (BBB) permeability and intracranial pressure (ICP) for the first 24 h after the return of spontaneous circulation (ROSC) and their association with injury severity of cardiac arrest. METHODS: This prospective study analysed the BBB permeability assessed using the albumin quotient (Qa) and ICP every 2 h for the first 24 h after ROSC. The injury severity of cardiac arrest was assessed using Pittsburgh Cardiac Arrest Category (PCAC) scores. The primary outcome was the time course of changes in the BBB permeability and ICP for the first 24 h after ROSC and their association with injury severity (PCAC scores of 1-4). RESULTS: Qa and ICP were measured 274 and 197 times, respectively, in 32 enrolled patients. Overall, the BBB permeability increased progressively over time after ROSC, and then it increased significantly at 18 h after ROSC compared with the baseline. In contrast, the ICP revealed non-significant changes for the first 24 h after ROSC. The Qa in the PCAC 2 group was < 0.01, indicating normal or mild BBB disruption at all time points, whereas the PCAC 3 and 4 groups showed a significant increase in BBB permeability at 14 and 22 h, and 12 and 14 h after ROSC, respectively. CONCLUSION: BBB permeability increased progressively over time for the first 24 h after ROSC despite post-resuscitation care, whereas ICP did not change over time. BBB permeability has an individual pattern when stratified by injury severity.

Acute Kidney Injury in Neonatal Hypoxic-Ischemic Encephalopathy Patients Treated with Therapeutic Hypothermia: Incidence and Risk Factors.

Studies in infants with hypoxic-ischemic encephalopathy (HIE) due to perinatal asphyxia have generally focused on neurological outcomes. Although acute kidney injury (AKI) rate decreased in advent of therapeutic hypothermia (TH), it is still a common and important entity. In this retrospective study, we aimed to investigate the risk factors for AKI in HIE patients treated with hypothermia. Infants treated with TH due to HIE were reviewed retrospectively and infants who developed AKI and not were compared. Ninety-six patients were enrolled in the study. AKI developed in 27 (28%) patients and 4 (14.8%) of them were stage III AKI. In the AKI group, gestational age of the patients was significantly higher (p = 0.035), the 1st minute Apgar score was significantly lower (p = 0.042), and convulsions (p = 0.002), amplitude-integrated electroencephalography disorders (p = 0.025), sepsis (p = 0.017), need for inotropic therapy (p = 0.001), need of invasive mechanical ventilation (p = 0.03), and systolic dysfunction in echocardiography (p = 0.022) were significantly higher. In logistic regression tests, Apgar score at the 1st minute was found to be independent risk factor for developing AKI. AKI has the potential to worsen the neurological damage and correlates with morbidities of perinatal asphyxia. It is important to determine the incidence and risk factors for developing AKI in this delicate group of patients to prevent further renal damage.

A phase I trial of caffeine to evaluate safety in infants with hypoxic-ischemic encephalopathy.

OBJECTIVE: Caffeine provides neuroprotection following hypoxic-ischemic injury in animals. We characterized the safety of escalating doses of caffeine in infants with hypoxic-ischemic encephalopathy (HIE) receiving therapeutic hypothermia. STUDY DESIGN: Phase I trial of infants undergoing therapeutic hypothermia for HIE receiving IV caffeine 20 mg/kg followed by up to two daily doses of 5 mg/kg (n = 9) or 10 mg/kg (n = 8). Safety was evaluated based on adverse events and frequency of pre-specified outcomes compared to data from the Whole-Body Hypothermia for HIE trial (Shankaran, 2005). RESULTS: Twelve of 17 (71%) infants had ≥1 adverse event during the study period. The frequency of clinical outcomes related to HIE were not statistically different from outcomes in infants receiving hypothermia in the Whole-Body Hypothermia for HIE trial. CONCLUSION: Caffeine administration was well tolerated. A larger study is required to determine the optimal dose and evaluate drug safety and efficacy. CLINICAL TRIAL: ClinicalTrials.gov Identifier: NCT03913221.

A comparative proteomic analysis for non-invasive early prediction of hypoxic-ischemic injury in asphyxiated neonates.

AIM: Hypoxic Ischemic Encephalopathy (HIE) is one of the principal causes of neonatal mortality and long-term morbidity worldwide. The neonatal signs of mild cerebral injury are subtle, making an early precise diagnosis difficult. Delayed detection, poor prognosis, and lack of specific biomarkers for the disease are increasing mortality rates. In this study, we intended to identify specific biomarkers using comparative proteomic analysis to predict the severity of perinatal asphyxia so that its outcome can also be prevented. EXPERIMENTAL DESIGN: A case-control study was conducted on 38 neonates, and urine samples were collected within 24 and 72 h of life. A tandem mass spectrometry-based quantitative proteomics approach, followed by validation via sandwich ELISA, was performed. RESULTS: The LC-MS/MS-based proteomics analysis resulted in the identification of 1201 proteins in urine, with 229, 244, and 426 being differentially expressed in HIE-1, HIE-2, and HIE-3, respectively. Axon guidance, Diseases of programmed cell death, and Detoxification of reactive oxygen species pathways were significantly enriched in mild HIE versus severe HIE. Among the differentially expressed proteins in various stages of HIE, we chose to validate four proteins - APP, AGT, FABP1, and FN1 - via sandwich ELISA. Individual and cumulative ROC curves were plotted. AGT and FABP1 together showed high sensitivity, specificity, and accuracy as potential biomarkers for early diagnosis of HIE. CONCLUSION: Establishing putative urinary biomarkers will facilitate clinicians to more accurately screen neonates for brain injury and monitor the disease progression. Prompt treatment of neonates may reduce mortality and neurodevelopmental impairment.

Safety and efficacy of therapeutic hypothermia in neonates with mild hypoxic-ischemic encephalopathy.

BACKGROUND: Though there has been an increase in the number of neonates with hypoxic-ischemic encephalopathy (HIE) treated by therapeutic hypothermia (TH) in recent years, the effect of therapeutic hypothermia on mild HIE neonates is still uncertain. OBJECTIVES: This study aims to explore the safety and efficacy of therapeutic hypothermia in neonates with mild HIE. METHODS: Retrospectively collected between January 2010 to December 2022 at Children's Hospital of Fudan University, neonates with mild HIE were divided into TH and non-TH groups. Clinical data of the mild HIE neonates and their mothers' general information during pregnancy were collected. SPSS 23.0 was used to compare the general condition, the incidence of adverse events, and efficacy in the two groups. RESULTS: A total of 71 neonates with mild HIE were included, including 31 in the TH group and 40 in the non-TH group. Compared with the non-TH group, the TH group had significantly lower 5-minute Apgar scores [6 (5-7) points vs. 7 (5-8) points, p = 0.033 ], but a higher rate of tracheal intubation at birth (68%, 21/31 vs. 40%, 16/40, p = 0.02), a higher rate of chest compressions > 30 s (39%, 12/31 vs. 15%, 6/40, p = 0.023), the later initiation enteral feeding [4 (3-4) days vs. 1 (1-2) days, p < 0.001], a higher usage rate of analgesic and sedative drugs (45%, 14/31 vs. 18%, 7/40, p = 0.011) and the longer hospital stay [12.5 (11-14) days vs. 9 (7-13.9) days, p = 0.003]. There was no death in 71 mild HIE neonates. TH group had lower incidence of brain injury (16%, 5/31 vs. 43%, 17/40, p = 0.017) and encephalopathy progression (10%, 3/31 vs. 45%, 18/40, p = 0.001) than the non-TH group. There was no statistical significance in the incidence of adverse events between the two groups. CONCLUSION: Therapeutic hypothermia can reduce the incidence of brain injury in neonates with mild HIE.

[Neonatal hypoxic ischemic encephalopathy. Progress and new treatments according to the pathophysiological basis of the injury]. / Encefalopatía hipóxica isquémica neonatal. Avances y nuevos tratamientos basados en las bases patofisiológicas de la injuria.

Neonatal hypoxic ischemic encephalopathy (HIE) is a type of injury caused by lack of oxygen in the brain during the neonatal period. It is a clinical syndrome clearly recognizable in term and premature newborns secondary to asphyxia at the time of delivery. HIE is estimated to occur at a frequency of 1-3 for each 1000 alive newborns per year in developed countries. In countries of low or medium income, the incidence is up to 10-20 times higher, equivalent to 1-8 alive newborns per each 1000. The social and economic impact has been estimated near US$ 50.2 million per year of life adjusted to disability. At the same time, it is estimated in 7, the number of patients needed to treat with corporal cooling therapy (CCT)to prevent one case of death or severe disability. The etiology is multifactorial and includes prenatal, perinatal and postnatal factors. The diagnosis is based in the inability to support spontaneous breath at the time of delivery requiring assisted ventilation, Apgar less than 5 at 5 and 10 minutes, altered level of consciousness, neonatal reflexes and muscle tone. This article is a review of the stablished and emergent therapeutic strategies based on the pathophysiological disease process.

La encefalopatía hipóxica isquémica del neonato (EIH) es un tipo de injuria causada por la falta de oxígeno en el cerebro durante el periodo neonatal. Es un síndrome clínico claramente reconocible en recién nacidos a término y prematuros debido a asfixia fetal en el momento del nacimiento. Se estima que EHI ocurre a una frecuencia de1 a 3 por cada 1000 nacimientos vivos al año en países desarrollados. En países de bajo o mediano ingreso, la incidencia es hasta 10-20 veces más alta, equivalente a 1-8 nacidos vivos por cada 1000. El impacto social y económico ha sido estimado en cerca de 50.2 millones de dólares por año de vida ajustados a discapacidad. Así mismo, se estima que 7 es el número necesario de pacientes a tratar con hipotermia corporal terapéutica (HCT) para evitar un caso de muerte o minusvalía severa. La etiología es multifactorial e incluye factores prenatales, perinatales o post natales. El diagnóstico se basa en la incapacidad para respirar en el momento del nacimiento requiriendo ventilación asistida, Apgar menos de 5 a los 5 y 10 minutos, alteración del estado normal de conciencia, reflejos neonatales y de tono muscular. Este artículo revisa los avances y estrategias terapéuticas establecidas y emergentes basadas en las fases pato-fisiológicas de este proceso.

Association of cerebral metabolic rate following therapeutic hypothermia with 18-month neurodevelopmental outcomes after neonatal hypoxic ischemic encephalopathy.

BACKGROUND: Therapeutic hypothermia (TH) is standard of care for moderate to severe neonatal hypoxic ischemic encephalopathy (HIE) but many survivors still suffer lifelong disabilities and benefits of TH for mild HIE are under active debate. Development of objective diagnostics, with sensitivity to mild HIE, are needed to select, guide, and assess response to treatment. The objective of this study was to determine if cerebral oxygen metabolism (CMRO2) in the days after TH is associated with 18-month neurodevelopmental outcomes as the first step in evaluating CMRO2's potential as a diagnostic for HIE. Secondary objectives were to compare associations with clinical exams and characterise the relationship between CMRO2 and temperature during TH. METHODS: This was a prospective, multicentre, observational, cohort study of neonates clinically diagnosed with HIE and treated with TH recruited from the tertiary neonatal intensive care units (NICUs) of Boston Children's Hospital, Brigham and Women's Hospital, and Beth Israel Deaconess Medical Center between December 2015 and October 2019 with follow-up to 18 months. In total, 329 neonates ≥34 weeks gestational age admitted with perinatal asphyxia and suspected HIE were identified. 179 were approached, 103 enrolled, 73 received TH, and 64 were included. CMRO2 was measured at the NICU bedside by frequency-domain near-infrared and diffuse correlation spectroscopies (FDNIRS-DCS) during the late phases of hypothermia (C), rewarming (RW) and after return to normothermia (NT). Additional variables were body temperature and clinical neonatal encephalopathy (NE) scores, as well as findings from magnetic resonance imaging (MRI) and spectroscopy (MRS). Primary outcome was the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) at 18 months, normed (SD) to 100 (15). FINDINGS: Data quality for 58 neonates was sufficient for analysis. CMRO2 changed by 14.4% per °C (95% CI, 14.2-14.6) relative to its baseline at NT while cerebral tissue oxygen extraction fraction (cFTOE) changed by only 2.2% per °C (95% CI, 2.1-2.4) for net changes from C to NT of 91% and 8%, respectively. Follow-up data for 2 were incomplete, 33 declined and 1 died, leaving 22 participants (mean [SD] postnatal age, 19.1 [1.2] month; 11 female) with mild to moderate HIE (median [IQR] NE score, 4 [3-6]) and 21 (95%) with BSID-III scores >85 at 18 months. CMRO2 at NT was positively associated with cognitive and motor composite scores (ß (SE) = 4.49 (1.55) and 2.77 (1.00) BSID-III points per 10-10 moL/dl × mm2/s, P = 0.009 and P = 0.01 respectively; linear regression); none of the other measures were associated with the neurodevelopmental outcomes. INTERPRETATION: Point of care measures of CMRO2 in the NICU during C and RW showed dramatic changes and potential to assess individual response to TH. CMRO2 following TH outperformed conventional clinical evaluations (NE score, cFTOE, and MRI/MRS) at predicting cognitive and motor outcomes at 18 months for mild to moderate HIE, providing a promising objective, physiologically-based diagnostic for HIE. FUNDING: This clinical study was funded by an NIH grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States (R01HD076258).

Value of EEG in outcome prediction of hypoxic-ischemic brain injury in the ICU: A narrative review.

Prognostication of comatose patients after cardiac arrest aims to identify patients with a large probability of favourable or unfavouble outcome, usually within the first week after the event. Electroencephalography (EEG) is a technique that is increasingly used for this purpose and has many advantages, such as its non-invasive nature and the possibility to monitor the evolution of brain function over time. At the same time, use of EEG in a critical care environment faces a number of challenges. This narrative review describes the current role and future applications of EEG for outcome prediction of comatose patients with postanoxic encephalopathy.

Associations between clinical characteristics of cardiac arrest and early CT head findings of hypoxic ischaemic brain injury following out-of-hospital cardiac arrest.

BACKGROUND/OBJECTIVE: Post-cardiac arrest patients are vulnerable to hypoxic-ischaemic brain injury (HIBI), but HIBI may not be identified until computed tomography (CT) scan of the brain is obtained post-resuscitation and stabilization. We aimed to evaluate the association of clinical arrest characteristics with early CT findings of HIBI to identify those at the highest risk for HIBI. METHODS: This is a retrospective analysis of out-of-hospital cardiac arrest (OHCA) patients who underwent whole-body imaging. Head CT reports were analyzed with an emphasis on findings suggestive of HIBI; HIBI was present if any of the following were noted on the neuroradiologist read: global cerebral oedema, sulcal effacement, blurred grey-white junction, and ventricular compression. The primary exposure was duration of cardiac arrest. Secondary exposures included age, cardiac vs noncardiac etiology, and witnessed vs unwitnessed arrest. The primary outcome was CT findings of HIBI. RESULTS: A total of 180 patients (average age 54 years, 32% female, 71% White, 53% witnessed arrest, 32% cardiac etiology of arrest, mean CPR duration of 15 ± 10 minutes) were included in this analysis. CT findings of HIBI were seen in 47 (48.3%) patients. Multivariate logistic regression demonstrated a significant association between CPR duration and HIBI (adjusted OR = 1.1, 95% CI 1.01-1.11, p < 0.01). CONCLUSION: Signs of HIBI are commonly seen on CT head within 6 hours of OHCA, occurring in approximately half of patients, and are associated with CPR duration. Determining risk factors for abnormal CT findings can help clinically identify patients at higher risk for HIBI and target interventions appropriately.

Predictive performance of multiple organ dysfunction in asphyxiated newborns treated with therapeutic hypothermia on 24-month outcome: a cohort study.

BACKGROUND: Perinatal asphyxia may be followed by multiple organ dysfunction (MOD) and is often included in prognostication of the individual patient, but evidence of discriminating accuracy is lacking. The aim of this study was to assess whether MOD in asphyxiated neonates during therapeutic hypothermia (TH) predicts mortality or neurodevelopmental impairment (NDI) at 24 months of age and which peripartum variables are associated with the onset of MOD. METHODS: A retrospective analysis of a prospective cohort study of asphyxiated newborns undergoing TH was performed. MOD was defined as dysfunction of the brain (encephalopathy) combined with two or more organ systems. Outcome was routinely assessed by standardised developmental testing at the age of 24 months. The predictive accuracy of MOD on the combined outcome and its components (death and NDI) was expressed as areas under the receiver operating characteristic curves (AUROCs). The associations of peripartum variables and development of MOD were expressed as ORs and their CIs. RESULTS: 189 infants (median gestation 40 (range 36-42 weeks) with moderate to severe hypoxic ischaemic encephalopathy were included. 47% developed MOD. The prediction of the combined 24-month outcome or its components showed AUROCs <0.70. Associated with MOD were pH at birth (OR 0.97, CI 0.95 to 0.99), lactate at birth (OR 1.09, CI 1.04 to 1.15), Base Excess (BE) at birth (OR 0.94, CI 0.90 to 0.99) and epinephrine administration during resuscitation (OR 2.09, CI 1.02 to 4.40). CONCLUSION: MOD has a low discriminating accuracy in predicting mortality or NDI at 24 months age and might not be useful for prognostication. Signs of acid-base disturbance and adrenalin use at birth are associated with the development of MOD.

Duration of cardiopulmonary resuscitation and phenotype of post-cardiac arrest brain injury.

BACKGROUND: Patients resuscitated from cardiac arrest have variable severity of primary hypoxic ischemic brain injury (HIBI). Signatures of primary HIBI on brain imaging and electroencephalography (EEG) include diffuse cerebral edema and burst suppression with identical bursts (BSIB). We hypothesize distinct phenotypes of primary HIBI are associated with increasing cardiopulmonary resuscitation (CPR) duration. METHODS: We identified from our prospective registry of both in-and out-of-hospital CA patients treated between January 2010 to January 2020 for this cohort study. We abstracted CPR duration, neurological examination, initial brain computed tomography gray to white ratio (GWR), and initial EEG pattern. We considered four phenotypes on presentation: awake; comatose with neither BSIB nor cerebral edema (non-malignant coma); BSIB; and cerebral edema (GWR ≤ 1.20). BSIB and cerebral edema were considered as non-mutually exclusive outcomes. We generated predicted probabilities of brain injury phenotype using localized regression. RESULTS: We included 2,440 patients, of whom 545 (23%) were awake, 1,065 (44%) had non-malignant coma, 548 (23%) had BSIB and 438 (18%) had cerebral edema. Only 92 (4%) had both BSIB and edema. Median CPR duration was 16 [IQR 8-28] minutes. Median CPR duration increased in a stepwise manner across groups: awake 6 [3-13] minutes; non-malignant coma 15 [8-25] minutes; BSIB 21 [13-31] minutes; cerebral edema 32 [22-46] minutes. Predicted probability of phenotype changes over time. CONCLUSIONS: Brain injury phenotype is related to CPR duration, which is a surrogate for severity of HIBI. The sequence of most likely primary HIBI phenotype with progressively longer CPR duration is awake, coma without BSIB or edema, BSIB, and finally cerebral edema.

Comparing Three Methods of Therapeutic Hypothermia Among Transported Neonates with Hypoxic-Ischemic Encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) and associated multiorgan injury are significant causes of morbidity and mortality in term and near-term neonates. Therapeutic hypothermia (TH) is the current standard of care for neuroprotection in neonates with HIE. In our experience, the majority of babies born with HIE were found in nontertiary care facilities in our region, where effective methods of cooling during transport to tertiary care centers are desirable. Most centers initiate passive TH at referral hospitals, while active cooling is typically initiated during transport. The objective of this study was to evaluate the effectiveness of three methods of cooling during transport of neonates with HIE in southern Alberta. In this prospective cohort study, 186 neonates with HIE were transported between January 2013 and December 2021. Among the 186 neonates, 47 were passively cooled, 36 actively cooled with gel packs, and 103 cooled with a servo-controlled cooling device. The clinical characteristics were comparable for the three groups, with no difference in adverse events. Fifteen neonates (8%) died and 54 neonates (29%) suffered radiologically determined brain injury. Servo-controlled cooling was found to be superior to other methods in maintaining a target temperature without significant fluctuation during transport and with temperature in the target range on arrival at tertiary care facilities. The rate of overcooling was also lower in the servo-controlled group compared with other groups. There were no statistically significant differences between the groups in relation to mortality and brain MRI changes associated with HIE. Adjusting for GA, 10-minute Apgar score, base excess, HIE stage, and need for intubation during transport, passive cooling increased the odds of temperature fluctuation outside the range by 12-fold and gel pack cooling by 13-fold compared with servo-controlled cooling. The use of servo-controlled TH devices should be the preferred practice wherever feasible. (REB17-1334_REN3).

Perinatal brain damage - what the obstetrician needs to know.

Perinatal brain damage is still one of the leading contributors to perinatal death and postnatal disability worldwide. However, the term perinatal brain damage encompasses very different aetiological entities that result in an insult to the developing brain and does not differentiate between the onset, cause and severity of this insult. Hypoxic-ischemic encephalopathy (HIE), intraventricular haemorrhage, periventricular leukomalacia and perinatal stroke are often listed as the major aetiologies of perinatal brain damage. They differ by type and timing of injury, neuropathological and imaging findings and their clinical picture. Along the timeline of neurodevelopment in utero, there appears to be a specific "window of vulnerability" for each type of injury, but clinical overlap does exist. In the past, peripartum acute hypoxia was believed to be the major, if not the only, cause of perinatal brain damage, but intrauterine inflammation, prematurity, chronic hypoxia/growth retardation and genetic abnormalities appear to be at least equally important contributors.

Is Selective Head Cooling Combined with Whole-Body Cooling the Most Effective Hypothermia Method for Neonatal Hypoxic-Ischemic Encephalopathy?

This study aimed to compare combined hypothermia (CH) to the 2 classical therapeutic hypothermia (TH) methods selective head cooling (SHC) and whole-body cooling (WBC). This retrospective cohort study included neonates who underwent CH, SHC, and WBC between 2012 and 2020. Mean rectal temperature was maintained at 33.5 ± 0.5°C by cooling the head and the body in the CH group, at 34.5 ± 0.5°C by cooling the head in the SHC group, and at 33.5 ± 0.5°C by cooling the body in the WBC group. The groups were compared in terms of side effects, magnetic resonance imaging (MRI) scores, and status at discharge. The study included 60 neonates in the CH group, 112 in the WBC group, and 27 in the SHC group. There was no significant difference in side effects between the groups (p > 0.05). There was no significant difference in brain MRI scores between the groups (p > 0.05); however, gray matter, white matter, and total MRI scores in the CH group were lower than in the WBC group. Duration of hospitalization was shorter in the CH group than in the other two groups (p = 0.022). CH was not associated with more side effects than the two classical TH methods. In addition, some of these findings suggest that CH might result in better clinical outcome than the two classical TH methods.

Glucose-to-lactate ratio and neurodevelopment in infants with hypoxic-ischemic encephalopathy: an observational study.

We aimed to assess the glucose and lactate kinetics during therapeutic hypothermia (TH) in infants with hypoxic-ischemic encephalopathy and its relationship with longitudinal neurodevelopment. We measured glucose and lactate concentrations before TH and on days 2 and 3 in infants with mild, moderate, and severe hypoxic-ischemic encephalopathy (HIE). Neurodevelopment was assessed at 2 years. Participants were grouped according to the neurodevelopmental outcome into favorable (FO) or unfavorable (UFO). Eighty-eight infants were evaluated at follow-up, 34 for the FO and 54 for the UFO group. Severe hypo- (< 2.6 mmol/L) and hyperglycemia (> 10 mmol/L) occurred in 18% and 36% from the FO and UFO groups, respectively. Glucose-to-lactate ratio on day 1 was the strongest predictor of unfavorable metabolic outcome (OR 3.27 [Formula: see text] 1.81, p = 0.032) when adjusted for other clinical and metabolic variables, including Sarnat score. CONCLUSION: Glucose-to-lactate ratio on day 1 may represent a new risk marker for infants with HIE undergoing TH. WHAT IS KNOWN: • Glucose and lactate are key metabolic fuels during neonatal hypoglycemia. This suggests that their concentrations may influence the neurodevelopmental outcome of neonates experiencing hypoxic-hischemic encephalopathy (HIE). WHAT IS NEW: • We describe the relative availbility of glucose and lactate before and during theraputic hypothermia in neonates with HIE.

Risk factors for hypoxic-ischemic encephalopathy or neonatal death in placental abruption.

OBJECTIVE: To identify risk factors for moderate or severe hypoxic-ischemic encephalopathy (HIE), or neonatal death in clinical placental abruption. MATERIAL AND METHODS: A nested case-control study within a cohort of singleton pregnancies complicated by placental abruption with a live born infant at two academic reference centers in France, from 2006 to 2019. Cases were patients who gave birth to an infant with moderate or severe HIE or death within 28 days (HIE/death group), and controls were patients whose infant did not have any of these outcomes (no-HIE group). Independent risk factors were identified by logistic regression. Binary decision tree discriminant (CART) analysis was performed to define high-risk subgroups of HIE or death. RESULTS: Among 152 patients, the infants of 44 (29%) had HIE or death. Out-of-hospital placental abruption and fetal bradycardia at admission were more frequent in cases than in controls: 39 (89%) vs 61 (56%), p < .01 and 24 (59%) vs 19 (18%), p < .01, respectively. In multivariate analysis, out-of-hospital placental abruption (aOR, 7.05; 95% CI, 1.94-25.66) and bradycardia at admission (aOR, 8.60; 95% CI, 2.51-29.42) were independently associated with an increased risk of HIE or death. The combination of out-of-hospital placental abruption and bradycardia was the highest risk situation associated with HIE or death (67%). The decision-to-delivery interval was 15 [12-20] minutes among cases. CONCLUSION: Out-of-hospital placental abruption combined with bradycardia at admission was associated with a major risk of moderate or severe HIE or death. An optimal decision-to-delivery interval does not guarantee the absence of an adverse neonatal outcome.