Abstract: We demonstrated that MR imaging scores combined with either lactate-Nacetylaspartate ratios at 1H MR spectroscopy or apparent diffusion coefficients in the basal ganglia is associated with outcome when these parameters are obtained during the 1st week of life in term neonates with hypoxic-ischemic encephalopathy following asphyxia.

Abstract: Background: Acute kidney injury (AKI) is one of the commonest manifestations of end-organ damage associated with birth asphyxia.Objective: To evaluate glomerular and tubular dysfunction in neonates with moderate to severe birth asphyxia.Design: Prospective cohort study.Setting: Neonatal unit of a teaching hospital.Methods: Subjects were inborn neonates of ⩾34 completed weeks of gestation with an APGAR score <7 at 1 min after birth. Renal function tests including serum electrolytes were measured daily until 96 hrs of life along with urinary output. Fractional excretion of sodium (FeNa), renal failure index (RFI), urinary myoglobin and creatinine clearance (CrCl) were calculated using timed urine collection. Staging of AKI was undertaken using Acute Kidney Injury Network criteria (AKIN).Primary outcome measurement: Recovery of glomerular function.Results: A total of 2196 neonates were born during the study period (September 2006 to April 2007), 44 of whom met the inclusion criteria. Data from 36 neo...

Abstract: Perinatal Asphyxia—oxygen deficit at delivery—can lead to severe hypoxic ischaemic organ damage in newborns followed by a fatal outcome or severe life-long pathologies. The severe insults often cause neurodegenerative diseases, mental retardation and epilepsies. The mild insults lead to so-called “minimal brain-damage disorders” such as attention deficits and hyperactivity, but can also be associated with the development of schizophrenia and life-long functional psychotic syndromes. Asphyxia followed by re-oxygenation can potentially lead to development of several neurodegenerative pathologies, diabetes type 2 and cancer. The task of individual prediction, targeted prevention and personalised treatments before a manifestation of the life-long chronic pathologies usually developed by newborns with asphyxic deficits, should be given the extraordinary priority in neonatology and paediatrics. Socio-economical impacts of educational measures and advanced strategies in development of robust diagnostic approaches targeted at effected molecular pathways, biomarker-candidates and potential drug-targets for tailored treatments are reviewed in the paper.

Abstract: Objective International guidelines recommend a compression to ventilation (C:V) ratio of 3:1 in neonates, and 15:2 for other paediatric age groups. The authors aimed to compare these two C:V ratios in a neonatal swine model of cardiac arrest following asphyxia. Design Experimental animal study. Setting Facility for animal research. Subjects 22 newborn pigs (age 12–36 h, weight 2.0–2.7 kg). Interventions Progressive asphyxia until asystole. Animals were randomised to receive C:V 3:1 (n=11) or 15:2 (n=11). Main outcome measures Return of spontaneous circulation (ROSC) was defined as a heart rate ≥100 bpm. Also of interest were haemodynamic parameters, cerebral and systemic oxygen saturation and the proinflammatory cytokine interleukin-1β (IL-1β). Results Two animals in each group did not achieve ROSC. Mean (SD) increase in diastolic blood pressure (DBP; mm Hg) during compression cycles was significantly higher at a C:V ratio of 15:2 than 3:1 (7.1 (2.8) vs 4.8 (2.6)). Median time (IQR) to ROSC for the 3:1 group was 150 (140–180) s, and 195 (145–358) s for the 15:2 group. There were no significant differences in the temporal changes in haemodynamic parameters or oxygen saturation indices between the groups. IL-1β levels in cerebrospinal and bronchoalveolar lavage fluid was comparable between the groups. Conclusion In neonatal pigs with asphyxia-induced cardiac arrest, the response to a C:V ratio of 15:2 is not better than the response to a C:V ratio of 3:1 despite better generation of DBP during resuscitation.

Abstract: An increase in oxygen tension is an important factor in decreasing pulmonary vascular resistance (PVR) at birth. Birth asphyxia results in acidosis and increased PVR. We determined the effect of re...

Abstract: Delivery is a stressful and risky event menacing the newborn. The mother-dependent respiration has to be replaced by autonomous pulmonary breathing immediately after delivery. If delayed, it may lead to deficient oxygen supply compromising survival and development of the central nervous system. Lack of oxygen availability gives rise to depletion of NAD+ tissue stores, decrease of ATP formation, weakening of the electron transport pump and anaerobic metabolism and acidosis, leading necessarily to death if oxygenation is not promptly re-established. Re-oxygenation triggers a cascade of compensatory biochemical events to restore function, which may be accompanied by improper homeostasis and oxidative stress. Consequences may be incomplete recovery, or excess reactions that worsen the biological outcome by disturbed metabolism and/or imbalance produced by over-expression of alternative metabolic pathways. Perinatal asphyxia has been associated with severe neurological and psychiatric sequelae with delayed clinical onset. No specific treatments have yet been established. In the clinical setting, after resuscitation of an infant with birth asphyxia, the emphasis is on supportive therapy. Several interventions have been proposed to attenuate secondary neuronal injuries elicited by asphyxia, including hypothermia. Although promising, the clinical efficacy of hypothermia has not been fully demonstrated. It is evident that new approaches are warranted. The purpose of this review is to discuss the concept of sentinel proteins as targets for neuroprotection. Several sentinel proteins have been described to protect the integrity of the genome (e.g. PARP-1; XRCC1; DNA ligase IIIα; DNA polymerase β, ERCC2, DNA-dependent protein kinases). They act by eliciting metabolic cascades leading to (i) activation of cell survival and neurotrophic pathways; (ii) early and delayed programmed cell death, and (iii) promotion of cell proliferation, differentiation, neuritogenesis and synaptogenesis. It is proposed that sentinel proteins can be used as markers for characterising long-term effects of perinatal asphyxia, and as targets for novel therapeutic development and innovative strategies for neonatal care.

Abstract: Vasopressin is one of the most important physiological stress and shock hormones. Copeptin, a stable vasopressin precursor, is a promising sepsis marker in adults. In contrast, its involvement in neonatal diseases remains unknown. The aim of this study was to establish copeptin concentrations in neonates of different stress states such as sepsis, chorioamnionitis and asphyxia. Copeptin cord blood concentration was determined using the BRAHMS kryptor assay. Neonates with early-onset sepsis (EOS, n = 30), chorioamnionitis (n = 33) and asphyxia (n = 25) were compared to a control group of preterm and term (n = 155) neonates. Median copeptin concentration in cord blood was 36 pmol/l ranging from undetectable to 5498 pmol/l (IQR 7 - 419). Copeptin cord blood concentrations were non-normally distributed and increased with gestational age (p < 0.0001). Neonates born after vaginal compared to cesarean delivery had elevated copeptin levels (p < 0.0001). Copeptin correlated strongly with umbilical artery pH (Spearman's Rho -0.50, p < 0.0001), umbilical artery base excess (Rho -0.67, p < 0.0001) and with lactate at NICU admission (Rho 0.54, p < 0.0001). No difference was found when comparing copeptin cord blood concentrations between neonates with EOS and controls (multivariate p = 0.30). The highest copeptin concentrations were found in neonates with asphyxia (median 993 pmol/l). Receiver-operating-characteristic curve analysis showed that copeptin cord blood concentrations were strongly associated with asphyxia: the area under the curve resulted at 0.91 (95%-CI 0.87-0.96, p < 0.0001). A cut-off of 400 pmol/l had a sensitivity of 92% and a specifity of 82% for asphyxia as defined in this study. Copeptin concentrations were strongly related to factors associated with perinatal stress such as birth acidosis, asphyxia and vaginal delivery. In contrast, copeptin appears to be unsuitable for the diagnosis of EOS.

Abstract: To determine the feasibility and safety of whole body cooling in newborn infants with perinatal asphyxial encephalopathy in a low resource setting. Feasibility trial. Tertiary care perinatal centre. Infants born at ≥ 35 weeks gestation with perinatal asphyxia were included in the study. Infants were cooled to a rectal temperature of 33±0.5°C for 72 hours using cloth-covered ice-gel packs. Vital parameters were monitored continuously. The primary outcome was the achievement of target temperature within 1 hour of initiation of treatment and maintaining the target temperature for 72 hours. Adverse events and possible complications of hypothermia were the secondary outcomes measured. Twenty infants were included in the study. The mean time taken to achieve target rectal temperature was 52±25 minutes. The mean rectal temperature during cooling was 32.9±0.11°C. The target temperature could be maintained for 72 hours without difficulty in all babies. Adverse events observed during cooling were thrombocytopenia (25%), sinus bradycardia (25%), deranged bleeding parameters (20%), aposteatonecrosis (15%), hyperglycemia (15%), hypoglycemia (10%), hypoxemia (5%), life-threatening coagulopathy (5%) and death (5%). Shivering was noted in many of the babies, especially in the initial phase of cooling. Whole body cooling in term infants with perinatal asphyxia is achievable, safe and inexpensive in a low-resource setting.

Abstract: The objective of the present study was to test the hypothesis that parturition duration is related to birth asphyxia in lambs and that asphyxia affects newborn lamb viability and vigor. Two sire and dam genotypes (Texel: TX; Polwarth: PW) and their crosses were represented in the study. Eighty lambs (25 PW sire × PW dam, 13 TX × TX, 25 TX × PW, and 17 PW × TX) born to 69 grazing ewes were used. At birth, the log₁₀ length of the second stage of parturition, birth weight, placental weight, and several body measurements were recorded on all lambs, and jugular blood samples were analyzed with the i-Stat Portable Clinical Analyzer (Abbott, Montevideo, Uruguay). A modified Apgar viability score at birth and lamb behavior during their first hour of life were recorded. Brain weight, muscle:bone ratio, and bone density were recorded in 20 male lambs (5 from each breed group) that were euthanized and dissected 24 h after birth. Data were analyzed by linear regression, least squares ANOVA, and ordinal and binary logistic regressions. Mean blood gas and acid-base variables were 7.21 ± 0.09 for pH, 18.4 ± 9.8 mmHg for partial pressure of oxygen, 53 ± 12.5 mmHg for partial pressure of carbon dioxide, and -4 ± 5.1 mmol/L for extracellular fluid base excess. Parturition duration increased with birth weight (P < 0.001) and was shorter in TX ewes (P < 0.001), female lambs (P < 0.05), twins (P < 0.09), and twin females (sex × litter size interaction, P < 0.02). Twenty-six (32.9%) lambs were born asphyxiated (pO₂ < 10 mmHg or pH <7.1). Parturition duration increased the risk of asphyxia (P < 0.001), decreased the viability score (P < 0.001), and increased the latency to suckle the udder (P < 0.05). Twin-born lambs presented at birth a 16-fold greater risk of asphyxia (P < 0.01) and reduced placental efficiency (P < 0.05). Texel-sired lambs appeared immature at birth, with less bone density (P < 0.05), smaller brain (P < 0.05), shorter forelimbs (P < 0.05), greater anterior (P < 0.001) and posterior (P < 0.05) neck circumference, and greater muscle:bone ratio (P < 0.05). Immaturity may explain greater TX biotype survival. Together these results demonstrate that a relationship exists between parturition duration, neonatal viability and behavior, and acid-base balance values in single- and twin-born lambs, suggesting that birth asphyxia is an important risk factor in perinatal lamb mortality.

Abstract: The objective of this study was to define potential clinical prognostic factors for term infants with neonatal seizures subsequent to intrapartum asphyxia. The authors completed a retrospective analysis of 62 term infants with clinical neonatal seizures subsequent to intrapartum asphyxia. Logistic regression analysis was applied to determine the independent prognostic indicators of an adverse outcome. A total of 23 (37%) infants had a normal outcome, 34 (55%) survived with 1 or more neurodevelopmental impairments (23 cerebral palsy, 28 global developmental delay, 15 epilepsy, with 18 combination of two, and 9 all three), and 5 (8%) died. Six variables were associated with an adverse outcome, but only the presence of meconium aspiration, a low (≤ 3) 1-minute Apgar score, seizure type other than focal clonic, and moderately severely abnormal electroencephalography (EEG) background findings were independently associated with an adverse outcome. Signs of acute distress are predictors of adverse outcome, alongside seizure semiology and moderate to severe EEG background abnormalities.

Abstract: There are several potential causes of retinal hemorrhages (RH) in neonates. Hemorrhages at birth may occur after traumatic deliveries; neonatal coagulopathies are associated with sepsis, shaken baby syndrome and intracranial hemorrhage [1]. The reported incidence of neonatal retinal hemorrhages varies widely, from 2.6% to 50%, which is possibly due to different patient demographics, how soon after birth examinations are conducted, and different examination techniques [2]. In general, birth-related RH resolves quickly and does not cause subsequent visual or neurological deficits [2]. Despite the number of articles documenting the incidence and duration of RH in healthy newborns, there have been no prior reports on RH in asphyxiated newborns. Asphyxia or respiratory distress is defined as a condition of impaired gas exchange that leads to hypoxemia, hypercapnia and metabolic acidosis [3]. Clinical criteria include the following: abnormalities in electronic fetal monitoring, meconium-stained amniotic fluid, metabolic acidemia, low Apgar scores, and post-asphyxia neurological and/or extra neurological abnormalities [4]. In this report, we discuss the incidence, pattern and duration of RH and vitreous hemorrhages (VH) associated with perinatal distress in newborns and evaluate their clinical significance.

Abstract: Although asphyxial deaths often have very characteristic death scene features, the pathological diagnosis of asphyxia is often difficult as there are no pathognomonic findings at autopsy; i.e. features such as fluidity of the blood, congestion, oedema, engorgement of the right side of the heart and petechial haemorrhages are no longer considered diagnostic. For this reason, accurate evaluation of the death scene is required, with careful exclusion of injuries and underlying organic diseases that may have caused or contributed to death. Particular difficulties arise in infants and in the elderly. Classifying asphyxia by underlying pathophysiological processes as being due to failure in the supply, transfer, transport, uptake and utilization of oxygen provides a clearer indication of underlying mechanisms than categorizations based on circumstances.

Abstract: Perinatal asphyxia is a leading cause of brain injury in neonates, occurring in 2–4 per 1,000 live births, and there are limited treatment options. Because of their similarity to humans, nonhuman primates are ideal for performing preclinical tests of safety and efficacy for neurotherapeutic interventions. We previously developed a primate model of acute perinatal asphyxia using 12–15 min of umbilical cord occlusion. Continuing this research, we have increased cord occlusion time from 15 to 18 min and extended neurodevelopmental follow-up to 9 months. The purpose of this report is to evaluate the increase in morbidity associated with 18 min of asphyxia by comparing indices obtained from colony controls, nonasphyxiated controls and asphyxiated animals. Pigtail macaques were delivered by hysterotomy after 0, 15 or 18 min of cord occlusion, then resuscitated. Over the ensuing 9 months, for each biochemical and physiologic parameters, behavioral and developmental evaluations, and structural and spectroscopic MRI were recorded. At birth, all asphyxiated animals required resuscitation with positive pressure ventilation and exhibited biochemical and clinical characteristics diagnostic of hypoxic-ischemic encephalopathy, including metabolic acidosis and attenuated brain activity. Compared with controls, asphyxiated animals developed long-term physical and cognitive deficits. This preliminary report characterizes the acute and chronic consequences of perinatal asphyxia in a nonhuman primate model, and describes diagnostic imaging tools for quantifying correlates of neonatal brain injury as well as neurodevelopmental tests for evaluating early motor and cognitive outcomes.

Abstract: BACKGROUND: Perinatal asphyxial encephalopathy occurs in 1-per 1000 live births and is associated with high mortality and morbidity. Therapeutic hypothermia increases intact survival and improves neurodevelopmental outcome in survivors.AIMS: To evaluate (i) the opinion and practice of therapeutic hypothermia as a therapy for moderate to severe perinatal asphyxial encephalopathy amongst Swiss neonatologists and paediatric intensive care specialists, (ii) the current clinical management of infants with perinatal asphyxial encephalopathy and (iii) the need for a national perinatal asphyxia and therapeutic hypothermia registry.METHODS: Two web-based questionnaires were sent to 18 senior staff physicians within the Swiss Neonatal Network.RESULTS: Therapeutic hypothermia was considered effective by all responders, however only 11 of 18 units provided therapeutic hypothermia. Cooling was initiated during transfer and performed passively in 82% of centres with a target rectal temperature of 33-34 degrees C. Most units ventilated infants with perinatal asphyxial encephalopathy if clinically indicated and 73% of responders gave analgesia routinely to cooled infants. Neuromonitoring included continuous amplitude integrated EEG (aEEG) and EEG. Neuroimaging included cranial ultrasound (cUS), magnetic resonance imaging (MRI) and computed tomography (CT). Sixty-seven percent of units treating infants with perinatal asphyxial encephalopathy performed MRI routinely. All heads of departments questioned indicated that a "Swiss National Asphyxia and Cooling Registry" is needed.CONCLUSIONS: In Switzerland, access to therapeutic hypothermia is widespread and Swiss neonatologists believe that therapeutic hypothermia for perinatal asphyxia is effective. National cooling protocols are needed for the management of infants with perinatal asphyxial encephalopathy in order to ensure safe cooling, appropriate monitoring, imaging and follow-up assessment. A national registry is needed to collect data on diagnosis, treatment, adverse events and outcome.

Abstract: SUMMARY Theeffect ofapplying brain-orientated neonatal intensive care forterminfants with severeneonatal asphyxia was studied. Suchtreatment included protective phenobarbitone administration together withassisted ventilation andother measures tocounteract postasphyxial cerebral oedemaandanyabrupt changes inblood pressureandoxygenation. Themortality rateandincidence oflong-term sequelae were reduced appreciably, resulting ina 0-1year mortality rateof14% (previously 50%)andanincidence ofneurodevelopmental handicap at18months of17% (previously 50%).Itisimportant inthemanagementofinfants with severeasphyxia atbirth toavoid blood pressurefluctuations andtocontrol neuronal epileptic activity bytheuse ofbarbiturates andearly ventilator treatment.

Abstract: Asphyxia is a serious problem in the neonate worldwide. Incidence of birth asphyxia are 4 million baby a year. There are many reasons as baby may be not able to take enough oxygen before, during and after delivery. The objective of this study was to identify the risk factors of neonatal asphyxia from maternal, neonatal and mode of delivery. Materials and Methods case control study. The data was retrospectively collected from medical record of pregnant women and neonate that was born in Dr Soetomo Hospital between 1 January 2009 to Desember 2009. Data of the inborn neonate (birth weight, gestational age, Apgar score) and the data of pregnant mother (age, preeclampsia, antepartum bleeding, premature rupture of the membrane and mode of delivery) was collected. Risk factors that associated with asphyxia were antepartum bleeding, p 0.009, OR 2.607 (1.242-5.473), preeclampsia, p 0.000, OR 2.372 (1.688-3.333), prematurity p 0.000, OR 4.055 (2.939-5.595), post mature, p 0.001, OR 3.811 (1.637 – 8.872), low birth weight, p 0.000, OR 5.833 (4.245-8.016), and caesarian section, p 0.000, OR 3.778 (2.750-5.190). In conclusion, risk factor for asphyxia were antepartum bleeding, preeclampsia, low birth weight, prematurity, post date delivery and caesarian section.

Abstract: Neonatal mortality rate (NMR) or infant mortality rate (IMR) are the rate of deaths per 1,000 live births at which babies of either less than four weeks or of one year of age die, respectively. The NMR and IMR are commonly accepted as a measure of the general health and wellbeing of a population. Korea's NMR and IMR fell significantly between 1993 and 2009 from 6.6 and 9.9 to 1.7 and 3.2, respectively. Common causes of infantile death in 2008 had decreased compared with those in 1996 such as other disorders originating in the perinatal period, congenital malformation of the heart, bacterial sepsis of newborns, disorders related to length of gestation and fetal growth, intra-uterine hypoxia, birth asphyxia. However, some other causes are on the increase, such as respiratory distress of newborn, other respiratory conditions originating in the perinatal period, other congenital malformation, diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism. In this study, we provide basic data about changes of NMR and IMR and the causes of neonatal and infantile death from 1983 to 2009 in Korea.

Abstract: Introduction Clinical registration of the cause of death is available for less than one-third of the global newborn deaths, but the need for good quality data on causes of death for public health planning has renewed the interest in the Verbal Autopsy (VA). We aimed to determine the cause of neonatal deaths by VA in Morang district of Nepal. Methods Caretakers of the deceased were interviewed using a semi-structured VA questionnaire by female community health volunteers. The cause of death was assigned by two senior paediatricians independently and disagreements in ascertaining the proximate cause of death were resolved by consensus. Results The proximate causes of deaths were infections (41 %), birth asphyxia (37.2 %), prematurity (11.5 %), and low birth weight related causes (6.9 %). There was no significant statistical difference in deaths due to infection seen in non-institutional deliveries (43.5 %) than institutional deliveries (34.6 %). More than half of the deaths (58.5 %) occurred within the first three days of life where the predominant cause of death was birth asphyxia (60.7 %). Conclusions Analysis of verbal autopsies demonstrates that the major causes of death still are infections and birth asphyxia. The timing of deaths suggests that neonatal interventions should be aimed at the first week of life. There is no comparative advantage between institutional deliveries at below district level institutions and non-institutional deliveries to prevent neonatal infection. Thus, further study on the quality of care at institutes below the district level should be conducted. Disparities still occur in deaths, with most deaths in Morang occurring in non-institutional deliveries and in disadvantaged groups.

Abstract: Objective: To compare the outcome of subarachnoid block (spinal anesthesia) and general anesthesia in Cesarean delivery for women with severe pre-eclampsia. Methods: A retrospective study of women with severe pre-eclampsia requiring Cesarean section from January 2005 to June 2009 was carried out. Maternal age, parity, gestational age at delivery, booking status, Apgar scores, maternal and perinatal mortality of the sub-arachnoid block group were compared with those of general anesthesia group using c2 , Student t-test and Fischer exact test. Results: There were no significant difference between the two groups in overall maternal mortality (5.4% vs. 11.9%, P=0.5) and perinatal mortality (2.7% vs. 11.9%, P=0.15). The general anesthesia group had significantly more birth asphyxia than the spinal group (55.9% vs. 27.0%, P=0.0006). Conclusion: There was no significant difference in the maternal and perinatal mortality outcome of cesarean delivery between women with severe pre-eclampsia who had regional anesthesia and those that had general anesthesia. There was significantly higher proportion of birth asphyxia in babies of women who received general anesthesia.