TL;DR: Administration of xenon within the delayed timeframe used in this trial is feasible and apparently safe, but is unlikely to enhance the neuroprotective effect of cooling after birth asphyxia.
Abstract: Summary Background Moderate cooling after birth asphyxia is associated with substantial reductions in death and disability, but additional therapies might provide further benefit. We assessed whether the addition of xenon gas, a promising novel therapy, after the initiation of hypothermia for birth asphyxia would result in further improvement. Methods Total Body hypothermia plus Xenon (TOBY-Xe) was a proof-of-concept, randomised, open-label, parallel-group trial done at four intensive-care neonatal units in the UK. Eligible infants were 36–43 weeks of gestational age, had signs of moderate to severe encephalopathy and moderately or severely abnormal background activity for at least 30 min or seizures as shown by amplitude-integrated EEG (aEEG), and had one of the following: Apgar score of 5 or less 10 min after birth, continued need for resuscitation 10 min after birth, or acidosis within 1 h of birth. Participants were allocated in a 1:1 ratio by use of a secure web-based computer-generated randomisation sequence within 12 h of birth to cooling to a rectal temperature of 33·5°C for 72 h (standard treatment) or to cooling in combination with 30% inhaled xenon for 24 h started immediately after randomisation. The primary outcomes were reduction in lactate to N-acetyl aspartate ratio in the thalamus and in preserved fractional anisotropy in the posterior limb of the internal capsule, measured with magnetic resonance spectroscopy and MRI, respectively, within 15 days of birth. The investigator assessing these outcomes was masked to allocation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00934700, and with ISRCTN, as ISRCTN08886155. Findings The study was done from Jan 31, 2012, to Sept 30, 2014. We enrolled 92 infants, 46 of whom were randomly assigned to cooling only and 46 to xenon plus cooling. 37 infants in the cooling only group and 41 in the cooling plus xenon group underwent magnetic resonance assessments and were included in the analysis of the primary outcomes. We noted no significant differences in lactate to N-acetyl aspartate ratio in the thalamus (geometric mean ratio 1·09, 95% CI 0·90 to 1·32) or fractional anisotropy (mean difference −0·01, 95% CI −0·03 to 0·02) in the posterior limb of the internal capsule between the two groups. Nine infants died in the cooling group and 11 in the xenon group. Two adverse events were reported in the xenon group: subcutaneous fat necrosis and transient desaturation during the MRI. No serious adverse events were recorded. Interpretation Administration of xenon within the delayed timeframe used in this trial is feasible and apparently safe, but is unlikely to enhance the neuroprotective effect of cooling after birth asphyxia. Funding UK Medical Research Council.
TL;DR: The pathophysiology of asphyxia generally results from interruption of placental blood flow with resultant fetal hypoxia, hypercarbia, and acidosis, with permanent brain injury the most severe long-term consequence.
TL;DR: The cardiovascular response to asphyxia involves redistribution of cardiac output to maintain oxygen delivery to critical organssuch as the adrenal gland, heart, and brain, at the expense of other organs such as the gut, kidneys and skin.
TL;DR: Early-term birth was associated with low Apgar score, increased neurologic morbidity, and perinatal mortality and asphyxia and intellectual disability were more common among postterm births, but general neurologic mortality and per inatal mortality were not increased.
Abstract: BACKGROUND AND OBJECTIVES: Neonatal outcomes vary by gestational age. We evaluated the association of early-term, full-term, and postterm birth with asphyxia, neurologic morbidity, and perinatal mortality. METHODS: Our register-based study used retrospective data on 214 465 early-term (37+0–38+6 gestational weeks), 859 827 full-term (39+0–41+6), and 55 189 postterm (≥42+0) live-born singletons during 1989–2008 in Finland. Asphyxia parameters were umbilical cord pH and Apgar score at 1 and 5 minutes. Neurologic morbidity outcome measures were cerebral palsy (CP), epilepsy, intellectual disability, and sensorineural defects diagnosed by the age of 4 years. Newborns with major congenital anomalies were excluded from perinatal deaths. RESULTS: Multivariate analysis showed that, compared with full-term pregnancies, early-term birth increased the risk for low Apgar score ( CONCLUSIONS: Early-term birth was associated with low Apgar score, increased neurologic morbidity, and perinatal mortality. Asphyxia and intellectual disability were more common among postterm births, but general neurologic morbidity and perinatal mortality were not increased.
TL;DR: Lower gestational age, low birth weight, asphyxia resuscitation, and maternal chorioamnionitis are independent risk factors for IVH in preterm infants born at 34 weeks of gestation or less following pPROM.
Abstract: Objective The objective of this study is to identify possible perinatal risk factors related to intraventricular hemorrhage (IVH) in preterm infants born at 34 weeks of gestation or less following preterm premature rupture of membranes (pPROM). Methods A total of 292 preterm infants born at 34 weeks of gestation or less following pPROM were enrolled in the study, while 155 newborns with incomplete data, especially those that lack histological examination of the placenta, maternal details, and neonatal characteristics, have been further excluded. Finally, data of 137 preterm infants were included in the analysis. All infants underwent ultrasonographic screening for IVH. Thirty-three infants with IVH were considered as cases and 104 infants without IVH were considered as controls. The association between risk factors and IVH was evaluated by univariate and multivariate logistic regression analyses. Results The incidence of IVH in preterm infants born at 34 weeks of gestation or less following pPROM was 24.1%, while the incidence of maternal chorioamnionitis was 43.8%. By univariate analysis, gestational age, birth weight, asphyxia resuscitation, maternal chorioamnionitis, fetal distress, amniotic fluid index, and latency of the rupture of membranes to birth were found to be significantly different between the 2 groups. By logistic regression analysis, lower gestational age, low birth weight, asphyxia resuscitation, and maternal chorioamnionitis were found to be independent risk factors for IVH. Conclusion Lower gestational age, low birth weight, asphyxia resuscitation, and maternal chorioamnionitis are independent risk factors for IVH in preterm infants born at 34 weeks of gestation or less following pPROM.
TL;DR: Interventions such as intrauterine resuscitation or operative delivery may decrease the risk of severe hypoxia from intrauterines insults and improve long-term neurologic outcomes.
TL;DR: To the authors' knowledge, this is the largest study, which evaluated the utility of urinary biomarkers in the diagnosis of AKI in newborns with perinatal asphyxia, and found that first day, urine NGAL and IL-18 levels have an important diagnostic power in such patients.
Abstract: Background: Acute kidney injury (AKI) affects up to 60% of severely asphyxiated neonates. The diagnosis of AKI can be and is further challenged by a lack of good biomarkers. We studied the role of novel markers for AKI, neutrophil gelatinase-associated lipocalin (NGAL), interleukin-8 (IL-18), Netrin-1 (NTN-1), and sodium hydrogen exchanger isoform 3 (NHE3) on development and early diagnosis of AKI in newborns with perinatal asphyxia (PA). Methods: Forty-one newborns with a diagnosis of PA (15 with AKI and 26 without AKI) and 20 healthy matched controls were involved to the study. Urinary samples were obtained on postnatal days 1 and 4 for patients with PA and on postnatal day 1 for the control subjects. AKI was defined using a serum creatinine-based modification of the acute kidney injury network criteria. Results: The levels of NGAL, NTN-1, NHE3, and IL-18 on the first postnatal day urine samples were higher in patients compared to controls (p < 0.001, p <0.001, p <0.02, p <0.001, respectively)...
TL;DR: Placental and umbilical cord abnormalities have a profound association with HIE and a prompt examination of the placentas of newborns suffering from asphyxia can provide important information on the pathogenesis behind the incident and contribute to make a better early prognosis.
Abstract: Objective: Birth asphyxia and hypoxic ischemic encephalopathy (HIE) of the newborn remain serious complications. We present a study investigating if placental or umbilical cord abnormalities in newborns at term are associated with HIE.Materials and methods: A prospective cohort study of the placenta and umbilical cord of infants treated with hypothermia (HT) due to hypoxic brain injury and follow-up at 12 months of age has been carried out. The study population included 41 infants treated for HT whose placentas were submitted for histopathological analysis. Main outcome measures were infant development at 12 months, classified as normal, cerebral palsy, or death. A healthy group of 100 infants without HIE and normal follow-up at 12 months of age were used as controls.Results: A velamentous or marginal umbilical cord insertion and histological abruption was associated with the risk of severe HIE, OR = 5.63, p = 0.006, respectively, OR = 20.3, p = 0.01 (multiple-logistic regression). Velamentous or ...
TL;DR: The changes in diaphragm fatigue and structure induced by birth asphyxia persist long-term but are prevented by maternal creatine supplementation.
Abstract: Using a model of birth asphyxia, we previously reported significant structural and functional deficits in the diaphragm muscle in spiny mice, deficits that are prevented by supplementing the maternal diet with 5% creatine from mid-pregnancy. The long-term effects of this exposure are unknown. Pregnant spiny mice were fed control or 5% creatine-supplemented diet for the second half of pregnancy, and fetuses were delivered by caesarean section with or without 7.5 min of in-utero asphyxia. Surviving pups were raised by a cross-foster dam until 33±2 days of age when they were euthanized to obtain the diaphragm muscle for ex-vivo study of twitch tension and muscle fatigue, and for structural and enzymatic analyses. Functional analysis of the diaphragm revealed no differences in single twitch contractile parameters between any groups. However, muscle fatigue, induced by stimulation of diaphragm strips with a train of pulses (330ms train/sec, 40Hz) for 300sec, was significantly greater for asphyxia pups compared with controls (p<0.05), and this did not occur in diaphragms of creatine + asphyxia pups. Birth asphyxia resulted in a significant increase in the proportion of glycolytic, fast-twitch fibres and a reduction in oxidative capacity of Type I and IIb fibres in male offspring, as well as reduced cross-sectional area of all muscle fibre types (Type I, IIa, IIb/d) in both males and females at 33 days of age. None of these changes were observed in creatine + asphyxia animals. Thus, the changes in diaphragm fatigue and structure induced by birth asphyxia persist long-term but are prevented by maternal creatine supplementation.
TL;DR: It is demonstrated that MgSO4 may increase perfusion of peripheral vascular beds during adverse perinatal events such as asphyxia.
Abstract: Magnesium sulphate is a standard therapy for eclampsia in pregnancy and is widely recommended for perinatal neuroprotection during threatened preterm labour. MgSO4 is a vasodilator and negative inotrope. Therefore the aim of this study was to investigate the effect of MgSO4 on the cardiovascular and cerebrovascular responses of the preterm fetus to asphyxia. Fetal sheep were instrumented at 98 ± 1 days of gestation (term = 147 days). At 104 days, unanaesthetised fetuses were randomly assigned to receive an intravenous infusion of MgSO4 (n = 6) or saline (n = 9). At 105 days all fetuses underwent umbilical cord occlusion for 25 min. Before occlusion, MgSO4 treatment reduced heart rate and increased femoral blood flow (FBF) and vascular conductance compared to controls. During occlusion, carotid and femoral arterial conductance and blood flows were higher in MgSO4-treated fetuses than controls. After occlusion, fetal heart rate was lower and carotid and femoral arterial conductance and blood flows were higher in MgSO4-treated fetuses than controls. Femoral arterial waveform height and width were increased during MgSO4 infusion, consistent with increased stroke volume. MgSO4 did not alter the fetal neurophysiological or nuchal electromyographic responses to asphyxia. These data demonstrate that a clinically comparable dose of MgSO4 increased FBF and stroke volume without impairing mean arterial pressure (MAP) or carotid blood flow (CaBF) during and immediately after profound asphyxia. Thus, MgSO4 may increase perfusion of peripheral vascular beds during adverse perinatal events.
TL;DR: The respiratory, metabolic, and behavioral responses to asphyxia of three gobiid fishes are compared in this paper, showing that the resting oxygen consumption of Typhlogobius is extremely low; the one gram intercept for the wet weight-oxygen uptake regression is 17 µl O2/g/hr.
Abstract: 1. The respiratory, metabolic, and behavioral responses to asphyxia of three gobiid fishes are compared. Adult specimens of Typhlogobius californiensis and Gillichthys mirabilis are subject to hypoxic stress in their natural habitats, while Coryphopterus nicholsii generally is not.2. Oxygen tensions in burrows of the ghost shrimp Callianassa affinis, commensal host of Typhlogobius, fall rapidly to nearly anoxic levels following exposure of the burrow openings by the outgoing tide.3. The resting oxygen consumption of Typhlogobius is extremely low; the one gram intercept for the wet weight-oxygen uptake regression is 17 µl O2/g/hr. The other two species consume oxygen 3 to 5 times as rapidly at rest.4. Resting specimens of Typhlogobius are capable of maintaining a constant rate of oxygen uptake down to a critical ambient oxygen tension of 9-16 mm Hg. Gillichthys and Coryphopterus are capable of regulating oxygen uptake down to critical levels of 16-25 mm Hg and 19-28 mm Hg respectively.5. Both Typhlogobius ...
TL;DR: Baseline plasma hypoxanthine and lipoprotein concentrations were inversely correlated to the duration of hypoxia sustained before asystole occurred, but there was no evidence for a differential metabolic response to the different resuscitation protocols or in terms of survival.
Abstract: Background
Optimizing resuscitation is important to prevent morbidity and mortality from perinatal asphyxia. The metabolism of cells and tissues is severely disturbed during asphyxia and resuscitation, and metabolomic analyses provide a snapshot of many small molecular weight metabolites in body fluids or tissues. In this study metabolomics profiles were studied in newborn pigs that were asphyxiated and resuscitated using different protocols to identify biomarkers for subject characterization, intervention effects and possibly prognosis.
TL;DR: To evaluate the antiepileptic effect of hypothermia and its association with neurological outcome in infants with moderate and severe hypoxic–ischemic encephalopathy (HIE).
Abstract: Aim
To evaluate the antiepileptic effect of hypothermia and its association with neurological outcome in infants with moderate and severe hypoxic–ischemic encephalopathy (HIE).
Method
We compared polygraphic electroencephalography monitoring and outcome data in 39 cooled and 33 non-cooled term newborn infants, born between January 2005 and March 2013, and hospitalized because of signs of asphyxia and moderate to severe HIE.
Results
Cooled newborn infants had fewer seizures (14/39 vs 20/33 p=0.036) and status epilepticus (7/39 vs 13/33, p=0.043), a lower mean duration of seizures (18mins vs 133mins, p=0.026), fewer administered antiepileptic drugs (median 0 vs 1, p=0.045), and more commonly a good outcome at 24 months (normal/mild motor impairment in 32/39 vs 16/33, p=0.003). Seizure burden (accumulated duration of seizures over a defined period) in cooled patients with both moderate (0.0 vs 0.1; p=0.045) and severe HIE (0.3 vs 4.9; p=0.018) was lower than in non-cooled patients. Compared with non-cooled patients, a good outcome was more common in cooled newborn infants with severe HIE (p=0.003).
Interpretation
Hypothermia has an antiepileptic effect in both moderate and severe neonatal HIE. The lower seizure burden in cooled newborn infants with severe HIE is more commonly associated with normal outcome at 24 months.
TL;DR: Early and adequate treatment could improve the adverse pregnancy outcomes among women with syphilis, especially in infants born to mothers treated inadequately.
Abstract: Objectives To determine the effectiveness of treatment in improving pregnancy outcomes among women with syphilis. Methods This is a retrospective study based on the provincial prevention of mother-to-child transmission of syphilis database. All women with syphilis with singleton pregnancies were recruited. We evaluated their pregnancy outcomes by group-specific analyses according to their treatment time and adequacy. Results The syphilis prevalence among pregnant women was 0.3% (4214/1 338 739) in Zhejiang Province, China, during 2013–2014, considering all live births and abortions. Women with singleton pregnancies (3767) were included in the study, including live births and stillbirths (≥28 weeks). The treatment coverage for all women with syphilis was 80.2% (3022/3767), and 68.2% (2062/3022) of the women were treated adequately. Of 745 infants born to untreated pregnant women with syphilis, 1.2% manifested pneumonia, 2.7% asphyxia, 1.6% birth defects, 3.8% congenital syphilis (CS), 14.2% were preterm, 10.1% had low birth weight (LBW) and 3.1% experienced perinatal death. The risks of asphyxia (OR=2.7), CS (OR=3.1), preterm birth (OR=1.5), LBW (OR=1.9) and perinatal death (OR=3.1) were much higher in infants born to mothers treated inadequately than from those treated adequately. Moreover, mothers with syphilis who initiated treatment in the third trimester suffered an increased risk for asphyxia (OR=3.0), CS (OR=6.0) and LBW (OR=1.7) compared with those who initiated treatment in the first trimester. Conclusions Early and adequate treatment could improve the adverse pregnancy outcomes among women with syphilis.
TL;DR: The terminology, classification, mechanisms, and lesions associated with asphyxial deaths in companion animals and significant comparative differences of the response to various types of asphyxia in animals and people are highlighted.
Abstract: Asphyxia in a forensic context refers to death by rapid cerebral anoxia or hypoxia due to accidental or nonaccidental injury. Death due to nondrowning asphyxia can occur with strangulation, suffocation, and mechanical asphyxia, each of which is categorized based on the mechanism of injury. Individuals dying due to various types of asphyxia may or may not have lesions, and even those lesions that are present may be due to other causes. The interpretation or opinion that death was due to asphyxia requires definitive and compelling evidence from the postmortem examination, death scene, and/or history. Beyond the postmortem examination, pathologists may be faced with questions of forensic importance that revolve around the behavioral and physiological responses in animals subjected to strangulation, suffocation, or mechanical asphyxia to determine if the animal suffered. While there is no prescriptive answer to these questions, it is apparent that, because of physiological and anatomical differences between humans and animals, for some mechanisms of asphyxia, consciousness is maintained for longer periods and the onset of death is later in animals than that described for people. Veterinary pathologists must be cognizant that direct extrapolation from the medical forensic literature to animals may be incorrect. This article reviews the terminology, classification, mechanisms, and lesions associated with asphyxial deaths in companion animals and highlights significant comparative differences of the response to various types of asphyxia in animals and people.
TL;DR: This research sought to investigate how brain injury and severity, and neurological subtype of cerebral palsy differed in term‐born children with CP after neonatal encephalopathy, between those with suspected birth asphyxia and those without.
Abstract: Aim
We sought to investigate how brain injury and severity, and neurological subtype of cerebral palsy (CP) differed in term-born children with CP after neonatal encephalopathy, between those with suspected birth asphyxia and those without.
Method
Using the Canadian CP Registry, which included 1001 children, those with CP born at ≥36wks after moderate or severe neonatal encephalopathy, were dichotomized according to the presence or absence of suspected birth asphyxia. Gross Motor Function Classification System (GMFCS) scores, neurological subtypes, comorbidities, and magnetic resonance imaging findings were compared.
Results
Of the 147 term-born children with CP (82 males, 65 females; median age 37 months, interquartile range [IQR] 26–52.5) who after moderate or severe neonatal encephalopathy had the required outcome data, 61 (41%) met criteria for suspected birth asphyxia. They had a higher frequency of non-ambulatory GMFCS status (odds ratio [OR] 3.4, 95% confidence interval [CI] 1.72–6.8), spastic quadriplegia (OR 2.8, 95% CI 1.4–5.6), non-verbal communication skills impairment (OR 4.2, 95% CI 2.0–8.6), isolated deep grey matter injury (OR 4.1, 95% CI 1.8–9.5), a lower frequency of spastic hemiplegia (OR 0.17, 95% CI 0.07–0.42), focal injury (OR 0.20; 95% CI 0.04–0.93), and more comorbidities (p=0.017) than those who did not meet criteria.
Interpretation
Term-born children who develop CP after neonatal encephalopathy with suspected birth asphyxia have a greater burden of disability than those without suspected birth asphyxia.
TL;DR: Maternal antenatal creatine supplementation protects the brain, kidney, and diaphragm against the effects of birth asphyxia in the spiny mouse and demonstrates that creatine loading before birth protects the muscle from asphyxiating damage at birth.
Abstract: Maternal creatine supplementation during pregnancy prevents acute and long-term deficits in skeletal muscle after birth asphyxia: a study of structure and function of hind limb muscle in the spiny mouse
TL;DR: In this cohort of neonates with seizures asphyxia requiring neonatal resuscitation was the primary risk factor for death.
Abstract: OBJECTIVE The aim of this study was to analyze prognostic indicators for mortality in neonates with seizures in a level III Neonatal Intensive Care Unit (NICU). PATIENTS AND METHODS A cohort of 100 neonates with clinically manifested seizures hospitalized in the NICU during 4 years period was prospectively monitored for the first year of life. The cohort consisted of 33 preterm and 67 full-term babies with 60 male and 40 female infants. RESULTS The mortality rate in the first year of life of infants with seizures in the neonatal period was 23%. The most common cause of seizures was birth asphyxia for full-term infants and intra-periventricular hemorrhage for preterm infants. Death was more common in pre-term than term infants (p <0,005). Simple regression demonstrated statistically significant associations between death in the first year of life and a cluster of highly associated variables: resuscitation (p<0, 01), mechanical ventilation (p<0,01) and asphyxia (p<0,05). This cluster of variables significantly correlates with: gestational age (p<0, 05), birth weight (p<0, 05) and intracranial hemorrhage (p<0, 05). CONCLUSION In this cohort of neonates with seizures asphyxia requiring neonatal resuscitation was the primary risk factor for death.
TL;DR: A beneficial effect of RIPostC therapy in the preclinical piglet model of neonatal asphyxia is demonstrated, which appears to be mediated by modulation of nitrosative stress, despite glial activation.
Abstract: Remote ischemic postconditioning (RIPostC) is a promising therapeutic intervention that could be administered as an alternative to cooling in cases of perinatal hypoxia-ischemia (HI). In the current study we hypothesized that RIPostC in the piglet model of birth asphyxia confers protection by reducing nitrosative stress and subsequent nitrotyrosine formation, as well as having an effect on glial immunoreactivity. Postnatal day 1 (P1) piglets underwent HI brain injury and were randomised to HI (control) or HI + RIPostC. Immunohistochemistry assessment 48 hours after HI revealed a significant decrease in brain nitrotyrosine deposits in the RIPostC-treated group (p = 0.02). This was accompanied by a significant increase in eNOS expression (p < 0.0001) and decrease in iNOS (p = 0.010), with no alteration in nNOS activity. Interestingly, RIPostC treatment was associated with a significant increase in GFAP (p = 0.002) and IBA1 (p = 0.006), markers of astroglial and microglial activity, respectively. The current study demonstrates a beneficial effect of RIPostC therapy in the preclinical piglet model of neonatal asphyxia, which appears to be mediated by modulation of nitrosative stress, despite glial activation.
TL;DR: AKI is not uncommon in preterm infants and the early recognition and aggressive management of episodes of shock which often precede AKI could be life-saving.
Abstract: OBJECTIVES This study was carried out to determine the incidence, clinical features, etiology and outcome of functional and intrinsic acute kidney injury (AKI) in preterm neonates. METHODS This is a prospective observational study on premature infants admitted to the neonatal intensive care unit (NICU) over an eight month period. All biochemical parameters of renal function tests were monitored and statically analyzed. RESULTS The study included 450 infants; of them 300 were inborn and 150 infants were outborn and transported to the NICU. Mean gestational age, weight, and age at the time of AKI diagnosis were 32.3 weeks, 1.66 kg and 3.23 days respectively. The male: female ratio was 1.84:1. Incidence of AKI was higher in low birth weight babies. Sluggishness and refusal for feed were most common symptoms. Birth asphyxia and septicemia were the most common early and late cause of AKI. Hyponatremia was the most common electrolyte disturbance. The incidences of AKI, functional renal failure, and intrinsic renal failure were 12%, 48.14%, and 51.85% respectively. CONCLUSIONS AKI is not uncommon in preterm infants. The early recognition and aggressive management of episodes of shock which often precede AKI could be life-saving.
TL;DR: This new PA piglet model is able to induce moderate/severe HIE, and the efficacy of hydrogen post-treatment to preserve neuronal activity/function in this PA/HIE model suggests the feasibility of this safe and inexpensive approach in the treatment of asphyxiated babies.
Abstract: Hypoxic-ischemic encephalopathy (HIE) is the major consequence of perinatal asphyxia (PA) in term neonates. Although the newborn piglet is an accepted large animal PA/HIE model, there is no consensus on PA-induction methodology to produce clinically relevant HIE. We aimed to create and to characterize a novel PA model faithfully reproducing all features of asphyxiation including severe hypercapnia resulting in HIE, and to test whether H2 is neuroprotective in this model. Piglets were anaesthetised, artificially ventilated, and intensively monitored (electroencephalography, core temperature, O2 saturation, arterial blood pressure and blood gases). Asphyxia (20 min) was induced by ventilation with a hypoxic-hypercapnic (6%O2 - 20%CO2) gas mixture. Asphyxia-induced changes in the cortical microcirculation were assessed with laser-speckle contrast imaging and analysis. Asphyxia was followed by reventilation with air or air containing hydrogen (2.1%H2, 4 hours). After 24 hours survival, the brains were harvested for neuropathology. Our PA model was characterized by the development of severe hypoxia (pO2 = 27 ± 4 mmHg), and combined acidosis (pH = 6.76 ± 0.04; pCO2 = 114 ± 11 mmHg; lactate = 12.12 ± 0.83 mmol/L), however, cortical ischemia did not develop during the stress. Severely depressed electroencephalography (EEG), and marked neuronal injury indicated the development of HIE. H2 was neuroprotective shown both by the enhanced recovery of EEG and by the significant preservation of neurons in the cerebral cortex, hippocampus, basal ganglia, and the thalamus. H2 appeared to reduce oxidative stress shown by attenuation of 8-hydroxy-2'-deoxyguanosine immunostaining. In summary, this new PA piglet model is able to induce moderate/severe HIE, and the efficacy of hydrogen post-treatment to preserve neuronal activity/function in this PA/HIE model suggests the feasibility of this safe and inexpensive approach in the treatment of asphyxiated babies.
TL;DR: Investigation of whether HRV features differ during contraction and rest periods, and whether these differences can improve the detection of asphyxia found no significant differences, but the ratio betweenHRV features calculated during and outside contractions can improve discrimination between fetuses with and withoutAsphyxia.
Abstract: During labor, uterine contractions can cause temporary oxygen deficiency for the fetus. In case of severe and prolonged oxygen deficiency this can lead to asphyxia. The currently used technique for detection of asphyxia, cardiotocography (CTG), suffers from a low specificity. Recent studies suggest that analysis of fetal heart rate variability (HRV) in addition to CTG can provide information on fetal distress. However, interpretation of fetal HRV during labor is difficult due to the influence of uterine contractions on fetal HRV. The aim of this study is therefore to investigate whether HRV features differ during contraction and rest periods, and whether these differences can improve the detection of asphyxia. To this end, a case-control study was performed, using 14 cases with asphyxia that were matched with 14 healthy fetuses. We did not find significant differences for individual HRV features when calculated over the fetal heart rate without separating contractions and rest periods (p > 0.30 for all HRV features). Separating contractions from rest periods did result in a significant difference. In particular the ratio between HRV features calculated during and outside contractions can improve discrimination between fetuses with and without asphyxia (p < 0.04 for three out of four ratio HRV features that were studied in this paper).
TL;DR: Data is presented suggesting that dietary creatine supplementation during pregnancy may be an effective prophylaxis that can protect the fetus from the multi-organ consequences of severe hypoxia at birth.
TL;DR: Inflammatory serum biomarkers in the setting of birth asphyxia that can help assess the degree or severity of encephalopathy at birth and neurodevelopmental outcomes are reviewed.
TL;DR: Hyaline membrane Disease was the commonest cause of respiratory distress followed by Birth asphyxia, Pneumonia, Meconium aspiration syndrome, Tracheo-oesophageal fistula, Transient tachypnea of new-born, congenital heart disease and others.
Abstract: Background: Respiratory distress is defined as tachypnea (respiratory rate>60/min), inter-costal/subcostal retractions/nasal flaring and grunting. Methods: The study was conducted on 1030 neonates with clinical diagnosis of Respiratory distress. Clinical and the demographic information were recorded; gestational age was calculated by LMP/New Bellard method. Severity of distress were assessed by using Silverman and Anderson score Results: The common causes of Respiratory distress observed in the study were Hyaline membrane disease 262 (25.44%), followed by birth asphyxia 254 (24.66%), Septicemia/Pneumonia242 (23.50%), meconium aspiration syndrome 73 (7.09%). Others cause of distress were Tracheoesophageal fistula 54 (5.24%), Congenital heart Disease 44 (4.27%), Transient tachypnoea of newborn 43 (4.17%) and others 58 (5.63%). Mortality was 230 (22.33%), mortality rate was directly related to Anderson Silverman score Conclusions: Hyaline membrane Disease was the commonest cause of respiratory distress followed by Birth asphyxia, Pneumonia, Meconium aspiration syndrome, Tracheo-oesophageal fistula, Transient tachypnea of new-born, congenital heart disease and others. Mortality was highest in Hyaline membrane disease 93 (35.49%) f/d by Birth asphyxia 54 (22.44%), Pneumonia 44 (18.03%), Congenital heart disease 7 (15.90%), Meconium aspiration syndrome 10 (13.69%), Tracheo-oesophageal fistula 10 (18.50).
TL;DR: Low vitamin D levels in early pregnancy may be associated with emergency caesarean section due to suspected fetal distress and birth asphyxia, and vitamin D supplementation/sun exposure in pregnancy may lower the risk of subsequent birthAsphyxia.
Abstract: Objective Vitamin D deficiency causes not only skeletal problems but also muscle weakness, including heart muscle. If the fetal heart is also affected, it might be more susceptible to fetal distress and birth asphyxia. In this pilot study, we hypothesised that low maternal vitamin D levels are over-represented in pregnancies with fetal distress/birth asphyxia.
Design and setting A population-based nested case–control study.
Patients Banked sera of 2496 women from the 12th week of pregnancy.
Outcome measures Vitamin D levels were analysed using a direct competitive chemiluminescence immunoassay. Vitamin D levels in early gestation in women delivered by emergency caesarean section due to suspected fetal distress were compared to those in controls. Birth asphyxia was defined as Apgar <7 at 5 min and/or umbilical cord pH≤7.15.
Results Vitamin D levels were significantly lower in mothers delivered by emergency caesarean section due to suspected fetal distress (n=53, 43.6±18 nmol/L) compared to controls (n=120, 48.6±19 nmol/L, p=0.04). Birth asphyxia was more common in women with vitamin D deficiency (n=95) in early pregnancy (OR 2.4, 95% CI 1.1 to 5.7).
Conclusions Low vitamin D levels in early pregnancy may be associated with emergency caesarean section due to suspected fetal distress and birth asphyxia. If our findings are supported by further studies, preferably on severe birth asphyxia, vitamin D supplementation/sun exposure in pregnancy may lower the risk of subsequent birth asphyxia.
TL;DR: Dexmedetomidine preconditioning protected against cerebral ischemic injury and was associated with upregulation of HIF-1α and VEGF expression after global cerebral ischemia following asphyxial CA.
Abstract: Background/Aims: To investigate the protection effect of dexmedetomidine preconditioning on global cerebral ischemic injury following asphyxial cardiac arrest (CA) in rats. Methods: Seventy-two rats were randomly assigned into three groups, sham group (no asphyxia), control group (asphyxia only), and dexmedetomidine preconditioned group (asphyxia + dexmedetomidine). Dexmedetomidine was administered 5 minutes before an 8 min of asphyxia. Rats were resuscitated by a standardized method. Blood O2 and CO2 partial pressures were, pH, base excess (BE), and blood glucose concentration measured before asphyxial CA and 1 h after resuscitation. Neurological deficit score (NDS) was measured at 12, 24, 48, and 72 h after CA. Histopathologic changes in the hippocampal region were observed by H&E staining and histopathologic damage score. Ultrastructural morphology was observed by transmission electron microscopy. HIF-1 and VEGF expression were measured by immunostaining of serial sections obtained from brain tissue. R...
TL;DR: This study points to the potential role ofMC in hypoxia and suggests that an evaluation of MC in the lungs may be a useful parameter when forensic pathologists are required to make a differential diagnosis between acute asphyxia deaths and other kinds of death.
Abstract: In a previous immunohistochemical (IHC) study, we documented the reaction of lung tissue vessels to hypoxia through the immunodetection of HIF1-α protein, a key regulator of cellular response to hypoxic conditions. Findings showing that asphyxia deaths are associated with an increase in the number of mast cell (MC)-derived tryptase enzymes in the blood suggests that HIF1-α production may be correlated with MC activation in hypoxic conditions. This hypothesis prompted us to investigate the possible role of pulmonary MC in acute asphyxia deaths. Lung of 47 medico-legal autopsy cases (35 asphyxia/hypoxia deaths, 11 controls, and 1 anaphylactic death) were processed by IHC analysis using anti-CD117 (c-Kit) antibody to investigate peri-airway and peri-vascular MC together with their counts and features. Results showed a significant increase in peri-vascular c-kit(+) MC in some asphyxia deaths, such as hanging, strangulation, and aspiration deaths. A strong activation of MC in peri-airway and peri-vascular areas was also observed in lung samples from the anaphylaxis case, which was used as a positive control. Our study points to the potential role of MC in hypoxia and suggests that an evaluation of MC in the lungs may be a useful parameter when forensic pathologists are required to make a differential diagnosis between acute asphyxia deaths and other kinds of death.
TL;DR: Data demonstrate that the FHR overshoot pattern after asphyxia is mediated by a combination of attenuated parasympathetic activity and increased β-adrenergic stimulation of the fetal heart.
Abstract: The role of cholinergic and β-adrenergic activity in mediating fetal cardiovascular recovery from brief repeated episodes of asphyxia consistent with established labor, remains unclear. In this study, we tested the effect of cholinergic and β-adrenergic blockade on the fetal chemoreflex and fetal heart rate (FHR) overshoot responses during brief repeated asphyxia at rates consistent with early or active labor. Chronically instrumented fetal sheep at 0.85 of gestation received either i.v. atropine sulfate (cholinergic blockade, n=8) or vehicle (n=7) followed by 3 x 1-minute umbilical cord occlusions repeated every 5 minutes (1:5; consistent with early labor), or i.v. propranolol hydrochloride (β-adrenergic blockade, n=6) or vehicle (n=6) followed by 3 x 2-minute occlusions repeated every 5 minutes (2:5; consistent with active labor). In vehicle-controls, 1:5 occlusions were associated with rapid and sustained FHR decelerations followed by rapid return of FHR to baseline values after release of the occlusion. Cholinergic blockade abolished FHR decelerations during occlusions and caused FHR overshoot after release of the occlusion (P<0.05 vs. control 1:5). In vehicle-controls, 2:5 occlusions caused rapid and sustained FHR decelerations followed by FHR overshoot after release of the occlusion. β-adrenergic blockade was associated with greater reduction in FHR during occlusions and attenuated FHR overshoot (P<0.05 vs. control 2:5). These data demonstrate that the FHR overshoot pattern after asphyxia is mediated by a combination of attenuated parasympathetic activity and increased β-adrenergic stimulation of the fetal heart.
TL;DR: The relatively high number of neonatal cases coupled with the mortality rate observed requires a holistic approach to pregnancy care from conception to delivery, aimed at reducing neonatal morbidity and mortality.
Abstract: Background: The burden of neonatal morbidity and mortality remains a major health challenge, and contributes
hugely to deaths among children under five years old, especially in developing countries.
Objective: This study established the pattern, causes and treatment outcomes of admitted babies at the neonatal
intensive care unit of the Tamale Teaching Hospital.
Method: A retrospective health facility based study was conducted by reviewing available data covering the
period January 2013 to December 2015.
Results: A total of 4409 cases were reviewed out of which demographic data were complete for 3973 cases.
Males were dominant 54.0% (2146) compared to females 46.0% (1827). Admissions were significantly common
(χ2=457.3, P<0.001) among neonates ≤ 2 days old 62.0% (2947). The commonest cause of neonatal admission was
sepsis (29.2%), followed by prematurity/low birth weight (26.9%), birth asphyxia (16.2%) and congenital anomalies
(7.1%). Majority 82.7% (3220) of the neonates were successfully treated and discharged. However, 16.0% (621) of
the neonates expired before or during treatment, while 1.1% (42) were transferred and 0.3% (10) absconded.
Neonatal deaths were commonly associated with prematurity/low birth weight (44.8%), birth asphyxia (24.6%),
neonatal sepsis (13.5%), and congenital anomalies (6.8%).
Conclusion: The relatively high number of neonatal cases coupled with the mortality rate observed requires a
holistic approach to pregnancy care from conception to delivery, aimed at reducing neonatal morbidity and mortality.