Search

Introduction: Hypoxic-ischemic encephalopathy (HIE) affects 1–2 per 1,000 births and is associated with mortality and long-term neurodevelopmental challenges. At present, therapeutic hypothermia (TH) is the only neuroprotective intervention for these infants. This study examines whether HIE severity, clinical management during TH, and post-rewarming outcomes have changed since its introduction 15 years ago. Methods: Neonatal characteristics, HIE severity, management during TH, and post-rewarming MRI of all infants with HIE undergoing TH between 2008 and 2023 were compared across three five-year epochs. Linear regression was used to estimate annual changes over time. Results: In total, 252 infants underwent TH. Median gestational age (39.5 weeks), birth weight (3,376 g), and time to start TH (4.25 h) remained stable over time. Apgar score at 5 min (p = 0.031) and lowest pH <1 h postpartum (p = 0.020) increased over time. Thompson score at 1–3 h decreased across epochs (p = 0.046). There was an increase in percentage with normal-mild aEEG background patterns on admission (p = 0.041) and a decrease in aEEG-confirmed seizures (p < 0.001) and antiseizure medication (p < 0.001). Inotropic support decreased (p = 0.007), and use of invasive mechanical ventilation decreased over the last 5 years. Mortality (28.6%) and post-rewarming composite adverse outcome (i.e., neonatal mortality and/or adverse MRI score) (37.9%) remained unchanged. Number of infants seen at 2-year follow-up increased (p < 0.001). Conclusion: Over the last 15 years, we treated more infants with milder HIE, as indicated by lower Thompson and milder aEEG scores, and the need for invasive cardiorespiratory support declined. However, there were no improvements in composite adverse outcome (mortality and/or adverse MRI score). [ABSTRACT FROM AUTHOR]

• We use qEEG analysis to mimic a visual EEG analysis approach in neonatal hypoxic-ischemic encephalopathy. • Machine learning models were developed and validated on two independent EEG datasets. • The proposed model is effective in discriminating neonates requiring therapeutic hypothermia in the first 6 h of life. The study aimed to address the challenge of early assessment of neonatal hypoxic-ischemic encephalopathy (HIE) severity to identify candidates for therapeutic hypothermia (TH). The objective was to develop an automated classification model for neonatal EEGs, enabling accurate HIE severity assessment 24/7. EEGs recorded within 6 h of life after perinatal anoxia were visually graded into 3 severity groups (HIE French Classification) and quantified using 6 qEEG markers measuring amplitude, continuity and frequency content. Machine learning models were developed on a dataset of 90 EEGs and validated on an independent dataset of 60 EEGs. The selected model achieved an overall accuracy of 80.6% in the development phase and 80% in the validation phase. Notably, the model accurately identified 28 out of 30 children for whom TH was indicated after visual EEG analysis, with only 2 cases (moderate EEG abnormalities) not recommended for cooling. The combination of clinically relevant qEEG markers led to the development of an effective automated EEG classification model, particularly suited for the post-anoxic latency phase. This model successfully discriminated neonates requiring TH. The proposed model has potential as a bedside clinical decision support tool for TH. [ABSTRACT FROM AUTHOR]

Introduction: Perinatal asphyxia initiates cytokine release and complement activation with risk of brain damage. We assessed the effect of nicotine on innate immunity and hypothesized that nicotine infusion in a newborn piglet model of asphyxia would decrease the immune response and be neuroprotective. Methods: Newborn piglets (n = 41) were randomized to one of three groups after hypoxia: two groups receiving nicotine, (1) 18 µg/kg/h (n = 17), (2) 46 µg/kg/h (n = 15), and (3) control group receiving saline (n = 9). C3a, IL-6, TNF, and IL-10 were measured in plasma and IL-6 and IL-8 in microdialysis fluid from cerebral periventricular white matter, using immuno-assays. Results: Plasma C3a and IL-6 increased significantly from start to end hypoxia (mean 4.4 ± 0.55 to 5.6 ± 0.71 ng/mL and 1.66 ± 1.04 to 2.68 ± 0.71 pg/mL, respectively), while IL-10 and TNF increased significantly after 4 h (mean 1.4 ± 1.08 to 2.9 ± 1.87 and 3.3 ± 0.67 to 4.0 ± 0.58 pg/mL, respectively) (p < 0.001 for all). IL-6 increased significantly (p < 0.001) in microdialysis samples from end hypoxia to end experiment (mean 0.65 ± 0.88 to 2.78 ± 1.84 ng/mL). No significant differences were observed between the nicotine groups and the control group neither in plasma nor in microdialysis samples. Conclusion: Hypoxia leads to rapid release of cytokines in plasma and cerebral microdialysis fluid, and complement activation measured on C3a. However, low-dose nicotine administration did not affect the immune response. [ABSTRACT FROM AUTHOR]

Introduction: Brain injury patterns of preterm infants with perinatal asphyxia (PA) are underreported. We aimed to explore brain magnetic resonance imaging (MRI) findings and associated neurodevelopmental outcomes in these newborns. Methods: Retrospective multicenter study included infants with gestational age (GA) 24.0–36.0 weeks and PA, defined as ≥2 of the following: (1) umbilical cord pH ≤7.0, (2) 5-min Apgar score ≤5, and (3) fetal distress or systemic effects of PA. Findings were compared between GA <28.0 (group 1), 28.0–31.9 (group 2), and 32.0–36.0 weeks (group 3). Early MRI (<36 weeks postmenstrual age or <10 postnatal days) was categorized according to predominant injury pattern, and MRI around term-equivalent age (TEA, 36.0–44.0 weeks and ≥10 postnatal days) using the Kidokoro score. Adverse outcomes included death, cerebral palsy, epilepsy, severe hearing/visual impairment, or neurodevelopment <-1 SD at 18–24 months corrected age. Results: One hundred nineteen infants with early MRI (n = 94) and/or MRI around TEA (n = 66) were included. Early MRI showed predominantly hemorrhagic injury in groups 1 (56%) and 2 (45%), and white matter (WM)/watershed injury in group 3 (43%). Around TEA, WM scores were highest in groups 2 and 3. Deep gray matter (DGM) (aOR 15.0, 95% CI: 3.8–58.9) and hemorrhagic injury on early MRI (aOR 2.5, 95% CI: 1.3–4.6) and Kidokoro WM (aOR 1.3, 95% CI: 1.0–1.6) and DGM sub-scores (aOR 4.8, 95% CI: 1.1–21.7) around TEA were associated with adverse neurodevelopmental outcomes. Conclusion: The brain injury patterns following PA in preterm infants differ across GA. Particularly DGM abnormalities are associated with adverse neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

Background: Perinatal asphyxia continues to be a leading cause of neonatal morbidity and mortality worldwide. It causes multiorgan failure with brain involvement as the major organ of concern (hypoxic-ischemic encephalopathy). Cardiac dysfunction is also a feature of perinatal asphyxia. Aims and Objectives: The study and to correlate cardiac dysfunction detected by cardiac biomarkers and echocardiography with the severity of perinatal asphyxia as graded by the Thompson score. Materials and Methods: In this prospective observational study, babies with Apgar score

Introduction: Neonatal Thrombocytopenia (TCP) is frequently encountered in the Neonatal Intensive Care Unit (NICU), occurring either due to decreased production or increased destruction of platelets. This condition often leads to increased platelet transfusions in a NICU setting. Immature Platelet Fraction (IPF) and Absolute Immature Platelet Count (AIPC) are hypothesised to be surrogate markers of bone marrow activity and can help in differentiating between TCP caused by decreased production or increased destruction. Aim: To estimate the incidence of neonatal TCP in newborns admitted to a tertiary care NICU and to investigate the association of IPF percentage and AIPC values with the cause of TCP. Materials and Methods: This cross-sectional study was conducted in the Department of Paediatrics and Neonatology at Dr. D.Y. Patil Medical College, Navi Mumbai, Maharashtra, India, from April 2021 to May 2022. All 46 newborns admitted to the NICU with TCP were enrolled in the study. The total number of NICU admissions during the study period was used to calculate the incidence. The Complete Blood Count (CBC) with reticulocyte count and peripheral smear was examined using the impedance technique. The IPF and AIPC values were determined using an automated CBC counter based on flow cytometry principles. Statistical analysis was performed using the Chi-square test. Results: The study included a total of 46 neonates with TCP, with an incidence rate of 6.14%. Among the patients with TCP, 18 (39.13%) had mild, 17 (36.95%) had moderate, and 11 (23.91%) had severe TCP. The majority of neonates (21.7%) had a significant maternal history of Pregnancy Induced Hypertension (PIH). Of the neonates with TCP, 42 (91.3%) had high IPF and 4 (8.6%) had normal IPF. Regarding AIPC, 29 (63.04%) had normal values, 11 (23.91%) had high values, and 6 (13%) had low values. No significant association was found between IPF and AIPC values and the diagnosis of TCP in this study. Conclusion: The present study concludes that IPF and AIPC investigations cannot be recommended as markers to confirm the cause of TCP.

Objectives: To find the prevalence, and identify risk factors and outcome in neonates who were admitted into the Braithewaite Memorial Specialist Hospital (BMSH) for perinatal asphyxia. Method: This was a descriptive cross sectional observational study of neonates with low Apgar scores admitted over a period of ten months into the Special Care Baby Unit of the BMSH. All babies with Apgar scores lessthan six at one minute and for whom consent was obtained were recruited consecutively. For outborn babies with no Apgar score recording, a history of poor cry from birth with either poor colour, respiratory distress, floppiness or loss of primitive reflexes were used. Results: One hundred and fifty seven of 630 babies admitted had perinatal asphyxia giving a prevalence of 29.4%. Mean estational age of affected babies was 36.84±3.67 weeks, and mean birth weight was 3.0±0.9kg. Sixty two (39.5%) of their mothers had no antenatal care (ANC). Mode of delivery in 98 (62.4%) was caesarian section, of which 80 (81.6%) were emergencies, many of whom had complications before presentation. One hundred and seven (68.2%) and 38(24.2%) babies, had Apgar Score of 4-5 and 0 -3 in one minute respectively. The commonest risk factors were cephalopelvic disproportion (CPD) in the mothers and abnormal presentation, predominantly breech in the fetus. 31.6% of those with severe perinatal asphyxia died. Conclusion: Prevalence of perinatal asphyxia is high. Lack of ANC, CPD and breech presentation were contributory factors. There is urgent need for maternal education on need for ANC, early intervention and skilled care of babies at birth.

Abstract Acute kidney injury (AKI) is characterized by a sudden decline in the kidneys' abilities to remove waste products and maintain water and electrolyte homeostasis. This study aims to determine the incidence and predictors of acute kidney injury among neonates with perinatal asphyxia admitted at the neonatal intensive care unit of West Amhara Comprehensive Specialized Hospital, Northwest Ethiopia, 2023. Multicentred institution-based retrospective follow-up study was conducted from October 1, 2021, to September 30, 2023, among 421 perinatal asphyxia neonates. A simple random sampling technique was used. The data were collected using a data extraction checklist from the medical registry of neonates. The collected data were entered into EPI-DATA V.4.6.0.0. and analyzed using STATA V.14. The Kaplan–Meier failure curve and log-rank test were employed. Bivariable and multivariable Cox regression was carried out to identify predictors of Acute kidney injury. Statistical significance was declared at a p ≤ 0.05. The overall incidence of AKI was 54 (95% CI 47.07–62.51) per 100 neonate days. C/S delivery (AHR = 0.64; (95% CI 0.43–0.94), prolonged labor (AHR = 1.43; 95% CI 1.03–1.99) low-birth weight times (AHR = 1.49; (95% CI 1.01–2.20), stage three HIE(AHR: 1.68; (95% CI (1.02–2.77), No ANC follow up (AHR = 1.43; 95% CI 1.9 (1.07–3.43) and Hyperkalemia (AHR = 1.56; 95% CI 1.56 (1.05–2.29); 95% CI) were significant predictors. The incidence rate of acute kidney injury was higher than in other studies conducted on other groups of neonates. Cesarean section delivery, prolonged low birthweight, no Anc follow-up, stage 3 HIE, and neonatal hyperkalemia were predictors of acute kidney injury. However, it needs further prospective study. Therefore, the concerned stakeholders should give due attention and appropriate intervention to these predictors.

Perinatal asphyxia (PA) and hypoxic-ischemic encephalopathy can result in severe, long-lasting neurological deficits. In vitro models, such as oxygen–glucose deprivation (OGD), are used experimentally to investigate neuronal response to metabolic stress. However, multiple variables can affect the severity level of OGD/PA and may confound any measured treatment effect. Oxytocin (OXT) has emerged as a potential neuroprotective agent against the deleterious effects of PA. Previous studies have demonstrated OXT’s potential to enhance neuronal survival in immature hippocampal cultures exposed to OGD, possibly by modulating gamma-aminobutyric acid-A receptor activity. Moreover, OXT’s precise impact on developing hippocampal neurons under different severities of OGD/PA remains uncertain. In this study, we investigated the effects of OXT (0.1 µM and 1 µM) on 7-day-old primary rat hippocampal cultures subjected to 2 h OGD/sham normoxic conditions. Cell culture viability was determined using the resazurin assay. Our results indicate that the efficacy of 1 µM OXT treatment varied according to the severity of the OGD-induced lesion, exhibiting a protective effect (p = 0.022) only when cellular viability dropped below 49.41% in non-treated OGD cultures compared to normoxic ones. Furthermore, administration of 0.1 µM OXT did not yield significant effects, irrespective of lesion severity (p > 0.05). These findings suggest that 1 µM OXT treatment during OGD confers neuroprotection exclusively in severe lesions in hippocampal neurons after 7 days in vitro. Further research is warranted to elucidate the mechanisms involved in OXT-mediated neuroprotection.

The measurement of blood pH and gas analytes (BPGA), soon after birth, constitutes the first-line standard of care procedure in high-risk newborns. However, no data is available in capillary blood on perinatal bias such as gestational age (GA), weight at birth (BW), delivery mode, and gender. The aims of the present study were to investigate whether in a cohort of healthy preterm (PT) and term (T) infants BPGA were GA, BW, delivery mode and gender dependent, thus affecting BPGA reliability as diagnostic test.We performed a prospective case-control study in 560 healthy infants (PT: n=115, T: n=445). BPGA was measured within 24-h from birth. Perinatal characteristics, outcomes, and clinical examination were also recorded.PT infants showed higher (p<0.001) carbon dioxide partial pressure (pCO2), fraction of fetal hemoglobin (HbF), base excess (BE), bicarbonate (HCO3), and lower lactate (Lac) levels. When corrected for delivery mode, higher (p<0.001) HbF, BE, HCO3, and lower Lac levels were found. Similarly, higher (p<0.05, for all) pCO2, HbF, BE, HCO3 and lower Lac levels were found between female and male PT and T infants. Repeated multiple logistic regression analysis showed that BPGA was GA, BW, delivery mode and gender dependent.The present results showing that BPGA can be affected by a series of perinatal outcomes open the way to further investigations providing longitudinal BPGA reference curves in the transitional phase, thus empowering BPGA role as a reliable diagnostic and therapeutic strategies efficacy marker. [ABSTRACT FROM AUTHOR]

Background: Perinatal asphyxia remains a significant cause of morbidity and mortality among neonates, often leading to hypoxic-ischemic encephalopathy (HIE) and myocardial injury. Understanding the predictors and markers of these conditions is crucial for improving clinical management and outcomes. Methods: A prospective cohort study enrolled 50 asphyxiated neonates at Tirunelveli Medical College Hospital, assessing demographic factors, clinical parameters, and Troponin I levels. Data were analyzed using Chi-square test to determine associations and significance. Results: Demographic factors including gravida (χ²(2) = 0.499, p = 0.499), gestational age (χ² = 0.961, p = 0.961), mode of delivery (χ² = 0.507, p = 0.507), sex (χ² = 0.982, p = 0.982), and birth weight (χ² = 0.499, p = 0.499) showed no significant association with HIE severity. However, seizures (p = 0.001), ventilator requirement (p = 0.006), and shock (p = 0.001) were strongly associated with elevated Troponin I levels, indicative of myocardial injury. Conclusion: Clinical parameters such as seizures, ventilator requirement, and shock are critical indicators of myocardial injury in asphyxiated neonates. Early recognition and management of these factors may improve outcomes and guide therapeutic interventions in neonatal intensive care settings. [ABSTRACT FROM AUTHOR]

The reactivity of an electroencephalogram (EEG) to external stimuli is impaired in comatose patients showing burst-suppression (BS) patterns following hypoxic–ischemic brain injury (HIBI). We explored the reactivity of BS induced by isoflurane in rat models of HIBI and controls using intermittent photic stimulation (IPS) delivered to one eye. The relative time spent in suppression referred to as the suppression ratio (SR) was measured on the contralateral fronto-occipital cortical EEG channel. The BS reactivity (BSR) was defined as the decrease in the SR during IPS from the baseline before stimulation (SRPRE). We found that BSR increased with SRPRE. To standardize by anesthetic depth, we derived the BSR index (BSRi) as BSR divided by SRPRE. We found that the BSRi was decreased at 3 days after transient global cerebral ischemia in rats, which is a model of brain injury after cardiac arrest. The BSRi was also reduced 2 months after experimental perinatal asphyxia in rats, a model of birth asphyxia, which is a frequent neonatal complication in humans. Furthermore, Oxytocin attenuated BSRi impairment, consistent with a neuroprotective effect in this model. Our data suggest that the BSRi is a promising translational marker in HIBI which should be considered in future neuroprotection studies. [ABSTRACT FROM AUTHOR]

Neonatal acute liver failure (NALF), as a rare disease with high mortality, has limited relevant literature reports in China. We attempted to analyze a NALF cohort to improve the prognosis of this disease. We included all patients diagnosed with NALF at our institution between 2016 and 2021 and retrospectively reviewed their electronic records. NALF was defined as an INR ≥ 2.0 due to liver disease 28 days after birth. Comparisons were made according to etiology and outcome. The Kaplan-Meier method was used to estimate survival. Fifty-eight patients were included in this study. Etiologies included hypoxic/ischemic injury (29.3%), infection (27.6%), gestational alloimmune liver disease with neonatal hemochromatosis (GALD-NH) (10.3%), inherited metabolic diseases (5.2%), hemophagocytic lymphohistiocytosis (1.7%), other etiologies (12.1%), and unidentified causes (13.8%). Enteroviruses constituted 87.5% of the viral infections, whereas herpes simplex virus accounted for no infections. The median INR was significantly lower in the infection group than in the GALD-NH group (P < 0.05 for multiple comparisons). At the last follow-up, none of the patients had undergone liver transplantation, and the overall mortality rate was 50%. Liver function completely recovered in 31% of the patients, all of whom survived. The overall median survival time was 48 days; 26 days for hypoxic/ischemic injury and 43 days for GALD-NH. The incidence of cholestasis was significantly greater among surviving patients (P = 0.018). Conclusion: Hypoxic/ischemic injury and infection are the predominant etiologies of NALF in China. The overall prognosis of NALF is poor, but its short-term prognosis is determined by the etiology. What is Known: • Neonatal acute liver failure (NALF) is a rare disorder with limited cohort studies, especially in China. • Gestational alloimmune liver disease, viral infections (especially herpes simplex virus), metabolic diseases and ischemic insults are common etiologies of NALF, which are significantly different from other populations. • There are no reliable biochemical markers to predict the outcome of NALF. What is New: • In this first report on a Chinese NALF cohort, we demonstrate that hypoxic/ischemic injury and infection (excluding herpes simplex virus) are the predominant etiologies of NALF. • The overall prognosis of NALF is poor, and its etiology determines the short-term outcome. [ABSTRACT FROM AUTHOR]

Perinatal asphyxia (PA) poses a significant threat to multiple organs, particularly the kidneys. Diagnosing PA-associated kidney injury remains challenging, and treatment options are inadequate. Furthermore, there is a lack of long-term follow-up data regarding the renal implications of PA. In this study, 7-day-old male Wistar rats were exposed to PA using a gas mixture (4% O2; 20% CO2 in N2 for 15 min) to investigate molecular pathways linked to renal tubular damage, hypoxia, angiogenesis, heat shock response, inflammation, and fibrosis in the kidney. In a second experiment, adult rats with a history of PA were subjected to moderate renal ischemia-reperfusion (IR) injury to test the hypothesis that PA exacerbates renal susceptibility. Our results revealed an increased gene expression of renal injury markers (kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin), hypoxic and heat shock factors (hypoxia-inducible factor-1α, heat shock factor-1, and heat shock protein-27), proinflammatory cytokines (interleukin-1β, interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1), and fibrotic markers (transforming growth factor-β, connective tissue growth factor, and fibronectin) promptly after PA. Moreover, a machine learning model was identified through random forest analysis, demonstrating an impressive classification accuracy (95.5%) for PA. Post-PA rats showed exacerbated functional decline and tubular injury and more intense hypoxic, heat shock, proinflammatory, and profibrotic response after renal IR injury compared with controls. In conclusion, PA leads to subclinical kidney injury, which may increase the susceptibility to subsequent renal damage later in life. In addition, the parameters identified through random forest analysis provide a robust foundation for future biomarker research in the context of PA. NEW & NOTEWORTHY: This article demonstrates that perinatal asphyxia leads to subclinical kidney injury that permanently increases renal susceptibility to subsequent ischemic injury. We identified major molecular pathways involved in perinatal asphyxia-induced renal complications, highlighting potential targets of therapeutic approaches. In addition, random forest analysis revealed a model that classifies perinatal asphyxia with 95.5% accuracy that may provide a strong foundation for further biomarker research. These findings underscore the importance of multiorgan follow-up for perinatal asphyxia-affected patients. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is characterized by a sudden decline in the kidneys' abilities to remove waste products and maintain water and electrolyte homeostasis. This study aims to determine the incidence and predictors of acute kidney injury among neonates with perinatal asphyxia admitted at the neonatal intensive care unit of West Amhara Comprehensive Specialized Hospital, Northwest Ethiopia, 2023. Multicentred institution-based retrospective follow-up study was conducted from October 1, 2021, to September 30, 2023, among 421 perinatal asphyxia neonates. A simple random sampling technique was used. The data were collected using a data extraction checklist from the medical registry of neonates. The collected data were entered into EPI-DATA V.4.6.0.0. and analyzed using STATA V.14. The Kaplan–Meier failure curve and log-rank test were employed. Bivariable and multivariable Cox regression was carried out to identify predictors of Acute kidney injury. Statistical significance was declared at a p ≤ 0.05. The overall incidence of AKI was 54 (95% CI 47.07–62.51) per 100 neonate days. C/S delivery (AHR = 0.64; (95% CI 0.43–0.94), prolonged labor (AHR = 1.43; 95% CI 1.03–1.99) low-birth weight times (AHR = 1.49; (95% CI 1.01–2.20), stage three HIE(AHR: 1.68; (95% CI (1.02–2.77), No ANC follow up (AHR = 1.43; 95% CI 1.9 (1.07–3.43) and Hyperkalemia (AHR = 1.56; 95% CI 1.56 (1.05–2.29); 95% CI) were significant predictors. The incidence rate of acute kidney injury was higher than in other studies conducted on other groups of neonates. Cesarean section delivery, prolonged low birthweight, no Anc follow-up, stage 3 HIE, and neonatal hyperkalemia were predictors of acute kidney injury. However, it needs further prospective study. Therefore, the concerned stakeholders should give due attention and appropriate intervention to these predictors. [ABSTRACT FROM AUTHOR]

Introduction: Perinatal asphyxia is defined as the failure to initiate and sustain breathing at birth. Aim: compare functional echocardiographic parameters of perinatal asphyxiated term neonates with non asphyxiated term neonates. Methodology: This observational study, conducted at the Division of Pediatric Cardiology in M.D.M Hospital under the Department of Pediatrics, Dr. S.N. Medical College, Jodhpur, focused on perinatal asphyxia and hypoxic ischemic encephalopathy (HIE). Perinatal asphyxia severity was classified as moderate or severe based on breathing patterns and APGAR scores at 1 minute after birth. HIE diagnosis relied on physical examination, utilizing the modified Sarnat & Sarnat staging system to determine severity. Result: our observational study compared functional echocardiographic parameters between perinatal asphyxiated term neonates and non-asphyxiated term neonates. The findings revealed significant differences in certain parameters between the two groups: La and Ao did not differ significantly between the study and control groups.The ratio of La to Ao was significantly higher in the study group. LVES was significantly larger in the study group. EF and FS were significantly lower in the study group, indicating impaired cardiac function. Other parameters such as LVMPI, MAPSE and mitral E/A and E/e' ratios did not show significant differences between the two groups. However, the diastolic diameter of the tricuspid annulus was significantly larger in the study group compared to the control group. Conclusion: The perinatal asphyxia may impact specific echocardiographic parameters indicative of cardiac dysfunction, particularly in terms of left ventricular systolic function.Early recognition and management of cardiac involvement may improve outcomes in this vulnerable population. [ABSTRACT FROM AUTHOR]

Introduction: Perinatal asphyxia is an important cause of admission to neonatal intensive care units (NICU) with multi organ dysfunction.Aim: Determine the change in functional echocardiographic parameters with CKMB and Troponin I and time. Methodology:The study, conducted at the Division of Pediatric Cardiology in M.D.M Hospital under the Department of Paediatrics, Dr. S. N. Medical College, Jodhpur, focused on perinatal asphyxia and hypoxic ischemic encephalopathy (HIE).Functional echocardiographic parameters were studied with time. Result: Both left atrial and aortic diameters did not significantly change over time. However, La/Ao showed a significant decrease over time. LVED and LVES remained relatively stable over the measured time intervals. EF and FS increased significantly over time, indicating improvement in cardiac function. Parameters such as LVMPI, mvcf, MAPSE, and TAPSE did not show significant changes over time. Mitral E/A ratio, mitral E/e' medial, mitral E/e' lateral, tricuspid E/A ratio, tricuspid E/e' medial, and tricuspid E/e' lateral also remained relatively stable over the measured time intervals. Conclusion: It shows a complex interplay between structural and functional aspects of cardiac performance over time. While certain parameters remained stable, others demonstrated dynamic changes, underscoring the importance of comprehensive echocardiographic assessment in evaluating cardiac function and guiding clinical management. [ABSTRACT FROM AUTHOR]

Amorfrutin B is a selective PPARγ modulator that we demonstrated to be a promising neuroprotective compound in cellular models of stroke and perinatal asphyxia. Although neuronal mechanisms of amorfrutin B-evoked neuroprotection have been identified, none of them reflects the actions of the compound on microglia, which play a pivotal role in brain response to hypoxia/ischemia. Here, we provide evidence for amorfrutin B-induced effects on human microglia subjected to hypoxia/ischemia; the compound counteracts inflammation, and influences mitochondrial status and proliferation potential in a PPARγ-dependent manner. Post-treatment with amorfrutin B decreased the IBA1 fluorescence intensity, reduced caspase-1 activity, and downregulated IL1B/IL-1β and TNFA but not IL10/IL-10 expression, which was upregulated. Amorfrutin B also stimulated PPARγ signaling, as evidenced by increased mRNA and/or protein levels of PPARγ and PGC1α. In addition, amorfrutin B reversed the hypoxia/ischemia-evoked effects on mitochondria-related parameters, such as mitochondrial membrane potential, BCL2/BCL2 expression and metabolic activity, which were correlated with diminished proliferation potential of microglia. Interestingly, the inhibitory effect of amorfrutin B on the proliferation potential and mitochondrial function of microglia is opposite to the stimulatory effect of amorfrutin B on mouse neuronal survival, as evidenced by increased neuronal viability and reduced neurodegeneration. In summary, this study showed for the first time that amorfrutin B compromises hypoxia/ischemia-induced activation of human microglia in a PPARγ-dependent manner, which involves inhibiting inflammation, normalizing mitochondrial status, and controlling proliferation potential. These data extend the protective potential of amorfrutin B in the pharmacotherapy of hypoxic/ischemic brain injury, targeting not only neurons but also activated microglia. [ABSTRACT FROM AUTHOR]

Aims: Little is known about the population pharmacokinetics (PPK) of vancomycin in neonates with perinatal asphyxia treated with therapeutic hypothermia (TH). We aimed to describe the PPK of vancomycin and propose an initial dosing regimen for the first 48 h of treatment with pharmacokinetic/pharmacodynamic target attainment. Methods: Neonates with perinatal asphyxia treated with TH were included from birth until Day 6 in a multicentre prospective cohort study. A vancomycin PPK model was constructed using nonlinear mixed‐effects modelling. The model was used to evaluate published dosing guidelines with regard to pharmacokinetic/pharmacodynamic target attainment. The area under the curve/minimal inhibitory concentration ratio of 400–600 mg*h/L was used as target range. Results: Sixteen patients received vancomycin (median gestational age: 41 [range: 38–42] weeks, postnatal age: 4.4 [2.5–5.5] days, birth weight: 3.5 [2.3–4.7] kg), and 112 vancomycin plasma concentrations were available. Most samples (79%) were collected during the rewarming and normothermic phase, as vancomycin was rarely initiated during the hypothermic phase due to its nonempirical use. An allometrically scaled 1‐compartment model showed the best fit. Vancomycin clearance was 0.17 L/h, lower than literature values for term neonates of 3.5 kg without perinatal asphyxia (range: 0.20–0.32 L/h). Volume of distribution was similar. Published dosing regimens led to overexposure within 24 h of treatment. A loading dose of 10 mg/kg followed by 24 mg/kg/day in 4 doses resulted in target attainment. Conclusion: Results of this study suggest that vancomycin clearance is reduced in term neonates with perinatal asphyxia treated with TH. Lower dosing regimens should be considered followed by model‐informed precision dosing. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of blood pH levels and base deficit on neonatal convulsions and amplitude electroencephalography measurements in patients with perinatal asphyxia. Methods: This study included 102 patients monitored in the neonatal intensive care unit for perinatal asphyxia. Amplitude electroencephalography measurements and convulsions were recorded from all patients for 80 hours. Blood samples were taken in the umbilical artery for the pH analysis and calculation of base deficit. Results: The mean gestational age was 38.13±1.30 weeks with 66/36 (64.7% / 35.3%), male/female ratio. Fifty-seven (55.9%) babies were delivered by normal spontaneous vaginal delivery, while 45 patients (44.1%) had a history of cesarean delivery. There were significant differences between the mean base deficit and amplitude electroencephalography recordings at the first 24th, 48th, and 72nd hours (KW=32.819, p<0.001; KW=23.687, p<0.001, and KW=24.992, p<0.001, respectively). Sixty-five (63.7%) of the patients had neonatal convulsions. The mean base deficit was 20.64±4.70 mmol/L and 17.48±2.92 mmol/L in patients with and without seizures, respectively. The mean base deficit was significantly higher in patients with neonatal seizures (Z=3.912; p=0.001). Conclusion: Our study showed patients with abnormal amplitude electroencephalography findings and epileptic electrical activity were found to have higher base deficits at the time of diagnosis. It suggests that high base deficit levels may have a negative effect on the neurodevelopmental process in the neonatal period. [ABSTRACT FROM AUTHOR]

Background: Therapeutic hypothermia is the standard treatment for neonates with hypoxic–ischemic encephalopathy. Preclinical evidence indicates that the time to initiate therapeutic hypothermia correlates with its therapeutic success. This study aims to explore whether there is a correlation between the early initiation of therapeutic hypothermia and improved short-term neurological outcomes in cooled asphyxiated newborns. Methods: A retrospective analysis was conducted, involving 68 neonates from two different neonatal intensive care units. The impact of time to initiate treatment, time to reach the target temperature, and time between initiation and target temperature was correlated with short-term outcomes on MRI. Results: We did not find a significant difference between outcomes regarding the time to start treatment and the time to achieve the target temperature. Interestingly, neonates with a poor outcome were treated on average earlier than neonates with a favorable outcome but required more time to reach the target temperature. Additionally, the study results did not support the hypothesis that a shorter time to initiate treatment would lead to shorter times to achieve the target temperature. Conclusion: Based on our findings, it is recommended to prioritize a thorough evaluation of neonatal encephalopathy before initiating therapeutic hypothermia. Early initiation of treatment should be balanced with the time required for precise assessment to ensure better outcomes. [ABSTRACT FROM AUTHOR]

Background: Population-based data show high proportions of severe cases of cerebral palsy (CP) in resource-poor regions such as sub-Saharan Africa, where most children have potentially preventable risk factors (factors that may increase the likelihood of CP occurrence but can be mitigated through medical interventions). Objectives: This study aimed to describe the demographic and clinical profile of children living with CP accessing services at Tygerberg Hospital over a period of 10 years (2010–2020), identify the potential gaps in care (proportion of individuals in a country requiring but not receiving suboptimal or inadequate care), and comparison with a similar study at the same centre two decades ago. Method: This 10-year retrospective study investigated causes and morbidities in children with CP, attending a central hospital in the Western Cape, South Africa. Results: A total of 613 children with CP were identified. Perinatal causes were predominant, especially in 57.7% (n = 354) of the cohort: perinatal asphyxia (41.1%) and preterm birth (16.6%). Postnatal causes constituted 15.2% (n = 93), which included tuberculous meningitis (3.6%) and bacterial meningitis (3.6%). The most common complications were intellectual impairment (61.8%; n = 379); epilepsy (30.8%; n = 189) and visual impairment (54.7%; n = 234). A third of the cohort had severe CP, classified as Gross Motor Function Classification System IV and V (38%). Conclusion: Most of the previously documented main drivers of CP are still present and the implementation of healthcare prevention strategies remains inadequate. Contribution: This study provides longitudinal evidence to confirm that CP in a South African setting is associated with a high burden of potentially preventable causes.

Not available

Abstract Background Hypoxic-ischemic encephalopathy (HIE) appears in neurological conditions where some brain areas are likely to be injured, such as deep grey matter, basal ganglia area, and white matter subcortical periventricular áreas. Moreover, modeling these brain areas in a newborn is challenging due to significant variability in the intensities associated with HIE conditions. This paper aims to evaluate functional measurements and 3D machine learning models of a given HIE case by correlating the affected brain areas with the pathophysiology and clinical neurodevelopmental. Case presentation A comprehensive analysis of a term infant with perinatal asphyxia using longitudinal 3D brain information from Machine Learning Models is presented. The clinical analysis revealed the perinatal asphyxia diagnosis with APGAR

Abstract The integrity of the intestinal mucus barrier is crucial for human health, as it serves as the body's first line of defense against pathogens. However, postnatal development of the mucus barrier and interactions between maturity and its ability to adapt to external challenges in neonatal infants remain unclear. In this study, we unveil a distinct developmental trajectory of the mucus barrier in preterm piglets, leading to enhanced mucus microstructure and reduced mucus diffusivity compared to term piglets. Notably, we found that necrotizing enterocolitis (NEC) is associated with increased mucus diffusivity of our large pathogen model compound, establishing a direct link between the NEC condition and the mucus barrier. Furthermore, we observed that addition of sodium decanoate had varying effects on mucus diffusivity depending on maturity and health state of the piglets. These findings demonstrate that regulatory mechanisms governing the neonatal mucosal barrier are highly complex and are influenced by age, maturity, and health conditions. Therefore, our results highlight the need for specific therapeutic strategies tailored to each neonatal period to ensure optimal gut health.

Background. Hypoxic ischemic encephalopathy (HIE) is a major cause of neurological disabilities in infants. Several possible early biomarkers for hypoxic injury have been investigated but none of them have been completely utilized in clinical practice. Serum S100b is one such early biomarker. Objective. The above study aims to assess the usefulness of the biomarker S100b in predicting the severity as well as the outcome of neonates having HIE. Materials and methods. A prospective cohort study was done on 80 term newborns admitted to the neonatal intensive care unit (NICU), Institute of medical sciences & SUM hospital, Bhubaneswar from August 2019 to February 2021. Out of the total 80 term newborns, 20 newborns without any evidence of perinatal hypoxia were categorized as the Controls, and the rest of 60 newborns with perinatal hypoxia were categorized as Cases. Cases were further divided into 3 subgroups based on Sarnat and Sarnat staging with 27 newborns in HIE I, 17 newborns in HIE II, and 16 newborns in HIE III. Serum S100b was measured in all the above children at 4 and 48 hours of life. Result. In our study, the mean serum S100b level at 4h & 48h of life was 1.15 & 1.05 respectively in controls and 3.24 & 2.36 (p

Seizures (SZ) are one of the main complications occurring in infants undergoing therapeutic hypothermia (TH) due to perinatal asphyxia (PA) and hypoxic ischemic encephalopathy (HIE). Phenobarbital (PB) is the first-line therapeutic strategy, although data on its potential side-effects need elucidation. We investigated whether: i) PB administration in PA-HIE TH-treated infants affects S100B urine levels, and ii) S100B could be a reliable early predictor of SZ. We performed a prospective case-control study in 88 PA-HIE TH infants, complicated (n=44) or not (n=44) by SZ requiring PB treatment. S100B urine levels were measured at 11 predetermined monitoring time-points from first void up to 96-h from birth. Standard-of-care monitoring parameters were also recorded. S100B significantly increased in the first 24-h independently from HIE severity in the cases who later developed SZ and requested PB treatment. ROC curve analysis showed that S100B, as SZ predictor, at a cut-off of 2.78 μg/L achieved a sensitivity/specificity of 63 and 84 %, positive/negative predictive values of 83 and 64 %. The present results offer additional support to the usefulness of S100B as a trustable diagnostic tool in the clinical daily monitoring of therapeutic and pharmacological procedures in infants complicated by PA-HIE. [ABSTRACT FROM AUTHOR]

Background: Hypoxic-ischemic encephalopathy (HIE) appears in neurological conditions where some brain areas are likely to be injured, such as deep grey matter, basal ganglia area, and white matter subcortical periventricular áreas. Moreover, modeling these brain areas in a newborn is challenging due to significant variability in the intensities associated with HIE conditions. This paper aims to evaluate functional measurements and 3D machine learning models of a given HIE case by correlating the affected brain areas with the pathophysiology and clinical neurodevelopmental. Case presentation: A comprehensive analysis of a term infant with perinatal asphyxia using longitudinal 3D brain information from Machine Learning Models is presented. The clinical analysis revealed the perinatal asphyxia diagnosis with APGAR <5 at 5 and 10 minutes, umbilical arterial pH of 7.0 BE of -21.2 mmol / L), neonatal seizures, and invasive ventilation mechanics. Therapeutic interventions: physical, occupational, and language neurodevelopmental therapies. Epilepsy treatment: vagus nerve stimulation, levetiracetam, and phenobarbital. Furthermore, the 3D analysis showed how the volume decreases due to age, exhibiting an increasing asymmetry between hemispheres. The results of the basal ganglia area showed that thalamus asymmetry, caudate, and putamen increase over time while globus pallidus decreases. Clinical outcomes: spastic cerebral palsy, microcephaly, treatment-refractory epilepsy. Conclusions: Slight changes in the basal ganglia and cerebellum require 3D volumetry for detection, as standard MRI examinations cannot fully reveal their complex shape variations. Quantifying these subtle neurodevelopmental changes helps in understanding their clinical implications. Besides, neurophysiological evaluations can boost neuroplasticity in children with neurological sequelae by stimulating new neuronal connections. [ABSTRACT FROM AUTHOR]

The integrity of the intestinal mucus barrier is crucial for human health, as it serves as the body's first line of defense against pathogens. However, postnatal development of the mucus barrier and interactions between maturity and its ability to adapt to external challenges in neonatal infants remain unclear. In this study, we unveil a distinct developmental trajectory of the mucus barrier in preterm piglets, leading to enhanced mucus microstructure and reduced mucus diffusivity compared to term piglets. Notably, we found that necrotizing enterocolitis (NEC) is associated with increased mucus diffusivity of our large pathogen model compound, establishing a direct link between the NEC condition and the mucus barrier. Furthermore, we observed that addition of sodium decanoate had varying effects on mucus diffusivity depending on maturity and health state of the piglets. These findings demonstrate that regulatory mechanisms governing the neonatal mucosal barrier are highly complex and are influenced by age, maturity, and health conditions. Therefore, our results highlight the need for specific therapeutic strategies tailored to each neonatal period to ensure optimal gut health. [ABSTRACT FROM AUTHOR]

Background: Perinatal asphyxia (PNA) is one of the three major cause of morbidity and mortality in India. ABG analysis may help to predict outcome of babies with Perinatal asphyxia. Aim of study was to identify Arterial blood gas analysis parameter as a predictor of outcome of newborns with perinatal asphyxia. Methods: We included 144 newborns, with perinatal asphyxia who were born in our tertiary health care centre during March 2021 to September 2022. Extremely low birth weight babies and any baby with major congenital malformation were excluded from study. Babies were resuscitated in delivery room, then shifted immediately to NICU, stabilised and sample for arterial blood gas analysis (ABGA) was taken within first hour of life, then the babies were intervened accordingly. The outcomes were analyzed, correlated with the initial ABGA and compared among the study group. Conclusion: We found that pH and HCO3 are better markers in predicting the outcome of perinatal asphyxia in newborns. HCO3 had the highest specificity (99.18%) followed by pH (97.54%). Discharge was higher with HCO3(mmol/L) >10 while death was significantly higher in HCO3(mmol/L)<10.This study gives an advantage over other studies conducted on cord blood sampling at birth as resuscitation of the baby is of more priority than sampling for the outcome while the amount of time taken for result and interpretation is the same. Along with the APGAR score, Arterial blood gas analysis within one hour can be used as a better predictive tool for outcome in newborns with perinatal asphyxia. [ABSTRACT FROM AUTHOR]

Aim: To compare Presepsin (presepsin) levels in plasma and urine of uninfected newborn infants with perinatal asphyxia with those of controls. Methods: In this prospective study, we enrolled 25 uninfected full‐term infants with perinatal asphyxia and 19 controls. We measured presepsin levels in whole blood or urine. In neonates with perinatal asphyxia, we compared presepsin levels in blood and urine at four time points. Results: In neonates with perinatal asphyxia, blood and urinary presepsin levels matched each other at any time point. At admission, the median presepsin value in blood was similar in both groups (p = 0.74), while urinary levels were higher in hypoxic neonates (p = 0.05). Perinatal asphyxia seemed to increase serum CRP and procalcitonin levels beyond normal cut‐off but not those of presepsin. Conclusion: In uninfected neonates with perinatal asphyxia, median blood and urinary presepsin levels matched each other at any point in the first 72 h of life and seemed to be slightly affected by the transient renal impairment associated with perinatal hypoxia in the first 12 h of life. Perinatal asphyxia did not influence presepsin levels within the first 72 h of life, while those of CRP and procalcitonin increased. [ABSTRACT FROM AUTHOR]

Aim: Perinatal asphyxia affects whole body systems and depending on compensation mechanisms, the central nervous system is primarily protected. In this study, we aimed to evaluate brain electrophysiological activity in cases with postnatal feeding intolerance due to perinatal asphyxia and to investigate whether the compensation mechanism is adequate or whether there is a minimal electrophysiological disorder. Methods: This study was conducted prospectively to compare the amplitude electroencephalography (EEG) recordings of 22 patients who were followed up with the diagnosis of feeding intolerance due to perinatal asphyxia and 10 control groups. Eeg probes were applied by gluing. Conventional EEG was performed in the patient group and the recordings were evaluated with an amplitude integrated electroencephalography (aEEG). It was also compared with feeding time, length of hospital stay, maternal ages, cord blood gas pH and base deficit values, electrolyte values at the 24th hour, appearance pulse grimace activity and respiration (APGAR) and Burdjalov scores. Results: When aEEG Vmin values, Burdjalov scores, and 1st min APGAR scores were compared, statistically significant difference was found between the patient and control groups. There was an inverse weak correlation between the patients' aEEG Vmin values and their length of hospital stay. A weak correlation was found between the cases’ cord blood gas base deficit and aEEG Vmax values. When cases were divided into two groups as less than 7 days of hospitalization and more than 7 days of hospitalization, a statistically significant difference was found between the groups in terms of maternal age. Conclusion: In our study, it was aimed to show whether there is a minimal effect of perinatal asphyxia on EEG findings in newborns with nutritional deficiency. The difference in the aEEG Vmin values of the case and control groups indicates that brain electrical activity is affected. This is also supported by the fact that those with higher Vmin values had shorter hospital stays.

Background: Perinatal asphyxia (PA) is a neonatal emergency causing multi-organ dysfunction, and neurological insult called hypoxic-ischemic encephalopathy (HIE). The traditional focus is on neuroprotection. However, the immature cardiovascular system simultaneously undergoes tremendous hypoxic-ischemic insult especially during the secondary phase of HIE. The hemodynamic consequences, comprehensive cardiac assessment, and care are often overlooked in bedside practice. Objective: The objective is to quantitatively document myocardial dysfunction in neonates with PA using electrocardiography (ECG), echocardiography, and cardiac enzymes (creatinine kinase-MB [CK-MB], B-type natriuretic peptide [BNP], and troponin I). Design and Methods: This was a single center, case–control prospective study. Sixty-four neonates with PA were enrolled. Myocardial function was assessed by clinical, ECG, echocardiography, and biomarkers assay. The same number of healthy neonates was taken as control. Results: 15 (23.4%) had mild, 28 (43.7%) moderate, and 21 (32.8%) severe HIE in the case arm. Abnormal ECG was observed in 42 (65.6%), of which 20 (47.6%) had Grade I, 13 (30.9%) Grade II, 8 (19.04%) Grade III, and 1 (2.38%) had Grade IV changes. Serum levels of CK-MB, BNP and Troponin I were raised in 29 (45.3%), 30 (46.8%) and 10 (15.6%) neonates, respectively. Echocardiographic parameters such as ductal shunting pattern, mitral and tricuspid regurgitation, pulmonary hypertension, and systolic and diastolic ventricular function were significantly abnormal in cases versus controls as demonstrated by P value. Conclusion: Abnormal ECG, echocardiography, and cardiac enzymes in PA are markers and prognosticators of cardiac injury affecting overall outcomes in neonates with PA. Early detection can help in better management and survival of these neonates.

Abstract Background Despite therapeutic hypothermia (TH) and neonatal intensive care, 45–50% of children affected by moderate-to-severe neonatal hypoxic-ischemic encephalopathy (HIE) die or suffer from long-term neurodevelopmental impairment. Additional neuroprotective therapies are sought, besides TH, to further improve the outcome of affected infants. Allopurinol — a xanthine oxidase inhibitor — reduced the production of oxygen radicals and subsequent brain damage in pre-clinical and preliminary human studies of cerebral ischemia and reperfusion, if administered before or early after the insult. This ALBINO trial aims to evaluate the efficacy and safety of allopurinol administered immediately after birth to (near-)term infants with early signs of HIE. Methods/design The ALBINO trial is an investigator-initiated, randomized, placebo-controlled, double-blinded, multi-national parallel group comparison for superiority investigating the effect of allopurinol in (near-)term infants with neonatal HIE. Primary endpoint is long-term outcome determined as survival with neurodevelopmental impairment versus death versus non-impaired survival at 2 years. Results The primary analysis with three mutually exclusive responses (healthy, death, composite outcome for impairment) will be on the intention-to-treat (ITT) population by a generalized logits model according to Bishop, Fienberg, Holland (Bishop YF, Discrete Multivariate Analysis: Therory and Practice, 1975) and .”will be stratified for the two treatment groups. Discussion The statistical analysis for the ALBINO study was defined in detail in the study protocol and implemented in this statistical analysis plan published prior to any data analysis. This is in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. Trial registration ClinicalTrials.gov NCT03162653. Registered on 22 May 2017.

Background: The presence of perinatal asphyxia and its severity appear to correlate with increasing incidence of Acute kidney injury (AKI). The objective of this study is to determine the frequency of AKI and its outcome in birth asphyxia. Methods: This cross-sectional study was carried out in the Department of Pediatric Medicine from March 2019 to September 2019. A total of 111 newborns with birth asphyxia of gestational age 37–41 weeks were included. Neonates born to mothers having hypertension and diabetes mellitus, patients with congenital kidney anomalies like polycystic kidney disease and renal agenesis, and mothers taking nephrotoxic drugs or any other known cause of AKI like hypovolemic shock were excluded. Urine output (UOP) and final outcome of the patient were also noted. AKI was noted. Results: The mean gestational age was 38.29 ± 1.07 weeks. The mean weight of neonates was 3.08 ± 0.31 kg. The frequency of AKI in birth asphyxia was 20 (18.02%) neonates. Complete recovery in AKI patients was seen in 07 (35.0%) and death in 13 (65.0%) patients. Conclusion: This study has shown that the frequency of AKI in birth asphyxia was found in 18.02% neonates with complete recovery seen in 35.0% and death in 65.0% patients.

Perinatal asphyxia refers to an acute event of cerebral ischemia and hypoxia during the perinatal period, leading to various degrees of brain injury. The mechanisms involved in perinatal asphyxia include the production of reactive oxygen species (ROS), accumulation of intracellular calcium, lipid peroxidation, excitatory amino acid receptor overactivation, energy failure, and caspase-mediated cell death. Both primary and secondary neuronal damage are caused by the overproduction of ROS following a hypoxic/ischemic event. ROS can react with nearly any type of molecule, including lipids, proteins, polysaccharides, and DNA. Neonates who suffer from perinatal asphyxia are prone to oxidative stress, which is characterized by a disruption in the oxidant/antioxidant balance, favoring oxidants over the intracellular and extracellular antioxidant scavenging mechanisms. Current research has focused on developing treatment strategies that potentially improve the endogenous antioxidant neuroprotective mechanisms or minimize injury resulting from hypoxia/ischemia. In this narrative review, we aim to present evidence regarding the contribution of oxidant/antioxidant balance to the pathogenesis and progression of perinatal asphyxia. Also, we aim to explore the role of potential antioxidant therapies as promising treatment strategies for perinatal asphyxia, especially as an adjunct to therapeutic hypothermia in infants with perinatal asphyxia. The current literature on antioxidant treatments in newborns is limited; however, allopurinol, melatonin, and erythropoietin have shown some positive effects in clinical trials. Inhibitors of nitric oxide synthase, N-acetylcysteine, and docosahexaenoic acid have shown promising neuroprotective effects in preclinical studies. Finally, nanotherapeutics could potentially modulate oxidative stress in hypoxemic/ischemic brain injury by targeted medication delivery. Future research on neuroprotectants and their processes is warranted to develop innovative treatments for hypoxia/ischemia in clinical practice.

Background: Despite therapeutic hypothermia (TH) and neonatal intensive care, 45–50% of children affected by moderate-to-severe neonatal hypoxic-ischemic encephalopathy (HIE) die or suffer from long-term neurodevelopmental impairment. Additional neuroprotective therapies are sought, besides TH, to further improve the outcome of affected infants. Allopurinol — a xanthine oxidase inhibitor — reduced the production of oxygen radicals and subsequent brain damage in pre-clinical and preliminary human studies of cerebral ischemia and reperfusion, if administered before or early after the insult. This ALBINO trial aims to evaluate the efficacy and safety of allopurinol administered immediately after birth to (near-)term infants with early signs of HIE. Methods/design: The ALBINO trial is an investigator-initiated, randomized, placebo-controlled, double-blinded, multi-national parallel group comparison for superiority investigating the effect of allopurinol in (near-)term infants with neonatal HIE. Primary endpoint is long-term outcome determined as survival with neurodevelopmental impairment versus death versus non-impaired survival at 2 years. Results: The primary analysis with three mutually exclusive responses (healthy, death, composite outcome for impairment) will be on the intention-to-treat (ITT) population by a generalized logits model according to Bishop, Fienberg, Holland (Bishop YF, Discrete Multivariate Analysis: Therory and Practice, 1975) and."will be stratified for the two treatment groups. Discussion: The statistical analysis for the ALBINO study was defined in detail in the study protocol and implemented in this statistical analysis plan published prior to any data analysis. This is in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. Trial registration: ClinicalTrials.gov NCT03162653. Registered on 22 May 2017. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to evaluate neuronal injury and immuno-inflammatory biomarkers in umbilical cord blood (UCB) at birth, in cases with perinatal asphyxia with or without hypoxic-ischemic encephalopathy (HIE), compared with healthy controls and to assess their ability to predict HIE. Study Design: In this case-control study, term infants with perinatal asphyxia were recruited at birth. UCB was stored at delivery for batch analysis. HIE was diagnosed by clinical Sarnat staging at 24 h. Glial fibrillary acidic protein (GFAP), the neuronal biomarkers tau and neurofilament light protein (NFL), and a panel of cytokines were analyzed in a total of 150 term neonates: 50 with HIE, 50 with asphyxia without HIE (PA), and 50 controls. GFAP, tau, and NFL concentrations were measured using ultrasensitive single-molecule array (Simoa) assays, and a cytokine screening panel was applied to analyze the immuno-inflammatory and infectious markers. Results: GFAP, tau, NFL, and several cytokines were significantly higher in newborns with moderate and severe HIE compared to a control group and provided moderate prediction of HIE II/III (AUC: 0.681–0.827). Furthermore, the levels of GFAP, tau, interleukin-6 (IL-6), and interleukin-8 (IL-8) were higher in HIE II/III cases compared with cases with PA/HIE I. IL-6 was also higher in HIE II/III compared with HIE I cases. Conclusions: Biomarkers of brain injury and inflammation were increased in umbilical blood in cases with asphyxia. Several biomarkers were higher in HIE II/III versus those with no HIE or HIE I, suggesting that they could assist in the prediction of HIE II/III. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a common cause of mortality and morbidity in asphyxiated newborns. Recent research suggests serum neutrophil gelatinase-associated lipocalin (sNGAL) as an early biomarker of AKI in newborns with perinatal asphyxia. The prospect of sNGAL is yet to be studied in Nigeria, with a huge burden of asphyxia-related neonatal deaths. Methods: A cross-sectional analytic study was conducted on 53 asphyxiated term newborns and 53 healthy babies at the newborn unit of the Wesley Guild Hospital Ilesa, Nigeria. sNGAL was assessed in all neonates with perinatal asphyxia at baseline (within 30 min of delivery), 2 h, and 48 h of life. Results: Mean sNGAL was significantly higher in asphyxiated newborns than in the control group, 81.4 (45.9) vs. 53.7 (29.2), p < 0.001. However, the mean 2-h sNGAL levels were similar in asphyxiated babies with and without AKI 100.5 (36.7) ng/ml vs. 85.3 (31.4) ng/ml, p = 0.115. The 2-h sNGAL with an AUC of 0.61 at an 83.0 ng/ml cut-off had an acceptable discriminating capability of predicting AKI. The sensitivity, specificity, positive predictive value, and negative predictive value were 80%, 51.5%, 50%, and 81%, respectively. Conclusion: This study shows that sNGAL levels were significantly elevated in newborns with perinatal asphyxia compared to healthy neonates, but the 2-h sNGAL is less predictive of AKI in newborns with perinatal asphyxia. The negative predictive value is high, and this may find some relevance in the attempts at early exclusion of asphyxiated babies prone to AKI. [ABSTRACT FROM AUTHOR]

Background: The presence of perinatal asphyxia and its severity appear to correlate with increasing incidence of Acute kidney injury (AKI). The objective of this study is to determine the frequency of AKI and its outcome in birth asphyxia. Methods: This cross-sectional study was carried out in the Department of Pediatric Medicine from March 2019 to September 2019. A total of 111 newborns with birth asphyxia of gestational age 37–41 weeks were included. Neonates born to mothers having hypertension and diabetes mellitus, patients with congenital kidney anomalies like polycystic kidney disease and renal agenesis, and mothers taking nephrotoxic drugs or any other known cause of AKI like hypovolemic shock were excluded. Urine output (UOP) and final outcome of the patient were also noted. AKI was noted. Results: The mean gestational age was 38.29 ± 1.07 weeks. The mean weight of neonates was 3.08 ± 0.31 kg. The frequency of AKI in birth asphyxia was 20 (18.02%) neonates. Complete recovery in AKI patients was seen in 07 (35.0%) and death in 13 (65.0%) patients. Conclusion: This study has shown that the frequency of AKI in birth asphyxia was found in 18.02% neonates with complete recovery seen in 35.0% and death in 65.0% patients. [ABSTRACT FROM AUTHOR]

Background. Hypoxic ischemic encephalopathy (HIE) is a major cause of neurological disabilities in infants. Several possible early biomarkers for hypoxic injury have been investigated but none of them have been completely utilized in clinical practice. Serum S100b is one such early biomarker. Objective. The above study aims to assess the usefulness of the biomarker S100b in predicting the severity as well as the outcome of neonates having HIE. Materials and methods. A prospective cohort study was done on 80 term newborns admitted to the neonatal intensive care unit (NICU), Institute of medical sciences & SUM hospital, Bhubaneswar from August 2019 to February 2021. Out of the total 80 term newborns, 20 newborns without any evidence of perinatal hypoxia were categorized as the Controls, and the rest of 60 newborns with perinatal hypoxia were categorized as Cases. Cases were further divided into 3 subgroups based on Sarnat and Sarnat staging with 27 newborns in HIE I, 17 newborns in HIE II, and 16 newborns in HIE III. Serum S100b was measured in all the above children at 4 and 48 hours of life. Result. In our study, the mean serum S100b level at 4h & 48h of life was 1.15 & 1.05 respectively in controls and 3.24 & 2.36 (p

The reactivity of an electroencephalogram (EEG) to external stimuli is impaired in comatose patients showing burst-suppression (BS) patterns following hypoxic–ischemic brain injury (HIBI). We explored the reactivity of BS induced by isoflurane in rat models of HIBI and controls using intermittent photic stimulation (IPS) delivered to one eye. The relative time spent in suppression referred to as the suppression ratio (SR) was measured on the contralateral fronto-occipital cortical EEG channel. The BS reactivity (BSR) was defined as the decrease in the SR during IPS from the baseline before stimulation (SRPRE). We found that BSR increased with SRPRE. To standardize by anesthetic depth, we derived the BSR index (BSRi) as BSR divided by SRPRE. We found that the BSRi was decreased at 3 days after transient global cerebral ischemia in rats, which is a model of brain injury after cardiac arrest. The BSRi was also reduced 2 months after experimental perinatal asphyxia in rats, a model of birth asphyxia, which is a frequent neonatal complication in humans. Furthermore, Oxytocin attenuated BSRi impairment, consistent with a neuroprotective effect in this model. Our data suggest that the BSRi is a promising translational marker in HIBI which should be considered in future neuroprotection studies.

Background: Therapeutic hypothermia is the standard treatment for neonates with hypoxic–ischemic encephalopathy. Preclinical evidence indicates that the time to initiate therapeutic hypothermia correlates with its therapeutic success. This study aims to explore whether there is a correlation between the early initiation of therapeutic hypothermia and improved short-term neurological outcomes in cooled asphyxiated newborns. Methods: A retrospective analysis was conducted, involving 68 neonates from two different neonatal intensive care units. The impact of time to initiate treatment, time to reach the target temperature, and time between initiation and target temperature was correlated with short-term outcomes on MRI. Results: We did not find a significant difference between outcomes regarding the time to start treatment and the time to achieve the target temperature. Interestingly, neonates with a poor outcome were treated on average earlier than neonates with a favorable outcome but required more time to reach the target temperature. Additionally, the study results did not support the hypothesis that a shorter time to initiate treatment would lead to shorter times to achieve the target temperature. Conclusion: Based on our findings, it is recommended to prioritize a thorough evaluation of neonatal encephalopathy before initiating therapeutic hypothermia. Early initiation of treatment should be balanced with the time required for precise assessment to ensure better outcomes.

Neonatal seizures can lead to long-term neurodevelopmental problems. This study aims to identify predictors of poor developmental outcomes in neonates with seizures to aid in early intervention and referral for follow-up and rehabilitation.This observational study was conducted in the Department of Neonatology and Institute of Paediatric Neurodisorder and Autism, Bangabandhu Sheikh Mujib Medical University. Among 75 study cases of neonatal seizure, 23 died, and 46 were followed-up at 6 and 9 months after discharge. EEGs were performed on every patient. A comprehensive neurological examination and developmental evaluation were performed using Bayley Scales of Infant and Toddler Development, Third Edition (Bayley III).Three-fourths of neonates were born at term (76.1 %), and over half were male (56.5 %). The majority were appropriate for gestational age (79.7 %) and had an average birth weight of 2607 ± 696 g (±SD). Over half of the neonates (52.2 %) had adverse neurodevelopmental outcomes, with global developmental delay being the most common. Recurrent seizures, the number of anticonvulsants needed to control seizures, and abnormal Electroencephalograms were identified as independent predictors of adverse neurodevelopmental outcomes.The study highlights the need for early referral for follow-up and rehabilitation of neonates with seizures having abnormal electroencephalograms, recurrent seizures and requiring more anticonvulsants to control seizures.

BackgroundHypoxic-ischemic encephalopathy (HIE) represents one of the major causes of neonatal death and long-term neurological disability. Both hypoxic-ischemic insults and therapeutic hypothermia (TH) can affect respiratory function. Currently, there is no evidence regarding optimal respiratory management in these infants.MethodsThis is a retrospective cohort study examining newborns with HIE treated with TH between January 2015 and September 2020. The study population was divided into two groups based on different respiratory assistance during TH: spontaneous breathing (Group A) or mechanical ventilation (Group B). The primary outcome of the study was the mean pCO2 ± SD evaluation during TH in ventilated and non-ventilated asphyxiated infants. The secondary outcome was the correlation between ventilation strategy and short-term neurologic outcome according to Rutherford et al.'s MRI scoring system.ResultsA total of 126 newborns were enrolled, 75 in Group A and 51 in Group B. Respiratory management was individualized, and volume guarantee (VG) ventilation was the first choice for ventilated infants. Group B infants showed more severe conditions at birth. During TH, ventilated infants showed optimal mean pCO2 comparable with those breathing spontaneously (40.6 mmHg vs. 42.3 mmHg, respectively, p 0.091), with no significant difference in pCO2 standard deviation between (7.7 mmHg vs. 8.1 mmHg, respectively, p 0.522). Mean pH, pH standard deviation, mean pO2, pO2 standard deviation, and mean respiratory rate also did not differ between groups. MRI patterns of brain injury predictive of abnormal neurodevelopmental outcomes were similar in both groups. Logistic regression analysis demonstrated that only umbilical cord arterial blood pH-affected MRI lesions were associated with poor neurodevelopmental outcomes (OR 1.505; CI 95% 1.069–2.117).ConclusionsInfants cooled after HIE should receive individualized respiratory management, not necessarily involving intubation. In those infants requiring mechanical ventilation, a volume-targeted strategy appeared to be effective in maintaining stable blood gas levels. Short-term neurological outcomes appeared comparable in ventilated and non-ventilated infants.