Degree Of Hypoxic-ischemic Encephalopathy Research Articles

Adherence to hypothermia guidelines in newborns with hypoxic-ischemic encephalopathy

IntroductionWe do not have population data in Spain on the application of therapeutic hypothermia (TH). The objective was to examine adherence to management standards during TH of infants with hypoxic-ischemic encephalopathy (HIE). MethodMulticenter observational cohort study from the beginning of TH (year 2010) in 5 hospitals in a Spanish region, until year 2019. Results133 patients were recruited, 72% diagnosed with moderate HIE and the rest of them with severe HIE. In 84% of infants, passive hypothermia was started at birth. Active TH was started at a median age of 5 h of life (IQR 3.3; 6.3), although the central targeted temperature (33−34 °C) was reached at a median age of 3.5 h (IQR 1; 6). Those born extramural, initiated active TH 3.3 h on average later than those born intramural, but without differences in the age at which the targeted temperature was reached.Sedoanalgesia was used in 97%. 100% were monitored with amplitude-integrated EEG and 59% with cerebral oxymetry. MRI was performed in 94% with moderate HIE vs. 65% with severe; P < .001. Neuron-specific enolase in cerebrospinal fluid was determined in 42%. The average duration of rewarming was median 10 h (IQR 8; 12), with no differences depending on the degree of HIE (P = .57). ConclusionsThe implementation of TH successfully met the standards. However, aspects of care that could be improved were detected. Auditing newborn care with HIE is crucial to achieving programs with a high quality of care in each region

Proteomic profiles in cerebrospinal fluid predicted death and disability in term infants with perinatal asphyxia: A pilot study.

AimPerinatal asphyxia, resulting in hypoxic‐ischaemic encephalopathy (HIE), has been associated with high mortality rates and severe lifelong neurodevelopmental disabilities. Our aim was to study the association between the proteomic profile in cerebrospinal fluid (CSF) and the degree of HIE and long‐term outcomes.MethodsWe prospectively enrolled 18‐term born infants with HIE and 10‐term born controls between 2000 and 2004 from the Karolinska University Hospital. An antibody suspension bead array and FlexMap3D analysis was used to characterise 178 unique brain‐derived and inflammation associated proteins in their CSF.ResultsIncreased CSF concentrations of several brain‐specific proteins were observed in the proteome of HIE patients compared with the controls. An upregulation of neuroinflammatory pathways was also noted and this was confirmed by pathway analysis. Principal component analysis revealed a gradient from favourable to unfavourable HIE grades and outcomes. The proteins that provided strong predictors were structural proteins, including myelin basic protein and alpha‐II spectrin. The functional proteins included energy‐related proteins like neuron‐specific enolase and synaptic regulatory proteins. Increased CSF levels of 51 proteins correlated with adverse outcomes in infants with HIE.ConclusionBrain‐specific proteins and neuroinflammatory mediators in CSF may predict HIE degrees and outcomes after perinatal asphyxia.

Adherencia a los estándares en el tratamiento con hipotermia del recién nacido con encefalopatía hipóxico-isquémica

IntroductionWe do not have population data in Spain on the application of therapeutic hypothermia (TH). The objective was to examine adherence to management standards during TH of infants with hypoxic-ischemic encephalopathy (HIE). MethodMulticenter observational cohort study from the beginning of TH (year 2010) in 5 hospitals in a Spanish region, until year 2019. Results133 patients were recruited, 72% diagnosed with moderate HIE and the rest of them with severe HIE. In 84% of infants, passive hypothermia was started at birth. Active TH was started at a median age of 5hours of life (IQR: 3.3-6.3), although the central targeted temperature (33-34°C) was reached at a median age of 3.5hours (IQR: 1-6). Those born extramural, initiated active TH 3.3hours on average later than those born intramural, but without differences in the age at which the targeted temperature was reached.Sedoanalgesia was used in 97%. The 100% were monitored with amplitude-integrated EEG and 59% with cerebral oxymetry. MRI was performed in 94% with moderate HIE vs. 65% with severe; P<.001. Neuron-specific enolase in cerebrospinal fluid was determined in 42%. The average duration of rewarming was median 10hours (IQR: 8-12), with no differences depending on the degree of HIE (P=.57). ConclusionsThe implementation of TH successfully met the standards. However, aspects of care that could be improved were detected. Auditing newborn care with HIE is crucial to achieving programs with a high quality of care in each region.

Clinico-Biochemical Correlation in Birth Asphyxia and Its Effects on Outcome.

BackgroundBirth asphyxia is a major cause of early neonatal death and leads to severe consequences such as epilepsy, cerebral palsy, and developmental delay. This study aims to determine the correlation between dyselectrolytemia and the degree of hypoxic-ischemic encephalopathy (HIE) and to find out major risk factors contributing to the severity of HIE and neonatal death.MethodsIn this prospective cohort study (n=150), term babies weighing ≥ 2.5 kg at birth, with the diagnosis of birth asphyxia, admitted in a medical college in Odisha state from September 2014 to August 2016 were included. Clinical findings, biochemical parameters, treatment, and outcome of HIE babies were recorded.ResultThe majority of the asphyxiated babies were having moderate HIE (HIE II) (57.33%), whereas mild and severe stages were seen in 15.33%, and 27.34% of babies, respectively. Factors like prolonged labor (87.8%) and meconium-stained liquor (63.4%) were mostly attributed to the severe degree of birth asphyxia (p < 0.001). Apnea, lethargy, and hypothermia were the most remarkable feature of HIE III. The degree of hyponatremia, hypocalcemia, and hyperkalemia (124.4±4.4 mmol/l, 0.83±0.08 mmol/l, and 6.17± 0.89 mmol/l, respectively) were more severely affected in HIE III as compared to HIE l (137.5±3.8 mmol/l, 1.06±0.17 mmol/l, and 5.0±0.79 mmol/l, respectively). Serum urea and creatinine increased proportionately with an increase in the severity of HIE grade. The mildly asphyxiated neonates recovered completely, whereas all the cases who died (n=29,19.3%) belonged to the moderate or severe degree of birth asphyxia.ConclusionThe asphyxiated neonates had hyponatremia, hypocalcemia, hyperkalemia, raised serum urea, and creatinine and correlated with the severity of birth asphyxia. Prolonged labor and meconium-stained liquor were the most attributable factor for the severe degree of birth asphyxia. Effective neonatal resuscitation and quick correction of electrolyte imbalances will help in the reduction of neonatal mortality and long-term neurological sequelae.

Prevalence of Acute Kidney Injury in Patients with Perinatal Asphyxia in Tertiary Hospital

Introduction: Perinatal asphyxia has multisystem involvement, kidneys are most frequently affected. This study was conducted to determine the relation between severity of Hypoxic Ischaemic Encephalopathy (HIE) with acute kidney injury in term neonates.&#x0D; Methods: Retrospective study was done over a period of six months (Sept 2016 to Feb 2017) at Department of Neonatology of a tertiary level maternity hospital. Total 98 cases of Perinatal asphyxia cases which were diagnosed with certain degree of HIE were evaluated for its relation with renal involvement in different stage of HIE.&#x0D; Results: Out of 98 cases of perinatal asphyxia, HIE I was 21%, HIE II was 69% and HIE III was 10%, among which 72% cases had some degree of renal problem. seventy two cases had renal problem, oliguric cases were 41 (57%) among which 33% case had persistent symptoms and associated renal function deterioration. Among 42 cases of deranged RFTs, 40% of cases has persistently deranged RFTs. In comparison to HIE II in HIE III, 22% of cases had one time derangement of RFTs and 33% cases had at least one observation of oliguria, while remaining 45% cases had persistent deterioration of RFTs and urine output, suggesting that progression in HIE stage has significant association with renal dysfunction (p &lt; 0.05). More than half of the cases of HIE III had mortality while 20.3% of HIE II cases had mortality, indicating that the mortality is highly significant with higher HIE grade (p &lt; 0.05).&#x0D; Conclusions: Renal involvement is very common in cases of perinatal asphyxia, and severity of renal involvement increases as the HIE grading increases.

Diffusion-weighted MRI and urinary Activin-A are potential predictors of severity in neonates with hypoxic ischemic encephalopathy

BackgroundEarly diagnosis and treatment are important to reduce neonatal morbidity and mortality occurring from hypoxic ischemic encephalopathy (HIE). ObjectiveWe aimed to correlate between urinary Activin-A and MRI (conventional and diffusion-weighted) and the degree of HIE according to Sarnat and Sarnat staging. MethodsSixty full term neonates (37–42 weeks) selected from Minia University hospital for children from May 2014 to July 2016 were enrolled into the study. We measured urinary Activin-A using enzyme immunoassay and MRI using MRI scanner (Philips Achieva) and correlations between urinary Activin-A and MRI with the degree of HIE were done. ResultsNeonates with HIE had higher levels of urinary Activin-A than controls (P < .001) and it was positively correlated with the clinical grading of HIE at cutoff value of 0.08 µg/l on day-1 after birth with a sensitivity 98.2% and specificity 97.1% for prediction of HIE. DW-MRI detected HIE with a high sensitivity (85%) compared to the low sensitivity of conventional MRI (35%). Apparent diffusion coefficient (ADC) value of ≤0.8 was the best sensitivity-specificity cutoff point for detecting severe ischemic injury. DW-MRI imaging was positively correlated with the urinary Activin-A and both of them were positively correlated with the degree of HIE (P < .001). ConclusionsDW-MRI imaging is correlated well with urinary Activin-A in full-term neonates with HIE and both of them are correlated with the degree of HIE. Early determination of urinary Activin-A combined with DW-MRI imaging can early detect HIE and its degree of severity in full-term neonates with HIE.

Corrected QT interval during therapeutic hypothermia in hypoxic ischaemic encephalopathy

Abstract Introduction Therapeutic hypothermia is the standard treatment for hypoxic ischaemic encephalopathy (HIE), despite not knowing all its effects and complications. Sinus bradycardia is one of the consequences of cooling that has been previously documented in the literature, but little is known about the cardiac electrical activity in these patients. Objective To determine the corrected QT (QTc) interval in newborns treated with therapeutic hypothermia for HIE. Materials and methods A prospective observational study was conducted in all patients treated with hypothermia for HIE that were admitted to our Unit between November 2012 and October 2013. ECGs were performed during hypothermia (every 24 h), during the re-warming period (at 34.5 °C, 35.5 °C, 36.5 °C), and on the 7th day of life. Results A total of 19 patients were included. A prolonged QTc was observed in all patients during hypothermia, and 84% (n = 16) had prolonged QTc in all the ECGs during treatment. In 3 patients, one of the ECGs did not have a prolonged QTc. After re-warming, the QTc interval returned to normal in all patients. No statistically significant differences were seen when the degree of HIE (P = .192) or the use of inotropic support (P = .669) were considered. Conclusions Therapeutic hypothermia applied to asphyxiated newborns with HIE seems to induce a QTc prolongation that resolves when the patient regains physiological temperature.

Serum and Urinary Malondialdehyde (MDA), Uric acid, and Protein as markers of perinatal asphyxia.

IntroductionPerinatal asphyxia (PA) is among the leading causes of neonatal morbidity and death in neonatal intensive care units (NICUs). The aims of this research were to determine the concentrations of malondialdehyde (MDA), urine MDA, uric acid, and protein in the cord blood of neonates with perinatal asphyxia and to determine their relationship with the severity of perinatal asphyxia.MethodsThis matched case-control study was conducted from October 2012 to March 2013. All of the cases and controls were selected from the Gynecology & Obstetrics Department and the NICUs, at Qous Central Hospital in Qena, Egypt. We allocated 20 full-term neonates who had perinatal asphyxia to the case group. Also, we selected 20 healthy neonates for the control group. The subjects were matched with respect to age and gender. At birth and 48 hours later, measurements were made of MDA in cord blood and urine, and uric acid, protein, and creatinine also were measured in both groups. The data were analyzed by SPSS, version 17, using the independent-samples t-test, ANOVA, Tukey’s test, and Spearman’s correlation coefficient.ResultsAt birth and 48 hr later, the newborns’ with PA had significantly higher levels of MDA in the cord blood, mean urinary uric acid/creatinine (UUA:Cr), protein/creatinine (UP:Cr), and MDA/creatinine ratio (UMDA:Cr) than the controls; their PA levels were correlated with the degree of hypoxic-ischemic encephalopathy (HIE). The babies who died due to PA had significantly higher levels of cord blood MDA, and they also had higher UUA:Cr, UP:Cr, and UMDA:Cr ratios than the babies who survived.ConclusionThe concentration of MDA in cord blood can be used as a diagnostic marker of oxidative stress in asphyxiated neonates. The ratios of the urinary excretion rates of uric acid, protein, and MDA to creatinine increased as the severity of perinatal asphyxia and associated brain damage increased.

El intervalo QT corregido durante la hipotermia terapéutica en la encefalopatía hipóxico-isquémica

IntroductionTherapeutic hypothermia is the standard treatment for hypoxic ischaemic encephalopathy (HIE), despite not knowing all its effects and complications. Sinus bradycardia is one of the consequences of cooling that has been previously documented in the literature, but little is known about the cardiac electrical activity in these patients. ObjectiveTo determine the corrected QT (QTc) interval in newborns treated with therapeutic hypothermia for HIE. Material and methodsA prospective observational study was conducted in all patients treated with hypothermia for HIE that were admitted to our Unit between November 2012 and October 2013. ECGs were performed during hypothermia (every 24h), during the re-warming period (at 34.5°C, 35.5°C, 36.5°C), and on the 7th day of life. ResultsA total of 19 patients were included. A prolonged QTc was observed in all patients during hypothermia, and 84% (n=16) had prolonged QTc in all the ECGs during treatment. In 3 patients, one of the ECGs did not have a prolonged QTc. After re-warming, the QTc interval returned to normal in all patients. No statistically significant differences were seen when the degree of HIE (P=.192) or the use of inotropic support (P=.669) were considered. ConclusionsTherapeutic hypothermia applied to asphyxiated newborns with HIE seems to induce a QTc prolongation that resolves when the patient regains physiological temperature.

Nontraumatic Intradural and Subdural Hemorrhage and Hypoxic Ischemic Encephalopathy in Fetuses, Infants, and Children up to Three Years of Age: Analysis of Two Audits of 636 Cases from Two Referral Centers in the United Kingdom

We analyzed the presence or absence of intradural hemorrhage (IDH) and subdural hemorrhage (SDH) and the degree of hypoxic-ischemic encephalopathy (HIE) in the brain of all nonmacerated fetuses of >24 weeks, neonates, and children up to 3 years of age who died of natural causes over a defined period. We looked into the cause of death and the performance of cardiopulmonary resuscitation in our cohort. The IDH was classified as macroscopic or negative/microscopic only; the HIE was classified as absent, indeterminate, or definite. In fetuses, SDH with IDH was present in 22%; IDH alone was present in 31%, and there was no or minimal hemorrhage in 47% of cases. In infants and children SDH with IDH was present in 19%; IDH alone was present in the 32%, and there was no or minimal hemorrhage in 49% of cases. There was a statistically significant correlation between SDH and HIE, especially in infants and children (P < 0.001). When cases were grouped per age, a significant association between age and hemorrhage (P < 0.0001) was demonstrated, SDH being more common in infants ≤1 month corrected age. Intradural hemorrhage can be the source of thin-film SDH in fetuses, infants, and young children. The presence of SDH is associated with hypoxia. Intradural and subdural hemorrhages are more common in autopsies of infants under 1 month corrected age. Although more rare, they can also be found in children between 1 month and 3 years of age in the absence of trauma.

Changes and clinical significance of blood sugar and serum cortisol in neonates with hypoxic-ischemic encephalopathy

Objective To investigate the changes and clinical significance of glucose (GLU) and serum cortical (COR) in neonates with hypoxic-ischemic encephalopathy (HIE).Methods A total of 81 neonates with HIE and 30 healthy neonates were enrolled in this study for measurement of serum concentrations of GLU and COR.Results The level of serum GLU in HIE groups except slight was higher than that of control group (P ＜ 0.05); the concentration of serum COR of neonate with HIE was significantly higher than that of control group (P＜ 0.01).The more severe degree of HIE was,the higher level of GLU and COR increased; after treatment,the concentration of serum COR of 81 neonates with hyperglycemia decreased.Conclusions Clinical treatment during the process of HIE need strict observation to the COR and GLU changes,strictly control the amount of glucose infusion and speed.Use of corticosteroids strictly grasps its indication and dose,preventing adrenal cortical atrophy and high blood sugar from happening,in order to reduce sequels and HIE children mortality. Key words: Hypoxic-ischemic encephalopathy; Glucose ; Cortical; Neonate

Iron in the Brain

After completing this article, readers should be able to: 1. Describe the role of iron in proteins involved in neuronal and glial energy metabolism, myelin production, and monoamine neurotransmitter metabolism. 2. Indicate the neonates who are at risk for iron deficiency. 3. Explain how iron deficiency affects the biochemistry, structure, signaling molecules, and electrophysiology of the hippocampus. 4. Describe the primary causes of iron overload in the neonate. 5. Explain why the preterm infant is at particular risk for iron deficiency. This article is designed to acquaint readers with the role of iron in early brain development. Several important principles that govern the effects of nutrients on the immature brain are discussed, followed by an explanation of the roles of iron during development. Because the developing brain is sensitive to iron overload as well as iron deficiency, both are discussed in the context of human studies and in model systems. The first guiding principle of nutrient-brain interactions during development is the concept of timing, dose, and duration. (1) The positive or negative effects of any nutrient depend on which brain regions or processes are developing at the time that nutrient status is altered and the requirements of those regions for the nutrient during that time of development. Generally, the more rapidly an area is developing, the more vulnerable it is. Dependence on specific nutrients during phases of rapid proliferation or differentiation results in the second principle, a regionalization of brain effects during periods of nutrient deficiency. In the case of iron deficiency, certain brain areas that are dependent on iron for proper development are more vulnerable than areas that are less dependent on iron. Additionally, these same brain areas are likely to be more vulnerable at certain time points than at others. To exert a maximal effect on regional brain development, the timing of iron …

Umbilical cord interleukin‐6 levels are elevated in term neonates with perinatal asphyxia

A correlation between elevation of pro-inflammatory cytokines and white matter injury or abnormal neurologic outcome has been established in the preterm infant. In the full-term neonate, few studies exist linking elevation of cytokines with encephalopathy and poor neurodevelopmental outcome. Our aims were to investigate if serum interleukin-6 concentrations in delivering mothers and their offspring at birth are associated with perinatal asphyxia, and to examine the relation of interleukin-6 levels to the severity of hypoxic-ischemic encephalopathy and to the neurological outcome. Serum interleukin-6 levels were measured at birth, 24 and 48 h of life in 50 consecutive term uninfected newborns with perinatal asphyxia and 113 randomly selected healthy term newborns, and at delivery in their mothers. The median cord interleukin-6 concentrations in the infants who developed hypoxic-ischemic encephalopathy was 376-fold as high as the values in the normal infants (P < 0.0001) and 5.5-fold as high as those in the infants with asphyxia who did not develop hypoxic-ischemic encephalopathy (P < 0.05). There was also a significant relationship between interleukin-6 and the degree of hypoxic-ischemic encephalopathy, and between interleukin-6 and neurodevelopmental outcome at 2 years of age. Regardless of outcome, in the asphyxiated infants the interleukin-6 values were significantly lower at both 24 and 48 h of life than at birth, with a significant decline from 24 to 48 h of life. Among mothers of the asphyxiated neonates, there were no significant differences in interleukin-6 concentrations between those delivering neonates with and without hypoxic-ischemic encephalopathy. Measurement of IL-6 concentrations in the umbilical cord of neonates with perinatal asphyxia may be useful to identify early, and in a relatively simple way, those who are most likely to have subsequent brain injury and adverse outcome.

Biochemical alterations in neonatal hypoxic ischaemic brain damage

Asphyxiated ( n = 39) and control ( n = 23) were elected for the study. Free radical-mediated lipid peroxidation, prostaglandin E 2 and vitamin E levels were studied and the degree of hypoxic ischaemic encephalopathy was determined in each case. In the hypoxic group the concentration of prostaglandin E 2 activity ( P < 0.05) and malondialdehyde levels ( P < 0.01) were significantly higher when compared to that of controls. The high vitamin E concentrations in the asphyxiated infants supports the role of oxygen free radicals in hypoxic ischaemic encephalopathy of newborns.

Visual function in full-term infants with hypoxic-ischaemic encephalopathy.

Thirty-one full term infants with hypoxic-ischaemic encephalopathy (HIE) were studied with a battery of tests designed to evaluate visual function in infancy and with serial MRI. Their age ranged between 5 and 31 months. The aim of the study was to evaluate whether the degree of HIE or the site and size of lesions on MRI could predict visual outcome. Twenty of the 31 infants studied showed abnormal results on at least one of the visual tests used. While visual function was generally normal in grade I HIE and severely impaired in grade III, visual outcome was variable in grade II. MRI findings were better predictors of visual impairment than the degree of HIE. Normal scans tended to be associated with normal visual function, irrespective of the severity of HIE. All but one of the infants with diffuse hemispheric involvement also showed multiple visual abnormalities. The concomitant involvement of basal ganglia was always associated with more severe visual outcome. These results suggest that infants with generalised lesions secondary to global insults are at high risk of severe visual impairment even in presence of normal acuity and require early assessment of various aspects of visual function.

Diagnostic and prognostic value of cerebral 31P magnetic resonance spectroscopy in neonates with perinatal asphyxia.

The impact of depressed neonatal cerebral oxidative phosphorylation for diagnosing the severity of perinatal asphyxia was estimated by correlating the concentrations of phosphocreatine (PCr) and ATP as determined by magnetic resonance spectroscopy with the degree of hypoxic-ischemic encephalopathy (HIE) in 23 asphyxiated term neonates. Ten healthy age-matched neonates served as controls. In patients, the mean concentrations +/- SD of PCr and ATP were 0.99 +/- 0.46 mmol/L (1.6 +/- 0.2 mmol/L) and 0.99 +/- 0.35 mmol/L (1.7 +/- 0.2 mmol/L), respectively (normal values in parentheses). [PCr] and [ATP] correlated significantly with the severity of HIE (r = 0.85 and 0.9, respectively, p < 0.001), indicating that the neonatal encephalopathy is the clinical manifestation of a marred brain energy metabolism. Neurodevelopmental outcome was evaluated in 21 children at 3, 9, and 18 mo. Seven infants had multiple impairments, five were moderately handicapped, five had only mild symptoms, and four were normal. There was a significant correlation between the cerebral concentrations of PCr or ATP at birth and outcome (r = 0.8, p < 0.001) and between the degree of neonatal neurologic depression and outcome (r = 0.7). More important, the outcome of neonates with moderate HIE could better be predicted with information from quantitative 31P magnetic resonance spectroscopy than from neurologic examinations. In general, the accuracy of outcome predictability could significantly be increased by adding results from 31P magnetic resonance spectroscopy to the neonatal neurologic score, but not vice versa. No correlation with outcome was found for other perinatal risk factors, including Apgar score.

Glial Fibrillary Acidic Protein in the Cerebrospinal Fluid: A Possible Indicator of Prognosis in Full-Term Asphyxiated Newborn Infants?

Glial fibrillary acidic protein (GFAP) is the structural protein of intermediate filaments in astroglia. GFAP has extensively been used as a marker of gliosis in neuropathology. It also appears in excessive amounts in the cerebrospinal fluid in various acute brain disorders. Hypoxic-ischemic encephalopathy after perinatal asphyxia is a condition in which levels of GFAP could be expected to be elevated if brain cell damage occurs. We examined levels of GFAP by a sensitive ELISA in the cerebrospinal fluid of full-term infants between 12 and 48 h after birth. Cerebrospinal fluid-GFAP increased 5-fold in infants after perinatal asphyxia compared with a reference group (675 versus 137 ng/L, p < 0.001). The levels of GFAP also increased gradually in accordance with the severity of the neurologic symptoms ranked as degree of hypoxic-ischemic encephalopathy. We conclude that the cerebrospinal fluid levels of GFAP might be an important adjunct in the neonatal assessment of infants subject to perinatal asphyxia, and together with other neuronal or glial proteins, it might also help in defining temporal relationships in asphyxia.