Diagnosis Of Hypoxic-ischemic Encephalopathy Research Articles

Trends in HIE and Use of Hypothermia in California: Opportunities forImprovement.

Hypoxic-ischemic encephalopathy (HIE) is a leading cause of neonatal morbidity and mortality. Therapeutic hypothermia (TH), a proven treatment of moderate-severe HIE, was first used clinically after 2006. We describe trends in HIE diagnosis and use of TH over a 10-year period in California. We identified 62 888 infants,≥36 weeks gestation, who were cared for in California Perinatal Quality Care Collaborative-participating NICUs between 2010 and 2019, and linked them to birth certificate data. We evaluated trends in HIE diagnosis and use of TH. Over time, rates of HIE diagnosis increased from 0.6 to 1.7 per 1000 live births, and use of TH increased from 26.5 to 83.0 per 1000 infants. Rates of moderate HIE increased more than mild or severe, although use of TH for mild HIE increased more than for moderate. Of those with moderate-severe HIE, 25% remain untreated. Treatment varied by NICU level of care. The rates of HIE and TH increased steadily. Some infants with moderate-severe HIE remain untreated, suggesting a need for ongoing education. Further evaluation of systems of care is needed to assure all qualifying infants are treated.

Dried Blood Spot Metabolome Features of Ischemic-Hypoxic Encephalopathy: A Neonatal Rat Model.

Hypoxic-ischemic encephalopathy (HIE) is a severe neurological disorder caused by perinatal asphyxia with significant consequences. Early recognition and intervention are crucial, with therapeutic hypothermia (TH) being the primary treatment, but its efficacy depends on early initiation of treatment. Accurately assessing the HIE severity in neonatal care poses challenges, but omics approaches have made significant contribution to understanding its complex pathophysiology. Our study further explores the impact of HIE on the blood metabolome over time and investigated changes associated with hypothermia's therapeutic effects. Using a rat model of hypoxic-ischemic brain injury, we comprehensively analyzed dried blood spot samples for fat-soluble compounds using HPLC-MS. Our research shows significant changes in the blood metabolome after HIE, with a particularly rapid recovery of lipid metabolism observed. Significant changes in lipid metabolites were observed after 3 h of HIE, including increases in ceramides, carnitines, certain fatty acids, phosphocholines, and phosphoethanolamines, while sphingomyelins and N-acylethanolamines (NAEs) decreased (p < 0.05). Furthermore, NAEs were found to be significant features in the OPLS-DA model for HIE diagnosis, with an area under the curve of 0.812. TH showed a notable association with decreased concentrations of ceramides. Enrichment analysis further corroborated these observations, showing modulation in several key metabolic pathways, including arachidonic acid oxylipin metabolism, eicosanoid metabolism via lipooxygenases, and leukotriene C4 synthesis deficiency. Our study reveals dynamic changes in the blood metabolome after HIE and the therapeutic effects of hypothermia, which improves our understanding of the pathophysiology of HIE and could lead to the development of new rapid diagnostic approaches for neonatal HIE.

Effectiveness and Safety of Dexmedetomidine in Neonates With Hypoxic Ischemic Encephalopathy Undergoing Therapeutic Hypothermia.

The objective of this study was to evaluate and compare the effectiveness and safety of dexmedetomidine as monotherapy between neonates with mild hypoxic ischemic encephalopathy (HIE) and moderate to severe HIE treated with therapeutic hypothermia (TH). This retrospective study included neonates of gestational age ≥36 weeks with a diagnosis of HIE and undergoing TH between January 2014 and December 2021. Patients were included if they received at least 6 hours of continuous sedation with dexmedetomidine. Baseline characteristics, dose and duration of medication, adverse events, liver and kidney function tests, and hospital course were reviewed. Of the 97 neonates included, 46 had mild, 42 had moderate, and 9 had severe HIE. Dexmedetomidine was initiated at a median 5 hours of life, and the median infusion duration was 77 (46-87) hours. Fifty-two (53.6%) required at least 1 breakthrough opioid or sedative during the first 24 hours of dexmedetomidine infusion. Overall, 40 patients (41.2%) had at least 1 bradycardia episode with heart rate <80 beats/min and 14 patients (14.4%) had heart rate <70 beats/min. Hypotension was experienced by 7 patients (7.2%). Fifty-two patients (53.6%) were intubated in the delivery room and 33/52 (63.5%) were extubated on day of life 1 during dexmedetomidine infusion. Dexmedetomidine as monotherapy was effective and safe sedation for infants with HIE undergoing hypothermia. The most common side effect of dexmedetomidine was bradycardia. -Dexmedetomidine may be considered as first and single agent for neonates with HIE undergoing TH.

Sudden unexpected postnatal collapse and BUB1B mutation: first forensic case report

Sudden unexpected postnatal collapse (SUPC) is a sudden collapse of the clinical conditions of a full-term or near-term newborn, within the first 7 days of life, that requires resuscitation with positive ventilation and who either dies, has hypoxic-ischemic encephalopathy, or requires intensive care. The incidence of SUPC is very low, and most often presents a negative prognosis. The BUB1B gene is a mitotic checkpoint of serine/threonine kinase B that encodes a protein crucial for maintaining the correct number of chromosomes during cell division. Mutations in the BUB1B gene are linked to mosaic variegated aneuploidy syndrome 1 (MVA1), a rare autosomal recessive disorder characterized by diffuse mosaic aneuploidies involving several chromosomes and tissues. This paper discusses a case of a newborn who had a spontaneous delivery. After 2 h and 10 min, the infant showed generalized hypotonia and cyanosis, and his doctors performed orotracheal intubation, cardiac massage, pharmacological hemodynamic therapy, mechanical ventilation, antibiotic therapy, and hypothermic treatment. The newborn was discharged after 5 months with the diagnosis of hypoxic-ischemic encephalopathy. Suspecting an SUPC, a complete genetic analysis was performed demonstrating a compound heterozygous mutations in the BUB1B gene. The newborn died at 6 months of life, 1 month after discharge. A complete autopsy was performed, determining that the cause of death was due to sepsis starting from a brocopneumonic process, with outcomes of hypoxic-ischemic encephalopathy (HIE). In this scenario, it is not possible to demonstrate the causal effect of this mutation, considering that it could play a causal or concausal role in the onset of SUPC. Further research based on multicenter studies, as well as on animal models, could be very useful to clarify the pathological effect of this mutation.

Magnesium sulfate and risk of hypoxic ischemic encephalopathy in a high-risk cohort

Hypoxic ischemic encephalopathy contributes to morbidity and mortality among neonates ≥ 360 weeks' gestation. Evidence of preventative antenatal treatment is limited. Magnesium sulfate has neuroprotective properties among preterm fetuses. Hypertensive disorders of pregnancy are a risk factor for hypoxic ischemic encephalopathy and magnesium sulfate is recommended for maternal seizure prophylaxis among patients with pre-eclampsia with severe features. 1) Determine trends in incidence of hypertensive disorders of pregnancy, antenatal magnesium sulfate and hypoxic ischemic encephalopathy, 2) evaluate the association between hypertensive disorders of pregnancy and hypoxic ischemic encephalopathy and 3) evaluate if, among patients with hypertensive disorders of pregnancy, the odds of hypoxic ischemic encephalopathy is mitigated by receipt of antenatal magnesium sulfate. STUDY DESIGN: We conducted an analysis of a prospective cohort of live births ≥360 weeks' gestation between 2012-2018 within the California Perinatal Quality Care Collaborative registry, linked with the California Department of Health Care Access and Information files. We used Cochran-Armitage tests to assess trends in hypertensive disorders, encephalopathy diagnoses, and magnesium sulfate utilization, and compared demographic factors between patients with or without hypertensive disorders of pregnancy or treatment with magnesium sulfate. Hierarchical logistic regression models were built to explore if hypertensive disorders of pregnancy were associated with any severity and moderate/severe hypoxic ischemic encephalopathy. Separate hierarchical logistic regression models were built among those with hypertensive disorders of pregnancy to evaluate the association of magnesium sulfate with hypoxic ischemic encephalopathy. Among 44,314 unique infants, the diagnosis of hypoxic ischemic encephalopathy, maternal hypertensive disorders of pregnancy and the use of magnesium sulfate increased over time. Compared to patients with hypertensive disorders of pregnancy alone, patients with hypertensive disorders treated with magnesium sulfate represented a higher risk population. They were more likely to be publicly insured, born 36-38 weeks' gestation, be small for gestational age, have lower Apgar scores, require a higher level of resuscitation at delivery, have prolonged rupture of membranes, preterm labor, fetal distress, and undergo operative delivery (all p-values <0.002). Hypertensive disorders of pregnancy were associated with hypoxic ischemic encephalopathy (aOR 1.26, 95% CI 1.13-1.40, p-value <.001) and specifically moderate/severe hypoxic ischemic encephalopathy (aOR 1.26, 95% CI 1.11-1.42, p-value <.001). Among patients with hypertensive disorders of pregnancy, treatment with magnesium sulfate was associated with 29% reduction in the odds of neonatal hypoxic ischemic encephalopathy (aOR 0.71, 95% CI 0.52-0.97, p-value= 0.03) and a 37% reduction in the odds of moderate/severe neonatal hypoxic ischemic encephalopathy (aOR 0.63, 95% CI 0.42-0.94, p-value=0.03). Hypertensive disorders of pregnancy are associated with hypoxic ischemic encephalopathy and specifically, moderate/severe disease. Among people with hypertensive disorders, receipt of antenatal magnesium sulfate is associated with significant reduction in the odds of hypoxic ischemic encephalopathy and moderate/severe disease in a neonatal cohort admitted to the NICU ≥360 weeks' gestation. The findings of this observational study cannot prove causality and are intended to be hypothesis generating for future clinical trials on MgSO4 in term infants.

Quality improvement and outcomes for neonates with hypoxic-ischemic encephalopathy: obstetrics and neonatal perspectives

Despite significant improvement in perinatal care and research, hypoxic ischemic encephalopathy (HIE) remains a global healthcare challenge. From both published research and reports of QI initiatives, we have identified a number of distinct opportunities that can serve as targets of quality improvement (QI) initiatives focused on reducing HIE. Specifically, (i) implementation of perinatal interventions to anticipate and timely manage high-risk deliveries; (ii) enhancement of team training and communication; (iii) optimization of early HIE diagnosis and management in referring centers and during transport; (iv) standardization of the approach when managing neonates with HIE during therapeutic hypothermia; (v) and establishment of protocols for family integration and follow-up, have been identified as important in successful QI initiatives. We also provide a framework and examples of tools that can be used to support QI work and discuss some of the perceived challenges and future opportunities for QI targeting HIE.

Clinical exome sequencing uncovers genetic disorders in neonates with suspected hypoxic-ischemic encephalopathy: A retrospective analysis.

Hypoxic-ischemic encephalopathy (HIE) occurs in up to 7 out of 1000 births and accounts for almost a quarter of neonatal deaths worldwide. Despite the name, many newborns with HIE have little evidence of perinatal hypoxia. We hypothesized that some infants with HIE have genetic disorders that resemble encephalopathy. We reviewed genetic results for newborns with HIE undergoing exome or genome sequencing at a clinical laboratory (2014-2022). Neonates were included if they had a diagnosis of HIE and were delivered ≥35 weeks. Neonates were excluded for cardiopulmonary pathology resulting in hypoxemia or if neuroimaging suggested postnatal hypoxic-ischemic injury. Of 24 patients meeting inclusion criteria, six (25%) were diagnosed with a genetic condition. Four neonates had variants at loci linked to conditions with phenotypic features resembling HIE, including KIF1A, GBE1, ACTA1, and a 15q13.3 deletion. Two additional neonates had variants in genes not previously associated with encephalopathy, including DUOX2 and PTPN11. Of the six neonates with a molecular diagnosis, two had isolated HIE without apparent comorbidities to suggest a genetic disorder. Genetic diagnoses were identified among neonates with and without sentinel labor events, abnormal umbilical cord gasses, and low Apgar scores. These results suggest that genetic evaluation is clinically relevant for patients with perinatal HIE.

Metabolite Biomarkers for Early Ischemic-Hypoxic Encephalopathy: An Experimental Study Using the NeoBase 2 MSMS Kit in a Rat Model.

Hypoxic-ischemic encephalopathy (HIE) is one of the most common causes of childhood disability. Hypothermic therapy is currently the only approved neuroprotective approach. However, early diagnosis of HIE can be challenging, especially in the first hours after birth when the decision to use hypothermic therapy is critical. Distinguishing HIE from other neonatal conditions, such as sepsis, becomes a significant problem in diagnosis. This study explored the utility of a metabolomic-based approach employing the NeoBase 2 MSMS kit to diagnose HIE using dry blood stains in a Rice-Vannucci model of HIE in rats. We evaluated the diagnostic fidelity of this approach in a range between 3 and 6 h after the onset of HIE, including in the context of systemic inflammation and concomitant hypothermic therapy. Discriminant analysis revealed several metabolite patterns associated with HIE. A logistic regression model using glycine levels achieved high diagnostic fidelity with areas under the receiver operating characteristic curve of 0.94 at 3 h and 0.96 at 6 h after the onset of HIE. In addition, orthogonal partial least squares discriminant analysis, which included five metabolites, achieved 100% sensitivity and 80% specificity within 3 h of HIE. These results highlight the significant potential of the NeoBase 2 MSMS kit for the early diagnosis of HIE and could improve patient management and outcomes in this serious illness.

Neurodevelopmental evaluation of newborns who underwent hypothermia with a diagnosis of hypoxic ischemic encephalopathy based on the Bayley-III scale.

Hypoxic ischemic encephalopathy (HIE) is one of the common causes of mortality and morbidity in newborns. Despite therapeutic hypothermia, an important treatment with proven efficacy, the morbidity and mortality rates remain high. The aim of this study was to neurodevelopmentally evaluate patients who underwent therapeutic hypothermia. Included herein were patients who underwent hypothermia between 2018 and 2020. Their medical files were reviewed retrospectively, and their demographic and clinical information was recorded. Patients whose contact information was available were called to the developmental pediatrics outpatient clinic for a neurodevelopmental evaluation. The Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III) was used as the evaluation tool. Laboratory values and clinical parameters of the patients were further analyzed. It was found that 42 patients underwent hypothermia in 3 years, of whom 14 (33.3%) had died. Of the 28 patients who were discharged, 20 children could be reached, and a neurodevelopmental evaluation was performed. Developmental delay in the cognitive area was detected in 11 (55%) patients, delay in the language area was found in 9 (45%) patients, and delay in the motor area was found in 11 (55%) patients. The correlation and regression analysis results determined that the time to start cooling was the most effective common factor in all 3 fields of scoring. The time to start cooling is related to the neurodevelopmental outcomes of patients with HIE. The earlier cooling is started, the better the neurodevelopmental results. Despite therapeutic hypothermia, the neurodevelopmental development of infants may be adversely affected. These patients should be followed-up neurodevelopmentally for a long time.

An audit of electronic discharge summaries of neonates admitted with hypoxic ischaemic encephalopathy to tertiary hospitals in [City], 2018–2019.

Background. A discharge summary may be the only available health record for a patient, especially in resource-limited settings with suboptimal record-keeping. Considering the risk of adverse neurodevelopmental outcomes secondary to hypoxic ischaemic encephalopathy (HIE) and litigation, the quality of summaries for neonates with HIE is particularly important. &#x0D; Objectives. To audit electronic discharge summaries of neonates admitted with HIE to two tertiary hospitals in [City], South Africa. &#x0D; Methods. A retrospective, quantitative study was conducted. Electronic discharge summaries of late preterm and term neonates with HIE, admitted in 2018 and 2019 were audited for relevant information: final diagnosis, birth history, clinical evaluation, management, investigations, plan at discharge, and counselling of parents. &#x0D; Results. Of the 165 identified cases, 34 (20.6%) were excluded. Ten patients did not have electronic discharge summaries. Details of the other 24 cases in admission registers were incomplete. The final diagnosis of HIE appeared in 87 (66.4%) of 131 audited summaries. More than half (52.7%) lacked correct ICD-10 coding for HIE. Information on foetal distress and sentinel events was absent in 61.1% and 42.0%. Requirement for resuscitation was recorded in 90.8% of summaries. Performance of cardiac compressions and adrenaline administration were not specified in 46.6% and 54.2%. Admission blood gas results, particularly base deficit, lactate and glucose, were absent in 42.7%, 63.4% and 90.8% of summaries. Eligibility for therapeutic hypothermia was not captured in 41.2%. Cranial ultrasound, neuro-imaging, exclusion of meningitis, or multisystem involvement was not mentioned in 80.9%, 99.2%, 80.2% and 96.2%, respectively. Notes on counselling of parents were lacking (83.2%). Final cause of death was unspecified in 12 of 14 (85.7%) patients who died. &#x0D; Conclusion. Discharge summaries of neonates at risk of adverse neurodevelopmental outcomes secondary to HIE lacked essential information. Quality improvement and regular auditing of patient records must be prioritised.

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

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. A case-control study was conducted on 38 neonates, and urine samples were collected within 24 and 72h of life. A tandem mass spectrometry-based quantitative proteomics approach, followed by validation via sandwich ELISA, was performed. 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. 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.

Placental pathology in perinatal asphyxia: a case-control study.

Placentas of term infants with birth asphyxia are reported to have more lesion such as maternal vascular malperfusion (MVM), fetal vascular malperfusion (FVM) and chorioamnionitis with fetal response (FIR) than those of term infants without birth asphyxia. We compared the placental pathology of asphyxiated newborns, including those who developed hypoxic-ischemic encephalopathy (HIE), with non-asphyxiated controls. We conducted a retrospective case-control study of placentas from neonates with a gestational age ≥ 35 weeks, a birthweight ≥ 1,800 g, and no malformations. Cases were asphyxiated newborns (defined as those with an umbilical artery pH ≤ 7.0 or base excess ≤ -12 mMol, 10-minute Apgar score ≤ 5, or the need for resuscitation lasting >10 min) from a previous cohort, with (n=32) and without (n=173) diagnosis of HIE. Controls were non-asphyxiated newborns from low-risk l (n= 50) or high-risk (n= 68) pregnancies. Placentas were analyzed according to the Amsterdam Placental Workshop Group Consensus Statement 2014. Cases had a higher prevalence of nulliparity, BMI>25, thick meconium, abnormal fetal heart monitoring, and acute intrapartum events than controls (p<0.001). MVM and FVM were more frequent among non-asphyxiated than asphyxiated newborns (p<0.001). There was no significant difference in inflammatory lesions or abnormal umbilical insertion site. Histologic meconium-associated changes (MAC) were observed in asphyxiated newborns only (p= 0.039). Our results confirm the role of antepartum and intrapartum risk factors in neonatal asphyxia and HIE. No association between neonatal asphyxia and placental lesions was found, except for in the case of MAC. The association between clinical and placental data is crucial to understanding and possibly preventing perinatal asphyxia in subsequent pregnancies.

Perinatal Hypoxic-Ischemic Encephalopathy: Incidence Over Time Within a Modern US Birth Cohort

BackgroundRecent studies suggest that the incidence of perinatal hypoxic-ischemic encephalopathy (HIE) may be increasing in developed countries. However, this observed increase may be due to increased ascertainment and increased treatment with therapeutic hypothermia rather than an increase in disease burden. In a US population-based cross-sectional study, we determined the incidence of perinatal HIE over time. MethodsThe study population included all 289,793 live-born infants ≥35 weeks gestational age born at 15 Kaiser Permanente Northern California hospitals between 2012 and 2019. Perinatal HIE was defined as the presence of both neonatal acidosis (i.e., cord blood pH < 7 or base deficit ≥10, or base deficit ≥10 on first infant gas) and neonatal encephalopathy confirmed by medical record review. Hospital discharge diagnoses of HIE were determined by extracting International Classification of Disease diagnostic codes for HIE assigned upon hospital discharge. ResultsThe population incidence of perinatal HIE was 1.7 per 1000. Although the incidence of perinatal HIE did not change significantly, both hospital discharge diagnoses of HIE and treatment with therapeutic hypothermia increased significantly during the study period. The sensitivity and positive predictive value of a hospital discharge diagnosis of HIE for identifying perinatal HIE confirmed by chart review were 72% and 79%, respectively. ConclusionsDuring the study years, the incidence of perinatal HIE remained stable despite increases in hospital discharge diagnoses of HIE and in the use of therapeutic hypothermia. Our findings underscore the importance of applying stringent diagnostic criteria when diagnosing this complex condition.

The Role of Transcranial Grayscale and Doppler Ultrasound Examination in Diagnosis of Neonatal Hypoxic-Ischemic Encephalopathy

Objectives To evaluate role of transcranial grayscale ultrasound (TC-GSUS) and transcranial color Doppler (TCD) in diagnosis of neonatal Hypoxic-ischemic encephalopathy (HIE). Materials &amp; Methods 26 neonates with suspected HIE underwent sonographic examinations using SonoScape SSI-6000 ultrasound device that is equipped by L743 linear array probe with frequency 5-10 MHz. TC-GSUS was performed at levels of anterior, mastoid and posterior fontanelles and at level of temporal window. TCD was performed using Color-coded Doppler study of the intracerebral vessels to assess brain perfusion and detect ischemic brain changes. Resistance index (RI) was considered abnormal in preterm neonates if it was &amp;lt;0.54 or &amp;gt; 0.86 and if it was &amp;lt;0.52 or &amp;gt; 0.8 for term neonates. Results According to cranial biometry, TC-GSUS has negative and positive rates for HIE of 7.7% and 92.3%, respectively. Using TC-GSUS periventricular leukomalacia, intraventricular hemorrhage, brain edema and hydrocephalus were detected in 17, 19, 14 and 16 patients, respectively. According to RI of intracranial vessels, TCD excluded HIE in 11 patients and assured diagnosis of HIE in 15 patients. TC-GSUS can diagnose HIE in neonates with sensitivity, specificity and accuracy rates of 87.5%, 30% and 65.4%, respectively. ROC curve analysis defined abnormally high RI of intracranial arteries as the significant specific predictor for the presence of NHIE and as the significant sensitive predictor for HIE severity grade. Regression analysis defined high RI of internal carotid artery (ICA) as the most specific predictor for presence of HIE, while high RI of anterior cerebral artery (ACA) was the most sensitive predictor for high grade HIE. Conclusion TCD can diagnose HIE in neonates with high sensitivity and specificity and abnormal RI of ICA and ACA could be used as accurate diagnostic tests. Whenever, TCD was unavailable, TC-GSUS could diagnose HIE with accuracy rate of 65.4% versus TCD.

An Exploratory Analysis of Gastrointestinal Morbidities and Feeding Outcomes Associated with Neonatal Hypoxic-Ischemic Encephalopathy With or Without Hypothermia Therapy.

This study investigates the clinical profile and predictors of gastrointestinal/hepatic morbidities and feeding outcomes among neonates with hypoxic-ischemic encephalopathy (HIE). A single-center retrospective chart review of consecutive neonates >35 weeks of gestation admitted with a diagnosis of HIE between January 1, 2015, and December 31, 2020, and treated with therapeutic hypothermia, if met the institutional eligibility criteria. Outcomes assessed included necrotizing enterocolitis (NEC), conjugated hyperbilirubinemia, hepatic dysfunction, assisted feeding at discharge, and time to reach full enteral and oral feeds. Among 240 eligible neonates (gestational age 38.7 [1.7] weeks, birth weight 3279 [551] g), 148 (62%) received hypothermia therapy, and 7 (3%) and 5 (2%) were diagnosed with stage 1 NEC and stage 2-3 NEC, respectively. Twenty-nine (12%) were discharged home with a gastrostomy/gavage tube, conjugated hyperbilirubinemia (first week 22 [9%], at discharge 19 [8%]), and hepatic dysfunction (74 [31%]). Time to reach full oral feeds was significantly longer in hypothermic neonates compared with neonates who did not receive hypothermia (9 [7-12] days vs. 4.5 [3-9] days, p < 0.0001). Factors significantly associated with NEC were renal failure (odds ratio [OR] 9.24, 95% confidence interval [CI] 2.7-33), hepatic dysfunction (OR 5.69, 95% CI 1.6-26), and thrombocytopenia (OR 3.6, 95% CI 1.1-12), but no significant association with hypothermia, severity of brain injury, or stage of encephalopathy. Transient conjugated hyperbilirubinemia, hepatic dysfunction within first week of life, and need for assistive feeding are more common than NEC in HIE. Risk of NEC was associated with the severity of end-organ dysfunction in the first week of life, rather than severity of brain injury and hypothermia therapy per se.

Literature review: neonatal therapeutic hypothermia – treatment, which is not meeting the standart

Viktorija Zamaliauskaitė1, Renata Dzikienė2 1Lithuanian University of Health Sciences, Faculty of Medicine, Kaunas, Lithuania 2Hospital of Lithuanian University of Health Sciences Kaunas Clinics, Department of Neonatology, Kaunas, Lithuania Abstract Bacground. Perinatal asphyxia and neonatal hypoxic ischemic encephalopathy (HIE) result in high mortality. Therapeutic hypothermia (TH) is known to improve the outlying outcomes of these patients, but there are still questions about how to treat patients who do not meet the eligibility criteria for treatment set out in the guidelines. The aim: to analyze and compare the outcome of preterm infants diagnosed with hypoxic-ischemic encephalopathy and treated with therapeutic hypothermia, and patients with therapeutic hypothermia applied after more than 6 hours after birth. Methods. Analysis of articles published in the last 5 years evaluating outcomes of preterm infants (<36 weeks) with hypoxic ischemic encephalopathy diagnosis and treated with therapeutic hypotermia, and neonates treated with therapeutic hypothermia after 6 hours after birth. Results. The review included 4 studies analyzing issues of effectiveness and safety of substandard treatments. No significant results of neonatal survival were found between the comparator patient groups. Data on mental and psychomotor developmental disorders between term and preterm infants in the adjusted age of 18 and 24 months also did not differ significantly. The studies showed better outcomes in those neonates who did not meet the criteria for therapeutic hypothermia than in those who did not receive therapeutic treatment at all. Conclusions. Studies show that therapeutic hypothermia is increasingly being attempted in preterm infants diagnosed with hypoxic-ischemic encephalopathy and in neonates with more than 6 hours postpartum, but this is not included in the general guidelines due to a lack of evidence. There is a lack of a large-sample studies. This demonstrates the need for more researches to evaluate the safety and efficacy of treatment in this population. Keywords: preterm infants, late therapeutic hypothermia, hypoxic-ischemic encephalopathy, hypoxia. Full article https://doi.org/10.53453/ms.2023.2.10

Clinical Characteristics and Risk Factors of Neonatal Hypoxic-Ischaemic Encephalopathy and Its Associated Neurodevelopmental Outcomes During the First Two Years of Life: A Retrospective Study in Saudi Arabia.

This study aimed to determine the clinical characteristics and factors associated with neonatal hypoxic-ischaemic encephalopathy (HIE) and its neurodevelopmental outcomes. We conductedretrospective case-control researchto investigate the clinical and labour-related risk factors for HIE. In addition, a single-centre cohort study was conducted on infants with HIE to describe their neurodevelopment from birth to 24 months. For this investigation, cases with a diagnosis of HIE who were born at King Abdullah Children's Specialist Hospital (KASCH), Riyadh, Saudi Arabia, between 2015 and 2019 were identified and matched with controls from the same facility (1:4). Each case's clinical information was extracted using electronic medical records. In addition,24-monthfollow-up HIE cases were included in a cohort study to describe their neurodevelopmental outcomes. The sample includes 60 infants diagnosed with HIE and 234 infants serving as controls, with a mean gestational age of 38.8 weeks (SD 1.6)and a predominance of males (56.4%). Around one-thirdof the HIE cases (36.6%) had moderate HIE (stage 2), whereas 35.1% of infants had severe HIE (stage 3), according to Sarnat staging. Compared to the control group, children with HIE were twice as likely to be born to mothers with maternal comorbidities and more likely to have prepartum and intrapartum complications. A 24-month follow-up of neurodevelopmental outcomes for HIE babies revealed that approximately 24% exhibited delays in gross motor skill development, 22% in fine motor skill development, 33% in language skill development, and 22% in social skill development. In the HIE group, maternal comorbidities and prepartumor intrapartum complications were more common. The severity grade of HIE can be used to predict neurodevelopmental consequences. Enhancing patient care and rehabilitation requires a minimum of 24 months of neurodevelopmental follow-up.

La Neonatologia… caso per caso

Neonatal hypotonia, bronchopulmonary dysplasia, necrotizing enterocolitis and persistent hypoglycemia are some of the main topics in neonatology. This work aims to summarize these four neonatal conditions through illustrative clinical cases. The first issue concerns neonatal hypotonia, which can constitute a pivotal sign in the diagnosis of hypoxic ischemic encephalopathy. However, neonatal hypotonia can be present in several other conditions, such as sepsis and neurological or neuromuscular diseases. The second issue is about bronchopulmonary dysplasia, a disease that mainly affects extremely premature infants. Many therapeutic strategies have been proposed to prevent this disease, such as less invasive ventilation and an early use of inhaled and systemic corticosteroids. Long-term respiratory sequelae in infants with bronchopulmonary dysplasia remain one of the main causes of hospitalization in these children in their early years of life. The third issue is necrotizing enterocolitis, a disease that can affect both term and preterm newborns. Multiple risk factors are involved in the pathogenesis of this disease such as an abnormal peripheral perfusion due to congenital heart diseases, small for gestational age (SGA), sepsis, hypoxic-ischemic encephalopathy, chorioamnionitis, intrauterine growth restriction (IUGR). On the other hand, breastfeeding can play as a preventive factor. Finally, the last topic is about the management of persistent hypoglycaemia, a condition that can be caused by the combination of one of the following mechanisms: inadequate glucose supply in an infant with low glycogen stores (preterm, IUGR, SGA); excessive insulin production (maternal diabetes, large for gestational age); failure of counter-regulatory response to hy-poglycaemia (pituitary or adrenal deficiency

Volumetric apparent diffusion coefficient (ADC) histogram analysis of the brain in paediatric patients with hypoxic ischaemic encephalopathy.

To evaluate the whole brain, hippocampus, thalamus, and lentiform nucleus by volumetric apparent diffusion coefficient (ADC) histogram analysis in paediatric patients with hypoxic-ischaemic encephalopathy (HIE). This retrospective study included 25 patients with HIE and 50 patients as the control group. Diffusion-weighted imaging was obtained at b-values of 1000 mm2/s. The histogram parameters of ADC values, including the mean, minimum, maximum, 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles, as well as skewness, kurtosis, and variance were determined. The interclass correlation coefficient (ICC) was used to assess the inter-observer agreement. ADCmin, ADCmean, and ADCmax, as well as the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of ADC values for the HIE group were all lower than those of the control group (p < 0.001) in the volumetric histogram analysis of the hippocampus, thalamus, and lentiform nucleus. In the whole-brain histogram analysis, ADC min, and the 50th and 75th percentiles of ADC values did not differ significantly, while other parameters were lower in the HIE group. The ROC curve revealed that the ADC histogram parameters of the hippocampus provided the most accurate results for the diagnosis of HIE. The area under the curve (AUC) of the 95th percentile of ADC values was the highest (AUC = 0.915; cut-off 1.262 × 10-3 mm2/s; sensitivity 88% and specificity 84%). Volumetric ADC histogram analysis of the whole brain, hippocampus, thalamus, and lentiform nucleus with b-values of 1000 mm2/s can serve as an imaging marker for determining HIE.

Graphic Intelligent Diagnosis of Hypoxic-Ischemic Encephalopathy Using MRI-Based Deep Learning Model

Introduction: Heterogeneous MRI manifestations restrict the efficiency and consistency of neuroradiologists in diagnosing hypoxic-ischemic encephalopathy (HIE) due to complex injury patterns. This study aimed to develop and validate an intelligent HIE identification model (termed as DLCRN, deep learning clinical-radiomics nomogram) based on conventional structural MRI and clinical characteristics. Methods: In this retrospective case-control study, full-term neonates with HIE and healthy controls were collected in two different medical centers from January 2015 to December 2020. Multivariable logistic regression analysis was implemented to establish the DLCRN model based on conventional MRI sequences and clinical characteristics. Discrimination, calibration, and clinical applicability were used to evaluate the model in the training and validation cohorts. Grad-class activation map algorithm was implemented to visualize the DLCRN. Results: 186 HIE patients and 219 healthy controls were assigned to the training, internal validation, and independent validation cohorts. Birthweight was incorporated with deep radiomics signatures to create the final DLCRN model. The DLCRN model achieved better discriminatory power than simple radiomics models, with an area under the curve (AUC) of 0.868, 0.813, and 0.798 in the training, internal validation, and independent validation cohorts, respectively. The DLCRN model was well calibrated and has clinical potential. Visualization of the DLCRN highlighted the lesion areas that conformed to radiological identification. Conclusion: Visualized DLCRN may be a useful tool in the objective and quantitative identification of HIE. Scientific application of the optimized DLCRN model may save time for screening early mild HIE, improve the consistency of HIE diagnosis, and guide timely clinical management.