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Introduction: There is large variability in kidney function and injury in neonates with neonatal encephalopathy (NE) treated with therapeutic hypothermia (TH). Acute kidney injury (AKI) definitions that apply categorical approaches may lose valuable information about kidney function in individual patients. Centile serum creatinine (SCr) over postnatal age (PNA) may provide more valuable information in TH neonates. Methods: Data from seven TH neonates and one non-TH-treated, non-NE control cohorts were pooled in a retrospective study. SCr centiles over PNA, and AKI incidence (definition: SCr ↑≥0.3 mg/dL within 48 h, or ↑ ≥1.5 fold vs. the lowest prior SCr within 7 days) and mortality were calculated. Repeated measurement linear models were applied to SCr trends, modeling SCr on PNA, birth weight or gestational age (GA), using heterogeneous autoregressive residual covariance structure and maximum likelihood methods. Findings were compared to patterns in the control cohort. Results: Among 1,136 TH neonates, representing 4,724 SCr observations, SCr (10th–25th–50th–75th–90th–95th) PNA centiles (day 1–10) were generated. In TH neonates, the AKI incidence was 132/1,136 (11.6%), mortality 193/1,136 (17%). AKI neonates had a higher mortality (37.2–14.3%, p < 0.001). Median SCr patterns over PNA were significantly higher in nonsurvivors (p < 0.01) or AKI neonates (p < 0.001). In TH-treated neonates, PNA and GA or birth weight explained SCr variability. Patterns over PNA were significantly higher in TH neonates to controls (801 neonates, 2,779 SCr). Conclusions: SCr patterns in TH-treated NE neonates are specific. Knowing PNA-related patterns enable clinicians to better assess kidney function and tailor pharmacotherapy, fluids, or kidney supportive therapies.

Objectives The early detection and stratification of asphyxiated infants at higher risk for impaired neurodevelopment is challenging. S100B protein is a well-established biomarker of brain damage, but lacks conclusive validation according to the “gold standard” methodology for hypoxic-ischemic encephalopathy (HIE) prognostication, i.e. brain MRI. The aim of the present study was to investigate the predictive role of urinary S100B concentrations, assessed in a cohort of HIE infants receiving therapeutic hypothermia (TH), compared to brain MRI. Methods Assessment of urine S100B concentrations was performed by immunoluminometric assay at first void and at 4, 8, 12, 16, 20, 24, 48, 72, 96, 108 and 120-h after birth. Neurologic evaluation, routine laboratory parameters, amplitude-integrated electroencephalography, and cerebral ultrasound were performed according to standard protocols. Brain MRI was performed at 7–10 days of life. Results Overall, 74 HIE neonates receiving TH were included in the study. S100B correlated, already at first void, with the MRI patterns with higher concentrations in infants with the most severe MRI lesions. Conclusions High S100B urine levels soon after birth constitute trustable predictors of brain injury as confirmed by MRI. Results support the reliability of S100B in clinical daily practice and open the way to its inclusion in the panel of parameters used for the selection of cases suitable for TH treatment.

Subcutaneous fat necrosis (SCFN) is inflammation and necrosis of adipose tissue associated with hypoxia and hypothermia. It leads to various metabolic abnormalities, of which the most dreaded is hypercalcaemia. We report a case of a 7-week-old boy with history of birth asphyxia (hypoxic ischaemic encephalopathy stage 3) who presented to us with features suggestive of hypercalcaemia with bilateral nephrocalcinosis. On examination, there were multiple subcutaneous nodules on both arms. Evaluation revealed suppressed parathyroid activity along with low levels of 25(OH)vitamin D3 and elevated 1,25-dihydroxyvitamin D3. Skin biopsy confirmed the diagnosis of SCFN. He was managed with intravenous fluids, single dose of intravenous furosemide and oral prednisolone. Hypercalcaemia responded within 14 days of admission, prednisolone was tapered and stopped in a month. SCFN, in our case, can be attributed to the underlying perinatal asphyxia along with use of therapeutic hypothermia. Through this case, we wish to sensitise practicing neonatologists for the need of screening and early identification of these abnormalities, which if missed can be fatal.

Hypoxic insults initiate a cascade of biochemical events that result in irreversible neuronal damage. Magnesium sulfate agent has a possible neuroprotective effect as it can work at different stages of hypoxic brain injury. Objectives: Magnesium sulfate is used in the neonatal management of HIE as an adjunct medication to reduce Hypoxic Neuronal injury. In this Vitro study, we aimed to examine the efficacy of using magnesium sulfate in human cells to reduce oxygen consumption. We used in-vitro method utilizing foreskin as human cell surrogate. Method: Foreskin specimens from healthy newborns were collected immediately after circumcision and processed within 1 h for measuring the cellular rate of O2 consumption. Samples were placed in the oxygen phosphorescence analyzer and allowed to run for approximately 1 h. Injection then added magnesium sulfate at different doses into the vial. We analyze the O2 consumption in the samples at different levels of Magnesium Sulfate; the results were plotted using Kaleida Graph TM software. Results: The rate of respiration reduced with increasing the dose of MgSo4. The Cumulative analysis of cellular respiration rate was before and after an addition of MgSO4 . Collectively yielding a (k) value of 0.08 μM O2 /min µM O2 min-1 mg- and 0.04 M O2 /min µM O2 min-1 mg- respectively with a significant P-value of

Animal models provide useful information on mechanisms in human disease conditions, but also on exploring (patho)physiological factors affecting pharmacokinetics, safety, and efficacy of drugs in development. Also, in pediatric patients, nonclinical data can be critical for better understanding the disease conditions and developing new drug therapies in this age category. For perinatal asphyxia (PA), a condition defined by oxygen deprivation in the perinatal period and possibly resulting in hypoxic ischemic encephalopathy (HIE) or even death, therapeutic hypothermia (TH) together with symptomatic drug therapy, is the standard approach to reduce death and permanent brain damage in these patients. The impact of the systemic hypoxia during PA and/or TH on drug disposition is largely unknown and an animal model can provide useful information on these covariates that cannot be assessed separately in patients. The conventional pig is proven to be a good translational model for PA, but pharmaceutical companies do not use it to develop new drug therapies. As the Göttingen Minipig is the commonly used pig strain in nonclinical drug development, the aim of this project was to develop this animal model for dose precision in PA. This experiment consisted of the instrumentation of 24 healthy male Göttingen Minipigs, within 24 h of partus, weighing approximately 600 g, to allow the mechanical ventilation and the multiple vascular catheters inserted for maintenance infusion, drug administration and blood sampling. After premedication and induction of anesthesia, an experimental protocol of hypoxia was performed, by decreasing the inspiratory oxygen fraction (FiO2) at 15%, using nitrogen gas. Blood gas analysis was used as an essential tool to evaluate oxygenation and to determine the duration of the systemic hypoxic insult to approximately 1 h. The human clinical situation was mimicked for the first 24 h after birth in case of PA, by administering four compounds (midazolam, phenobarbital, topiramate and fentanyl), frequently used in a neonatal intensive care unit (NICU). This project aimed to develop the first neonatal Göttingen Minipig model for dose precision in PA, allowing to separately study the effect of systemic hypoxia versus TH on drug disposition. Furthermore, this study showed that several techniques that were thought to be challenging or even impossible in these very small animals, such as endotracheal intubation and catheterization of several veins, are feasible by trained personnel. This is relevant information for laboratories using the neonatal Göttingen Minipig for other disease conditions or drug safety testing. ispartof: FRONTIERS IN PEDIATRICS vol:11 ispartof: location:Switzerland status: published

Birth asphyxia is the leading cause of death and disability in young children worldwide. Long non-coding RNAs (lncRNAs) may provide novel targets and intervention strategies due to their regulatory potential, as demonstrated in various diseases and conditions. We investigated cardinal lncRNAs involved in oxidative stress, hypoxia, apoptosis, and DNA damage using a piglet model of perinatal asphyxia. A total of 42 newborn piglets were randomized into 4 study arms: (1) hypoxia–normoxic reoxygenation, (2) hypoxia–3 min of hyperoxic reoxygenation, (3) hypoxia–30 min of hyperoxic reoxygenation, and (4) sham-operated controls. The expression of lncRNAs BDNF-AS, H19, MALAT1, ANRIL, TUG1, and PANDA, together with the related target genes VEGFA, BDNF, TP53, HIF1α, and TNFα, was assessed in the cortex, the hippocampus, the white matter, and the cerebellum using qPCR and Droplet Digital PCR. Exposure to hypoxia–reoxygenation significantly altered the transcription levels of BDNF-AS, H19, MALAT1, and ANRIL. BDNF-AS levels were significantly enhanced after both hypoxia and subsequent hyperoxic reoxygenation, 8% and 100% O2, respectively. Our observations suggest an emerging role for lncRNAs as part of the molecular response to hypoxia-induced damages during perinatal asphyxia. A better understanding of the regulatory properties of BDNF-AS and other lncRNAs may reveal novel targets and intervention strategies in the future.

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

Despite the development of new antiseizure drugs (ASDs), around one third of epilepsy patients become refractory to treatment or experience adverse events due to ASDs. Therefore, discovery of new ASDs and new therapy options are crucial to improve the quality of life. Herein, we report a 3-year-old child with multi-drug resistant epilepsy caused by perinatal asphyxia whose seizures were reduced by 90% after the introduction of ketogenic diet, vagal nerve stimulation (VNS) AspireSR (SR-seizure response) and oral cannabidiol.

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

Introduction: Hypoxic Ischaemic Injury (HII) also known as Hypoxic Ischaemic Encephalopathy (HIE) is one of the most common causes of neonatal morbidity and mortality in most countries of the world. Perinatal asphyxia being the most frequent cause of HII, some of its long term sequelae include impaired neurological development, cerebral palsy, recurrent seizures, etc. Magnetic Resonance Imaging (MRI) has been found to be most sensitive, in detecting lesions in the brain of neonates with HII. Aim: To evaluate the role of MRI in assessing neurologic damage in newborns with suspected HII and its association with clinical staging. Materials and Methods: An institution based descriptive crosssectional study was conducted in a tertiary care government hospital in Guwahati, Assam, India for a duration of 15 months from May 2017 to July 2018 on 50 neonates with history of perinatal asphyxia. Assessment of conventional T1 and T2 weighted images, Diffusion Weighted Imaging (DWI) and Susceptibility Weighted Imaging (SWI) was done and association of MRI findings with gestational maturity, Apgar Scores and clinical staging (Sarnat and Sarnat Staging system) was studied. Results: In majority of cases with clinically mild HII, MRI findings were either normal or of mild degree whereas in cases of clinically advanced stages of HII, MRI findings were moderate-to-severe, suggesting a positive association between clinical grading and severity of brain injury on MR. Term neonates sustained injuries mostly in cortical-subcortical/watershed zones of brain whereas preterm neonates were seen to sustain mainly periventricular lesions. Basal ganglia, thalamic and midbrain lesions were seen to be associated with severe degree of HII in term neonates whereas germinal matrix haemorrhage was observed in preterm neonates with severe HII. A positive association was seen between severity of brain lesions with both low Apgar scores and gestational prematurity. Conclusion: MRI is helpful to study the pattern of brain involvement in term and preterm neonates with suspected HII and to assess the severity of injury. MRI findings are seen to correlate well with clinical staging.

Magnetic resonance imaging (MRI) scoring systems are used in the neonatal period to predict outcome in infants with neonatal encephalopathy. Our aim was to assess the relationship between three MRI scores and neurodevelopmental outcome assessed using Bayley Scales of Infant and Toddler Development, third edition (Bayley-III), at two years in infants with neonatal encephalopathy.Term-born neonates with evidence of perinatal asphyxia born between 2011 and 2015 were retrospectively reviewed. MRI scanning was performed within the first two weeks of life and scored using Barkovich, National Institute of Child Health and Human Development (NICHD) Neonatal Research Network (NRN), and Weeke systems by a single assessor blinded to the infants clinical course. Neurodevelopmental outcome was assessed using composite scores on the Bayley-III at two years. Multiple linear regression analyses were used to assess the association between MRI scores and Bayley-III composite scores, with postmenstrual age at scan and sex included as covariates.Of the 135 recruited infants, 90 infants underwent MRI, and of these, 66 returned for follow-up. MRI abnormalities were detected with the highest frequency using the Weeke score (Barkovich 40%, NICHD NRN 50%, Weeke 77%). The inter-rater agreement was good for the Barkovich score and excellent for NICHD NRN and Weeke scores. There was a significant association between Barkovich, NICHD NRN, and Weeke scores and Bayley-III cognitive and motor scores. Only the Weeke score was associated with Bayley-III language scores.Our findings confirm the predictive value of existing MRI scoring systems for cognitive and motor outcome and suggest that more detailed scoring systems have predictive value for language outcome.

Background: Hypoxic-ischemic encephalopathy (HIE) is a severe pathology, and no unique predictive biomarker has been identified. Our aims are to identify associations of perinatal and outcome parameters with morphological anomalies and ADC values from MRI. The secondary aims are to define a predictive ADC threshold value and detect ADC value fluctuations between MRIs acquired within 7 days (MR0) and at 1 year (MR1) of birth in relation to perinatal and outcome parameters. Methods: Fifty-one term children affected by moderate HIE treated with hypothermia and undergoing MRI0 and MRI1 were recruited. Brain MRIs were evaluated through the van Rooij score, while ADC maps were co-registered on a standardized cerebral surface, on which 29 ROIs were drawn. Statistical analysis was performed in Matlab, with the statistical significance value at 0.05. Results: ADC0 < ADC1 in the left and right thalami, left and right frontal white matter, right visual cortex, and the left dentate nucleus of children showing abnormal perinatal and neurodevelopmental parameters. At ROC analysis, the best prognostic ADC cut-off value was 1.535 mm2/s × 10−6 (sensitivity 80%, specificity 86%) in the right frontal white matter. ADC1 > ADC0 in the right visual cortex and left dentate nucleus, positively correlated with multiple abnormal perinatal and neurodevelopmental parameters. The van Rooij score was significantly higher in children presenting with sleep disorders. Conclusions: ADC values could be used as prognostic biomarkers to predict children’s neurodevelopmental outcomes. Further studies are needed to address these crucial topics and validate our results. Early and multidisciplinary perinatal evaluation and the subsequent re-assessment of children are pivotal to identify physical and neuropsychological disorders to guarantee early and tailored therapy.

BACKGROUND Umbilical-cord acidemia may indicate perinatal asphyxia and places a neonate at increased risk for hypoxic ischemic encephalopathy (HIE). Our specific aim was to develop a standardized clinical care pathway, ensuring timely identification and evaluation of neonates with umbilical-cord acidemia at risk for HIE. METHODS A standardized clinical care pathway to screen inborn neonates ≥36 weeks with abnormal cord blood gases (a pH of ≤7.0 or base deficit of ≥10) for HIE was implemented in January 2016. Abnormal cord blood gases resulted in a direct notification from the laboratory to an on-call physician. Evaluation included a modified Sarnat examination, postnatal blood gas, and standardized documentation. The percentage of neonates in which physician notification, documented Sarnat examination, and postnatal blood gas occurred was examined for 6 months before and 35 months after implementation. RESULTS Of 203 neonates with abnormal cord gases in the post–quality improvement (QI) period, physician notification occurred in 92%. In the post-QI period, 94% had a documented Sarnat examination, and 94% had postnatal blood gas, compared with 16% and 11%, respectively, of 87 neonates in the pre-QI period. In the post-QI period, of those evaluated, >96% were documented within 4 hours of birth. In the post-QI period, 15 (7.4%) neonates were cooled; 13 were in the NICU at time of identification, but 2 were identified in the newborn nursery and redirected to the NICU for cooling. CONCLUSIONS A standardized screening pathway in neonates with umbilical-cord acidemia led to timely identification and evaluation of neonates at risk for HIE.

Background and Aim: One of the most significant organs frequently affected by the multiple organ dysfunction brought on by prenatal hypoxia is the kidney. Monitoring the serum urea, creatinine, and urine production aids in the early diagnosis of prenatal asphyxia's severity and so improves the result. The goal of the current study was to evaluate renal function and its relationship to the degree of HIE in term infants with HIE. Materials and Methods: The current study examined the relationship between renal function in term infants with HIE and HIE severity over the course of a year in the neonatal ward of a tertiary care facility in India. The total numbers of patients was 240 divided into cases and control 120 patients each. Neonatal patients in case groups received HIE diagnoses in accordance with WHO guidelines, and age and gender matching of infants was carried out. One baseline and one after 48 hours of life were used to calculate the serum creatinine. Results: Between cases and controls, there was a statistically significant difference in the Apgar score at 1 and 5 minutes. Serum creatinine, blood urea, urine salt, creatinine clearance, and renal indices showed statistically significant differences across the various stages of HIE. Except for urine potassium and urine specific gravity, all urine parameters exhibited statistically significant differences between patients and controls, including creatinine clearance, urine output, pH, fractional excretion of sodium, renal failure index, and osmolality. Conclusion: Renal dysfunction is a widespread finding present in subjects of perinatal asphyxia. Renal derangement increases with sternness of disease. Most common form of AKI among neonates with birth asphyxia is prerenal and it responds to fluid resuscitation with 100% recovery., http://impactfactor.org/PDF/IJTPR/12/IJTPR,Vol12,Issue12,Article13.pdf

One of the pressing issues of healthcare nowadays is applying methods of molecular genetics aimed at identifying and assessing genetic risk factors and early diagnosis of perinatal pathology. Numerous studies have contributed to identifying risk factors that affect the health of newborns. The aim of this work is to investigate the associations between the development of perinatal pathology in premature and full-term infants with polymorphism of genes of the glutathione transferase family (GSTT1, GSTM1, GSTP1), renin-angiotensin system (ACE, AGT2R1). Materials and methods. The study included 110 full-term infants with asphyxia, 30 healthy full-term infants for the control group, and 125 preterm infants with perinatal infections, 21 preterm infants with broncho-pulmonary dysplasia, and 70 conditionally healthy preterm infants. A set of routine clinical and laboratory methods of research and determining gene polymorphism was performed. Results. The presence of a non-functional allele of the GSTT1 gene and DD variant of the ACE gene in newborns is associated with the development of severe perinatal asphyxia (p = 0.006 and p = 0.003, respectively). Children with GSTT1 "-" and AC AG2TR1 genotypes have significantly higher levels of diastolic pressure in the first day after birth than children with functional genotypes of these genes (p

Background Therapeutic hypothermia (TH) is routinely provided to those with moderate or severe neonatal encephalopathy (NE). Subtle differences exist in the standardized exams used to define NE severity. We aimed to assess if an infant's TH eligibility status differed if they were evaluated using either the NICHD/Neonatal Research Network's (NICHD-NRN) or TOBY/British Association of Perinatal Medicine's (TOBY-BAPM) neurological exam. Methods Encephalopathic infants ≥36 weeks with evidence of perinatal asphyxia and complete documentation of the neurological exam Results Ninety-one encephalopathic infants were included. Despite good agreement between the two exams (κ = 0.715, p Conclusions Both the NICHD-NRN and TOBY-BAPM exams are evidence-based. Despite this, there is a significant difference in the number of infants eligible for TH depending on which exam is used. The NICHD-NRN exam identifies a greater proportion as eligible. Impact There are subtle differences in the NICHD-NRN and TOBY-BAPM's encephalopathy exams used to determine eligibility for TH. This results in a significant difference in the proportion of infants determined to be eligible for TH depending on which encephalopathy exam is used. The NICHD-NRN encephalopathy exam identifies more infants as being eligible for TH than the TOBY-BAPM encephalopathy exam. This may result in different rates of cooling depending on which evidence-based neurological exam for evaluation of encephalopathy a center uses.

Yitayeh Belsti,1 Zelalem Mehari Nigussie,2 Gebeyaw Wudie Tsegaye2 1Department of Physiology, School of Medicine, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia; 2Department of Epidemiology and Biostatistics, School of Public Health, College of Medicine and Health Science, Bahir Dar University, Bahir Dar, EthiopiaCorrespondence: Yitayeh BelstiDepartment of Physiology, School of Medicine, College of Medicine and Health Science, University of Gondar, Gondar, EthiopiaEmail yitayehbelsti@gmail.comBackground: Early neonatal death is death of infants in the first week of life. And 34% to 92% of neonatal deaths happen within 7 days of postnatal period. Thus, the early neonatal period is the most critical time for an infant, requiring different strategies to prevent mortality. Among strategies, deriving and implementing early warning scores is crucial to predict early neonatal mortality earlier upon hospital admission.Objective: To derive and validate a risk score to predict mortality of early neonates at Felege Hiwot Specialized Hospital neonatal intensive care unit, Bahir Dar, 2021.Methods: The document review was conducted from February 24, to April 08, 2021, on all early neonates admitted to neonatal intensive care unit from January 1, 2018 to December 31, 2020. The total number of early neonates included in the derivation study was 1100. Data were collected by using checklists prepared on EpiCollect5 software. After exporting the data to R version 4.0.5 software, variables with (p < 0.25) from the simple binary regression were entered into a multiple logistic regression model, and significant variables (p < 0.05) were kept in the model. The discrimination and calibration were assessed. The model was internally validated using bootstrapping technique.Results: Admission weight, birth Apgar score, perinatal asphyxia, respiratory distress syndrome, mode of delivery, sepsis, and gestational age at birth remained in the final multiple logistic regression prediction model. The area under curve of receiver operating characteristic curve for early neonatal mortality score was 90.7%. The model retained excellent discrimination under internal validation. The sensitivity, specificity, and positive predictive value, negative predictive value of the model was 89.4%, 82.5%, 55.5%, and 96.9%, respectively.Conclusion: The derived score has an excellent discriminative ability and good prediction performance. This is an important tool for predicting early neonatal mortality in neonatal intensive care units at admission.Keywords: derivation, validation, risk score, early neonatal mortality, NICU, Ethiopia

BackgroundIncreasing evidence recognizes the harm of excess oxygen to lungs, eyes, and brain of preterm infants, but not yet to the intestine. We assessed changes in splanchnic oxygenation during reoxygenation with 21% compared to 100% O-2 in a newborn piglet model of perinatal asphyxia.MethodsWe randomized 25 piglets to control or intervention. Intervention groups underwent global hypoxia until acidosis and hypotension occurred. Piglets were reoxygenated for 30 min with 21% or 100% O-2 and observed for 9 h. We continuously measured regional splanchnic oxygen saturation (r(s)SO(2)) using near-infrared spectroscopy (NIRS). We calculated mean r(s)SO(2) and r(s)CoVar (as SD/mean). We measured PaO2 and SaO(2), sampled from the right carotid artery. ResultsReoxygenation after global hypoxia restored r(s)SO(2). Reoxygenation with 100% O-2 increased r(s)SO(2) to values significantly higher than baseline. In intervention groups, r(s)CoVar decreased during observation compared to baseline. We found a correlation between r(s)SO(2) and PaO2 (r = 0.420, P < 0.001) and between r(s)SO(2) and SaO(2) (r = 0.648, P < 0.001) in pooled data from the entire experiment.ConclusionReoxygenation after global hypoxia improves splanchnic oxygenation, but is associated with reduced variability of r(s)SO(2). Reoxygenation with 100% O-2 exposes the intestine to hyperoxia. Splanchnic NIRS is able to detect intestinal hypoxia and hyperoxia.ImpactSplanchnic oxygenation improves during reoxygenation after global hypoxia, though reoxygenation with 100% O2 exposes the intestine to hyperoxia. Decreased variability of splanchnic oxygenation several hours after hypoxia and reoxygenation seems to be independent of the resuscitation strategy, and may indicate intestinal injury. Splanchnic NIRS monitoring was able to detect intestinal hypoxia and exposure to hyperoxia, as evidenced by a strong correlation between splanchnic oxygenation and arterial oxygen content.

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

Background: Perinatal asphyxia is the main cause of neurodevelopmental sequelae and perinatal death. Caspase-3 is a major enzyme associated with apoptosis and increases in hypoxic-ischemic events. There is still no reliable biomarker to predict the severity and outcome of an asphyxial event. In this regard, this study aimed to determine the caspase-3 level and its role as an outcome predictor in perinatal asphyxia. Methods: This paired-group observational analytical cross-sectional study lasted from September 2016 to February 2017. In total, 50 neonates were included in the research and Caspase-3 levels were examined at two different times. Student’s t-test and logistic regression analysis were used for statistical analysis.Results: There were 23 neonates (46%) with hypoxic-ischemic encephalopathy (HIE) and an increase in Caspase-3 level by 0.3135 points from the first to the second examination (t=6.555; P

AIM Neonatal encephalopathy (NE) is associated with an increased risk of multi-organ injury. The lack of standardised definitions for multi-organ dysfunction in NE hinders accurate quantification of these complications. METHODS A simple multi-organ dysfunction in neonatal encephalopathy scoring (MODE) system was created to include the cardiovascular, respiratory, gastrointestinal, haematological and neurological systems with a maximum score of 15. The MODE score was then compared with the grade of NE, Bayley Scales of Infant Development (Bayley-III) at 2 years of age and mortality. The Bayley score was used as it gave an objective score making it easier to compare the MODE score. Bayley score of

Subcutaneous fat necrosis of newborn is a rare cutaneous disorder affecting neonates. It usually presents as subcutaneous nodules or plaques, within the first few weeks of life, following an eventful delivery. It is characterized by hypercalcemia, which may present with lethargy, irritability, hypotonia and dehydration, mimicking sepsis. Histopathology is proven to be the gold standard in diagnosis with characteristic lobular panniculitis, mixed inflammatory cell infiltrate and radially arranged crystals. This needs to be differentiated from other causes of lobular panniculitis, as early diagnosis and treatment to prevent long-term complications are advocated. Education of parents regarding the disease and danger signs of hypercalcemia and weekly monitoring of serum calcium is recommended. Treatment based on rehydration, dietary vitamin D and calcium restriction, Furosemide and prednisolone are considered.We have discussed a case of subcutaneous fat necrosis, in an 8-week-old male baby. Key Messages: Subcutaneous fat necrosis is an important differential in neonates presenting with palpable subcutaneous nodules, along with sclerema neonatorum. Severe complications like hypercalcemia should be detected early and managed aggressively to prevent morbidities and mortalities associated with it. Symptomatic management, use of calcium lowering drugs and regular monitoring of calcium levels are recommended. Keywords: subcutaneous fat necrosis of newborn, perinatal asphyxia, hypercalcemia, lobular panniculitis, neonatal sepsis

Perinatal asphyxia (PA) is a devastating neonatal condition characterized by a lack of oxygen supporting the organ systems. PA can lead to hypoxic–ischemic encephalopathy (HIE), a brain dysfunction due to oxygen deprivation with a complex neurological sequela. The pathophysiology of HIE and PA is not entirely understood, with therapeutic hypothermia being the standard treatment with only limited value. However, alternative neuroprotective therapies can be a potential treatment modality. In this review, we will characterize the biochemical mechanisms of PA and HIE, while also giving insight into cerebrolysin, a neuroprotective treatment used for HIE and PA. We found that cerebrolysin has up to 6-month treatment window post-ischemic insult. Cerebrolysin injections of 0.1 ml/kg of body weight twice per week were found to provide gross motor and speech deficit improvement. Our literature search emphasizes the positive effects of cerebrolysin for general improvement outcomes. Nevertheless, biomarker establishment is warranted to improve patient outcomes.

Background Therapeutic hypothermia (TH) is the treatment of choice for neonates diagnosed with perinatal asphyxia (PA). Dosing recommendations of various therapeutic agents including antimicrobials were not specifically available for the neonates undergoing TH. Methods A systematic search methodology was used to identify pharmacokinetic (PK) studies of antimicrobials during TH. Antimicrobials with multiple PK studies were identified to create a generalizable PK model. Pharmacometric simulations were performed using the PUMAS software platform to reproduce the results of published studies. A suitable model that could reproduce the results of all other published studies was identified. With the help of a generalizable model, an optimal dosage regimen was designed considering the important covariates of the identified model. Results With the systematic search, only gentamicin had multiple PK reports during TH. A generalizable model was identified and the model predictions could match the reported/observed concentrations of publications. Birth weight and serum creatinine were the significant covariates influencing the PK of gentamicin in neonates. A dosage nomogram was designed using pharmacometric simulations to maintain gentamicin concentrations below 10 μg/mL at peak and below 2 μg/mL at trough. Conclusions A generalizable PK model for gentamicin during TH in neonates was identified. Using the model, a dosing nomogram for gentamicin was designed. Impact Dosing guidelines for antimicrobials during TH in neonates is lacking. This is the first study to identify the generalizable model for gentamicin during TH in neonates. Nomogram, proposed in the study, will aid the clinicians to individualize gentamicin dosing regimen for neonates considering the birth weight and serum creatinine.

Exploring new possibilities for the use of methylxanthines to prevent the development of acute kidney injury (AKI) in full-term infants with perinatal asphyxia. Aim: to evaluate the efficacy and safety of methylxanthines in full-term infants for the prevention and conservative treatment of acute kidney injury. Materials and methods. To test the effectiveness of the proposed method of AKI treatment, 38 infants were chosen and divided into 2 groups by random selection. Nursing and intensive care were according to current legislation (Order of the Ministry of Health of Ukraine No. 225 of March 28, 2014). The main group (n = 20) received therapy with caffeine citrate, the comparison group (n = 18) – theophylline. Both of these drugs were used to prevent the development of acute kidney injury – stage II and III according to KDIGO. Results. A significant difference in serum creatinine was found in the main group - the level of serum creatinine was higher than in the comparison group, but did not exceed the physiological norm. GFR on the 3rd day of life was higher with administration of theophylline, but in the group of caffeine did not exceed the reference values of the norm. No differences between urea levels and diuresis rates were found in the groups. The initial results indicate the lack of statistical significance when using various drugs of the methylxanthine group, namely theophylline and caffeine citrate. This is explained by the fact that in the main group 65.00 % (n = 13) of patients had AKI stage 0 according to KDIGO, and 35.00 % (n = 7) had stage I. In the comparison group, 55.56 % (n = 10) and 44.44 % (n = 8), respectively. Stages II and III in both groups of the study did not develop, the obtained data are equivalent – U = 163,00; P = 0,6296. However, the use of caffeine citrate may become a priority due to a better safety profile compared to theophylline. Caffeine is less likely to cause adverse effects in the form of non-pathological bile vomiting and has significantly lower relative risk of non-pathological bile vomiting in infants (RR 0.26 (95 % CI 0.10; 0.66)). Conclusions. Conservative methylxanthine therapy in full-term infants with perinatal asphyxia prevents the development of stages II and III of AKI according to KDIGO. However, it is necessary to continue the collection of material to increase the statistical significance, as well as to study the early and long-term consequences of this therapy.

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.

La restricción de crecimiento intrauterino trae consigo grandes retos en la obstetricia con alta tasa de eventos perinatales adversos y incluso la muerte fetal. En varias publicaciones se ha visto como aún se encuentran muchos vacíos respecto a cuando es el mejor momento para el nacimiento y antes de que los cambios secundarios a hipoxia crónica y acidosis sean irreversibles. El seguimiento con ecografía y doppler fetoplacentario a un feto con desaceleración en la curva de crecimiento son una gran herramienta en la toma de decisiones y evitar eventos adversos con mejoría de sobrevida y pronostico a estos fetos 1. FORMULACIÓN DEL PROBLEMA 8 1.1. Planteamiento del problema 8 1.2. Justificación 9 1.3. Pregunta de investigación 10 2. MARCO TEÓRICO 11 3. OBJETIVOS 31 4. HIPÓTESIS 32 5. METODOLOGÍA 33 6. RESULTADOS 51 7. DISCUSIÓN 68 8. CONCLUSIONES 72 9. BIBLIOGRAFIA 73 10. ANEXOS 82 Intrauterine growth restriction brings with it great challenges in obstetrics with a high rate of adverse perinatal events and even fetal death. In several publications, it has been seen how there are still many gaps regarding when is the best time for birth and before the changes secondary to chronic hypoxia and acidosis are irreversible. Follow-up with ultrasound and fetoplacental Doppler to a fetus with a slowdown in the growth curve are a great tool for decision-making and to avoid adverse events with improved survival and prognosis for these fetuses. Especialización

Controlled assessment of functional cortical networks is an unmet need in the clinical research of noncooperative subjects, such as infants. We developed an automated, pneumatic stimulation method to actuate naturalistic movements of an infant’s hand, as well as an analysis pipeline for assessing the elicited electroencephalography (EEG) responses and related cortical networks. Twenty newborn infants with perinatal asphyxia were recruited, including 7 with mild-to-moderate hypoxic–ischemic encephalopathy (HIE). Statistically significant corticokinematic coherence (CKC) was observed between repetitive hand movements and EEG in all infants, peaking near the contralateral sensorimotor cortex. CKC was robust to common sources of recording artifacts and to changes in vigilance state. A wide recruitment of cortical networks was observed with directed phase transfer entropy, also including areas ipsilateral to the stimulation. The extent of such recruited cortical networks was quantified using a novel metric, Spreading Index, which showed a decrease in 4 (57%) of the infants with HIE. CKC measurement is noninvasive and easy to perform, even in noncooperative subjects. The stimulation and analysis pipeline can be fully automated, including the statistical evaluation of the cortical responses. Therefore, the CKC paradigm holds great promise as a scientific and clinical tool for controlled assessment of functional cortical networks.

BACKGROUND Perinatal asphyxia (PA) is an important cause of neonatal morbidity, mortality, and neurologic handicap in children. Dysfunction of organs other than central nervous system is often recognised after perinatal asphyxia and manifests as hypoxic ischaemic insults to heart, lungs, kidneys and bowel. The purpose of this study was to assess the spectrum of multi-organ system involvement in perinatal asphyxia. METHODS This observational, descriptive study was conducted at SVRRGGH (Sri Venkateswara Ramnarayan Ruia Government General Hospital) - Tirupati from October 2010 to September 2011 and has Institutional Ethics Committee approval (Regd. No: 58647, Dt: 20 / 11 / 2010). After considering the inclusion and exclusion criteria, 204 neonates diagnosed with perinatal asphyxia who got admitted in our newborn intensive care unit (NICU) were included in this study. RESULTS In the present study, we had 118 (57.89 %) male babies and 86 (42.11 %) female babies. The mean birth weight was 2640 +/- 460 grams. Infants of birth weight 2500 - 4000 grams (appropriate for gestational age - AGA) accounted for 202 (98.96 %). Major maternal risk factors in this study were MSAF (meconium-stained amniotic fluid (66/204, 32.4 %), PIH (pregnancy induced hypertension) and Eclampsia (26/204, 12.7 %) and PROM (premature rupture of membranes) (26/204, 12.7 %). In the present study, we found higher mortality (19/117, 16.2 %) in babies born to multiparous mothers. Respiratory system involvement was seen in 80 (39.2 %) infants. Renal involvement was observed in 58 (27.5 %) infants. Acute renal failure was diagnosed in 22 (10.8 %) cases. CVS (cardiovascular system) involvement was seen in 56 (27.5 %) cases where as GIT (gastrointestinal tract) involvement was found in 32 (15.68 %) cases. CONCLUSIONS Epidemiological research is needed to accurately estimate the contribution of birth asphyxia to perinatal morbidity and mortality, especially in community settings where the burden of disease, due to high proportion of unattended deliveries, is likely to be larger than the hospital setting. KEYWORDS Perinatal Asphyxia, Neonatal Intensive Care Unit, Hypoxic Ischaemic Encephalopathy, Multi Organ Dysfunction, Cardiovascular System

Obwohl sich fast 40% aller Todesfalle im Kindes- und Jugendalter wahrend der Neugeborenenperiode ereignen, kommt es in der Neonatologie nur selten zur Organspende. Wir berichten uber ein Neugeborenes, bei dem nach perinataler Asphyxie der endgultige, nicht behebbare Ausfall der Gesamtfunktion des Groshirns, des Kleinhirns und des Hirnstamms („Hirntod“) gemas Transplantationsgesetz diagnostiziert wurde. Das Herz wurde nach der sogenannten zweiten richtliniengemasen „Hirntoddiagnostik“ zur Organspende entnommen und erfolgreich transplantiert. Besondere juristische Herausforderungen ergaben sich aus dem Umstand der anonymen Geburt, den notwendigen Regelungen der Vormundschaft sowie der Zuordnung des Totenfursorgerechts. Medizinisch standen die speziellen Regelungen der Diagnostik des irreversiblen Hirnfunktionsausfalls bei Neugeborenen und der optimale Erhalt der Organfunktion vor Entnahme im Vordergrund. Fur die Pflegenden stellte sich der Ablauf grundlegend anders dar als bei einer Therapiezielanderung mit anschliesender palliativen Versorgung in Anwesenheit der Eltern. Angesichts der grosen emotionalen Herausforderungen erwiesen sich die Einbindung aller Beteiligten in die Entscheidungsablaufe und die Ubernahme der besonderen Verantwortung als hilfreich. Although almost 40% of all deaths prior to 18 years of age occur within the neonatal period, organ donation is rare in neonatology. Herein we report about a newborn infant with perinatal asphyxia and permanent, irreversible loss of brain function (cerebrum, cerebellum and brain stem), managed according to the criteria and instructions defined by the German law of donor organ transplantation. After confirmation of irreversible loss of brain function, the heart was successfully transplanted. Specific legal challenges resulted from the instance of an anonymous birth, the guardianship required, and the specific regulations of welfare of the deceased individual. The most prominent medical challenges consisted in the specific regulatory purposes for the diagnosis of the irreversible loss of brain function in neonates and the optimal maintenance of organ functions prior to donation. From the nursing point of view, the proceeding differed entirely compared to redirection of care into palliation while parents are present. Involving all stakeholders in every step of decision making was regarded as emotionally helpful.

Background Hypoxic ischemic encephalopathy is a major cause of pediatric mortality and morbidity, with possible long-term neurologic sequel, such as cerebral palsy. With improvements in care of at-risk neonates, more children survive. This makes it increasingly important to assess, soon after birth, the prognosis of children with hypoxic-ischemic encephalopathy. The aim of the study was to assess the additive role of magnetic resonance spectroscopy over conventional MRI in diagnosis and early prediction of pathological motor development in neonates with hypoxic ischemic encephalopathy. Results MRS ratios showed significant difference between unfavorable and normal outcome infants. MRS ratios as Lac/Cr, NAA/Cr and NAA/Cho within basal ganglia, thalamus and white matter can significantly differentiate between patients with normal and pathological outcome at 1 year. Lac/Cr positively correlates with the severity of HIE. Both NAA/Cr and NAA/Cho negatively correlate with the severity of the disease. Ratios cutoff values as Lac/Cr above 0.38 and 0.42 in basal ganglia and white matter, respectively, NAA/Cr below 0.9 and 0.8 in basal ganglia and occipital white matter, respectively, and NAA/Cho below 0.29 and 0.31 in basal ganglia and frontal white matter, respectively, were significantly predictive of pathological outcome. Conclusion High Lac/Cr, low NAA/Cr and low NAA/Cho ratios within examined regions of the brain including deep grey matter nuclei as well as white matter are associated with an adverse outcome in infants with perinatal asphyxia. MRS is an accurate quantitative MR biomarker within the neonatal period for prediction of neurodevelopmental outcome after perinatal HIE. MRS may be useful in early clinical management decisions, and counseling parents thereby ensuring appropriate early intervention and rehabilitation.

Objective: This study aimed to determine the prevalence of abnormal biochemical parameters among neonates with perinatal asphyxia in comparison to their non-asphyxiated controls.Methodology: This is a prospective case - control study involving 54 asphyxiated term neonates and 54 non-asphyxiated term babies at LAUTECH teaching hospital, Osogbo. Serum levels of Sodium, Bicarbonate, Chloride, Calcium and Potassium were determined daily for 72 hours in both groups using standard methods. The results were compared.Results: The overall prevalence of abnormal biochemical parameters namely hyponatraemia, hypocalcaemia, metabolic acidosis, hypochloraemia and hypokalaemia among the asphyxiated versus non-asphyxiated babies in the first 72 hours of life were 30.9% vs 19.8% (p < 0.020); 28.4% vs 4.9% (p < 0.000); 30.9% vs 3.1% (p < 0.0001); 27.2% vs 25.9% (p < 0.200) and 24.7% vs 3.1% (p < 0.070) respectively.Conclusion: Babies with hypoxic ischaemic encephalopathy stage III significantly showed the worst biochemical parameters; early estimation of serum electrolytes in neonates with perinatal asphyxia may be appropriate for timely intervention.

Introduction Perinatal asphyxia is a complicated newborn health problem and applies a high contribution to the increased proportion of newborn mortality. It occurs in newborns due to altered breathing or inadequate inhalation and exhalation resulting in reduced oxygen perfusion to certain body tissues and organs. Irrespective of the increased progress in health care towards newborns and implementations in reductions in under-five, infant, and neonatal mortality in the past 10 years, perinatal asphyxia remained as the most common severe newborn health challenge that causes a high number of morbidity and mortality. Methods A prospective cohort longitudinal study was implemented among 573 newborns admitted with perinatal asphyxia at public hospitals in Southern Ethiopia from 1st March 2018 to 28th February 2020. The perinatal survival time was determined using Kaplan Meier survival curve together with a log-rank test. The dependent variable was time to death and the independent variables were classified as socio-demographic factors, obstetrics related factors, newborn related factors and maternal medical related factors. The study subjects were entered in to the cohort during admission with perinatal asphyxia in the hospital and followed until 7 days of life. Results The cumulative proportion of survival among the newborns admitted with perinatal asphyxia was 95.21% (95%CI:91.00,97.48), 92.82% (95%CI:87.95,95.77), 92.02%(95%CI:86.84,95.22) and 90.78%(95%CI:84.82,94.48) at the end of first, second, third and fourth follow-up days respectively. The mean survival date was 6.55(95%CI: 6.33, 6.77) and cord prolapse (AHR:6.5;95%CI:1.18,36.01), pregnancy induced hypertension (AHR:25.4;95%CI:3.68,175.0), maternal iron deficiency anemia (AHR:5.9;95%CI:1.19,29.5) and having convulsion of the newborn (AHR:10.23;95%CI:2.24,46.54) were statistically significant in multivariable cox proportional hazard model. Conclusion The survival status among newborns with perinatal asphyxia was low during the early follow-up periods after admission to the hospital and the survival status increased after fourth follow up days. In addition, cord prolapse, history of PIH, maternal iron deficiency anemia and newborns history of convulsion were the independent predictors of mortality.

BACKGROUND: Therapeutic hypothermia (TH) is an established intervention to improve the outcome of neonates with moderate-to-severe hypoxic-ischemic encephalopathy resulting from perinatal asphyxia. Despite this beneficial effect, TH may further affect drug elimination pathways such as the glomerular filtration rate. OBJECTIVES: The objective of this study was to quantify the effect of TH in addition to asphyxia on mannitol clearance as a surrogate for the glomerular filtration rate. METHODS: The effect of asphyxia and TH (mild vs moderate/severe) on mannitol clearance was assessed using a population approach, based on mannitol observations collected in the ALBINO (ALlopurinol in addition to TH for hypoxic-ischemic Brain Injury on Neurocognitive Outcome) trial, as some were exposed to a second dose of 10 mg/kg intravenous mannitol as placebo to ensure blinding. Pharmacokinetic analysis and model development were conducted using NONMEM version 7.4. RESULTS: Based on 77 observations from 17 neonates (TH = 13), a one-compartment model with first-order linear elimination best described the observed data. To account for prenatal glomerular filtration rate maturation, both birthweight and gestational age were implemented as clearance covariates using an earlier published three-quarters power function and a sigmoid hyperbolic function. Our final model predicted a mannitol clearance of 0.15 L/h for a typical asphyxia neonate (39.5 weeks, birthweight 3.25 kg, no TH), lower than the reported value of 0.33 L/h for a healthy neonate of similar age and weight. By introducing TH as a binary covariate on clearance, the additional impact of TH on mannitol clearance was quantified (60% decrease). CONCLUSIONS: Mannitol clearance was decreased by approximately 60% in neonates undergoing TH, although this is likely confounded with asphyxia severity. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03162653. ispartof: CLINICAL PHARMACOKINETICS vol:60 issue:7 pages:897-906 ispartof: location:Switzerland status: published

Background The current neonatal mortality rate in Nigeria (37/1000) is among the highest in the world and the major causes have consistently been reported as sepsis, perinatal asphyxia and prematurity. However, case-specific fatality which defines the risk of dying from these and other neonatal morbidities is rarely emphasized. Determination of case-specific fatality rates (CSFR) may inform a change in our current approach to neonatal care interventions which may eventually bring about the much-needed reduction in our neonatal mortality rate. Our aim was to determine the case-specific fatality rates for the common causes of mortality among hospitalized neonates at the National Hospital Abuja (NHA). Methods Relevant demographic and clinical data on all neonates admitted into the NICU at the NHA over a period of 13 months (January 2017 to February 2018) were extracted from the Neonatal Registry database and analyzed using appropriate statistical methods with the SPSS version 20 software. The case-specific fatality rates were computed for the predominant morbidities in addition to determination of the neonatal mortality rates and associated risk factors. Results and conclusion A total of 730 neonates were admitted, out of which 391 (53.6%) were females, 396 (54.5%) were inborn and 396 (54.2%) were term. The three most prevalent morbidities were prematurity 272(37.2%), neonatal Jaundice 208(28.4%) and perinatal asphyxia 91(12.5%) while the most common causes of mortality were prematurity 47/113(41.6%), congenital malformations 27/113(23.9%) and perinatal asphyxia 26/113(23%). Congenital malformations had the highest case-specific fatality 27/83(32.5%) followed by Perinatal Asphyxia 26/91(28.6%) and prematurity 47/272(20.7%). The mortality pattern differed between inborn and out born babies. Implications of these case-specific fatality rates for targeted interventions are discussed.

Perinatal asphyxia is a global neonatal problem, which significantly contributes to both neonatal morbidity and mortality. This study was therefore undertaken to determine the prevalence, risk factors and outcomes of perinatal asphyxia in Makurdi, Nigeria. A retrospective review of clinical data of all newborns managed at the Special Care Baby Unit of the Benue State University Teaching Hospital over a 5 year period (January 2015-December 2019) was carried out using the research clinical data form. Maternal information including biodata, obstetric history, perinatal events as well as neonates' presentation and outcomes were reviewed. All inborn neonates with Apgar scores

Perinatal asphyxia is a peripartum event that can cause permanent sequelae to the newborns, affecting the brain development. Recently, it has been demonstrated that epigenetics mechanisms play an important role in this injury and that folic acid (FA) supplementation during pregnancy can affect these epigenetics modifications as well as gene expression. We have identified both positive and negative effects of FA treatment in rats submitted to a model of neonatal hypoxia-ischemia (HI). Considering that FA supplementation is already used in pregnant women and that HI occurs in the peripartum period, this study was designated to evaluate how gestational FA supplementation and neonatal HI affect: apoptosis (caspase-3) and expression of synaptic proteins (synapsin and PSD-95) and the methylation of histone H3 lysine (K) 4 and 27 in the rat hippocampus. Pregnant Wistar rats were divided according to the diets: standard (SD), supplemented with 2 mg/kg of FA or with 20 mg/kg of FA. HI procedure was performed at the 7th PND. Protein expression and H3 methylation were evaluated at the 60th PND in the rats' hippocampus. Neonatal HI increased caspase-3 expression decreased synapsin expression and reduced H3K4me2, -me3 and H3K27me2, -me3 in the ipsilateral hippocampus. FA only prevented the augment in caspase-3 expression. In conclusion, neonatal HI caused lasting effects on caspase-3-mediated cell death (prevented by the FA) and synaptic proteins in the rats' hippocampus. This is the first study to show that histone modifications may contribute to these pathological findings in the hippocampus of HI animals.

The atypical hemolytic uremic syndrome (aHUS) in the newborn is a rare disease, with high morbidity. Eculizumab, considered a first-line drug in older children, is not approved in neonates and in children weighing less than 5 kg. We present a 5-day-old female newborn, born at 36 weeks' twin gestation, by emergency cesarean section due to cord prolapse, with birth weight of 2,035 g and Apgar score of 7/7/7, who develops microangiopathic hemolytic anemia, thrombocytopenia, and progressive acute renal failure. In day 5, after diagnosis of aHUS, a daily infusion of fresh frozen plasma begins, with improvement of thrombocytopenia and very slight improvement in renal function. The etiologic study (congenital infection, Shiga toxin, ADAMTS13 activity, directed metabolic study) was normal. C3c was slightly decreased. On day 16 for maintenance of anemia and severe renal failure, she started 300 mg/dose eculizumab. Anemia resolves in 10 weeks and creatinine has normal values after 13 weeks of treatment. The genetic study was normal. In this case, eculizumab is effective in controlling microangiopathy and in the recovery of renal function. Diagnosis of neonatal aHUS can be challenging because of phenotypic heterogeneity and potential overlap with other manifestations that may confound it, such as perinatal asphyxia or sepsis/disseminated intravascular coagulation.

Introduction: Acute kidney injury (AKI) is a major contributor of neonatal mortality and morbidity. Understanding the different anatomy of the neonatal kidney could help physician understand pathology of AKI and consequently could treat it efficiently. Aim of the study: This one year duration prospective Cohort study involved twenty seven admitted neonates who had acute kidney injury (AKI). Methods: Laboratory and radiologic diagnosis of AKI, further AKIN and pRIFLE classification and follow up after one and three months. Results: AKI had an incidence of 1.35%, mainly in full-term (59%). Hypertension was presented in full-term (75%) and preterm (45.5%). Hematuria presented by 18.8% (full-term) and 27.3% (preterm). Proteinuria occurred in full-term (46.7%) and preterm (36.4%). Urinary tract infection was more among (45.5%) preterm than full term (25%). Oliguric AKI was found in full term (68.8%) and preterm (72.7%). Anuric AKI present in full-term (31.1%) and preterm (9.1%). Post renal AKI were present 18.8 %( full term) and 9.1 %( preterm). Perinatal asphyxia (18.8%) and sepsis (27.3%) were the most common risk factor. Both full-term (37.5%) and preterm (18.2%) needed peritoneal dialysis. Ultrasonography showed bilateral Grade 2 (50%) and 1(25%) nephropathy and bilateral back pressure (18%). pRIFLE was inversely correlate with age and urine output and positively correlated with hypertension at baseline. At one month; 43.8% full-term, 18.2 % preterm were found hypertensive, 18.8% fullterm had proteinuria, pRIFLE was inversely correlated with urine output and proteinuria and eCCL was significantly improved after one month in both preterm and full-term. At three month, chronic kidney disease was 12.5% and 9.1% in full-term and preterm respectively. Total recovery was higher in preterm neonates than in full-term ones. Conclusion: Sepsis and asphyxia are considered the most common causes of AKI. Limitation: A longer follow up is mandatory. Further follow up studies of AKI in preterm neonates are mandatory.

Objective: To determine the diagnostic accuracy of 1H- magnetic resonance spectroscopy imaging findings in predicting neurodevelopmental abnorma-lities in term neonates having respiratory distress, using clinical neurological examination as reference standard. Study Design: Cross sectional validation study. Place and Duration of Study: Armed Forces Institute of Radiology and Imaging (AFIRI), Pak Emirates Military Hospital, Rawalpindi, from Oct 2017 to Apr 2018. Methodology: A total of 86 patients were included in study. All term neonates suspected of hypoxic ischemic encephalopathy (HIE) referred for magnetic resonance spectroscopy (MRS) meeting our inclusion criteria were enrolled for study acquisition after taking informed consent from attendants. Results: Approximately 47 out of 86 patients suspected to have perinatal asphyxia showed raised lactate peaks (resonating at 1.3 ppm) in both watershed and ganglionic regions and at 6 months neurological evaluation showed significantly delayed neurological development and delayed milestones. Seven (8.1%) patients clinically suspected to have birth asphyxia showed no specific detectable spectral spikes at 1.31 ppm. Twenty six (30.2%) patients presenting with delayed cry but no laboratory evidence of birth asphyxia showed no definite evidence of visualization of lactate peaks. Six (6.97%) patients showed normal magnetic resonance spectroscopy who had clinical, biochemical suspicion of systemic ischemic insult and later on showed retarded neurodevelopment at 6 months of age. Conclusion: Magnetic resonance spectroscopy (magnetic resonance spectroscopy) spectra in patients having high documented clinical and biochemical suspicion of transitory birth asphyxia from any cause, acquired at frontal watershed territory and deep grey matter showed a characteristic spectral resonance of...............

Background The current burden of >5 million deaths yearly is the focus of the Sustainable Development Goal (SDG) to end preventable deaths of newborns and children under 5 years old by 2030. To accelerate progression toward this goal, data are needed that accurately quantify the leading causes of death, so that interventions can target the common causes. By adding postmortem pathology and microbiology studies to other available data, the Child Health and Mortality Prevention Surveillance (CHAMPS) network provides comprehensive evaluations of conditions leading to death, in contrast to standard methods that rely on data from medical records and verbal autopsy and report only a single underlying condition. We analyzed CHAMPS data to characterize the value of considering multiple causes of death. Methods and findings We examined deaths identified from December 2016 through November 2020 from 7 CHAMPS sites (in Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa), including 741 neonatal, 278 infant, and 241 child, In an analysis of data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network, Robert Breiman, Dianna Blau, and colleagues investigate how considering all conditions in the causal chain leading to death informs the identification of deaths attributable to various diagnoses., Author summary Why was this study done? More than 5 million deaths occur annually in children

In this study, the expression of the genes of the amyloid protein precursor, β-secretase, presenilin 1 and 2 by RT-PCR in the lymphocytes of newborns after perinatal asphyxia and perinatal asphyxia treated with hypothermia was analyzed at the age of 15–21 days. The relative quantification of Alzheimer’s-disease-related genes was first performed by comparing the peripheral lymphocytes of non-asphyxia control versus those with asphyxia or asphyxia with hypothermia. In the newborns who had perinatal asphyxia, the peripheral lymphocytes presented a decreased expression of the amyloid protein precursor and β-secretase genes. On the other hand, the expression of the presenilin 1 and 2 genes increased in the studied group. The expression of the studied genes in the asphyxia group treated with hypothermia had an identical pattern of changes that were not statistically significant to the asphyxia group. This suggests that the expression of the genes involved in the metabolism of the amyloid protein precursor in the peripheral lymphocytes may be a biomarker of progressive pathological processes in the brain after asphyxia that are not affected by hypothermia. These are the first data in the world showing the role of hypothermia in the gene changes associated with Alzheimer’s disease in the peripheral lymphocytes of newborns after asphyxia.

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.

Neonatal seizures are common manifestations of several neurological or systemic disorders and associated with high morbidity, mortality and poor short- and long-term developmental outcomes. It is important to determine the aetiology and factors that determine the poor outcome, more so in a newly developed setting. The early detection of predictors of poor outcome will help in planning acute management, counselling, follow-up and rehabilitation services. In this prospective observational study, we looked at the clinical profile, aetiology, short-term outcomes and predictors of poor outcome of neonatal seizures among out-born neonates. The common causes were hypoxic ischaemic encephalopathy, sepsis and metabolic disturbances. One-third of neonates had poor outcome. Abnormal neurological and cardiorespiratory examination at admission; low oxygen saturation, glucose and pH; and hypoxic ischemic encephalopathy-III were predictors of poor outcome.

Infants with moderate and severe neonatal encephalopathy (NE) frequently suffer from long-term adverse outcomes. We hypothesize that the urinary metabolome of newborns with NE reflects the evolution of injury patterns observed with magnetic resonance imaging (MRI).Eligible patients were newborn infants with perinatal asphyxia evolving to NE and qualifying for therapeutic hypothermia (TH) included in the HYPOTOP trial. MRI was employed for characterizing brain injury. Urine samples of 55 infants were collected before, during, and after TH. Metabolic profiles of samples were recorded employing three complementary mass spectrometry-based assays, and the alteration of detected metabolic features between groups was assessed.The longitudinal assessment revealed significant perturbations of the urinary metabolome. After 24 h of TH, a stable disease pattern evolved characterized by the alterations of 4-8% of metabolic features related to lipid metabolism, metabolism of cofactors and vitamins, glycan biosynthesis and metabolism, amino acid metabolism, and nucleotide metabolism. Characteristic metabolomic fingerprints were observed for different MRI injury patterns.This study shows the potential of urinary metabolic profiles for the noninvasive monitoring of brain injury of infants with NE during TH.A comprehensive approach for the study of the urinary metabolome was employed involving a semi-targeted capillary electrophoresis-time-of-flight mass spectrometry (TOFMS) assay, an untargeted ultra-performance liquid chromatography (UPLC)-quadrupole TOFMS assay, and a targeted UPLC-tandem MS-based method for the quantification of amino acids. The longitudinal study of the urinary metabolome identified dynamic metabolic changes between birth and until 96 h after the initiation of TH. The identification of altered metabolic pathways in newborns with pathologic MRI outcomes might offer the possibility of developing noninvasive monitoring approaches for personalized adjustment of the treatment and for supporting early outcome prediction.

Developmental disorders are frequently overlooked in the developing countries, particularly in sub-Saharan Africa. Early identification of developmental delays (DDs) is critical to optimal outcomes. This study set out to determine the proportion of children who are at risk of DDs among infants attending immunization clinics at the University College Hospital, Ibadan, Nigeria. Infants 6 weeks to 12 months of age (median age 6 months) who presented for routine immunization were screened for DDs using the Ages and Stages Questionnaire. A total of 587 infants [312 (53.2%) males] were enrolled. A total of 198 (33.7%) children showed signs of DDs. For the domains of communication skills, fine motor skills, gross motor skills, problem solving/cognition skills and personal/social skills, the prevalences of DDs were 7.5%, 15.0%, 10.7%, 14.1% and 14.8%, respectively, and 14.3% had global DDs. Factors that significantly predicted DDs included prematurity (odds ratio [OR] 2.64 [95% confidence interval {CI} 1.45 to 2.05]) and a history of perinatal asphyxia (OR 1.74 [95% CI 1.77 to 2.49]). There is a need to incorporate routine developmental screening into the Nigerian healthcare system for timely recognition of DDs and prompt interventions.

Background: Perinatal stroke encompasses a heterogeneous group of focal neurological injuries early in brain development. In this study, we aimed to compare risk and prognostic factors in preterm and term infants with perinatal hemorrhagic stroke (PHS). Patients and Methods: The study includes 66 infants with PHS. The infants were evaluated for demographic characteristics, fetal and maternal risk factors, perinatal events, clinical and neuroimaging findings, complications, and sequales. Results: Of 66 infants with PHS, 44 (66.70%) were preterm and 22 (33.30%) were term infants. Primiparity, mucosal bleeding, and multiple lobes involvement were more common in term infants than preterm infants (P < 0.05); however, respiratory insufficiency, neonatal sepsis, perinatal asphyxia, respiratory distress syndrome, use of invasive mechanical ventilation, use of noninvasive mechanical ventilation, and prolonged hospitalization were more common in preterm infants than term infants (P < 0.05). Eight (12.12%) infants died during infancy period. Small for gestational age and mucosal bleeding were more common in infants who are dead than those alive (P < 0.05). Forty-two (63.63%) infants were followed. Cerebral palsy and/or epilepsy and/or hydrocephalus were diagnosed in 36 (85.72%) infants during follow-up. Conclusion: Our findings showed that PHS was much more common in preterm infants. Mucosal bleeding and multiple lobes involvement were more common in term infants. PHS has high morbidity and mortality rates. Small for gestational age and mucosal bleeding were more common in infants who are dead.

BACKGROUND AND PURPOSE: Cerebral venous oxygen saturation can be used as an indirect measure of brain health, yet it often requires either an invasive procedure or a noninvasive technique with poor sensitivity. We aimed to test whether cerebral venous oxygen saturation could be measured using quantitative susceptibility mapping, an MR imaging technique, in 3 distinct groups: healthy term neonates, injured term neonates, and preterm neonates. MATERIALS AND METHODS: We acquired multiecho gradient-echo MR imaging data in 16 neonates with perinatal asphyxia and moderate or severe hypoxic-ischemic encephalopathy (8 term age: average, 40.0 [SD, 0.8] weeks’ gestational age; 8 preterm, 33.5 [SD, 2.0] weeks’ gestational age) and in 8 healthy term-age controls (39.3 [SD, 0.6] weeks, for a total of n = 24. Data were postprocessed as quantitative susceptibility mapping images, and magnetic susceptibility was measured in cerebral veins by thesholding out 99.95% of lower magnetic susceptibility values. RESULTS: The mean magnetic susceptibility value of the cerebral veins was found to be 0.36 (SD, 0.04) ppm in healthy term neonates, 0.36 (SD, 0.06) ppm in term injured neonates, and 0.29 (SD, 0.04) ppm in preterm injured neonates. Correspondingly, the derived cerebral venous oxygen saturation values were 73.6% (SD, 2.8%), 71.5% (SD, 7.4%), and 72.2% (SD, 5.9%). There was no statistically significant difference in cerebral venous oxygen saturation among the 3 groups (P = .751). CONCLUSIONS: Quantitative susceptibility mapping–derived oxygen saturation values in preterm and term neonates agreed well with values in past literature. Cerebral venous oxygen saturation in preterm and term neonates with hypoxic-ischemic encephalopathy, however, was not found to be significantly different between neonates or healthy controls.