Hypoxic Ischemic Encephalopathy In Term Neonates Research Articles

Quantitative Evaluation of Brain Echogenicity in Hypoxic-Ischemic Encephalopathy in Term Neonates Compared with Controls.

Purpose Neurosonography evaluation of neonatal hypoxic-ischemic encephalopathy (HIE) is mainly qualitative. We aimed to quantitatively compare the echogenicity of several brain regions in patients with HIE to healthy controls. Materials and Methods 20 term neonates with clinical/MRI evidence of HIE and 20 term healthy neonates were evaluated. Seven brain regions were assessed [frontal, parietal, occipital, and perirolandic white matter (WM), caudate nucleus head, lentiform nucleus, and thalamus]. The echogenicity of the calvarial bones (bone) and the choroid plexus (CP) was used for ratio calculation. Differences in the ratios were determined between neonates with HIE and controls. Results Ratios were significantly higher for HIE neonates in each region (p<0.05). The differences were greatest for the perirolandic WM, with CP and bone ratios being 0.23 and 0.22 greater, respectively, for the HIE compared to the healthy neonates (p<0.001). The perirolandic WM had a high AUC, at 0.980 for both the CP and bone ratios. The intra-observer reliability for all ratios was high, with the caudate to bone ratio being the lowest at 0.832 and the anterior WM to CP ratio being the highest at 0.992. Conclusion When coupled with internal controls, quantitative neurosonography represents a potential tool to identify early neonatal HIE changes. Larger cohort studies could reveal whether a quantitative approach can discern between degrees of severity of HIE. Future neurosonography protocols should be tailored to evaluate the perirolandic region, which requires posterior coronal scanning.

Experimental Models for Testing the Efficacy of Pharmacological Treatments for Neonatal Hypoxic-Ischemic Encephalopathy.

Representing an important cause of long–term disability, term neonatal hypoxic-ischemic encephalopathy (HIE) urgently needs further research aimed at repurposing existing drug as well as developing new therapeutics. Since various experimental in vitro and in vivo models of HIE have been developed with distinct characteristics, it becomes important to select the appropriate preclinical screening cascade for testing the efficacy of novel pharmacological treatments. As therapeutic hypothermia is already a routine therapy for neonatal encephalopathy, it is essential that hypothermia be administered to the experimental model selected to allow translational testing of novel or repurposed drugs on top of the standard of care. Moreover, a translational approach requires that therapeutic interventions must be initiated after the induction of the insult, and the time window for intervention should be evaluated to translate to real world clinical practice. Hippocampal organotypic slice cultures, in particular, are an invaluable intermediate between simpler cell lines and in vivo models, as they largely maintain structural complexity of the original tissue and can be subjected to transient oxygen–glucose deprivation (OGD) and subsequent reoxygenation to simulate ischemic neuronal injury and reperfusion. Progressing to in vivo models, generally, rodent (mouse and rat) models could offer more flexibility and be more cost-effective for testing the efficacy of pharmacological agents with a dose–response approach. Large animal models, including piglets, sheep, and non-human primates, may be utilized as a third step for more focused and accurate translational studies, including also pharmacokinetic and safety pharmacology assessments. Thus, a preclinical proof of concept of efficacy of an emerging pharmacological treatment should be obtained firstly in vitro, including organotypic models, and, subsequently, in at least two different animal models, also in combination with hypothermia, before initiating clinical trials.

Immediate complications of hypoxic-ischemic encephalopathy in term neonates with resistive index as prognostic factor

Background: Hypoxemia, a decreased arterial concentration of oxygen, frequently results in hypoxia, or decreased oxygenation to cells or organs. Hypoxic-ischemic encephalopathy (HIE) is a leading cause of neonatal brain injury, morbidity, and mortality globally. In the developed world, incidence is estimated at 1-8 per 1,000 live births, and in the developing world, estimates are as high as 26 per 1,000. The objective of the study is use of resistive index as prognostic factor for immediate neonatal outcome by Doppler ultrasound in birth asphyxia.Methods: 50 babies were subjected to neurosonogram between 12-24 hours of life admitted to tertiary care centre. Resistive index (RI) was measured for all enrolled neonates within 24 hours of life using pulse wave Doppler ultrasound. RI was calculated as: , where S=peak systolic velocity and D=end diastolic velocity. RI was measured for all enrolled neonates within 24 hours of life using pulse wave Doppler ultrasound with 3.5 MHz transducer. RI was calculated as: . A RI between 0.56 and 0.90 was considered normal and neonates were classified as having either normal or abnormal RI.Results: The study conducted states that the mean age taken is 17.12 hours with a p value of 0.82 and the cord pH of mean 6.88 with p value of 0.70 which is suggestive of adverse outcomes in birth asphyxiated babies while the resistive index of cerebral arteries and renal arteries is 0.66 with p value of 0.115 which is statistically significant. The lesser the resistive indices the more severe is the adverse outcome.Conclusions: The immediate consequences of HIE like death, seizures, acute kidney injury which are the parameters in my study has a positive co relation with resistive indices of the cerebral arteries and renal arteries measures respectively.

Term Yenidoğanlarda Hipoksik-İskemik Ensefalopati Şiddetini Öngörmede Kraniyal MRG Bulguları

Objective: The aim of this study is to compare magnetic resonance imaging (MRI) findings with severity of hypoxic-ischemic encephalopathy (HIE) in term neonates. Methods: Sixty-three newborns with HIE in whom cranial MRIs were performed within the first 3 weeks of life between 2016 and 2020 were included in the study. Severity of HIE was graded using Sarnat &amp; Sarnat staging. In statistical analysis, Stage 1 was considered as mild, Stage 2 or 3 as severe HIE. The signal intensities of perirolandic cortex, posterior limb of internal capsule (PLIC), globus pallidus, and cerebrospinal tract on T1- weighted imaging (T1WI), and of perirolandic cortex, PLIC, ventrolateral thalamus, lateral edge of putamen and tegmentum on T2WI, and brain diffusion weighted imaging (DWI) findings were evaluated with consensus by two radiologists blinded to clinical findings. Gestational age, birth weight and MRI signal intensities were compared with HIE groups using t test, and Fisher-Exact test. Results: There were 31 and 32 infants with mild and severe HIE, respectively. Gestational age and birth weight were not different between mild and severe HIE groups. The number of cases with abnormal signals in PLIC and globus pallidus on T1WI, and PLIC on T2WI were significantly higher in severe HIE (p=0.022, p=0.008, and p=0.032, respectively). The presence of signal abnormality in other regions and DWI were not significantly different between HIE groups. Conclusion: Cranial MRI may play a remarkable role in determining pattern and severity of HIE. Signal abnormality in PLIC and globus pallidus may suggest severe HIE in term neonates.

Impact of sedative agents on cerebral blood flow and outcomes of hypoxic-ischemic encephalopathy in term infants

Мета роботи . Порівняти вплив морфіну та інших седативних засобів на стан мозкового кровотоку та результати лікування гіпоксично-ішемічної енцефалопатії у доношених новонароджених. Матеріали і методи . Досліджено 205 доношених новонароджених з гіпоксично-ішемічною енцефалопатією за Sarnat II-III ст. в терміні d”72 годин після пологів. Немовлята були стратифіковані за фармакологічним препаратом для медикаментозної седації під час проведення штучної вентиляції легень на групи із застосуванням морфіну (n=71) та групу порівняння (n=134), в яку увійшли оксибутират натрію, діазепам та дексмедетомідин в стандартних рекомендованих дозах. Проведений порівняльний аналіз впливу морфіну та інших лікарських засобів на стан церебральної перфузії та на результати лікування гіпоксично-ішемічної енцефалопатії. Результати і обговорення . Отримана достовірна відмінність поміж групами допплерівського індексу мозкового кровотоку RI у першу добу (0,64 [0,55-0,74] в групі морфіну та 0,68 [0,61-0,75] в групі контролю, р=0,037), і на третю добу лікування (відповідно 0,64 [0,55-0,70] проти 0,67 [0,61-0,75] при р=0,040), більш низькі показники САТ (51 [43-60] мм рт.ст. проти 56 [49-60] мм рт.ст. при р=0,017), більша у 2,2 рази частота судом (р=0,038) та вища майже у 2 рази концентрація протеїну S-100 на третю добу (р=0,029) у групі морфіну. Частота розвитку небажаного результату у вигляді церебральної лейкомаляції також була у 2 рази вище в групі морфіну (18,4%) ніж у контрольній групі (8,9%), хоча різниця виявилась недостовірною (р=0,051), але з очевидною тенденцією. Висновки . В гострому періоді гіпоксично-ішемічної енцефалопатії у доношених новонароджених застосування морфіну у якості препарату седативної дії у порівнянні з іншими фармакологічними препаратами призводить до низки негативних ефектів стосовно впливу на церебральну перфузію та на кінцеві результати лікування.

Using of dexmedetomidine in term neonates with hypoxic-ischemic encephalopathy.

The negative impacts of standard pharmacologic sedative agents suggest that alternative agents should be investigated. Dexmedetomidine could be the new option for sedation in newborns with hypoxic-ischemic encephalopathy requiring mechanical ventilation. The aim – to determine the impact of dexmedetomidine and other sedatives on the cerebral blood flow and outcomes of hypoxic-ischemic encephalopathy in term neonates. Data of 205 term infants with hypoxic-ischemic encephalopathy by Sarnat scale stage II-III were collected during ≤72 hours of life. The infants were divided using a simple open randomization by pharmacological sedative agents during mechanical ventilation into dexmedetomidine group (n=46) and the control group (n=159), which included morphine, sodium oxybutyrate, and diazepam in standard recommended doses. A comparative analysis of the effect of dexmedetomidine and other drugs on cerebral perfusion and outcomes of hypoxic-ischemic encephalopathy was performed. A significant difference between groups in days of trachea extubation (p=0.022) was found; the chance for babies to be extubated before the 7th day of treatment was significantly higher in the dexmedetomidine group 68% versus 33% in the control group (p=0.018) with HR 0.48 (95% CI 0.27-0.86, p=0.011). Also, the NIRS index rScO 2 differed significantly between the studied and control groups on the 1 st day of treatment (65% versus 79%, p=0.012) and on the 2 nd day of treatment (74% versus 81%, p=0.035). Mean arterial pressure was higher in the dexmedetomidine group compared to the control group – (58 [51-65] mm Hg versus 53 [46-60] mm Hg, p<0.001), with a lower dose of dobutamine (EV -1.87, 95% CI from -3.25 to -0.48, p=0.009). In the dexmedetomidine group, the rate of seizures was significantly lower on the 1 st day of obser­vation (4.3% versus 48.3%, p <0.001); the incidence of unfavorable outcome sueh as cerebral leukomalacia was also 7 times lower in the dexmedetomidine group compared to the control group (2.2% versus 15.1%, p=0.018). Dexme­detomidine is a safe sedative agent with a stable hemodynamic profile, without adverse influence on cerebral perfusion and possible neuroprotective effects in term infants with HIE, as addition to standard therapeutic hypothermia.

MRI Findings in Infants With Infantile Spasms After Neonatal Hypoxic-Ischemic Encephalopathy

BackgroundTo evaluate the predominant pattern of brain injury and the anatomic areas of injury in children with infantile spasms following neonatal hypoxic-ischemic encephalopathy. MethodsA nested case-control study of infantile spasms in children with term neonatal hypoxic-ischemic encephalopathy was performed. All patients had T1/T2-weighted magnetic resonance imaging with diffusion-weighted imaging performed on the third day of life. Using a validated scoring system, the magnetic resonance imaging was classified as: normal, watershed, basal ganglia/thalamus, total, or focal-multifocal. Two study investigators scored additional anatomic areas of injury (cortical extent, levels of the brainstem, hypothalamus) on T1/T2-weighted magnetic resonance imaging and diffusion-weighted imaging blinded to the outcome. The predominant pattern of brain injury and anatomic areas of injury were compared between patients who developed infantile spasms and randomly selected controls. ResultsEight patients who developed infantile spasms were identified among a cohort of 176 term newborns with hypoxic-ischemic encephalopathy (4.5%). There were no significant differences in the perinatal and neonatal course between newborns who developed infantile spasms and controls who did not. The development of infantile spasms after neonatal hypoxic-ischemic encephalopathy was significantly associated with basal ganglia/thalamus and total brain injury (P = 0.001), extent of cortical injury greater than 50% (odds ratio = 11.7, 95% confidence interval = 1.1-158.5, P = 0.01), injury to the midbrain (odds ratio = 13, 95% confidence interval = 1.3-172, P = 0.007) and hypothalamic abnormalities (P = 0.01). ConclusionsThe development of infantile spasms after hypoxic-ischemic encephalopathy is associated with injury to the basal ganglia and thalami on neonatal magnetic resonance imaging, particularly when extensive cortical injury and/or injury to the midbrain is present.

Antepartum and Intrapartum Factors Preceding Neonatal Hypoxic-Ischemic Encephalopathy

To determine whether antepartum factors alone, intrapartum factors alone, or both in combination, are associated with term neonatal hypoxic-ischemic encephalopathy (HIE). A total of 405 infants ≥ 35 weeks' gestation with early encephalopathy, born between 1992 and 2007, were compared with 239 neurologically normal infants born between 1996 and 1997. All cases met criteria for perinatal asphyxia, had neuroimaging findings consistent with acute hypoxia-ischemia, and had no evidence for a non-hypoxic-ischemic cause of their encephalopathy. Both antepartum and intrapartum factors were associated with the development of HIE on univariate analysis. Case infants were more often delivered by emergency cesarean delivery (CD; 50% vs 11%, P < .001) and none was delivered by elective CD (vs 10% of controls). On logistic regression analysis only 1 antepartum factor (gestation ≥ 41 weeks) and 7 intrapartum factors (prolonged membrane rupture, abnormal cardiotocography, thick meconium, sentinel event, shoulder dystocia, tight nuchal cord, failed vacuum) remained independently associated with HIE (area under the curve 0.88; confidence interval 0.85-0.91; P < .001). Overall, 6.7% of cases and 43.5% of controls had only antepartum factors; 20% of cases and 5.8% of controls had only intrapartum factors; 69.5% of cases and 31% of controls had antepartum and intrapartum factors; and 3.7% of cases and 19.7% of controls had no identifiable risk factors (P < .001). Our results do not support the hypothesis that HIE is attributable to antepartum factors alone, but they strongly point to the intrapartum period as the necessary factor in the development of this condition.

Hypothermie pour la neuroprotection cérébrale de l’encéphalopathie anoxo-ischémique: certitudes et incertitudes

Cerebral hypothermia is one of the first neuroprotective strategies that can improve outcome of experimental and human perinatal cerebral hypoxia-ischemia. Now, international guidelines for hypoxic-ischemic encephalopathy in term neonates recommend hypothermia. At several places, hypothermia could block the cascade of neurochemical events that mediate brain damage insult in term infants. Extended cooling must be initiated 6 h after injury, after obtaining accurate data about perinatal asphyxia and the severity of hypoxic-ischemic encephalopathy. At 18 months of life, hypothermia reduces the risk of death or disability in infants with moderate or severe hypoxic-ischemic encephalopathy. However, longer-term data have not been available to assess whether the benefits of hypothermia persist after 2 years of age. Extensions of indication are debated for late preterm infants or newborns admitted in intensive care unit after 6 hours of life, and clinical studies are actually performed on these subjects. However, if prognosis at 18 months is improved, more than 40% of treated newborns will have an unfavorable evolution. Other neuroprotective strategies as erythropoietin, melatonin, and xenon or magnesium sulfate are actually evaluated. Results of these last studies would be interesting in the future, because these strategies could be associated with hypothermia.

Evolution of pattern of injury and quantitative MRI on days 1 and 3 in term newborns with hypoxic–ischemic encephalopathy

Brain injury in term neonatal hypoxic-ischemic encephalopathy (HIE) emerges on magnetic resonance imaging (MRI) by day 3. This study aimed to address the relationship of MRI, diffusion tensor imaging (DTI), and MR spectroscopic imaging (MRSI) findings on days 1 and 3 in a prospective cohort of term newborns with HIE. A total of 24 term newborns with HIE were prospectively studied with MRI on days 1 and 3; 19 were imaged with DTI and MRSI on days 1 and 3. MRI was assessed using validated scores. The relationship between MRI, DTI, and MRSI values on days 1 and 3 was determined using linear regression for repeated measures. Conventional MRI showed a complex variation of findings from day 1 to 3. In gray matter, mean diffusivity (Dav) and metabolite ratios measured on day 1 were predictive of values on day 3 (all P ≤ 0.04). In white matter, Dav, fractional anisotropy (FA), and N-acetylaspartate (NAA)/choline on days 1 and 3 were strongly related (all P ≤ 0.003). Hypothermia appeared to attenuate the severity and progression of brain injury in the six treated newborns. In term newborns with HIE, quantitative MR values on days 1 and 3 are strongly associated, providing an objective measure of injury before qualitative images.

Regenerative Therapies in Neonatology: Clinical Perspectives

Regenerative therapy based on stem cells is applied as standard therapy in pediatric oncology. Furthermore, they are frequently used to treat immunodeficiency disorders of infants. For severe neonatal diseases, e. g. hypoxic-ischemic encephalopathy in term neonates or bronchopulmonary dysplasia in preterm infants, animal models have been established. According to some first preclinical results stem cell administration appears as a promising tool to improve the clinical outcome in high-risk infants. Provided the benefit of regenerative therapies can further be evaluated in appropriate preclinical neonate models, carefully controlled clinical trials to assess the significance of regenerative therapies, such as autologous stem cell administration, are indicated.

Hypoxic-ischemic encephalopathy in term neonates: Perinatal factors and outcome

Ninety-five infants of 37 weeks' gestation or greater with evidence of hypoxic-ischemic encephalopathy following perinatal asphyxia were prospectively identified in the neonatal period. The degree of encephalopathy was graded the staging system of Sarnat and Sarnat. Six infants died, 78 infants were sequentially followed in the Neonatal Follow-up Clinic, and in five additional infants, follow-up information was available. The mean duration of follow-up was 19.3 months. Fifty-eight (65%) of the 89 infants followed were normal or mildly handicapped, six (7%) died, and the remainder had significant handicap. There was no significant relationship between any of over 100 obstetrical antepartum or intrapartum variables and outcome. Infants with five-minute Apgar scores of 0 to 3, seizures within the first day of life, Stage II or III encephalopathy, or a suppressed electroencephalogram had a significantly greater incidence of severe handicap or death. In addition, although there were fewer females, they had a significantly greater incidence of handicap. There appeared to be an improved outcome in the last two years (1977-1978) compared to the first two years (1975-1976), suggesting that improved recognition and neonatal management may lead to a decrease in significant sequelae.