Predictive Value of Thompson-Score for Long-Term Neurological and Cognitive Outcome in Term Newborns with Perinatal Asphyxia and Hypoxic-Ischemic Encephalopathy Undergoing Controlled Hypothermia Treatment

Abstract Background Perinatal asphyxia is a major cause of mortality and morbidity in neonates: The aim of the present study was to investigate, by means of longitudinal assessment of urinary S100B, the effectiveness of hypothermia, in infants complicated by perinatal asphyxia and hypoxic-ischemic encephalopathy. Methods We performed a retrospective case-control study in 108 asphyxiated infants, admitted to nine tertiary departments for neonatal intensive care from January 2004 to July 2017, of whom 54 underwent hypothermia treatment and 54 did not. The concentrations of S100B protein in urine were measured using an immunoluminometric assay at first urination and 4, 8, 12, 16, 20, 24, 48, 72, 96, 108 and 120 h after birth. The results were correlated with the achievement of S100B levels within normal ranges at 72 h from hypothermia treatment. Routine laboratory parameters, longitudinal cerebral function monitoring, cerebral ultrasound and neurologic patterns were assessed according to standard protocols. Results Higher S100B concentrations were found in hypothermia-treated infants in both moderate (up to 12 h) and severe (up to 24 h) hypoxic-ischemic encephalopathy. S100B levels returned to normal ranges starting from 20 h of hypothermia treatment in moderate and from 36 h in severe hypoxic-ischemic encephalopathy. Conclusions The present results offer additional support to the usefulness of longitudinal neuro-biomarkers monitoring in asphyxiated infants treated by hypothermia. The pattern of S100B concentrations during hypothermia supports the need for further investigations aimed at reconsidering the time-window for patient recruitment and treatment, and the optimal duration of the cooling and rewarming phases of the hypothermia procedure.

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To evaluate the role of MRI in infants with suspected hypoxic ischemic encephalopathy and prognosticating neurological outcome at end of one year

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20171813 ◽

2017 ◽

Vol 5 (5) ◽

pp. 1893

Author(s):

Shreyas Ramachandran ◽

Smiti Sripathi

Keyword(s):

Clinical Outcome ◽

Motor Development ◽

Perinatal Asphyxia ◽

Hypoxic Ischemic Encephalopathy ◽

Neurological Outcomes ◽

Common Causes ◽

One Year ◽

Ischemic Encephalopathy

Background: Hypoxic ischemic encephalopathy (HIE) is one the common causes of neonatal fatality due to perinatal asphyxia. The long-term outcomes of HIE are impaired mental and motor development, hearing loss, recurrent seizures and cerebral palsy. MRI is increasingly becoming the gold standard in diagnosis of HIE as it involves no radiation and can be performed during a neonates physiological sleep. To evaluate the role of MRI in infants with suspected hypoxic ischemic encephalopathy in prognosticating neurological outcomes at end of one year.Methods: A total of 50 patients were included in the study who underwent MRI of brain. A clinical follow up was done at the end of one year.Results: The sensitivity of MRI in prognosticating clinical outcome was 72% and specificity was 71% while PPV and NPV was 86% and 50% respectively.Conclusions: MRI is a useful modality to assess early changes in HIE and it can prognosticate clinical outcome.

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High Urinary Concentrations of Activin A in Asphyxiated Full-Term Newborns with Moderate or Severe Hypoxic Ischemic Encephalopathy

Clinical Chemistry ◽

10.1373/clinchem.2005.062604 ◽

2007 ◽

Vol 53 (3) ◽

pp. 520-522 ◽

Cited By ~ 27

Author(s):

Pasquale Florio ◽

Stefano Luisi ◽

Bashir Moataza ◽

Michela Torricelli ◽

Iskander Iman ◽

...

Keyword(s):

Perinatal Asphyxia ◽

Activin A ◽

Good Prognosis ◽

Full Term ◽

Hypoxic Ischemic Encephalopathy ◽

Promising Tool ◽

Group A ◽

Term Newborns ◽

Group B ◽

Ischemic Encephalopathy

Abstract Background: Hypoxic ischemic encephalopathy (HIE) is a major cause of permanent neurological disabilities in full-term newborns. We measured activin A in urine collected immediately after birth in asphyxiated full-term newborns, and assessed the ability of the measurements to predict the occurrence of perinatal encephalopathy. Methods: We studied 30 infants with perinatal asphyxia and 30 healthy term neonates at the same gestational age. We recorded routine laboratory variables, cranial assessments by standard cerebral ultrasound, and the presence or absence of neurological abnormalities during the first 7 days after birth. Urinary activin A concentrations were measured at first urination and 12, 24, 48, and 72 h after birth. Results: Asphyxiated infants were subdivided as follows: group A (n = 18): no or mild HIE with good prognosis and group B (n = 12): moderate or severe HIE with a greater risk of neurological handicap. Activin A concentrations in urine collected at birth (median collection time at first urination <2 h) and at 12, 24, 48, and 72 h from birth were significantly (P <0.0001) higher in asphyxiated newborns with moderate or severe HIE (Group B) than in those with absent of mild HIE (group A) and controls. Concentrations did not differ between group A and controls. Activin A concentrations were >0.08 μg/L at first urination in 10 of 12 patients with moderate or severe HIE but in none of 18 patients with no or mild HIE. Conclusions: Activin A measurements in urine soon after birth may be a promising tool to identify which asphyxiated infants are at risk of neurological sequelae.

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Ultrasonography and Magnetic Resonance Imaging of the Brain in Hypoxic Full-Term Newborns

Medicina ◽

10.3390/medicina49010008 ◽

2013 ◽

Vol 49 (1) ◽

pp. 8 ◽

Cited By ~ 2

Author(s):

Aušrelė Kudrevičienė ◽

Saulius Lukoševičius ◽

Jūratė Laurynaitienė ◽

Vitalija Marmienė ◽

Rasa Tamelienė ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Flow Velocity ◽

Predictive Value ◽

Full Term ◽

Hypoxic Ischemic Encephalopathy ◽

Resonance Imaging ◽

Cranial Sonography ◽

Term Newborns ◽

Ischemic Encephalopathy

The aim of this article was to review the studies on diagnostic and prognostic value of radiological investigations (cranial sonography, Doppler ultrasonography, and magnetic resonance imaging) in the detection of hypoxic-ischemic brain injuries in full-term newborns. Materials and Methods. A systematic search of studies on the diagnostic and prognostic possibilities of radiological investigations for the detection of hypoxic-ischemic injuries in full-term newborns was performed. Results. A total of 13 prospective and 4 retrospective studies that analyzed the incidence of hypoxic-ischemic cerebral injuries, determined by means of cranial sonography, Doppler sonography, and magnetic resonance imaging, and associations with the stages of hypoxic-ischemic encephalopathy and long-term neurodevelopmental outcomes were included in this systematic review. Conclusions. Magnetic resonance imaging detects lesions in 75%–100% of cases. Magnetic resonance imaging performed at the age of 7–11 days demonstrated a high sensitivity (100%) and negative predictive value (100%) to predict unfavorable outcomes at 4 years of age. In newborns with hypoxic-ischemic encephalopathy, substantial cerebral hemodynamic alterations are detected after birth. The sensitivity and negative predictive value of cerebral blood flow velocities (peak systolic flow velocity, end-diastolic flow velocity) changes at 12±2 hours of age to predict the severity of hypoxic-ischemic encephalopathy and unfavorable outcomes at 18 months of age were found to be high (90% and 94%, respectively). A low resistive index (<0.56) at the age of 1–3 days had a specificity of 95% to predict unfavorable outcomes at 3 years of age. The data on the diagnostic and prognostic potential of cranial sonography are limited scarce and contrary.

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Melatonin Administration from 2000 to 2020 to Human Newborns with Hypoxic-Ischemic Encephalopathy

American Journal of Perinatology ◽

10.1055/s-0040-1719151 ◽

2020 ◽

Author(s):

Gabriella D'angelo ◽

Laura Cannavò ◽

Russel J. Reiter ◽

Eloisa Gitto

Keyword(s):

Oxidative Stress ◽

Clinical Trials ◽

Perinatal Asphyxia ◽

Hypoxic Ischemic Encephalopathy ◽

Melatonin Treatment ◽

The Past ◽

Melatonin Administration ◽

Key Points ◽

Ischemic Encephalopathy

Hypoxic-ischemic encephalopathy (HIE) is the main cause of long-term neurodevelopmental morbidity in term born infants worldwide. Melatonin is a hormone with antioxidant and anti-inflammatory effects that make it a promising molecule for the treatment of perinatal asphyxia. Probably, the synergistic use of hypothermia associated with melatonin treatment may improve the neurological outcome in infants with HIE. In the past 20 years, the efficacy of melatonin in reducing oxidative stress has been demonstrated in animals; however, clinical trials with sufficient sample size of newborns are lacking to date.Since in 2000 we were among the first to study the neuroprotective properties of melatonin on infants, in this review, we want to summarize the advantages and limitations of the investigations conducted to date. Key Points

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The Kynurenic Acid Analog SZR72 Enhances Neuronal Activity after Asphyxia but Is Not Neuroprotective in a Translational Model of Neonatal Hypoxic Ischemic Encephalopathy

International Journal of Molecular Sciences ◽

10.3390/ijms22094822 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4822

Author(s):

Viktória Kovács ◽

Gábor Remzső ◽

Tímea Körmöczi ◽

Róbert Berkecz ◽

Valéria Tóth-Szűki ◽

...

Keyword(s):

Neuronal Activity ◽

Kynurenic Acid ◽

Neuronal Damage ◽

Brain Regions ◽

Hypoxic Ischemic Encephalopathy ◽

Hippocampal Field ◽

Power Spectral ◽

Density Values ◽

Ischemic Encephalopathy

Hypoxic–ischemic encephalopathy (HIE) remains to be a major cause of long-term neurodevelopmental deficits in term neonates. Hypothermia offers partial neuroprotection warranting research for additional therapies. Kynurenic acid (KYNA), an endogenous product of tryptophan metabolism, was previously shown to be beneficial in rat HIE models. We sought to determine if the KYNA analog SZR72 would afford neuroprotection in piglets. After severe asphyxia (pHa = 6.83 ± 0.02, ΔBE = −17.6 ± 1.2 mmol/L, mean ± SEM), anesthetized piglets were assigned to vehicle-treated (VEH), SZR72-treated (SZR72), or hypothermia-treated (HT) groups (n = 6, 6, 6; Tcore = 38.5, 38.5, 33.5 °C, respectively). Compared to VEH, serum KYNA levels were elevated, recovery of EEG was faster, and EEG power spectral density values were higher at 24 h in the SZR72 group. However, instantaneous entropy indicating EEG signal complexity, depression of the visual evoked potential (VEP), and the significant neuronal damage observed in the neocortex, the putamen, and the CA1 hippocampal field were similar in these groups. In the caudate nucleus and the CA3 hippocampal field, neuronal damage was even more severe in the SZR72 group. The HT group showed the best preservation of EEG complexity, VEP, and neuronal integrity in all examined brain regions. In summary, SZR72 appears to enhance neuronal activity after asphyxia but does not ameliorate early neuronal damage in this HIE model.

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Development and Evaluation of Computable Phenotypes in Pediatric Epilepsy:3 Cases

Journal of Child Neurology ◽

10.1177/08830738211019578 ◽

2021 ◽

pp. 088307382110195

Author(s):

Sabrina Pan ◽

Alan Wu ◽

Mark Weiner ◽

Zachary M Grinspan

Keyword(s):

Positive Predictive Value ◽

Predictive Value ◽

Juvenile Myoclonic Epilepsy ◽

Myoclonic Epilepsy ◽

Hypoxic Ischemic Encephalopathy ◽

Pediatric Epilepsy ◽

Health Record ◽

Treatment Resistant ◽

Ischemic Encephalopathy ◽

F Measure

Introduction: Computable phenotypes allow identification of well-defined patient cohorts from electronic health record data. Little is known about the accuracy of diagnostic codes for important clinical concepts in pediatric epilepsy, such as (1) risk factors like neonatal hypoxic-ischemic encephalopathy; (2) clinical concepts like treatment resistance; (3) and syndromes like juvenile myoclonic epilepsy. We developed and evaluated the performance of computable phenotypes for these examples using electronic health record data at one center. Methods: We identified gold standard cohorts for neonatal hypoxic-ischemic encephalopathy, pediatric treatment-resistant epilepsy, and juvenile myoclonic epilepsy via existing registries and review of clinical notes. From the electronic health record, we extracted diagnostic and procedure codes for all children with a diagnosis of epilepsy and seizures. We used these codes to develop computable phenotypes and evaluated by sensitivity, positive predictive value, and the F-measure. Results: For neonatal hypoxic-ischemic encephalopathy, the best-performing computable phenotype (HIE ICD-9 /10 and [brain magnetic resonance imaging (MRI) or electroencephalography (EEG) within 120 days of life] and absence of commonly miscoded conditions) had high sensitivity (95.7%, 95% confidence interval [CI] 85-99), positive predictive value (100%, 95% CI 95-100), and F measure (0.98). For treatment-resistant epilepsy, the best-performing computable phenotype (3 or more antiseizure medicines in the last 2 years or treatment-resistant ICD-10) had a sensitivity of 86.9% (95% CI 79-93), positive predictive value of 69.6% (95% CI 60-79), and F-measure of 0.77. For juvenile myoclonic epilepsy, the best performing computable phenotype (JME ICD-10) had poor sensitivity (52%, 95% CI 43-60) but high positive predictive value (90.4%, 95% CI 81-96); the F measure was 0.66. Conclusion: The variable accuracy of our computable phenotypes (hypoxic-ischemic encephalopathy high, treatment resistance medium, and juvenile myoclonic epilepsy low) demonstrates the heterogeneity of success using administrative data to identify cohorts important for pediatric epilepsy research.

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