Some like it cool: hypothermia for newborn infants with hypoxic ischemic encephalopathy.
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Electroencephalography↗
Biomedical subjects
O D Saugstad
Publications and source records attributed to O D Saugstad.
Oxygen and retinopathy of prematurity.
Retinopathy of prematurity is on the rise and a third epidemic has been identified. In spite of extensive research and progress in the understanding of this disease in recent years, 50 000 children worldwide are blinded by this condition each year. The relation between hyperoxia, low-gestational age, growth retardation, oxygen dependent growth factors, and oxidative stress are now being understood more clearly. We know that in the first phase of retinopathy of prematurity, hyperoxia inhibits vascular endothelial growth factor. In the second phase, vascular endothelial growth factor rises, and when insulin-like growth factor-1 reaches a threshold around 32 to 34 weeks postconceptional age, uncontrolled neovascularization may occur. It is not known whether this new knowledge will have implications for future therapy. However, by strictly avoiding hyperoxia, that is, SaO2>92-93% and avoiding fluctuations in SaO2, it is possible to control and prevent severe retinopathy of prematurity in most cases.
Angiogenesis Inducing Agents↗
[Normoxemic resuscitation in the delivery room].
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Air↗
Meconium aspiration syndrome induces complement-associated systemic inflammatory response in newborn piglets.
The pathophysiology of meconium aspiration syndrome (MAS) is complex. We recently showed that meconium is a potent activator of complement. In the present study, we investigated whether the complement activation occurring in experimental MAS is associated with a systemic inflammatory response as judged by granulocyte activation and cytokine and chemokine release. MAS was induced by the instillation of meconium into the lungs of newborn piglets (n = 8). Control animals (n = 5) received saline under otherwise identical conditions. Haemodynamic and lung dynamic data were recorded. Complement activation, revealed by the terminal sC5b-9 complex (TCC), and cytokines [interleukin (IL)-6 and IL-8] were measured in plasma samples by enzyme immunoassays. The expression of CD18, CD11b and oxidative burst in granulocytes was measured in whole blood by flow cytometry. Plasma TCC increased rapidly in the MAS animals in contrast with controls (P < 0.0005). The TCC concentration correlated closely with oxygenation index (r = 0.48, P < 0.0005) and ventilation index (r = 0.57, P < 0.0005) and inversely with lung compliance (r = -0.63, P < 0.0005). IL-6 and IL-8 increased in MAS animals compared with the controls (P = 0.002 and P < 0.001, respectively). Granulocyte oxidative burst declined significantly in the MAS animals compared with the controls (P < 0.02). TCC correlated significantly with IL-6 (r = 0.64, P < 0.0005) and IL-8 (r = 0.32; P = 0.03) and inversely with oxidative burst (r = -0.37; P = 0.02). A systemic inflammatory response associated with complement activation is seen in experimental MAS. This reaction may contribute to the pathogenesis of MAS.
Animals↗
Restoration of cardiopulmonary function with 21% versus 100% oxygen after hypoxaemia in newborn pigs.
OBJECTIVE: To assess the consequences of hypoxaemia and resuscitation with room air versus 100% O(2) on cardiac troponin I (cTnI), cardiac output (CO), and pulmonary artery pressure (PAP) in newborn pigs. DESIGN: Twenty anaesthetised pigs (12-36 hours; 1.7-2.7 kg) were subjected to hypoxaemia by ventilation with 8% O(2). When mean arterial blood pressure fell to 15 mm Hg, or arterial base excess was < or = -20 mmol/l, resuscitation was performed with 21% (n = 10) or 100% (n = 10) O(2) for 30 minutes, then ventilation with 21% O(2) for 120 minutes. Blood was analysed for cTnI. Ultrasound examinations of CO and PAP (estimated from tricuspid regurgitation velocity (TR-Vmax)) were performed at baseline, during hypoxia, and at the start of and during reoxygenation. RESULTS: cTnI increased from baseline to the end point (p<0.001), confirming a serious myocardial injury, with no differences between the 21% and 100% O(2) group (p = 0.12). TR-Vmax increased during the insult and returned towards baseline values during reoxygenation, with no differences between the groups (p = 0.11) or between cTnI concentrations (p = 0.31). An inverse relation was found between increasing age and TR-Vmax during hypoxaemia (p = 0.034). CO per kg body weight increased during the early phase of hypoxaemia (p<0.001), then decreased. Changes in CO per kg were mainly due to changes in heart rate, with no differences between the groups during reoxygenation (p = 0.298). CONCLUSION: Hypoxaemia affects the myocardium and PAP. During this limited period of observation, reoxygenation with 100% O(2) showed no benefits compared with 21% O(2) in normalising myocardial function and PAP. The important issue may be resuscitation and reoxygenation without hyperoxygenation.
Animals↗
Increased myocardial matrix metalloproteinases in hypoxic newborn pigs during resuscitation: effects of oxygen and carbon dioxide.
BACKGROUND: Perinatal asphyxia is associated with cardiac dysfunction, and it is important to prevent further tissue injury during resuscitation. There is increasing evidence that myocardial matrix metalloproteinases (MMPs) are involved in myocardial hypoxaemia-reoxygenation injury. OBJECTIVE: To assess MMPs and antioxidant capacity in newborn pigs after global ischaemia and subsequent resuscitation with ambient air or 100% O(2) at different PaCO(2)-levels. METHODS: Newborn pigs (12-36 h of age) were resuscitated for 30 min by ventilation with 21% or 100% O(2) at different PaCO(2) levels after a hypoxic insult, and thereafter observed for 150 min. In myocardial tissue extracts, MMPs were analyzed by gelatin zymography and broad matrix-degrading capacity (total MMP). Total endogenous antioxidant capacity in myocardial tissue extracts was measured by the oxygen radical absorbance capacity (ORAC) assay. RESULTS: Matrix metalloproteinase-2 more than doubled from baseline values (P < 0.001), and was higher in piglets resuscitated with 100% O(2) than with ambient air (P = 0.012). The ORAC value was considerably decreased (P < 0.001). In piglets with elevated PaCO(2), total MMP-activity in the right ventricle was more increased than in the left ventricle (P = 0.008). In the left ventricle, total MMPactivity was higher in the piglets with low PaCO(2) than in the piglets with elevated PaCO(2) (P = 0.013). CONCLUSION: In hypoxaemia-reoxygenation injury the MMP-2 level was highly increased and was most elevated in the piglets resuscitated with 100% O(2). Antioxidant capacity was considerably decreased. Assessed by total MMP-activity, elevated PaCO(2) during resuscitation might protect the left ventricle, and probably increase right ventricle injury of the myocardium.
Animals↗
Resuscitation with 100% O(2) does not protect the myocardium in hypoxic newborn piglets.
BACKGROUND: Perinatal asphyxia is associated with cardiac dysfunction secondary to myocardial ischaemia. Cardiac troponin I (cTnI) is a marker of myocardial necrosis. Raised concentrations in the blood are related to perinatal asphyxia and increased morbidity. OBJECTIVE: To assess porcine myocardial damage from enzyme release during hypoxaemia induced global ischaemia, and subsequent resuscitation with ambient air or 100% O(2). To investigate whether CO(2) level during resuscitation influences myocardial damage. DESIGN: Newborn piglets (12-36 hours) were exposed to hypoxaemia by ventilation with 8% O(2) in nitrogen. When mean arterial blood pressure had fallen to 15 mm Hg, or base excess to < -20 mmol/l, the animals were randomly resuscitated by ventilation with either 21% O(2) (group A, n = 29) or 100% O(2) (group B, n = 29) for 30 minutes. Afterwards they were observed in ambient air for another 150 minutes. During resuscitation, the two groups were further divided into three subgroups with different CO(2) levels. ANALYSIS: Blood samples were analysed for cTnI, myoglobin, and creatine kinase-myocardial band (CK-MB) at baseline and at the end of the study. RESULTS: cTnI increased more than 10-fold (p < 0.001) in all the groups. Myoglobin and CK-MB doubled in concentration. CONCLUSION: The considerable increase in cTnI indicates seriously affected myocardium. Reoxygenation with 100% oxygen offered no biochemical benefit over ambient air. CK-MB and myoglobin were not reliable markers of myocardial damage. Normoventilation tended to produce better myocardial outcome than hyperventilation or hypoventilation.
Animals↗
Illness and exposure to negative life experiences in adolescence: two sides of the same coin? A study of 15-year-olds in Oslo, Norway.
AIM: To investigate associations between negative life experiences and common illnesses among adolescents. METHODS: Cross-sectional questionnaire study carried out at all lower secondary schools (10 grade) in Oslo. Norway, during 2000 and 2001 (n = 8316 pupils). Different negative life experiences and illnesses were addressed. RESULTS: The participation rate was 88%. Among reported negative life experiences last year were a pressure felt to succeed (62%), death of a close person (26%), exposure to physical violence (22%), bullying at school (15%) and sexual violation (4%). A large number of the pupils had some chronic illness: hay fever (38%), eczema (29%) and asthma (13%). Reported illnesses the previous 12 month were: headache (56%), painful neck or shoulders (35%), sore throat at least three times (15%), lower respiratory tract infection (9%) and mental problems for which help was sought (7%). During the week prior to the survey, 26% of all girls had symptoms of a depressive disorder, while this applied to 10% of all boys. Fifty-three percent of the boys (29% of the girls) who had depressive symptoms had been exposed to physical violence. Sexually violated boys had a high probability for seeking help for mental problems (OR = 4.9) and for frequent episodes of sore throat (OR = 2.5). Corresponding odds ratios for girls were 1.7 and 2.5, respectively. CONCLUSION: Common illnesses in adolescence are significantly associated with negative life experiences. In clinical encounters with adolescents not only should the presenting complaints be addressed, but also other common illnesses and relevant background factors such as negative life events.
Adolescent↗
Effects of recombinant human superoxide dismutase during reoxygenation with 21% or 100% oxygen after cerebral asphyxia in newborn piglets.
OBJECTIVE: Superoxide radicals (O2-) are generated during reoxygenation following asphyxia, possibly more when higher concentrations of O2 are used during resuscitation. Superoxide dismutase (SOD) is an antioxidant enzyme, which scavenges O2-. We tested the hypothesis that a single intravenous dose of recombinant human Cu,Zn SOD (rhSOD) could influence microcirculation and biochemical markers of asphyxia in piglets reoxygenated with 21% or 100% O2 after combined cerebral hypoxemia-ischemia-hypercapnia. METHODS: Anesthetized newborn piglets were randomized to asphyxia (n = 40) or control (n = 3). Asphyxia was induced by ventilation with 8% O2, adding CO2, and temporary occlusion of both common carotid arteries. After 20 min, 16 piglets received rhSOD 5 mg/kg intravenously and reoxygenation with 21% O2 (rhSOD, 21%; n = 8) or 100% O2 (rhSOD, 100%; n = 8), and 24 piglets received saline and reoxygenation with 21% O2 (21%, n = 13) or 100% O2 (100%, n = 11). The cortical microcirculation was assessed by laser Doppler flowmetry, and glutamate in the striatum and hypoxanthine in the cortex were measured by in vivo microdialysis. RESULTS AND CONCLUSION: rhSOD peaked in plasma after 5 min. No rhSOD was detected in brain tissue. There were no significant differences between rhSOD and non-rhSOD groups in any measured variable.
Animals↗
Treatment strategies for bronchopulmonary dysplasia with postnatal corticosteroids in Europe: the EURAIL survey.
AIM: To survey practices in 14 European countries and describe strategies for the prevention and treatment of bronchopulmonary dysplasia with postnatal steroids (PNS). METHODS: In 1999-2000 questionnaires covering the use of PNS were sent to every neonatal unit taking very preterm newborns in charge, in population-based areas covering at least 20000 births annually. One questionnaire was sent to surveyed unit. The participating areas were chosen by an expert from each country participating in the Europe Against Immature Lung (EURAIL) study group. RESULTS: Responses to 331 questionnaires were received; the mean response rate by countries was 84% (range 64-100%). Teaching hospitals accounted for 19% of the responding units. The number of extremely premature newborns (less than 28 wk of gestation) admitted yearly to these units was 0 in 16%, < 20 in 62%, 20-39 in 11% and > 39 in 11%. Overall, 67% of the centres used PNS: 48% initiated treatment in non-intubated infants and 53% at 7-14 d. Treatment duration was 4-15 d in 62% and > 15 d in 21%. PNS administration was limited to intubated infants less often in smaller units [odds ratio (OR) 0.2, 95% confidence interval (95% CI) 0.1-0.6] and more often in non-teaching hospitals (OR 2.5, 95% CI 2.5-5.0). CONCLUSIONS: Although PNS have important side effects, they were still widely used in 1999 to treat or prevent chronic lung disease. Surprisingly, steroids are still prescribed in non-ventilated infants. PNS use should be based on guidelines derived from the evidence from randomized controlled trials. This evidence should be regularly updated and disseminated.
Adrenal Cortex Hormones↗
Is lactate a reliable indicator of tissue hypoxia in the neonatal period?
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Biomarkers↗
New guidelines for resuscitation of the newly born infant.
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Cardiopulmonary Resuscitation↗
Comparative epidemiology of sudden infant death syndrome and sudden intrauterine unexplained death.
BACKGROUND: Unexplained antepartum stillbirth and sudden infant death syndrome (SIDS) are major contributors to perinatal and infant mortality in the western world. A relation between them has been suggested. As an equivalent of SIDS, only cases validated by post mortem examination are diagnosed as sudden intrauterine unexplained death (SIUD). OBJECTIVE: To test the hypothesis that SIDS and SIUD have common risk factors. METHODS: Registration comprised all stillbirths in Oslo and all infant deaths in Oslo and the neighbouring county, Akershus, Norway during 1986-1995. Seventy six cases of SIUD and 78 of SIDS were found, along with 582 random controls surviving infancy, all singletons. Odds ratios were obtained by multiple logistic regression analysis. RESULTS: Whereas SIUD was associated with high maternal age, overweight/obesity, smoking, and low education, SIDS was associated with low maternal age, smoking, male sex, multiparity, proteinuria during pregnancy, and fundal height exceeding +2 SD. Thus the effects of maternal age were opposite in SIUD and SIDS (adjusted odds ratio 1.39 (95% confidence interval 1.17 to 1.66) per year, p < 0.0005). Heavy smoking, male sex, and a multiparous mother was less likely in SIUD than in SIDS (0.22 (0.06 to 0.83), 0.22 (0.07 to 0.78), and 0.03 (<0.01 to 0.17) respectively). Overweight/obesity and low fundal height were more common in SIUD than in SIDS (7.45 (1.49 to 37.3) and 13.8 (1.56 to 122) respectively). CONCLUSIONS: The differences in risk factors do not support the hypothesis that SIDS and SIUD have similar determinants in maternal or fetal characteristics detectable by basic antenatal care.
Adult↗
Resuscitation of newborn infants with room air or oxygen.
Oxygen is a toxic agent and a critical approach regarding its use during resuscitation at birth is developing. Animal data indicate that room air is efficient for newborn resuscitation. Three clinical studies have established that normal ventilation is delayed after oxygen resuscitation. Oxidative stress is augmented for several weeks in infants exposed to oxygen at birth -- the long-term implications of these observations remain unclear. There are limited data regarding the use of room air during complicated resuscitations, i.e. in meconium aspiration, the severely asphyxiated infant and in the preterm infant. Thus, it is necessary to continue ongoing rigorous examination of the long-accepted practice of oxygen administration during neonatal resuscitation.
Air↗
Resuscitation of newborns.
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Asphyxia Neonatorum↗
Risk factors for sudden intrauterine unexplained death: epidemiologic characteristics of singleton cases in Oslo, Norway, 1986-1995.
OBJECTIVE: The epidemiologic characteristics of unexplained stillbirths are largely unknown or unreliable. We define sudden intrauterine unexplained death as a death that occurs antepartum and results in a stillbirth for which there is no explanation despite postmortem examinations, and we present risk factors for this type of stillbirth in singleton gestations. STUDY DESIGN: Singleton antepartum stillbirths (n = 291) and live births (n = 582) in Oslo were included and compared with national data (n = 2025 and n = 575,572, respectively). Explained stillbirths (n = 165) and live births in Oslo served as controls for the cases of sudden intrauterine unexplained death (n = 76) in multiple logistic regression analyses. RESULTS: One fourth of stillbirths remain unexplained. The risk of sudden intrauterine unexplained death (1/1000) increased with gestational age, high maternal age, high cigarette use, low education, and overweight or obesity. Primiparity and previous stillbirths or spontaneous abortions were not associated with sudden intrauterine unexplained death. CONCLUSIONS: Risk factors for sudden intrauterine unexplained death are identifiable by basic antenatal care. Adding unexplored stillbirths to the unexplained ones conceals several risk factors and underlines the necessity of a definition that includes thorough postmortem examinations.
Abortion, Spontaneous↗
Presence of ochratoxin A in human milk in relation to dietary intake.
Individual and geographical variations in ochratoxin A (OA) levels in human blood and milk samples may be due to differences in dietary habits. The purpose of this study was to examine the relationship between OA contamination of human milk and dietary intake. Human milk samples were collected from 80 Norwegian women. The usual food intake during the last year was recorded using a quantitative food frequency questionnaire. The concentration of OA in the human milk was determined by HPLC (detection limit 10 ng/l). Seventeen (21%) out of 80 human milk samples contained OA in the range 10-182 ng/l. The women with a high dietary intake of liver paste (liverwurst, liver pâté) and cakes (cookies, fruitcakes, chocolate cakes, etc.) were more likely to have OA-contaminated milk. The risk of OA contamination was also increased by the intake of juice (all kinds). In addition, the results indicate that breakfast cereals, processed meat products, and cheese could be important contributors to dietary OA intake. OA contamination of the milk was unrelated to smoking, age, parity, and anthropometric data other than body weight.
Adult↗
Chronic lung disease: oxygen dogma revisited.
Since the discovery of retrolental fibroplasia, and the role of oxygen in its development, oxygen has been considered a double-edged sword in neonatal medicine, the utmost care being exercised in order not to give too much oxygen (1). However, the important observation that hypoxaemia might induce pulmonary vasoconstriction (2) and airway constriction (3) in infants at risk for bronchopulmonary dysplasia has resulted in only a minor upward adjustment of oxygen supplementation in many neonatal units. Since oxygen toxicity has long been linked not only to retinopathy of prematurity but also to bronchopulmonary dysplasia (4), it is relevant to ask whether an increased FiO2 might have any detrimental effects on babies.
Bronchopulmonary Dysplasia↗