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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]

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]

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]

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: 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]

Children who experience adversities in the pre-perinatal period are at increased risk of developing impairment later in life, despite the absence of overt brain and neurological abnormalities. However, many of these children exhibit sequelae several years after a period of normal appearance. As a result, the need for reliable developmental assessments for the early detection of infants at high risk of adverse neurodevelopmental outcomes has emerged. The Griffiths Mental Developmental Scales have a promising but poorly explored prognostic ability. This longitudinal study evaluated the predictive power of the Griffiths Mental Developmental Scales at 12 and 24 months on the cognitive and neuropsychological profile at 6 years of age in a sample of 70 children with a history of prematurity or perinatal asphyxia but without brain and neurological abnormalities. We found that the Griffiths Mental Developmental Scales at 24 months had good predictive ability on the intelligence quotient at 6 years and the capacity to predict some neuropsychological performances. On the other hand, the Griffiths Mental Developmental Scale at 12 months was not associated with the performance at 6 years or 24 months. Conclusion: Data on brain development converge to indicate that the first two years of age represent a critical stage of development, particularly for children experiencing mild pre-perinatal adversities who are thought to exhibit white matter dysmaturity. For this reason, this age is crucial for identifying which children are at major risk, leaving enough time to intervene before overt deficits become apparent. Brain development in the first 2 years could explain the limited reliability of early neurodevelopmental testing. What is Known: • Pre-perinatal adversities increase the risk of developing neurodevelopmental disorders. • The predictive ability of the Griffith scale is poorly explored in low-grade conditions. What is New: • The predictive ability of the Griffith scale has been investigated in low-risk children. • A complete neuropsychological profile could offer a more accurate prediction than the intellectual quotient. [ABSTRACT FROM AUTHOR]

The practice of withholding feed during therapeutic hypothermia (TH) in neonates with hypoxemic ischemic encephalopathy (HIE) is based on conventions rather than evidence. Recent studies suggest that enteral feeding might be safe during TH. We systematically compared the benefits and harms of enteral feeding in infants undergoing TH for HIE. We searched electronic databases and trial registries (MEDLINE, CINAHL, Embase, Web of Science, and CENTRAL) until December 15, 2022, for studies comparing enteral feeding and non-feeding strategies. We performed a random-effects meta-analysis using RevMan 5.4 software. The primary outcome was the incidence of stage II/III necrotizing enterocolitis (NEC). Other outcomes included the incidence of any stage NEC, mortality, sepsis, feed intolerance, time to full enteral feeds, and hospital stay. Six studies ((two randomized controlled trials (RCTs) and four nonrandomized studies of intervention (NRSIs)) enrolling 3693 participants were included. The overall incidence of stage II/III NEC was very low (0.6%). There was no significant difference in the incidence of stage II/III NEC in RCTs (2 trials, 192 participants; RR, 1.20; 95% CI: 0.53 to 2.71, I2, 0%) and NRSIs (3 studies, no events in either group). In the NRSIs, infants in the enteral feeding group had significantly lower sepsis rates (four studies, 3500 participants, RR, 0.59; 95% CI: 0.51 to 0.67, I2—0%) and lower all-cause mortality (three studies, 3465 participants, RR: 0.43; 95% CI: 0.33 to 0.57, I2—0%) than the infants in the "no feeding" group. However, no significant difference in mortality was observed in RCTs (RR: 0.70; 95% CI: 0.28 to 1.74, I2—0%). Infants in the enteral feeding group achieved full enteral feeding earlier, had higher breastfeeding rates at discharge, received parenteral nutrition for a shorter duration, and had shorter hospital stays than the control group. Conclusion: In late preterm and term infants with HIE, enteral feeding appears safe and feasible during the cooling phase of TH. However, there is insufficient evidence to guide the timing of initiation, volume, and feed advancement. What is Known: • Many neonatal units withhold enteral feeding during therapeutic hypothermia, fearing an increased risk of complications (feed intolerance and necrotizing enterocolitis). • The overall risk of necrotizing enterocolitis in late-preterm and term infants is extremely low (< 1%). What is New: • Enteral feeding during therapeutic hypothermia is safe and does not increase the risk of necrotizing enterocolitis, hypoglycemia, or feed intolerance. It may reduce the incidence of sepsis and all-cause mortality until discharge. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) remains common among infants with hypothermia-treated hypoxic-ischaemic encephalopathy (HIE). Little is known about long-term kidney outcomes following hypothermia treatment. We recently reported that 21% of survivors of hypothermia-treated HIE had decreased estimated glomerular filtration rate (eGFR) based on plasma creatinine in early adolescence. Here, we assessed kidney functions more comprehensively in our population-based cohort of children born in Stockholm 2007–2009 with a history of hypothermia-treated HIE. Methods: At 10–12 years of age, we measured cystatin C (cyst C) to estimate GFR. Children with decreased cyst C eGFR also underwent iohexol clearance examination. We measured urine-albumin/creatinine ratio, blood pressure (BP) and kidney volume on magnetic resonance imaging. Fibroblast growth factor 23 (FGF 23) levels in plasma were assessed by enzyme-linked immunosorbent assay (ELISA). Outcomes were compared between children with and without a history of neonatal AKI. Results: Forty-seven children participated in the assessment. Two children (2/42) had decreased cyst C eGFR, for one of whom iohexol clearance confirmed mildly decreased GFR. One child (1/43) had Kidney Disease Improving Global Outcomes (KDIGO) category A2 albuminuria, and three (3/45) had elevated office BP. Subsequent ambulatory 24-h BP measurement confirmed high normal BP in one case only. No child had hypertension. Kidney volume and FGF 23 levels were normal in all children. There was no difference in any of the parameters between children with and without a history of neonatal AKI. Conclusion: Renal sequelae were rare in early adolescence following hypothermia-treated HIE regardless of presence or absence of neonatal AKI. [ABSTRACT FROM AUTHOR]

Reliably assessing the early neurodevelopmental outcomes in infants with neonatal encephalopathy (NE) is of utmost importance to advise parents and implement early and personalized interventions. We aimed to evaluate the accuracy of neuroimaging modalities, including functional magnetic resonance imaging (fMRI) in predicting neurodevelopmental outcomes in NE. Eighteen newborns with NE due to presumed perinatal asphyxia (PA) were included in the study, 16 of whom underwent therapeutic hypothermia. Structural magnetic resonance imaging (MRI), and fMRI during passive visual, auditory, and sensorimotor stimulation were acquired between the 10th and 14th day of age. Clinical follow-up protocol included visual and auditory evoked potentials and a detailed neurodevelopmental evaluation at 12 and 18 months of age. Infants were divided according to sensory and neurodevelopmental outcome: severe, moderate disability, or normal. Structural MRI findings were the best predictor of severe disability with an AUC close to 1.0. There were no good predictors to discriminate between moderate disability versus normal outcome. Nevertheless, structural MRI measures showed a significant correlation with the scores of neurodevelopmental assessments. During sensorimotor stimulation, the fMRI signal in the right hemisphere had an AUC of 0.9 to predict absence of cerebral palsy (CP). fMRI measures during auditory and visual stimulation did not predict sensorineural hearing loss or cerebral visual impairment. Conclusion: In addition to structural MRI, fMRI with sensorimotor stimulation may open the gate to improve the knowledge of neurodevelopmental/motor prognosis if proven in a larger cohort of newborns with NE. What is Known: • Establishing an early, accurate neurodevelopmental prognosis in neonatal encephalopathy remains challenging. • Although structural MRI has a central role in neonatal encephalopathy, advanced MRI modalities are gradually being explored to optimize neurodevelopmental outcome knowledge. What is New: • Newborns who later developed cerebral palsy had a trend towards lower fMRI measures in the right sensorimotor area during sensorimotor stimulation. • These preliminary fMRI results may improve future early delineation of motor prognosis in neonatal encephalopathy. [ABSTRACT FROM AUTHOR]

Amorfrutin B is a selective modulator of the PPARγ receptor, which has recently been identified as an effective neuroprotective compound that protects brain neurons from hypoxic and ischemic damage. Our study demonstrated for the first time that a 6-h delayed post-treatment with amorfrutin B prevented hypoxia/ischemia-induced neuronal apoptosis in terms of the loss of mitochondrial membrane potential, heterochromatin foci formation, and expression of specific genes and proteins. The expression of all studied apoptosis-related factors was decreased in response to amorfrutin B, both during hypoxia and ischemia, except for the expression of anti-apoptotic BCL2, which was increased. After post-treatment with amorfrutin B, the methylation rate of the pro-apoptotic Bax gene was inversely correlated with the protein level, which explained the decrease in the BAX/BCL2 ratio as a result of Bax hypermethylation. The mechanisms of the protective action of amorfrutin B also involved the inhibition of autophagy, as evidenced by diminished autophagolysosome formation and the loss of neuroprotective properties of amorfrutin B after the silencing of Becn1 and/or Atg7. Although post-treatment with amorfrutin B reduced the expression levels of Becn1, Nup62, and Ambra1 during hypoxia, it stimulated Atg5 and the protein levels of MAP1LC3B and AMBRA1 during ischemia, supporting the ambiguous role of autophagy in the development of brain pathologies. Furthermore, amorfrutin B affected the expression levels of apoptosis-focused and autophagy-related miRNAs, and many of these miRNAs were oppositely regulated by amorfrutin B and hypoxia/ischemia. The results strongly support the position of amorfrutin B among the most promising anti-stroke and wide-window therapeutics. [ABSTRACT FROM AUTHOR]

Background: Since the discovery more than half a century ago, cell-free DNA (cfDNA) has become an attractive objective in multiple diagnostic, prognostic, and monitoring settings. However, despite the increasing number of cfDNA applications in liquid biopsies, we still lack a comprehensive understanding of the nature of cfDNA including optimal assessment. In the presented study, we continued testing and validation of common techniques for cfDNA extraction and quantification (qRT-PCR or droplet digital PCR) of nuclear- and mitochondrial cfDNA (ncfDNA and mtcfDNA) in blood, using a piglet model of perinatal asphyxia to determine potential temporal and quantitative changes at the levels of cfDNA. Methods and Results: Newborn piglets (n = 19) were either exposed to hypoxia (n = 11) or were part of the sham-operated control group (n = 8). Blood samples were collected at baseline (= start) and at the end of hypoxia or at 40–45 min for the sham-operated control group. Applying the qRT-PCR method, ncfDNA concentrations in piglets exposed to hypoxia revealed an increasing trend from 7.1 ng/ml to 9.5 ng/ml for HK2 (hexokinase 2) and from 4.6 ng/ml to 7.9 ng/ml for β-globulin, respectively, whereas the control animals showed a more balanced profile. Furthermore, median levels of mtcfDNA were much higher in comparison to ncfDNA, but without significant differences between intervention versus the control group. Conclusions: Both, qRT-PCR and the droplet digital PCR technique identified overall similar patterns for the concentration changes of cfDNA; but, the more sensitive digital PCR methodology might be required to identify minimal responses. [ABSTRACT FROM AUTHOR]

This article is based on the contents of 'Dr. K. C. Chaudhuri Lifetime Achievement Award Oration' delivered on the Indian Journal of Pediatrics Annual Day 2022. The author shares glimpses of his academic journey from a remote village to a central Institute. This includes his career as a medical teacher and developing the Department of Neonatology at JIPMER, Pondicherry. This article is primarily focused on some of the significant research conducted during his tenure, like perinatal asphyxia, therapeutic hypothermia, neonatal sepsis, intrauterine growth restriction, and human milk banking. [ABSTRACT FROM AUTHOR]

Objective: This study was intended to evaluate the predictive values of serum procalcitonin (PCT), lactate, creatine kinase (CK-MB), and troponin I on the diagnosis and staging of neonatal hypoxic-ischemic encephalopathy (HIE). Materials and methods: We retrospectively retrieved data from electronic medical records at our children's hospital, and we included all term newborns admitted between December 2018 and June 2020 with features of perinatal asphyxia. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to measure and evaluate the predictive values of biomarkers. p values < 0.05 were set as statistical significance. Results: A total of 201 neonates were included. They were grouped as control (n = 40), mild HIE (n = 105), moderate HIE (n = 36), and severe HIE (n = 20). Serum lactate, PCT, CK-MB, and troponin I levels in severe hypoxic-ischemic brain injury group were significantly higher than those in mild to moderate hypoxic-ischemic brain injury group and control group (p < 0.05). Based on ROC and AUC analysis, troponin I showed highest predictive ability with AUC of 0.904, and sensitivity and specificity of 95.00% and 87.50% respectively. Conclusion: Serum troponin I has a good predictive value for neonatal hypoxic-ischemic encephalopathy after perinatal asphyxia. [ABSTRACT FROM AUTHOR]

Perinatal asphyxia (PA)-induced brain injury may present as hypoxic-ischemic encephalopathy in the neonatal period, and long-term sequelae such as spastic motor deficits, intellectual disability, seizure disorders and learning disabilities. The brain injury is secondary to both the hypoxic-ischemic event and oxygenation–reperfusion following resuscitation. Following PA, a time-dependent progression of neuronal insult takes place in terms of transition of cell death from necrosis to apoptosis. This transition is the result of time-dependent progression of pathomechanisms which involve excitotoxicity, oxidative stress, and ultimately mitochondrial dysfunction in developing brain. More precisely mitochondrial respiration is suppressed and calcium signalling is dysregulated. Consequently, Bax-dependent mitochondrial permeabilization occurs leading to release of cytochrome c and activation of caspases leading to transition of cell death in developing brain. The therapeutic window lies within this transition process. At present, therapeutic hypothermia (TH) is the only clinical treatment available for treating moderate as well as severe asphyxia in new-born as it attenuates secondary loss of high-energy phosphates (ATP) (Solevåg et al. in Free Radic Biol Med 142:113–122, 2019; Gunn et al. in Pediatr Res 81:202–209, 2017), improving both short- and long-term outcomes. Mitoprotective therapies can offer a new avenue of intervention alone or in combination with therapeutic hypothermia for babies with birth asphyxia. This review will explore these mitochondrial pathways, and finally will summarize past and current efforts in targeting these pathways after PA, as a means of identifying new avenues of therapeutic intervention. [ABSTRACT FROM AUTHOR]

Aminophylline has been demonstrated to be effective in improving renal functions of the infants suffering from acute kidney injury (AKI) due to perinatal asphyxia. We aimed to evaluate the effect of a single-dose aminophylline on estimated glomerular filtration rate (eGFR), urine output (UO), and incidence and severity of AKI according to the pediatric-modified RIFLE and neonatal RIFLE criteria in newborns with perinatal asphyxia under therapeutic hypothermia. This was a single-center, retrospective cohort study including newborns (gestational age ≥36 weeks) who underwent therapeutic hypothermia due to hypoxic ischemic encephalopathy between 2016 and 2019. Demographic and clinical data were obtained from electronic medical records and patient files. Two patient groups were established: aminophylline group and control group which were only under therapeutic hypothermia. Twenty-one newborns were in the aminophylline group and 13 newborns were in the control group. Our study revealed that on the third day of life (DOL), eGFR was significantly higher in the control group (p=0.025), but UO was significantly higher in the aminophylline group (p=0.021). In the aminophylline group, eGFR on the first DOL was higher than the value on the second DOL (p=0.017) while UO was higher on the second and third DOL compared to the first DOL (1–2 DOL p=0.006, and 1–3 DOL p=0.004). However, in the control group, there was no statistically significant difference in UO over the four DOL. Both groups were similar in the presence, severity, and outcome of AKI. Conclusion: This study demonstrated that aminophylline increases UO even in the infants under therapeutic hypothermia. However, the eGFR did not significantly increase in the aminophylline group. Understanding how therapeutic hypothermia affects pharmacokinetics may help us improve our results in future studies. What is known: • Therapeutic hypothermia (TH) reduces the incidence of acute kidney injury in asphyxiated newborns. • Aminophylline is effective in improving renal functions in asphyxiated newborns. What is new: • This is the first study evaluating the effect of a single dose of aminophylline on renal functions in newborns under TH. • A single dose of aminophylline administration in newborns under TH was associated with increased urine output especially on the third day of life. However, no significant increase was detected in glomerular filtration rate associated with aminophylline administration. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the presented study was to evaluate the differences between selected biochemical markers in infants with moderate or severe hypoxic-ischemic encephalopathy (HIE) and their impact on patient prognosis. Methods: A total of 57 cooled newborns were divided into groups according to Sarnat staging of HIE (A, moderate vs. B, severe). The differences between groups were evaluated depending on the mode of delivery, pregnancy and labor complications, gestational age at birth, birth weight, and Apgar score at 1.3 and 5 min. The differences in biochemical biomarkers of HIE (pH, base excess, serum lactate) as well as biomarkers of hepatic injury (aspartate transaminase, (AST), alanine transaminase (ALT), prothrombin time (PT), and activated partial thromboplastin time (APTT)), kidney failure (creatinine, urea), myocardial injury (troponin T (TnT)), levels of fibrinogen, and platelet counts were also examined. Univariate Kaplan-Meier method was used for survival analyses. Results: The biomarker levels in severe HIE newborns compared with moderate were as follows: pH (7.10 vs. 6.99), serum lactate (22.50 vs. 17.00 mg/dL), AST (109.50 vs. 270.55 IU/L), ALT (27.30 vs. 108.05 IU/L), PT (17.00 vs. 44.20 s), APTT (47.75 vs. 47.90 s), TnT (0.22 vs. 0.85 ng/mL), creatinine (0.68 vs. 1.15 mg/dL), urea (44.55 vs. 73.30 mg/dL), and fibrinogen (1.65 vs. 1.90 mg/dL). Survival analyses showed significantly reduced survival for severe HIE infants (75%) vs. moderate HIE (100%). Conclusion: In conclusion, the severity of HIE can be evaluated based on selected markers; however, their levels do not correspond with future prognosis of newborns. [ABSTRACT FROM AUTHOR]

Each year, 1 million children die due to perinatal asphyxia; however, there are no effective drugs to protect the neonatal brain against hypoxic/ischemic damage. In this study, we demonstrated for the first time the neuroprotective capacity of 3,3'-diindolylmethane (DIM) in an in vivo model of rat perinatal asphyxia, which has translational value and corresponds to hypoxic/ischemic episodes in human newborns. Posttreatment with DIM restored the weight of the ipsilateral hemisphere and normalized cell number in the brain structures of rats exposed to perinatal asphyxia. DIM also downregulated the mRNA expression of HIF1A-regulated Bnip3 and Hif1a which is a hypoxic marker, and the expression of miR-181b which is an indicator of perinatal asphyxia. In addition, DIM inhibited apoptosis and oxidative stress accompanying perinatal asphyxia through: downregulation of FAS, CASP-3, CAPN1, GPx3 and SOD-1, attenuation of caspase-9 activity, and upregulation of anti-apoptotic Bcl2 mRNA. The protective effects of DIM were accompanied by the inhibition of the AhR and NMDA signaling pathways, as indicated by the reduced expression levels of AhR, ARNT, CYP1A1, GluN1 and GluN2B, which was correlated with enhanced global DNA methylation and the methylation of the Ahr and Grin2b genes. Because our study provided evidence that in rat brain undergoing perinatal asphyxia, DIM predominantly targets AhR and NMDA, we postulate that compounds that possess the ability to inhibit their signaling are promising therapeutic tools to prevent stroke. [ABSTRACT FROM AUTHOR]

Differentiation of oligodendrocyte progenitors towards myelinating cells is influenced by a plethora of exogenous instructive signals. Insulin-like growth factor 1 (IGF-1) is one of the major factors regulating cell survival, proliferation, and maturation. Recently, there is an ever growing recognition concerning the role of autocrine/paracrine IGF-1 signaling in brain development and metabolism. Since oligodendrocyte functioning is altered after the neonatal hypoxic-ischemic (HI) insult, a question arises if the injury exerts any influence on the IGF-1 secreted by neural cells and how possibly the change in IGF-1 concentration affects oligodendrocyte growth. To quantify the secretory activity of neonatal glial cells, the step-wise approach by sequentially using the in vivo, ex vivo, and in vitro models of perinatal asphyxia was applied. A comparison of the results of in vivo and ex vivo studies allowed evaluating the role of autocrine/paracrine IGF-1 signaling. Accordingly, astroglia were indicated to be the main local source of IGF-1 in the developing brain, and the factor secretion was shown to be significantly upregulated during the first 24 h after the hypoxic-ischemic insult. And conversely, the IGF-1 amounts released by oligodendrocytes and microglia significantly decreased. A morphometric examination of oligodendrocyte differentiation by means of the Sholl analysis showed that the treatment with low IGF-1 doses markedly improved the branching of oligodendroglial cell processes and, in this way, promoted their differentiation. The changes in the IGF-1 amounts in the nervous tissue after HI might contribute to the resulting white matter disorders, observed in newborn children who experienced perinatal asphyxia. Pharmacological modulation of IGF-1 secretion by neural cells could be reasonable solution in studies aimed at searching for therapies alleviating the consequences of perinatal asphyxia. [ABSTRACT FROM AUTHOR]

We have recently reported that global perinatal asphyxia (PA) induces a regionally sustained increase in oxidized glutathione (GSSG) levels and GSSG/GSH ratio, a decrease in tissue-reducing capacity, a decrease in catalase activity, and an increase in apoptotic caspase-3-dependent cell death in rat neonatal brain up to 14 postnatal days, indicating a long-term impairment in redox homeostasis. In the present study, we evaluated whether the increase in GSSG/GSH ratio observed in hippocampus involves changes in glutathione reductase (GR) and glutathione peroxidase (GPx) activity, the enzymes reducing glutathione disulfide (GSSG) and hydroperoxides, respectively, as well as catalase, the enzyme protecting against peroxidation. The study also evaluated whether there is a shift in the metabolism towards the penthose phosphate pathway (PPP), by measuring TIGAR, the TP53-inducible glycolysis and apoptosis regulator, associated with delayed cell death, further monitoring calpain activity, involved in bax-dependent cell death, and XRCC1, a scaffolding protein interacting with genome sentinel proteins. Global PA was induced by immersing fetus-containing uterine horns removed by a cesarean section from on term rat dams into a water bath at 37 °C for 21 min. Asphyxia-exposed and sibling cesarean-delivered fetuses were manually resuscitated and nurtured by surrogate dams. Animals were euthanized at postnatal (P) days 1 or 14, dissecting samples from hippocampus to be assayed for glutathione, GR, GPx (all by spectrophotometry), catalase (Western blots and ELISA), TIGAR (Western blots), calpain (fluorescence), and XRCC1 (Western blots). One hour after delivery, asphyxia-exposed and control neonates were injected with either 100 μl saline or 0.8 mmol/kg nicotinamide, i.p., shown to protect from the short- and long-term consequences of PA. It was found that global PA produced (i) a sustained increase of GSSG levels and GSSG/GSH ratio at P1 and P14; (ii) a decrease of GR, GPx, and catalase activity at P1 and P14; (iii) a decrease at P1, followed by an increase at P14 of TIGAR levels; (iv) an increase of calpain activity at P14; and (v) an increase of XRCC1 levels, but only at P1. (vi) Nicotinamide prevented the effect of PA on GSSG levels and GSSG/GSH ratio, and on GR, GPx, and catalase activity, also on increased TIGAR levels and calpain activity observed at P14. The present study demonstrates that the long-term impaired redox homeostasis observed in the hippocampus of rats subjected to global PA implies changes in GR, GPx, and catalase, and a shift towards PPP, as indicated by an increase of TIGAR levels at P14. [ABSTRACT FROM AUTHOR]

Hypoxic-ischaemic encephalopathy (HIE) remains one of the leading causes of neurological disability worldwide. No blood biomarker capable of early detection and classification of injury severity in HIE has been identified. This study aimed to investigate the potential of miRNA-181b (miR-181b) and its downstream target, ubiquitin C-terminal hydrolase-L1 (UCH-L1), to predict the severity of HIE. Full-term infants with perinatal asphyxia were recruited at birth and observed for the development of HIE, along with healthy controls. Levels of miR-181b and messenger UCH-L1 (mUCH-L1) in umbilical cord blood were determined using qRT-PCR. In total, 131 infants; 40 control, 50 perinatal asphyxia without HIE (PA) and 41 HIE, recruited across two separate cohorts (discovery and validation) were included in this study. Significant and consistent downregulation of miR-181b was observed in infants with moderate/severe HIE compared to all other groups in both cohorts: discovery 0.25 (0.16–0.32) vs 0.61 (0.26–1.39), p = 0.027 and validation 0.33 (0.15–1.78) vs 1.2 (0.071–2.09), p = 0.035. mUCH-L1 showed increased expression in infants with HIE in both cohorts. The expression ratio of miR-181b to mUCH-L1 was reduced in those infants with moderate/severe HIE in both cohorts: discovery cohort 0.23 (0.06–0.44) vs 1.59 (0.46–2.54), p = 0.01 and validation cohort 0.41 (0.10–0.81) vs 1.38 (0.59–2.56) in all other infants, p = 0.009. We have validated consistent patterns of altered expression in miR-181b/mUCH-L1 in moderate/severe neonatal HIE which may have the potential to guide therapeutic intervention in HIE. [ABSTRACT FROM AUTHOR]

Perinatal asphyxia remains a significant cause of neonatal mortality and is associated with long-term neurodegenerative disorders. In the present study, we evaluated cellular and subcellular damages to brain development in a model of mild perinatal asphyxia. Survival rate in the experimental group was 67%. One hour after the insult, intraperitoneally injected Evans blue could be detected in the fetuses’ brains, indicating disruption of the blood-brain barrier. Although brain mass and absolute cell numbers (neurons and non-neurons) were not reduced after perinatal asphyxia immediately and in late brain development, subcellular alterations were detected. Cortical oxygen consumption increased immediately after asphyxia, and remained high up to 7 days, returning to normal levels after 14 days. We observed an increased resistance to mitochondrial membrane permeability transition, and calcium buffering capacity in asphyxiated animals from birth to 14 days after the insult. In contrast to ex vivo data, mitochondrial oxygen consumption in primary cell cultures of neurons and astrocytes was not altered after 1% hypoxia. Taken together, our results demonstrate that although newborns were viable and apparently healthy, brain development is subcellularly altered by perinatal asphyxia. Our findings place the neonate brain mitochondria as a potential target for therapeutic protective interventions. [ABSTRACT FROM AUTHOR]

There is growing evidence that neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker of acute kidney injury. The objective of this meta-analysis is to determine the accuracy of serum and urinary NGAL in the detection of acute kidney injury in neonates with perinatal asphyxia. Medline (1966-2018), Scopus (2004-2018), EMBASE (1980-2018), Clinicaltrials.gov (2008-2018), and Google Scholar (2004-2018) databases, along with the reference lists of the electronically retrieved articles, were systematically searched. Eleven studies were included, with a total number of 652 neonates. The summary sensitivity of serum NGAL was 0.818 (95% CI [0.668, 0.909]), the specificity 0.870 (95% CI [0.754, 0.936]), and the area under the curve 0.912. Regarding urinary NGAL, pooled sensitivity was calculated at 0.897 (95% CI [0.829, 0.940]), specificity at 0.729 (95% CI [0.561, 0.850]), and area under the curve at 0.899.Conclusion: Serum and urinary NGAL represent candidate biomarkers with high performance in the prediction of acute kidney injury in newborns with perinatal asphyxia. Before NGAL can be widely used in clinical practice, future large prospective studies are needed to define the optimal cutoffs and accurately determine which levels are suggestive of post-asphyxial acute kidney injury. What is Known: • Acute kidney injury is a major cause of morbidity and mortality in perinatal asphyxia. • Current markers are insufficient in predicting post-asphyxial acute kidney injury. What is New: • Area under the curve for serum and urinary neutrophil gelatinase-associated lipocalin is 0.818 and 0.899, respectively. • Neutrophil gelatinase-associated lipocalin is a useful marker for detecting asphyxiated neonates at risk of developing acute kidney injury. [ABSTRACT FROM AUTHOR]

The present report evaluates the effect of global perinatal asphyxia on several parameters of oxidative stress and cell viability in rat brain tissue sampled at an extended neonatal period up to 14 days, a period characterised by intensive neuritogenesis, synaptogenesis, synaptic consolidation, pruning and delayed cell death. Perinatal asphyxia was induced by immersing foetus-containing uterine horns removed by a caesarean section from on term rat dams into a water bath at 37 °C for 21 min. Asphyxia-exposed and sibling caesarean-delivered foetuses were manually resucitated and nurtured by surrogate dams for 1 to 14 postnatal (P) days. Brain samples (mesencephalon, telencephalon and hippocampus) were assayed for glutathione (reduced and oxidated levels; spectrophotometry), tissue reducing capacity (potassium ferricyanide reducing assay, FRAP), catalase (the key enzyme protecting against oxidative stress and reactive oxygen species, Western blots and ELISA) and cleaved caspase-3 (the key executioner of apoptosis, Western blots) levels. It was found that global PA produced a regionally specific and sustained increase in GSSG/GSH ratio, a regionally specific decrease in tissue reducing capacity and a regionally and time specific decrease of catalase activity and increase of cleaved caspase-3 levels. The present study provides evidence for regionally impaired redox homeostasis in the brain of rats subjected to global PA, an effect observed up to P14, mainly affecting mesencephalon and hippocampus, suggesting a sustained oxidative stress after the posthypoxia period. The oxidative stress observed postnatally can in part be associated to a respiratory apneic-like deficit, since there was a statistically significant decrease in respiration frequency in AS compared to CS neonates, also up to P14, together with the signs of a decreased peripheral blood perfusion (pink-blue skin colour in AS, compared to the pink colour observed in all CS neonates). It is proposed that PA implies a long-term metabolic insult, triggered by the length of hypoxia, the resuscitation/reoxigenation manoevres, but also by the developmental stage of the affected brain regions, and the integrity of cardiovascular and respiratory physiological functions, which are fundamental for warrantying a proper development. [ABSTRACT FROM AUTHOR]

Objectives: To describe the diagnostic test properties of Cardiac Troponin-T (cTnT) in predicting myocardial dysfunction in asphyxiated term neonates by taking echocardiography as the gold standard and to establish the optimum cut-off values of cTnT for myocardial dysfunction, shock, severe hypoxic ischemic encephalopathy (HIE) and mortality by receiver operator characteristic (ROC) curve analysis.Methods: This was a prospective study based on diagnostic test evaluation. The study included 120 term asphyxiated neonates in a tertiary care neonatal intensive care unit (NICU) in Southern India from June 2011 through June 2015. All the neonates were clinically evaluated. Venous blood was taken at 4 h of life for cTnT estimation. Echocardiography was done within 24 h of birth.Results: The mean cTnT level of asphyxiated term neonates was 0.207±0.289 ng/ml (mean ± SD). Asphyxiated neonates with myocardial dysfunction had higher cTnT levels (0.277±0.231) as compared to those without myocardial dysfunction (0.061±0.036, p = 0.0001). Using ROC curve, the cut-off cTnT values for myocardial dysfunction was 0.1145 ng/ml with sensitivity 92.4% and specificity 94.1%. Cardiac Troponin-T levels were significantly higher among asphyxiated neonates with shock (0.378±0.348, p = 0.0001) and the levels also correlated positively with increasing grades of HIE. The cut-off cTnT value for mortality was 0.2505 ng/ml with sensitivity 83.9% and specificity 96.6%.Conclusions: In asphyxiated term neonates, early cTnT elevation is a marker for predicting myocardial dysfunction and elevated cTnT levels had high sensitivity and specificity. There was significant relation with increasing cTnT values and increasing grades of HIE. [ABSTRACT FROM AUTHOR]

Perinatal asphyxia results from the action of different risk factors like complications during pregnancy, preterm delivery, or long and difficult labor. Nowadays, it is still the leading cause of neonatal brain injury known as hypoxic-ischemic encephalopathy (HIE) and resulting neurological disorders. A temporal limitation of oxygen, glucose, and trophic factors supply results in alteration of neural cell differentiation and functioning and/or leads to their death. Among the affected cells are oligodendrocytes, responsible for myelinating the central nervous system (CNS) and formation of white matter. Therefore, one of the major consequences of the experienced HIE is leukodystrophic diseases resulting from oligodendrocyte deficiency or malfunctioning. The therapeutic strategies applied after perinatal asphyxia are aimed at reducing brain damage and promoting the endogenous neuroreparative mechanisms. In this review, we focus on the biology of oligodendrocytes and discuss present clinical treatments in the context of their efficiency in preserving white matter structure and preventing cognitive and behavioral deficits after perinatal asphyxia. [ABSTRACT FROM AUTHOR]

Copyright of Monatsschrift Kinderheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Therapeutic hypothermia (TH) is now provided as standard care to infants with moderate-severe hypoxic ischemic encephalopathy (HIE). The role of TH in limiting neuronal injury is well recognized, but its effect on hepatic injury which occurs frequently in neonatal HIE is not known. Our objective was to characterize biomarkers of liver injury and function in the setting of neonatal HIE and to describe whether HIE severity and provision of TH influence these hepatic biomarkers. We performed a multicenter retrospective study and compared hepatic biomarkers obtained during the first postnatal week, according to the severity of HIE and whether treated with TH. Of a total of 361 infants with HIE, 223 (62%) received TH and 138 (38%) were managed at normal temperature. Most hepatic biomarkers and C-reactive protein (CRP) were significantly associated with the severity of HIE (p < 0.001). Infants treated with TH had lower peak alanine aminotransferase (ALT) concentrations (p = 0.025) and a delay in reaching peak CRP concentration (p < 0.001).Conclusion: We observed a significant association between the clinical grade of HIE and biomarkers of liver metabolism and function. Therapeutic hypothermia was associated with delayed CRP responses and with lower ALT concentrations and so may have the potential to modulate hepatic injury. What is Known: • Ischemic hepatic injury occurs frequently as a part of multiorgan dysfunction in infants with hypoxic ischemic encephalopathy (HIE). • The neuroprotective role of therapeutic hypothermia in management of infants with HIE is well recognized, but the potential hepato-protective effects of hypothermia are unclear. What is New/What this study adds: • Therapeutic hypothermia was associated with lower alanine aminotransferase and albumin concentrations and a delayed C-reactive protein (CRP) response and so may have the potential to modulate hepatic injury. • An elevated CRP concentration during the first postnatal week may be regarded as an expected finding in moderate and severe HIE and, in the overwhelming majority of cases, occurs secondary to hepatic hypoxia-ischemia in the absence of blood culture-positive sepsis. [ABSTRACT FROM AUTHOR]

The available data on the effectiveness of therapeutic hypothermia in different patient groups are heterogeneous. Although the benefits have been proven for some collectives, recommendations for the use of hypothermia treatment in other groups are based on less robust data and conclusions by analogy. This article gives a review of the current evidence of temperature management in all age groups and based on this state of knowledge, recommends active temperature management with the primary aim of strict normothermia (36-36.5 °C) for 72 hours after cardiopulmonary arrest or severe traumatic brain injury for children beyond the neonatal period. [ABSTRACT FROM AUTHOR]

In the context of medical professional liability, obstetrics is one of the most involved medical specialties because the unfavorable outcome of a pregnancy is difficult to accept for parents, who tend to reduce it to inappropriate care that occurred during pregnancy or birth. 32 cases of perinatal asphyxia were evaluated by the Institute of Forensic Medicine in Brescia during the period between 1999 and 2014 (13 in Civil Court and 19 in Penal Court). 9 out of the 32 pregnancies were twins, so the considerations were carried out on a total of 41 fetuses/newborns. Profiles of inadequacy were identified in 66% of cases (85% of the cases evaluated in Civil Court; 53% of the cases evaluated in Penal Court). The existence of a causal relationship between the medical conduct and the onset of asphyxia was recognized in 79% of civil cases and in 38% of penal cases. There is a “greater rigor” in the verification of causal relationship and malpractice profiles in penal cases compared to civil ones: this is in harmony with the most recent Italian Court decisions, characterized by compelling suspect’s protection in the presence of a reasonable doubt in criminal matters and by victim’s protection in civil ones. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the utility of urinary Neutrophil Gelatinase Associated Lipocalin (NGAL) as a biomarker for predicting Acute Kidney Injury (AKI) and its severity among neonates with perinatal asphyxia. Methods: This descriptive study included 120 term neonates with perinatal asphyxia. Renal parameters of neonates were monitored and AKI was ascertained as per Acute Kidney Injury Network criteria. Urinary NGAL was estimated and correlated with severity of AKI. Results: Among the 120 neonates with perinatal asphyxia, 55(46 %) had AKI. The median urinary NGAL level was 165 ng/ml (88.8-245.8) in neonates with AKI compared to 58.97(42.8-74.7) in those without AKI. The median NGAL was 134.45(112.2-162.5), 301.2(255.5-361.2), 416.2(412.2-465.5) in AKI stages 1, 2 and 3 respectively. An NGAL cut off value of 86.82 ng/ml had 87 % sensitivity and 87.7 % specificity in predicting AKI. Conclusions: Urinary NGAL is a useful biomarker for predicting AKI and its severity among neonates with perinatal asphyxia. [ABSTRACT FROM AUTHOR]

Cardiovascular compromise is a common complication of neonatal respiratory distress and perinatal asphyxia. Tei index is a Doppler-derived index for the assessment of overall left ventricular function that combines systolic and diastolic time intervals. Aim: Assess the role of MPI versus cardiac troponin I as early indicator of hypoxic cardiac damage in neonates with respiratory distress or perinatal asphyxia. The present work was conducted on forty neonates, 15 with neonatal respiratory distress (group I), 15 with perinatal asphyxia (group II), and 10 apparently healthy neonates as a control (group III). All have: Detailed history-thorough clinical examination-Plain X-ray-ECG-Two dimensional, M-mode and Doppler echocardiographic examination with the measurement of both myocardial performance index (MPI) of the right and left ventricle-Serum cardiac troponin I. Results: There was statistically significant increase in serum cardiac troponin I in groups I and II than group III. Left and right ventricular myocardial performance index (MPI) were increased in group I and II than the control group. No correlation between Tei index and each of postnatal age, apgar score at 5-min, heart rate, serum cardiac troponin I, ejection fraction and fractional shortening, but there was direct relationship between MPI and LVEDD and inverse relationship between MPI and each of EF% and FS%. But there was significant correlation between L.V. MPI and gestational age. Conclusion: Tei index was higher in neonates with respiratory distress and neonates with perinatal asphyxia than in normal neonates despite normal or even increased ejection fraction which indicates that these patients may have subclinical ventricular dysfunction which should be followed up carefully. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is the most common complication of perinatal asphyxia. Recent research indicates that urine neutrophil gelatinase-associated lipocalin (NGAL) is an early marker for AKI; yet, there is a paucity of data about its use in term neonates with perinatal asphyxia. Methods: A prospective cohort study was conducted on 108 term babies in the new-born unit of Pumwani Maternity Hospital and Kenyatta National Hospital. Urine NGAL and serum creatinine were measured in 108 term asphyxiated neonates on days 1 and 3 of life. Results: One-hundred and eight patients were recruited (male:female 1.4:1). At a cut-off of 250 ng/ml, urine NGAL had an acceptable discriminative capability of predicting AKI (area under the curve 0.724). The sensitivity, specificity, positive and negative predictive value and likelihood ratios were 88, 56, 30, 95 %, 2 and 0.2 respectively. Urine NGAL levels were significantly higher in patients with AKI compared with those without AKI. An NGAL level greater than 250 ng/ml on day 1 was significantly associated with severe hypoxic ischaemic encephalopathy (HIE); odds ratio = 8.9 (95 % CI 1.78-37.69) and mortality; odds ratio = 8.9 (95 % CI 1.78-37.69). Conclusion: Urine NGAL is a good screening test for the early diagnosis of AKI. It is also a predictor of mortality and severity of HIE in asphyxiated neonates. [ABSTRACT FROM AUTHOR]

Objectives: To identify biomarkers for neuronal injury and outcome in perinatal asphyxia. Methods: This prospective cohort study was done in authors' level III NICU involving 80 neonates - 40 babies with perinatal asphyxia and 40 weight and gender matched normal neonates. Levels of cytokines IL-6, IL -1β, IL-2 and TNF -α in cord blood of these neonates were estimated and correlated with the severity of asphyxia and developmental outcome at 6 mo using Baroda Developmental Score. Results: The baseline parameters revealed that there was no statistically significant difference between the two groups in terms of maternal age, parity, gestational age, gender and birth weight. The levels of cytokines IL-6 ( p < 0.001) and IL-1beta ( p < 0.03) were significantly higher in babies with perinatal asphyxia and correlated with the severity of asphyxia. The levels of IL-6 and IL-1β had significant negative correlation with developmental score at 6 mo. A cut off level of 14.18 pg/ml for IL-6 had 92.3 % sensitivity and 57.7 % specificity [Area under the curve = 0.80 (0.62-0.84)] for adverse neuro-developmental outcome while it was 11.17 pg/ml for IL-1β with a sensitivity of 69.2 % and specificity of 71.2 % [Area under the curve = 0.67 (0.57-0.80)]. Conclusions: IL-6 and IL-1 β are good predictive markers of severity of asphyxia and adverse neurological outcome. [ABSTRACT FROM AUTHOR]

Asphyctic brain injury is a major cause of neuronal inflammation in the perinatal period. Fetal asphyctic preconditioning has been shown to modulate the cerebral inflammatory cytokine response, hereby protecting the brain against asphyctic injury at birth. This study was designated to examine the effects of perinatal asphyxia and fetal asphyctic preconditioning on the inflammatory cytokine response in the cerebellum. Fetal asphyxia was induced at embryonic day 17 by clamping the uterine vasculature for 30 min. At term birth, global perinatal asphyxia was induced by placing the uterine horns in saline for 19 min. Pro- and anti-inflammatory cytokine expression were assessed by real-time PCR and immunohistochemistry in cerebella of newborn rats. We found that tumor necrosis factor alpha and interleukin-10 mRNA were increased 12 h after fetal asphyxia, while the inflammatory cytokine response was decreased 96 h postfetal asphyxia. When applied as preconditioning stimulus, fetal asphyxia attenuates the cerebellar cytokine response. These results indicate that sublethal fetal asphyxia may protect the cerebellum from perinatal asphyxia-induced damage via inhibition of inflammation. [ABSTRACT FROM AUTHOR]

Therapeutic hypothermia (TH) has been established as standard of care for term babies with perinatal asphyxia in developed countries. However, it is yet to gain momentum in India. This review summarizes some of the TH trials conducted in India and the various related issues in adapting the same for the Indian context. [ABSTRACT FROM AUTHOR]

Objective: To study the renal function in term newborns with perinatal asphyxia including urinary excretion of β microglobulin (βM). Methods: This case control study included 50 term newborn babies with perinatal asphyxia and 50 normal babies as matched controls. In all cases, asphyxia grading (using Apgar score) and Hypoxic ischemic encephalopathy (HIE) staging (Sarnat and Sarnat) were done. Blood and urinary parameters (including βM) for renal function were done in all and Fractional excretion of sodium (FENa) and Renal failure index (RFI) were calculated. The renal parameters were compared within subgroups as well as controls using analysis of variance test and the independent samples t test. Results: Acute kidney Injury (AKI) was noted in 56 % of cases (24 % prerenal and 32 % intrinsic type). All 9 babies who died had AKI. Serum parameters like urea, creatinine, sodium and potassium had better correlation with the renal function as compared to urine parameters. All individual urine parameters except βM showed wide variations. FENa, RFI and urinary βM increased with increasing severity of asphyxia and HIE staging. Conclusion: AKI is common in term babies with perinatal asphyxia. FENa and RFI are useful parameters for assessing the renal function and urinary βM is a good biomarker for diagnosis and prognosis of acute tubular injury in term babies with perinatal asphyxia. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the cardiac conduction system using P wave dispersion on electrocardiogram and its relationship with the short term mortality and development of arrhythmia in asphyxiated neonates. Methods: Thirty term babies with evidence of asphyxia and without any congenital abnormalities were consecutively evaluated as cases. They were compared with thirty healthy term babies without asphyxia. Twelve-lead surface electrocardiography was obtained from all the patients and the controls, and P wave dispersion was calculated according to its definition as the difference between P maximum duration and P minimum duration in 12-lead electrocardiogram. Results: A statically significant difference of P wave dispersion was observed between the patients and the control group (0.027 ± 0.011 mm/s and 0.016 ± 0.006 mm/s, respectively; P value = 0.0001). The P wave dispersion had a statistically significant correlation with the grade of asphyxia ( P = 0.004, r = 0.62), the P wave dispersion had no statistically significant correlation with Apgar scores, short term arrhythmia, and troponin I level in asphyxiated neonates ( P < 0.05). Conclusions: The P wave dispersion increased in asphyxiated neonates and correlated with grade of asphyxia; however, the increased P wave dispersion was not correlated with the short term mortality, arrhythmia and troponin I level of the asphyxiated neonates. [ABSTRACT FROM AUTHOR]

The aim of this study was to observe the dynamic changes of serum brain-derived neurotrophic factor (BDNF), S-100B, and Tau proteins levels in full-term newborns with hypoxic-ischemic encephalopathy (HIE) and to discuss their significance in brain damage. Serum samples of 28 full-term newborns diagnosed with HIE and 20 controls were obtained in the first 24 h of life. Another serum samples were also taken, respectively, at 3 and 7 days of life in HIE group. The concentrations of BDNF, S-100B, and Tau proteins were measured by the enzyme-linked immunosorbent assay method. Mean concentrations of BDNF, S-100B, and Tau proteins among different time period and in different grades of HIE group were calculated and compared. Compared with the control group, serum BDNF and proteins S-100B levels in HIE group were significantly elevated in 24 h after birth ( P < 0.05) and their concentrations were also significantly higher among patients with mod-severe HIE compared to those with mild HIE at 24 h and 7 days after asphyxia ( P < 0.05). Regardless of whether mod-severe HIE or mild HIE, there were no significant difference of serum BDNF and proteins S-100B among the three different time periods. There was no difference in Tau protein levels between HIE group and control group, also no difference between mod-severe HIE group and mild HIE group. BDNF and proteins S-100B are up-regulated early in asphyxia neonates with HIE; and the released amount of BDNF and proteins S-100B from nerve center system correlate with the extent of encephalopathy. [ABSTRACT FROM AUTHOR]

Copyright of Monatsschrift Kinderheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Worldwide, perinatal asphyxia is an important cause of morbidity and mortality among term-born children. Overactivation of the N-methyl- d-aspartate receptor (NMDAr) plays a central role in the pathogenesis of cerebral hypoxia-ischemia, but the role of both endogenous NMDAr co-agonists d-serine and glycine remains largely elusive. We investigated d-serine and glycine concentration changes in rat glioma cells, subjected to oxygen and glucose deprivation (OGD) and CSF from piglets exposed to hypoxia-ischemia by occlusion of both carotid arteries and hypoxia. We illustrated these findings with analyses of cerebrospinal fluid (CSF) from human newborns affected by perinatal asphyxia. Extracellular concentrations of glycine and d-serine were markedly increased in rat glioma cells exposed to OGD, presumably through increased synthesis from l-serine. Upon reperfusion glycine concentrations normalized and d-serine concentrations were significantly lowered. The in vivo studies corroborated the finding of initially elevated and then normalizing concentrations of glycine and decreased d-serine concentrations upon reperfusion These significant increases of both endogenous NMDAr co-agonists in combination with elevated glutamate concentrations, as induced by global cerebral ischemia, are bound to lead to massive NMDAr activation, excitotoxicity and neuronal damage. Influencing these NMDAr co-agonist concentrations provides an interesting treatment target for this common, devastating and currently poorly treatable condition. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The study aims to determine the high risk gestational week (GW) and/or birth weight (BW) of the preterm neonate, below which perinatal hypoxic cerebral injuries are expected to occur. Material and methods: Eighty preterm neonates, born at or before 37 GW, were included. Twenty-three of them were <32 GW and 57 >32 GW. Also, 28 of them were <1500g and 52 >1500g. Imaging was done by transcranial ultrasound with 4–9MHz curvilinear probe. CT scan was additionally performed for only 18 candidates. The study protocol was approved by the ethics committee in Al-Mana General Hospital (AGH). Results: Intraventricular hemorrhage (IVH) was diagnosed in six preterm neonates <32 GW and two >32 GW. Three <32 GW and one >32 GW presented with hypoxic ischemic encephalopathy (HIE) with no hemorrhage. Two preterm neonates <32 GW had both IVH & HIE. All positive cases were below 1500g BW. Conclusion: Preterm neonates <32 GW and/or <1500g are highly susceptible for HIE and/or IVH. Thus, special medical care, including post-labor hospitalization in well equipped special baby care units (SCBU) and routine transcranial ultrasound (TCUS) screening is recommended for those preterm neonates. [Copyright &y& Elsevier]

The aim of this study was to determine the effects of erythropoietin (EPO), moderate hypothermia, and a combination thereof on the kidneys of newborn rats damaged during perinatal asphyxia. An animal model of perinatal asphyxia (Wistar rats) was used in which after birth, newborn rats were divided into four groups of 15 animals each: G1, rats exposed only to asphyxia; G2, rats exposed to asphyxia and hypothermia (rectal temperature 32°C) and which received EPO (darbepoetin alpha) intraperitoneally; G3, rats exposed to asphyxia and hypothermia; G4, rats exposed to asphyxia and which received EPO. The rats were sacrificed on the 7th day of life and histopathological evaluation of kidneys was performed. Damage to the proximal tubules was significantly higher in group G1 rats than in groups G2, G3, and G4 rats ( p < 0.01). Damage to the distal tubules was found only in group G1 rats. Histological changes in the proximal tubules were more prominent than in the distal tubules ( p < 0.01). The immature glomeruli zone was less expressed in group G4 rats than in groups G1, G2, and G3 rats ( p < 0.01). Based on these results, we conclude that EPO and hypothermia, as well as the combination thereof, have a protective effect on rats' kidneys damaged during perinatal asphyxia. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of high dose phenobarbital on lipid peroxidation and antioxidant enzymes in perinatal asphyxia. Design: Open label, Randomized controlled trial. Setting: Neonatal intensive care unit of a tertiary care teaching hospital. Participants: 72 full term inborn neonates with severe birth asphyxia. Methods: Neonates were randomized to Study (phenobarbital) group and Control group. The infants in the study group received phenobarbital infusion (40mg/kg) within first two hours of life while babies in the control group did not receive any phenobarbital. Rest of the management in both the groups was as per the unit protocol for the management of hypoxic ischemic encephalopathy. A cerebrospinal fluid examination was done at 12 ± 2 hours of life to determine the levels of superoxide dismutase, glutathione peroxidise and malonyldialdehyde. 60 neonates were followed up at 1 month of age when a detailed neurological examination was done. Results: Four neonates in the study group and six neonates in the control group died during the study. Two neonates in the study group were lost to follow up. The cerebrospinal fluid lipid peroxides and antioxidant enzymes were significantly lower in the phenobarbital group as compared to the control group. The neurological outcome at one month follow up was found to be comparable between the two groups. Conclusion: Phenobarbital (40mg/kg) given in the first two hours of life in term neonates with perinatal asphyxia led to a decrease in CSF levels of lipid peroxides and antioxidant enzymes at 12 ± 2 hours of life. [ABSTRACT FROM AUTHOR]

Until now, brain MRIs in asphyxiated neonates who are receiving therapeutic hypothermia have been performed after treatment is complete. However, there is increasing interest in utilizing early brain MRI while hypothermia is still being provided to rapidly understand the degree of brain injury and possibly refine neuroprotective strategies. This study was designed to assess whether therapeutic hypothermia can be maintained while performing a brain MRI. Twenty MRI scans were obtained in 12 asphyxiated neonates while they were treated with hypothermia. The median difference between esophageal temperature on NICU departure and return was 0.1°C (range: −0.8 to 0.8°C). We found that therapeutic hypothermia can be safely and reproducibly maintained during a brain MRI. Hypothermia treatment should not prevent obtaining an early brain MRI if clinically indicated. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess myocardial performance of full-term infants with perinatal asphyxia using Doppler tissue imaging (DTI) and to correlate it with serum cardiac troponin T (cTnT) concentrations. Twenty-five asphyxiated and 20 nonasphyxiated term infants were investigated. Serum cTnT concentrations were measured between 12 and 24 h of life. Conventional two-dimensional Doppler echocardiography and DTI were done during the first 72 h of life. Right ventricular (RV) and left ventricular (LV) Tei indexes were significantly higher in asphyxiated neonates (mean ± SD: 0.45 ± 0.05 vs. 0.28 ± 0.05, P < 0.001 and 0.51 ± 0.04 vs. 0.38 ± 0.04, P < 0.001, respectively). Mitral and tricuspid systolic (Sm) velocities were significantly lower in asphyxiated neonates (mean ± SD: 5.06 ± 0.89 vs. 6.89 ± 0.94 cm/s, P < 0.001 and 5.78 ± 0.58 vs. 6.69 ± 0.87 cm/s, P < 0.001, respectively). cTnT concentrations were significantly higher in asphyxiated neonates [median (range): 0.17 (0.05–0.23) vs. 0.03 (0–0.07) μg/l, P < 0.001)], and they correlated positively with the LV Tei index ( r = 0.67, P < 0.001) and the RV Tei index ( r = 0.68, P < 0.001) and negatively with the mitral systolic (Sm) velocity ( r = –0.68, P < 0.001) and tricuspid systolic (Sm) velocity ( r = –0.41, P = 0.01). A higher cTnT was a significant predictor of mortality, whereas fractional shortening (FS) and DTI measurements did not show any significant predictive value. The DTI technique appears to be more sensitive than conventional echocardiography in the early detection of myocardial dysfunction induced by perinatal asphyxia in full-term infants. [ABSTRACT FROM AUTHOR]

Carbon monoxide (CO) intoxication has serious adverse effects to the mother and fetus and a result of intrauterine hypoxia, it leads to fetal death or severe neurological sequelae. In this article, a preterm infant who was acutely exposed to CO at the 33rd weeks of gestation before delivery was presented. The baby was delivered by emergent cesarean section at the 34th weeks of gestation due to findings of fetal distress and he had severe hypoxic ischemic encephalopathy leading to death. Results and treatment modalities of CO poisoning during pregnancy were reviewed. [ABSTRACT FROM AUTHOR]

To study electrolyte status in asphyxiated newborns of different severity in early neonatal period and compare with controls. Sodium, potassium and total calcium levels were estimated in the serum samples of asphyxiated newborns of different severity and control group immediately after birth. Mean serum sodium level was significantly lower (122.1 ± 6.0 mEq/L vs 138.8 ± 2.7 mEq/L; P < 0.001), mean serum potassium was higher (5.05 ± 0.63 mEq/L vs 4.19 ± 0.40 mEq/L; P < 0.001) and mean serum calcium level was found lower (6.85 ± 0.95 mg/dl vs 9.50 ± 0.51 mg/dl; P < 0.001) in cases than controls. Among cases, a strong positive linear correlation was found between the serum sodium, serum calcium levels and their Apgar scores, between sodium levels and total calcium levels and significant negative linear correlation between Apgar scores and serum potassium level. Among cases, hyponatremia and hypocalcemia developed early and simultaneously and the decrease in their serum levels was directly proportional to each other and to the degree of asphyxia. Though, mean potassium level was within the normal limit, the value was higher among cases than controls and directly proportional to asphyxia. [ABSTRACT FROM AUTHOR]

Objective:To evaluate an electroencephalography (EEG)-based index, the Cerebral Health Index in babies (CHI/b), for identification of neonates with high Sarnat scores and abnormal EEG as markers of hypoxic ischemic encephalopathy (HIE) after perinatal asphyxia.Study Design:This is a retrospective study using 30 min of EEG data collected from 20 term neonates with HIE and 20 neurologically normal neonates. The HIE diagnosis was made on clinical grounds based on history and examination findings. The maximum-modified clinical Sarnat score was used to grade HIE severity within 72 h of life. All neonates underwent 2-channel bedside EEG monitoring. A trained electroencephalographer blinded to clinical data visually classified each EEG as normal, mild or severely abnormal. The CHI/b was trained using data from Channel 1 and tested on Channel 2.Result:The CHI/b distinguished among HIE and controls (P<0.02) and among the three visually interpreted EEG categories (P<0.0002). It showed a sensitivity of 82.4% and specificity of 100% in detecting high grades of neonatal encephalopathy (Sarnat 2 and 3), with an area under the receiver operator characteristic (ROC) curve of 0.912. CHI/b also identified differences between normal vs mildly abnormal (P<0.005), mild vs severely abnormal (P<0.01) and normal vs severe (P<0.002) EEG groups. An ROC curve analysis showed that the optimal ability of CHI/b to discriminate poor outcome was 89.7% (sensitivity: 87.5%; specificity: 82.4%).Conclusion:The CHI/b identified neonates with high Sarnat scores and abnormal EEG. These results support its potential as an objective indicator of neurological injury in infants with HIE. [ABSTRACT FROM AUTHOR]

Unlabelled: This is a comparative study between 60 asphyxiated newborns (cases) and 60 normal neonates (controls) in respect of their plasma glucose and uric acid levels and also their clinical and neurological status. The mean plasma glucose level was significantly lower (35.1 +/- 11.4 mg/dl vs. 56.9 +/- 5.5 mg/dl; P < 0.001) and the mean serum uric acid level was higher (8.0 +/- 1.2 mg/dl vs. 4.5 +/- 0.83 mg/dl; P < 0.001) in the asphyxiated group when compared to the controls. Within the perinatal asphyxia group, the plasma glucose level and Apgar scores showed a significant positive linear correlation (r = 0.740, P < 0.001), whereas a significant negative linear correlation was observed between the glucose level and different stages of hypoxic ischemic encephalopathy (HIE) (r = -0.875, P < 0.001). Although a strong positive linear correlation was found between uric acid and HIE stages (r = 0.734, P < or = 0.001), the linear correlation between uric acid and Apgar scores (r = -0.885, P < 0.001) and uric acid and the plasma glucose level (r = -0.725, P < 0.001) were found to be significantly negative among the cases.Conclusion: The severity of encephalopathy and cellular damage varies with the severity of hypoglycemia. [ABSTRACT FROM AUTHOR]