Cerebral rScO2 Measured by Near-Infrared Spectroscopy (NIRS) During Therapeutic Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy: A Systematic Review.

INTRODUCTION: Perinatal asphyxia, a leading cause of neonatal mortality and neurological sequelae, necessitates early detection of pathophysiological neurologic changes during hypoxic-ischaemic encephalopathy (HIE). This study aimed to review published data on rScO2 monitoring during hypothermia treatment in neonates with perinatal asphyxia to predict short- and long-term neurological injury. METHODS: A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Study identification was performed through a search between November and December 2021 in the electronic databases PubMed, Embase, Lilacs, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL). The main outcome was short-term (Changes in brain magnetic resonating imaging) and long-term (In neurodevelopment) neurological injury. The study protocol was registered in PROSPERO (International Prospective Register of Systematic Reviews) with CRD42023395438. RESULTS: 380 articles were collected from databases in the initial search. Finally, 15 articles were selected for extraction and analysis of the information. An increase in rScO2 measured by NIRS (Near-infrared spectroscopy) at different moments of treatment predicts neurological injury. However, there exists a wide variability in the methods and outcomes of the studies. CONCLUSION: High rScO2 values were found to predict negative outcomes, with substantial discord among studies. NIRS is proposed as a real-time bedside tool for predicting brain injury in neonates with moderate to severe HIE.

Prevalence of Perinatal Asphyxia Using Apgar Scores and Cord Blood pH and the Relationship between the Two Methods: A Study of FMC Umuahia.

BACKGROUND: Perinatal asphyxia contributes significantly to neonatal morbidity and mortality. It occurs worldwide, and the Apgar score is the most widely used method of diagnosis. Recently, umbilical cord arterial pH has been reported as the most objective way to assess fetal acidosis at birth as it predicts the adverse outcome of perinatal asphyxia. It is imperative to establish the concordance between these two diagnostic methods to reinforce the practicality of the Apgar score as the preferred diagnostic tool for perinatal asphyxia in developing nations, such as Nigeria. AIM: To determine the prevalence of perinatal asphyxia by using the Apgar score and arterial cord blood pH and the relationships between these methods at the Federal Medical Center (FMC), Umuahia. MATERIALS AND METHODS: This cross-sectional study enrolled 245-term newborns. Perinatal asphyxia was diagnosed using both Apgar scoring and arterial cord blood pH measurements. Data obtained were analyzed using SPSS version 20 and a P value < 0.05 was considered significant. RESULTS: Perinatal asphyxia was reported in 33.1% and 31.4% by using the Apgar score and arterial cord blood pH, respectively. There was a moderate agreement between the two methods for diagnosing perinatal asphyxia (κ = 0.44), and no statistically significant difference was observed in the prevalence of perinatal asphyxia between these methods (McNemar's χ2 = 0.27, P = 0.699). Furthermore, a strong positive correlation was observed between the Apgar score at 1 and 5 minutes of life and arterial cord blood pH (rs = 0.87, P ≤ 0.001 and rs = 0.80, P ≤ 0.001 respectively). CONCLUSION: The prevalence of perinatal asphyxia by the two methods was high, and there was no significant difference between both methods of assessing perinatal asphyxia. Thus, the diagnosis of perinatal asphyxia can effectively be made using either the Apgar score or arterial cord blood pH, affirming the practicality and reliability of the Apgar score in resource-limited healthcare settings.

Perinatal asphyxia and hypothermic treatment from the endocrine perspective.

Introduction: Perinatal asphyxia is one of the three most important causes of neonatal mortality and morbidity. Therapeutic hypothermia represents the standard treatment for infants with moderate-severe perinatal asphyxia, resulting in reduction in the mortality and major neurodevelopmental disability. So far, data in the literature focusing on the endocrine aspects of both asphyxia and hypothermia treatment at birth are scanty, and many aspects are still debated. Aim of this narrative review is to summarize the current knowledge regarding the short- and long-term effects of perinatal asphyxia and of hypothermia treatment on the endocrine system, thus providing suggestions for improving the management of asphyxiated children. Results: Involvement of the endocrine system (especially glucose and electrolyte disturbances, adrenal hemorrhage, non-thyroidal illness syndrome) can occur in a variable percentage of subjects with perinatal asphyxia, potentially affecting mortality as well as neurological outcome. Hypothermia may also affect endocrine homeostasis, leading to a decreased incidence of hypocalcemia and an increased risk of dilutional hyponatremia and hypercalcemia. Conclusions: Metabolic abnormalities in the context of perinatal asphyxia are important modifiable factors that may be associated with a worse outcome. Therefore, clinicians should be aware of the possible occurrence of endocrine complication, in order to establish appropriate screening protocols and allow timely treatment.

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

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

A comparative analysis of APGAR score and the gold standard in the diagnosis of birth asphyxia at a tertiary health facility in Kenya.

BACKGROUND: Birth asphyxia is a consistent key contributor to neonatal morbidity and mortality, notably in sub-Saharan Africa. The APGAR score, though a globally used diagnostic tool for birth asphyxia, remains largely understudied especially in resource-poor settings. OBJECTIVE: This study determined how effectively the APGAR score is used to diagnose birth asphyxia in comparison to the gold standard (umbilical cord blood pH <7 with neurologic involvement) at Moi Teaching and Referral Hospital (MTRH), and identified healthcare provider factors that affect ineffective use of the score. METHODS: Using a quantitative cross-sectional hospital-based design, term babies born in MTRH who weighed ≥2500g were randomly and systematically sampled; and healthcare providers who assign APGAR scores were enrolled via a census. Umbilical cord blood was drawn at birth and at 5minutes for pH analysis. APGAR scores assigned by healthcare providers were recorded. Effective use of the APGAR score was determined by sensitivity, specificity, positive and negative predictive values. At a significance level of 0.05, multiple logistic regression analysis identified the independent provider-associated factors affecting ineffective use of the APGAR score. RESULTS: We enrolled 102 babies, and 50 (49%) were females. Among the 64 healthcare providers recruited, 40 (63%) were female and the median age was 34.5years [IQR: 31.0, 37.0]. Assigned APGAR scores had a sensitivity of 71% and specificity of 89%, with positive and negative predictive values of 62% and 92% respectively. Healthcare provider factors associated with ineffective APGAR score use included: instrumental delivery (OR: 8.83 [95% CI: 0.79, 199]), lack of access to APGAR scoring charts (OR: 56.0 [95% CI: 12.9, 322.3]), and neonatal resuscitation (OR: 23.83 [95% CI: 6.72, 101.99]). CONCLUSION: Assigned APGAR scores had low sensitivity and positive predictive values. Healthcare provider factors independently associated with ineffective APGAR scoring include; instrumental delivery, lack of access to APGAR scoring charts, and neonatal resuscitation.

Biomarkers of hypoxic-ischemic encephalopathy: a systematic review.

BACKGROUND: Current diagnostic criteria for hypoxic-ischemic encephalopathy in the early hours lack objective measurement tools. Therefore, this systematic review aims to identify putative molecules that can be used in diagnosis in daily clinical practice (PROSPERO ID: CRD42021272610). DATA SOURCES: Searches were performed in PubMed, Web of Science, and Science Direct databases until November 2020. English original papers analyzing samples from newborns > 36 weeks that met at least two American College of Obstetricians and Gynecologists diagnostic criteria and/or imaging evidence of cerebral damage were included. Bias was assessed by the Newcastle-Ottawa Scale. The search and data extraction were verified by two authors separately. RESULTS: From 373 papers, 30 met the inclusion criteria. Data from samples collected in the first 72 hours were extracted, and increased serum levels of neuron-specific enolase and S100-calcium-binding protein-B were associated with a worse prognosis in newborns that suffered an episode of perinatal asphyxia. In addition, the levels of glial fibrillary acidic protein, ubiquitin carboxyl terminal hydrolase isozyme-L1, glutamic pyruvic transaminase-2, lactate, and glucose were elevated in newborns diagnosed with hypoxic-ischemic encephalopathy. Moreover, pathway analysis revealed insulin-like growth factor signaling and alanine, aspartate and glutamate metabolism to be involved in the early molecular response to insult. CONCLUSIONS: Neuron-specific enolase and S100-calcium-binding protein-B are potential biomarkers, since they are correlated with an unfavorable outcome of hypoxic-ischemic encephalopathy newborns. However, more studies are required to determine the sensitivity and specificity of this approach to be validated for clinical practice.

Machine learning models based on clinical indices and cardiotocographic features for discriminating asphyxia fetuses-Porto retrospective intrapartum study.

Introduction: Perinatal asphyxia is one of the most frequent causes of neonatal mortality, affecting approximately four million newborns worldwide each year and causing the death of one million individuals. One of the main reasons for these high incidences is the lack of consensual methods of early diagnosis for this pathology. Estimating risk-appropriate health care for mother and baby is essential for increasing the quality of the health care system. Thus, it is necessary to investigate models that improve the prediction of perinatal asphyxia. Access to the cardiotocographic signals (CTGs) in conjunction with various clinical parameters can be crucial for the development of a successful model. Objectives: This exploratory work aims to develop predictive models of perinatal asphyxia based on clinical parameters and fetal heart rate (fHR) indices. Methods: Single gestations data from a retrospective unicentric study from Centro Hospitalar e Universitário do Porto de São João (CHUSJ) between 2010 and 2018 was probed. The CTGs were acquired and analyzed by Omniview-SisPorto, estimating several fHR features. The clinical variables were obtained from the electronic clinical records stored by ObsCare. Entropy and compression characterized the complexity of the fHR time series. These variables' contribution to the prediction of asphyxia perinatal was probed by binary logistic regression (BLR) and Naive-Bayes (NB) models. Results: The data consisted of 517 cases, with 15 pathological cases. The asphyxia prediction models showed promising results, with an area under the receiver operator characteristic curve (AUC) >70%. In NB approaches, the best models combined clinical and SisPorto features. The best model was the univariate BLR with the variable compression ratio scale 2 (CR2) and an AUC of 94.93% [94.55; 95.31%]. Conclusion: Both BLR and Bayesian models have advantages and disadvantages. The model with the best performance predicting perinatal asphyxia was the univariate BLR with the CR2 variable, demonstrating the importance of non-linear indices in perinatal asphyxia detection. Future studies should explore decision support systems to detect sepsis, including clinical and CTGs features (linear and non-linear).

Maximizing the detection rate of hypoglycemia among preterm neonates admitted in Neonatal intensive care unit in Ethiopia, 2021.

The burden of hypoglycemia is high in resource limited countries, such as Ethiopia. However, there are no sufficient studies conducted in Ethiopia in general and in the study setting in particular in the previous era. Hence, this study aims to assess the proportion of hypoglycemia and associated factors among preterm neonates admitted to the neonatal intensive care unit at Debre Tabor Comprehensive Specialized Hospital, Ethiopia, in 2021. A hospital-based cross-sectional study was conducted from October 1 to December 30, 2021, at Debre Tabor Comprehensive Specialized Hospital in the neonatal intensive care unit ward. The data was entered in Epi-info 7 and exported to STATA version 14. A binary and multivariable logistic regression was computed at 95% confidence interval (CI). During bivariable analysis, variables having a p-value of less than 0.25 were chosen for multivariable logistic regression analysis, and variables having a p-value of less than 0.05 in multivariable analysis, were significant associations with the dependent variable. The study included 267 preterm neonates, and 23.59% (95% CI 18.9-29.1) were develop hypoglycemia. Moreover, 49 (18.35%) preterm neonates died during the study period. In this study, preterm neonates with hypothermia [Adjusted Odds Ratio (AOR = 4.5; 95 CI 3.4, 7.2)], birth asphyxia (AOR = 5.1; 95 CI 3.9, 27.1), seizure (AOR = 4.7; 95 CI 2.8, 17.8), and also preterm neonates born from diabetic mothers (AOR = 6.7; 95 CI 3.3, 27.2) were significantly associated with the occurrence of hypoglycemia in the neonatal intensive care. The proportion of hypoglycemia and associated factors among preterm neonates admitted to the neonatal intensive care unit at Debre Tabor Comprehensive Specialized Hospital was found to be high. The associated factors for the occurrence of hypoglycemia were discovered to be neonates with hypothermia, birth asphyxia, seizure, and neonates born with a diabetes mother. Thus, recognizing and treating the above associated factors is essential to preventing, and controlling hypoglycemia.

The Utility of Simulation-Based Training in Teaching Frontline Providers Modified Sarnat Encephalopathy Examination: A Randomized Controlled Pilot Trial.

BACKGROUND: Limited training in targeted neurological examination makes it challenging for frontline providers to identify newborns with perinatal asphyxia eligible for therapeutic hypothermia. This training is important in the era of telemedicine, where the experts can remotely guide further care of these newborns. METHODS: This randomized controlled pilot study was conducted in a South Indian tertiary hospital. Neonatal nurses, who had no previous hands-on experience in MSEE, were trained in modified Sarnat staging by a didactic teaching session using online teaching module. The nurses were then randomized into two groups for hands-on demonstration by the same trainer (low-fidelity mannequin versus a healthy term newly born infant). After the training period, MSEEs of a normal newborn were performed independently by nurses and were video recorded and assessed by three blinded neonatologists with expertise in neonatal neurology. A follow-up examination was performed by the same nurses after three months to assess skill retention. RESULTS: The 10 global ratings of the components of the MSEE were comparable among both groups in both initial and follow-up assessments. The overall diagnostic value was comparable between the simulation and traditional groups (93.75%, 94.11%, respectively). Follow-up examination after three months showed better skill retention in the simulation group (84%) compared with the traditional group (66.7%). CONCLUSIONS: Online-based and low-fidelity mannequin training was equally effective as the traditional method of teaching MSEE in term neonates.

High incidence of poor in-hospital outcomes of term newborns with hypoxic-ischaemic encephalopathy admitted at a regional referral hospital in Dodoma, Tanzania.

AIM: Hypoxic-ischaemic encephalopathy (HIE) is one of the leading causes of neonatal deaths and neurological impairment with the highest impact in resource-limited settings. This study aimed to determine the incidence of poor in-hospital outcomes and related factors among newborns with HIE in Tanzania. METHODS: A prospective observational study in which 170 newborns with HIE (diagnosed using the Thompson clinical score) were followed from 1 September 2020 to 28 February 2021 at the neonatal ward of Dodoma Regional Referral Hospital in Dodoma, central Tanzania, until discharge or death. Clinical parameters were recorded. Multinomial logistic regression analysis was applied to determine factors associated with adverse outcomes. RESULTS: Out of 170 newborns, 44.7% (76/170) had poor outcomes (death 27.1% (46/170); neurological deficits 17.6% (30/170)). Severe HIE (Thompson score > 14) (p < 0.0001), history of aspiration (adjusted odds ratio (AOR) = 3.06, 95% confidence interval (CI) [1.170, 8.014], p = 0.0226) and 5th-min APGAR of <7 (AOR = 2.88, 95% CI [1.133, 7.310], p = 0.0262) were associated with mortality. Severe HIE, delivery at other facilities (AOR = 3.106 CI [1.158, 8.332], p = 0.0244) and abnormal heart rate (<100 or ≥160 beats/min) on admission (AOR = 3.469 [1.200, 10.030], p = 0.0216) predicted neurological impairment at discharge. CONCLUSION: Hypoxic-ischaemic encephalopathy is associated with a high incidence of poor outcomes in resource-limited settings. To improve outcomes newborns with severe HIE, history of aspiration, referred from other facilities, 5th-min APGAR score of <7 and abnormal heart rate need improved quality of neonatal care.

Prognostic risk score development to predict birth asphyxia using maternal and fetal characteristics in South Gondar zone hospitals, north West Ethiopia.

BACKGROUND: Birth asphyxia leads to profound systemic and neurological sequela to decrease blood flow or oxygen to the fetus followed by lethal progressive or irreversible life-long pathologies. In low resource setting countries, birth asphyxia remains a critical condition. This study aimed to develop and validate prognostic risk scores to forecast birth asphyxia using maternal and neonatal characteristics in south Gondar zone hospitals. METHODS: Prospective cohorts of 404 pregnant women were included in the model in south Gondar Zone Hospitals, Northwest Ethiopia. To recognize potential prognostic determinants for birth asphyxia, multivariable logistic regression was applied. The model discrimination probability was checked using the receiver operating characteristic curve (AUROC) and the model calibration plot was assessed using the 'givitiR' R-package. To check the clinical importance of the model, a cost-benefit analysis was done through a decision curve and the model was internally validated using bootstrapping. Lastly, a risk score prediction measurement was established for simple application. RESULTS: Of 404, 108 (26.73%) (95% CI: 22.6-31.3) newborns were exposed to birth asphyxia during the follow-up time. Premature rupture of membrane, meconium aspiration syndrome, malpresentation, prolonged labor, Preterm, and tight nuchal was the significant prognostic predictors of birth asphyxia. The AUROC curve for birth asphyxia was 88.6% (95% CI: 84.6-92.2%), which indicated that the tool identified the newborns at risk for birth asphyxia very well. The AUROC of the simplified risk score algorithm, was 87.9 (95% CI, 84.0- 91.7%) and the risk score value of 2 was selected as the optimal cut-off value, with a sensitivity of 78.87%, a specificity of 83.26%, a positive predictive value of 63.23%, and a negative predictive value of 91.52%. CONCLUSIONS: We established birth asphyxia prediction tools by applying non-sophisticated maternal and neonatal characteristics for resource scares countries. The driven score has very good discriminative ability and prediction performance. This risk score tool would allow reducing neonatal morbidity and mortality related to birth asphyxia. Consequently, it will improve the overall neonatal health / under-five child health in low-income countries.

Hearing Impairment in Infants with Asphyxia.

In recent decades, despite significant advances in medicine and perinatal care, asphyxia remains a serious condition, leading to significant mortality and morbidity. The incidence of severe perinatal asphyxia varies from 1 to 3 per 1000 live births, in developed countries 5-10 per 1000 or more in developing countries, and is the third most common cause of neonatal death (23%) after preterm birth (28%) and severe infection (26%). Neonatal asphyxia is often accompanied by multiple organ failure, mainly involving the kidneys, brain, and heart. Asphyxia results in significant tissue hypoperfusion and reduced oxygen supply, which can cause neurological damage and damage to cochlear hair cells. Under our supervision were 35 (n=30) newborns who were in the neonatal intensive care unit of the Perinatal Center of the Khorezm region in the period from 2018 to 2019. Of these, 22 (I (main) group n=22), who were in the neonatal pathology department, had signs of perinatal CNS damage; The comparison group included 13 newborns (n=13), with Apgar scores >7 in the first minute. There is a clear correlation between the degree of hearing impairment in infants and the degree of pathology of the CNS. However, the degree of impairment of the auditory analyzer increased in parallel with the degree of asphyxia and severity (P≤0,05).

Inter-observer reliability for amplitude-integrated electroencephalography in the newborn with perinatal asphyxia.

INTRODUCTION: Amplitude integrated electroencephalography (aEEG) is a tool widely used for neuromonitoring in the critical neonate. In the patient with perinatal asphyxia, its interpretation is key to identifying candidates for therapeutic hypothermia, detecting subclinical seizures and providing pronostic information. Our aim was to analyze the concordance in the interpretation of aEEG among neonatologists with different levels of experience. MATERIAL AND METHODS: Unicenter retrospective study of newborns ≥ 35 weeks with perinatal asphyxia included consecutively over a two-year period and monitored with aEEG for at least 6 h. The bedside neonatologist interpreted aEEG regarding background pattern, sleep-wake cycling, and seizures. The aEEG tracings were blindly reviewed by two neonatologists with different experience. The aEEG tracings were divided into periods of 0-3 h and 3-6 h of life, and the concordance (Cohen Kappa coefficient, k), between the two examiners and that of their consensus with the bedside neonatologist, was analyzed. RESULTS: Seventy-five newborns were included, 5 of them were not aEEG-monitored. 132 tracings were analyzed with a very good concordance between the two examiners in the three characteristics of the aEEG. The k for the bedside neonatologist was very good for background pattern (k = 0.93), moderate (k = 0.52) for sleep-wake cycling, and weak (k = 0.32) for seizures. CONCLUSIONS: This study supports that background pattern is easily interpreted compared to sleep-wake cycling or crisis, improving when targeted training on aEEG is received.

Predictive accuracy of admission cardiotocography as a screening tool for perinatal asphyxia in high-risk parturients in Northern Nigeria.

OBJECTIVE: To determine the predictive accuracy of admission cardiotocography (CTG) as a screening test for perinatal asphyxia in high-risk parturients. METHODS: A prospective study was done on a group of 180 high-risk parturients in the labor ward of Aminu Kano Teaching Hospital were subjected to a 30-min admission cardiotocography. Results were categorized based on the RCOG criteria. Those with normal results were allowed to progress in labor, while those with abnormal results had their delivery expedited. Umbilical artery blood gas analysis was done at delivery. Measured variables were expressed in descriptive statistics. Tests of association for categorical variables were done using the non-parametric chi-square test (P-value of ≤0.05). The Binary logistic regression model was used to control potential confounders. RESULTS: After excluding five cord blood samples, 175 samples were analyzed. The CTG was reassuring in 149 (85.1%), non-reassuring in 15 (8.6%), and abnormal in 11 (6.3%) women. Fetal distress developed in 5 (3.4%) and 7 (46.7%) of reassuring and non-reassuring groups, respectively. The test had 91% sensitivity, specificity was 68.8%, and the predictive accuracy was 88.6% for asphyxia using base deficit. CONCLUSION: The admission that cardiotocography is useful in detecting fetuses at risk of perinatal asphyxia in high-risk deliveries.

Two Useful Umbilical Biomarkers for Therapeutic Hypothermia Decision in Patients with Hypoxic Ischemic Encephalopathy with Perinatal Asphyxia: Netrin-1 and Neuron Specific Enolase.

Hypoxic-ischemic encephalopathy (HIE) has a high risk of mortality in addition to serious neurological damage. In this study, we investigated the values of umbilical cord netrin-1 (NT-1) and neuron specific enolase (NSE) levels in the early diagnosis of HIE stage II/III induced by neonatal asphyxia.In the study group, infants with gestational age ≥ 36 weeks who were diagnosed with HIE II/III were included. NT-1 and NSE levels were measured from the umbilical cord immediately after birth. Results were compared between HIE II/III and the healthy control group. Cutoff values for serum NT-1 and NSE were determined with receiver-operating characteristics curves and the area under the curve (AUC) was used to determine the diagnostic value of NT-1 and NSE levels in infants diagnosed with HIE II/III.NT-1 (358.3 ± 108.3 pg/mL) and NSE (52.97 ± 17.8 ng/mL) levels in the cord blood in the HIE group were significantly higher (p = .030, p = .001, respectively) than cord blood values in the control group (NT-1 (275.1 ± 84.6 pg/mL) and NSE (28.7 ± 16.3 ng/mL)). NT-1 cutoff value for HIE was 292.3 pg/mL and 34.7 ng/mL for NSE (AUC: 990, sensitivity: 94%, specificity 100% and AUC: 1.0, sensitivity: 100% vs. specificity 100%, respectively).NT-1 and NSE represent candidate biomarkers with high reliability in the prediction in newborns with moderate-to-severe HIE.

Use of cardiac troponin I (cTnI) levels to diagnose severe hypoxia and myocardial injury induced by perinatal asphyxia in neonatal dogs.

Prolonged perinatal asphyxia and subsequent severe hypoxia are the main causes of mortality in neonatal dogs in the first days of life. In medicine, specific cardiac biochemical markers, such as troponin I, are used to diagnose ischemic and nonischemic myocardial injury in asphyxiated newborns after birth. Thus, the objectives of this study were to compare the levels of cardiac troponin I (cTnI) between asphyxiated and nonasphyxiated newborn dogs and evaluate the correlations of cTnI levels with the modified Apgar score, the levels of oxygen saturation, blood glucose, and lactatemia, and blood gas parameters. This study aimed to determine the possible use of cTnI as a marker of severe hypoxia and myocardial ischemic injury in neonatal dogs. Fifteen animals in a eutocic vaginal delivery group (VG), 15 animals in a cesarean section group (CG), and 13 animals in a hypoxia (asphyxiated) group (HG) were evaluated. The animals in the asphyxiated group were from dystocic deliveries and born by vaginal delivery or cesarean section. All groups were evaluated at birth and after 60 min. The newborns in the VG and CG exhibited mixed acidosis (respiratory acidosis due to increased partial pressure of CO2 (pCO2) and metabolic acidosis due to reduced pH and bicarbonate (HCO3) levels, base excess/deficit in the extracellular fluid compartment (BEecf), and increased lactate levels) due to transient physiological hypoxemia at birth. The cTnI levels in the VG and CG were within the reference standards for healthy dogs. No correlations between cTnI level and the other parameters were observed in the VG and CG. Newborns in the HG exhibited prominent mixed acidosis (p < 0.05) due to severe hypoxemia. The Apgar score and blood gas parameters showed that these dogs were born asphyxiated, and they presented low vitality and the need for resuscitation maneuvers. The cTnI levels in the HG were significantly higher than those in the VG and CG (p < 0.05) and above the reference standards for healthy dogs, which indicated ischemic myocardial injury. The cTnI level was negatively correlated (p < 0.05) with the parameters Apgar score, heart rate, peripheral oxygen saturation (sO2) level, reflex score, and total carbon dioxide (TCO2) level and positively correlated (p < 0.01) with lactate level. This study showed that asphyxiated newborn dogs have higher serum cTnI levels than nonasphyxiated newborn dogs; thus, the cTnI can be used as a marker of severe hypoxia and ischemic myocardial damage in newborn dogs.

MicroRNA Expression Profiles as Diagnostic and Prognostic Biomarkers of Perinatal Asphyxia and Hypoxic-Ischaemic Encephalopathy.

INTRODUCTION: Perinatal asphyxia is a leading cause of neonatal death. Up to one-third of asphyxiated neonates suffer from hypoxic-ischaemic encephalopathy (HIE) with substantial long-term morbidity. Currently available diagnostic and prognostic tools bear limitations, and additional reliable biomarkers are needed for all stages of clinical management. A novel tool in neuroscientific research is micro-ribonucleic acid (miRNA) profiling. The aim of the present study was to determine miRNA expression profiles of healthy and asphyxiated neonates with and without HIE and to assess their potential as diagnostic and prognostic biomarkers. METHODS: We prospectively enrolled 49 neonates with a gestational age of ≥36 weeks, 15 of which fulfilled the diagnostic criteria of perinatal asphyxia and 34 served as healthy controls. Dried blood spots were collected from umbilical cord blood (UCB) and from venous blood upon admission to neonatal intensive care unit (NICU) and at 48 h of life. Samples were analysed by means of FirePlex™ technology (Abcam, Cambridge, MA, USA). RESULTS: In the UCB, miRNA expression levels of hsa-mir-124-3p, hsa-mir-1285-5p, and hsa-mir-331-5p were significantly lower in asphyxiated neonates compared to healthy controls. Asphyxiated neonates requiring therapeutic hypothermia had significantly increased expression of hsa-miR-30e-5p and significantly decreased expression of hsa-miR-142-3p, hsa-miR-338-3p, hsa-miR-34b-3p, hsa-miR-497-5p, and hsa-miR-98-5p at the time of admission to the NICU. At 48 h, infants suffering from moderate/severe HIE with a poor long-term neurodevelopmental outcome showed a significant increase in hsa-mir-145-5p. DISCUSSION/CONCLUSION: MiRNA profiling shows promise as a biomarker for perinatal asphyxia, hypothermia-requiring HIE, and poor neurodevelopmental outcome. Confirmatory studies are called for.

Prospective observational study of the challenges in diagnosing common neonatal conditions in Nigeria and Kenya.

OBJECTIVES: Accurate and timely diagnosis of common neonatal conditions is crucial for reducing neonatal deaths. In low/middle-income countries with limited resources, there is sparse information on how neonatal diagnoses are made. The aim of this study was to describe the diagnostic criteria used for common conditions in neonatal units (NNUs) in Nigeria and Kenya. DESIGN: Prospective observational study. Standard case report forms for suspected sepsis, respiratory disorders, birth asphyxia and abdominal conditions were co-developed by the Neonatal Nutrition Network (https://www.lstmed.ac.uk/nnu) collaborators. Clinicians completed forms for all admissions to their NNUs. Key data were displayed using heatmaps. SETTING: Five NNUs in Nigeria and two in Kenya comprising the Neonatal Nutrition Network. PARTICIPANTS: 2851 neonates, which included all neonates admitted to the seven NNUs over a 6-month period. RESULTS: 1230 (43.1%) neonates had suspected sepsis, 874 (30.6%) respiratory conditions, 587 (20.6%) birth asphyxia and 71 (2.5%) abdominal conditions. For all conditions and across all NNUs, clinical criteria were used consistently with sparse use of laboratory and radiological criteria. CONCLUSION: Our findings highlight the reliance on clinical criteria and extremely limited use of diagnostic technologies for common conditions in NNUs in sub-Saharan Africa. This has implications for the management of neonatal conditions which often have overlapping clinical features. Strategies for implementation of diagnostic pathways and investment in affordable and sustainable diagnostics are needed to improve care for these vulnerable infants.

Differences in standardized neonatal encephalopathy exam criteria may impact therapeutic hypothermia eligibility.

BACKGROUND: Therapeutic hypothermia (TH) is routinely provided to those with moderate or severe neonatal encephalopathy (NE). Subtle differences exist in the standardized exams used to define NE severity. We aimed to assess if an infant's TH eligibility status differed if they were evaluated using either the NICHD/Neonatal Research Network's (NICHD-NRN) or TOBY/British Association of Perinatal Medicine's (TOBY-BAPM) neurological exam. METHODS: Encephalopathic infants ≥36 weeks with evidence of perinatal asphyxia and complete documentation of the neurological exam <6 h of age were included. TH eligibility using the NICHD-NRN and TOBY-BAPM criteria was determined based upon the documented exams. RESULTS: Ninety-one encephalopathic infants were included. Despite good agreement between the two exams (κ = 0.715, p < 0.001), TH eligibility differed between them (p < 0.001). A total of 47 infants were deemed eligible by at least one method-46 using NICHD-NRN and 35 using TOBY-BAPM. Of the 12 infants eligible per NICHD-NRN, but ineligible per TOBY-BAPM, two developed electrographic seizures and seven demonstrated hypoxic-ischemic cerebral injury. CONCLUSIONS: Both the NICHD-NRN and TOBY-BAPM exams are evidence-based. Despite this, there is a significant difference in the number of infants eligible for TH depending on which exam is used. The NICHD-NRN exam identifies a greater proportion as eligible. IMPACT: There are subtle differences in the NICHD-NRN and TOBY-BAPM's encephalopathy exams used to determine eligibility for TH. This results in a significant difference in the proportion of infants determined to be eligible for TH depending on which encephalopathy exam is used. The NICHD-NRN encephalopathy exam identifies more infants as being eligible for TH than the TOBY-BAPM encephalopathy exam. This may result in different rates of cooling depending on which evidence-based neurological exam for evaluation of encephalopathy a center uses.