Oxygen saturations immediately after birth.
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Humans↗
Biomedical subjects
Ola Didrik Saugstad
Publications and source records attributed to Ola Didrik Saugstad.
Fetal brain injury in experimental intrauterine asphyxia and inflammation in Göttingen minipigs.
OBJECTIVE: To examine fetal brain injury in the Göttingen minipig following intrauterine asphyxia and infection/inflammation induced at 3/4 of gestational length. METHODS: We performed laparotomy after anesthesia in six pregnant sows. We randomized 29 fetuses to one of four groups: pretreatment with saline or endotoxin followed by 30 min of umbilical cord occlusion or no occlusion. After 48 h we performed a re-laparotomy and examined the fetal brains. RESULTS: After total asphyxia, brain stem injury was present in the group pretreated with saline (P < 0.01 vs. controls) and with endotoxin (P < 0.005 vs. controls). Microglia activation was more marked in the brain stem (P < 0.05) and posterior white matter (P < 0.05) in the asphyxia group than in controls. Two of five fetuses in the asphyxia group had white matter injury, while no white matter lesions were found in the asphyxia/inflammation or endotoxin only groups. CONCLUSIONS: In this Göttingen minipig model, a species closer to humans than animals commonly used in experimental studies of perinatal brain injuries, intrauterine asphyxia following pretreatment with saline caused brain stem and white matter injury. This model can be further developed to study the impact of other intrauterine exposures on brain injury.
Animals↗
Non-selective fetal reduction is malpractice.
Non-selective multifetal pregnancy reduction is carried out to reduce healthy higher order multiple fetuses to one or two fetuses. No studies exist to show any benefit of this practice and a Cochrane review, as well as investigators in the field, have not found any justification for such practice. From a medical point of view, this non evidence-based practice is not following good clinical practice. Any practice that transfers more than one or two embryos, for instance due to commercial interests, should be abandoned by the international medical community because multifetal pregnancies can, to a large extent, be avoided by transferring only one or a maximum of two fertilized eggs by in vitro fertilization. Further, ovarian stimulating programs should strictly adhere to protocols aiming at mono-ovulation.
Evidence-Based Medicine↗
Earlier Apgar score increase in severely depressed term infants cared for in Swedish level III units with 40% oxygen versus 100% oxygen resuscitation strategies: a population-based register study.
OBJECTIVES: The aim of this study was to evaluate whether a resuscitation strategy based on administration of 40% oxygen influences mortality rates and rates of improvement in 5-minute Apgar scores, compared with a strategy based on 100% oxygen administration. METHODS: A population-based study evaluated data from 4 Swedish perinatal level III centers during the period of 1998 to 2003. During this period, the centers used either of 2 resuscitation strategies (initial oxygen administration of 40% or 100%). Live-born, singleton, term infants with 1-minute Apgar scores of <4, with a birth weight appropriate for gestational age, and without major malformations were included in the study (n = 1223). RESULTS: Infants born in hospitals using a 40% oxygen strategy had a more rapid Apgar score increase than did infants born in hospitals using a 100% oxygen strategy; however, no difference remained at 10 minutes. The mean Apgar score increased from 2.01 at 1 minute to 6.74 at 5 minutes in the 2 hospitals initiating resuscitation with 40% oxygen, compared with 2.01 to 6.38 in the 2 hospitals using 100% oxygen, with a mean difference in Apgar score increases of 0.36. At 5 minutes, 44.3% of infants born in the hospitals using 100% oxygen had an Apgar score of <7, compared with 34.0% of infants at the hospitals using 40% oxygen. At 10 minutes, the mean Apgar scores were 8.16 at the hospitals using 40% oxygen and 8.07 at the hospitals using 100% oxygen. There were no significant differences in rates of neonatal death, hypoxic ischemic encephalopathy, or seizures in relation to the 2 oxygen strategies. CONCLUSION: Severely depressed term infants born in hospitals initiating resuscitation with 40% oxygen had earlier Apgar score recovery than did infants born in hospitals using a 100% oxygen strategy.
Apgar Score↗
Oxygen for newborn resuscitation: how much is enough?
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Air↗
Reoxygenation of hypoxic mice with 100% oxygen induces brain nuclear factor-kappa B.
Oxidative stress is closely related to inflammation, a pathologic process characterized by activation of the transcriptional factor nuclear factor-kappa B (NF-kappaB). We have used transgenic NF-kappaB luciferase reporter mice to assess brain NF-kappaB activity noninvasively in living mice. We have studied NF-kappaB activation in hypoxic mice reoxygenated with either 21% O2 (room air) or 100% O2. Forty-one mice exposed for 2 h to 4% oxygen and then randomized to reoxygenation with pure oxygen or room air were investigated. A control mouse was dedicated to every mouse exposed to hypoxia. In vivo luminescence originated from brain was measured from mice 2 d before hypoxia, and 3 h after reoxygenation. A change in luminescence between the mouse exposed to hypoxia and its control demonstrates an alteration in NF-kappaB activity. Because of high mortality among males, only females were included. Six female mice died. Nineteen female mice were reoxygenated with room air, 16 with pure oxygen. We observed a significantly higher luminescence in the brain of the 100% O2 group versus the 21% O2 group. Our data indicate that brain NF-kappaB activity is increased in mice subjected to 4% oxygen followed by reoxygenation with 100% oxygen. However, when reoxygenation occurs with 21% O2 (room air), no elevation in NF-kappaB activity is observed. Thus, reoxygenation with room air may induce less brain inflammation than reoxygenation with pure oxygen.
Acid-Base Equilibrium↗
Quality of reaching and postural control in young preterm infants is related to neuromotor outcome at 6 years.
A substantial proportion of the "apparently normal" preterm infants exhibit minor and moderate dysfunctions in neuromotor outcome as they grow older. Birth characteristics, minor abnormalities on the neonatal ultrasound scan of the brain, and motor milestones have only limited value in the early detection of these children. The aim of the present study was to investigate whether nonoptimal reaching and relatively immobile postural behavior at an early age are associated with dysfunctional neuromotor and behavioural development at school age. The preterm children and full-term children of the present follow-up study participated in a previous study on the characteristics of reaching kinematics and the kinetics of posture at 4 and 6 mo corrected age. At the age of 6 y, the children were re-assessed by means of the Touwen neurologic assessment, the Movement ABC, and the Child Behavior Check List. The results demonstrated that in preterm children without cerebral palsy, a lack of successful reaching at 4 mo and a nonoptimal quality of reaching at 6 mo are related to the development of a complex form of minor neurologic dysfunction (MND) and fine manipulative disability at 6 y. Thus, these early signs indicate the presence of clinically significant brain dysfunction. A relatively immobile postural behavior at 4 mo was associated with simple MND, coordination problems, and at 6 mo with a worse score on the Movement ABC and internalizing behavior. This suggests that a relatively immobile postural behavior points to a mild form of brain dysfunction.
Brain↗
[Should some newborn infants not be treated?].
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Humans↗
Effect of interleukin-10 on newborn piglet brain following hypoxia-ischemia and endotoxin-induced inflammation.
OBJECTIVE: Previous animal studies indicated that interleukin (IL)-10 attenuates the inflammatory response to a challenge by inflammation and hypoxia-ischemia, but the effect of IL-10 administration after onset of inflammation has not been studied. We wanted to assess (1) whether IL-10 had a beneficial effect on brain metabolism and microcirculation in newborn piglets after an inflammatory, hypoxic and ischemic challenge, and (2) whether IL-10 had any harmful effects per se. METHODS: Anesthetized piglets were randomized to control (n = 8), IL-10 (n = 10), endotoxin (ETX) (n = 10), or ETX and IL-10 (ETX/IL-10) (n = 10) groups. IL-10 was administered after pretreatment with saline in the IL-10 group or ETX in the ETX/IL-10 group. Then, cerebral hypoxia and ischemia was induced by bilateral clamping of the common carotid arteries and ventilation with 8% O(2) for 30 min, followed by 4 h of reoxygenation and reperfusion. Extracellular levels of lactate, pyruvate, and glycerol were measured with microdialysis in periventricular white matter and parasagittal subcortical tissue, and tissue oxygenation and microcirculation were measured with Doppler technique. We compared the areas under the concentration-time and flow-time curves and maximum concentrations between (1) the ETX/IL-10 and ETX groups, and (2) the control and IL-10 groups. RESULTS: We found no differences between (1) the ETX/IL-10 and ETX groups, and also no differences between (2) the control and IL-10 groups. CONCLUSION: We could not show that the treatment with IL-10 after onset of inflammation had neuroprotective effects in the newborn piglet brain. IL-10 did not attenuate metabolism in the absence of ETX-induced inflammation.
Animals↗
Inflammation increases vulnerability to hypoxia in newborn piglets: effect of reoxygenation with 21% and 100% O2.
OBJECTIVE: The purpose of this study was to assess whether inflammation increases vulnerability to hypoxia, and influences the effect of 100% O(2) and 21% O 2 reoxygenation on brain. STUDY DESIGN: Newborn piglets (n = 31) were randomized to 4 interventional groups: pretreatment with saline or endotoxin. After hypoxia they were reoxygenated with 21% or 100% oxygen for 30 minutes, followed by 21% oxygen for all groups. To assess brain injury we measured extracellular brain tissue glucose, glycerol, and lactate/pyruvate by microdialysis, brain tissue oxygen tension, and laser Doppler flow. RESULTS: Administration of endotoxin reduced the time to reach base excess (BE) -20 mmol/L by median 32 minutes compared with saline ( P < .05). We found no differences in changes in biochemical markers, brain tissue microcirculation, or oxygen tension between piglets in the 4 groups. CONCLUSION: Endotoxin and hypoxia acted synergistically in inducing metabolic acidosis. In the presence of experimental inflammation, 21% oxygen seems as effective as 100% O(2) in reoxygenating piglets.
Analysis of Variance↗
Do negative life experiences predict the health-care-seeking of adolescents? A study of 10th-year students in Oslo, Norway.
PURPOSE: To analyze associations among the negative life experiences and health-care-seeking of adolescents during the 12 months before the study. METHODS: Cross-sectional questionnaire study among 10th-year students at all secondary schools in Oslo. RESULTS: In 2000 and in 2001, 7329 (88%) of Oslo's 8316 secondary-school students responded to the questionnaire. Some contacts with primary health care during the previous year were reported by 71% of respondents, and 6% had seen a mental health practitioner (psychologist or psychiatrist). Health care utilization was not correlated with the family's financial situation as reported by the student (boys = 1019; girls = 1258), or with a parent's unemployment (boys = 253; girls = 325). The 2112 boys (59% of all) and 2378 girls (64%) who reported feeling strong pressure from others to succeed, had more contacts with all primary health care services. Girls, but not boys, who reported being bullied by others reported more psychologist or psychiatrist visits than did their nonbullied peers. Exposure to physical violence was associated with a significant increase in visits to the School Health Service, family physician, and emergency medical service, and was related to more than doubling the probability of visiting a mental health practitioner. Being sexually violated during the previous year increased the likelihood of boys visiting mental health practitioner more than four times (odds ratio [OR] 4.6; 95% confidence interval [CI] 1.7-12.2); and visiting School Health Service by nearly four times, (OR 3.7; 95% CI 1.0-13.5). CONCLUSION: Variation in adolescent health care seeking can, by and large, be predicted by negative life experiences.
Adolescent↗
Oxygen for newborns: how much is too much?
International guidelines for newborn resuscitation recommend the use of 100% oxygen. However, high concentrations of oxygen after asphyxiation activate reactive oxygen species that may contribute to a number of morbidities. Animal models have been useful in describing their mechanisms, but only large-scale clinical trials can provide evidence that may be used to alter clinical practice. It has been demonstrated that neonates recover faster when resuscitated with room air as opposed to pure oxygen and neonatal mortality rates are improved. Increases in saturation are equal with oxygen and room air resuscitation. Studies of normal oxygen saturation immediately after birth suggest that clinicians may unnecessarily be rushing to high saturations. In the first weeks of life, lower saturation targets in preterm infants reduce retinopathy of prematurity and pulmonary complications and may improve growth. The neonatologist would be well served to think of oxygen as a medication, and use it sparingly.
Animals↗
When newborn infants are bound to die.
UNLABELLED: Withholding and withdrawing of intensive care of severely ill newborns may occasionally be needed when there is severe injury and extremely poor prognosis. In such cases, strict guidelines and procedures should be followed. In this issue of Acta Paediatrica, Arlettaz et al. describe such guidelines and report practice from the University Hospital in Zürich. To ensure an unbiased discussion, it is important that those who make decisions regularly receive input from external sources regarding indications of viability. This may be the case if, for instance, a unit has decided that the limit of viability is <26 wk, and many children with good life expectancy would in such units be denied intensive care. Does a liberal view on withholding or withdrawing treatment lead to poorer overall outcome results even for babies above the threshold of viability specified by the institution? CONCLUSION: Strict procedures should be followed in the case of withholding or withdrawing intensive care of severely ill newborn infants. In every institution, the indications for ending life should be discussed on a regular basis, preferably with external input. However, euthanasia of newborn infants is not compatible with Western cultural traditions and should be abandoned.
Decision Making↗
Positive factors associated with promoting health in low-risk and high-risk populations of 15- and 16-year-old pupils in Oslo, Norway.
AIM: To explore possible risk-reducing factors associated with the incidence of common illnesses and use of healthcare services among adolescents. METHODS: Cross-sectional questionnaire study conducted in all Oslo schools among all 15- and 16-y-olds in 2000 and 2001. The adolescent population was divided into a low-risk (LR) and a high-risk (HR) group, and into quartiles, based on a sum score of different negative life experiences. The groups were compared with respect to potential risk-reducing factors. RESULTS: 88% of the 8316 pupils filled in the questionnaires. The difference between the LR and HR groups was largest for the possible risk-reducing factor "my family values my opinion" (LR group = 92%; HR group = 82%), and "I manage to solve serious problems myself" (LR = 91%; HR = 86%). The family valuing the adolescents' opinions was the risk-reducing factor most often associated with lower incidences of illness and healthcare utilization. Among the adolescents at highest risk, less depression was strongly related to positive relationships with friends, boys: odds ratio = 0.1 (CI 95%: 0.0-0.7); and girls: 0.2 (0.1-0.5). Adolescents reporting that they managed their own problems had about half the risk of depression. CONCLUSION: Good relations with family and friends, and a feeling of managing one's own life, are significantly related to lower rates of illness, in particular depression, and less healthcare-seeking behaviour. The risk-reducing effects increase with increasing risk. Healthcare workers therefore need to pay more attention to HR patients.
Adolescent↗
Oxidative stress in the newborn--a 30-year perspective.
In this review the development of the concept 'hypoxia-reoxygenation injury' is outlined. An update of some important factors and mechanisms related to oxidative stress injury in newborn infants is presented, including the metabolism of glutathione, the role of antioxidants, iron and nitric oxide, and how these may influence health and disease in the newborn and contribute to 'oxygen radical disease of the newborn'. New insight into how hyperoxia and hypoxia may induce changes leading to retinopathy of prematurity by vascular endothelial growth factor acting in concert with insulin-like growth factor is briefly summarized. Inflammation and oxidative stress seem to be two sides of the same coin in newborn babies both contributing to injury partly through similar mechanisms.
Antioxidants↗
Resuscitation of hypoxic piglets with 100% O2 increases pulmonary metalloproteinases and IL-8.
We hypothesized that resuscitation with 100% O2 compared with 21% O2 is detrimental to pulmonary tissue. The pulmonary injury was assessed by matrix metalloproteinase (MMP) activity, oxidative stress, IL-8, and histology 2.5 h after resuscitation from a hypoxic state. In pulmonary tissue extracts, MMP activity was analyzed by broad matrix-degrading capacity (total MMP) and zymography. MMP-2 mRNA expression was evaluated by quantitative real-time PCR. Total endogenous antioxidant capacity was measured by the oxygen radical absorbance capacity (ORAC) assay, and IL-8 was analyzed by ELISA technique. In bronchoalveolar lavage (BAL) fluid, MMPs were analyzed by zymography. In pulmonary tissue, pro- and active MMP-2 levels were increased in piglets that were resuscitated with 100% O2 compared with 21% O2. Pro-MMP-9, total MMP activity, and MMP-2 mRNA levels were significantly increased in resuscitated piglets compared with baseline. Net gelatinolytic activity increased in submucosa and blood vessels after 100% O2 and only in the blood vessels after 21% O2. Compared with baseline, ORAC values were considerably lowered in the resuscitated piglets and significantly reduced in the 100% O2 versus 21% O2 group. In BAL fluid, both pro-MMP-9 and pro-MMP-2 increased 2-fold in the 100% O2 group compared with 21% O2. Moreover, IL-8 concentration increased significantly in piglets that were resuscitated with 100% O2 compared with 21% O2, suggesting a marked proinflammatory response in the pulmonary tissue. Altogether, these data strongly suggest that caution must be taken when applying pure O2 to the newborn infant.
Animals↗
Room air resuscitation-two decades of neonatal research.
Experimental as well as clinical studies have demonstrated that room air is as efficient as pure oxygen for newborn resuscitation. Recent data even indicate that outcome is improved if pure oxygen is avoided. Thus, in a meta-analysis, neonatal mortality was significantly lower in those newly born infants resuscitated with 21% than with 100% oxygen. Short-term recovery is also improved in the room air group since time to first breath is shorter, heart rate at 90 s and 5 min Apgar score are higher. Animal data indicate that injury in a number of organs, including the brain, is aggravated by giving pure oxygen to newly born depressed infants even for a brief period. Although the optimal oxygen concentration probably is not known for newborn infants in need of resuscitation, pure oxygen should be avoided. These data should be reflected in new guidelines that are under way.
Air↗
Resuscitation of depressed newborn infants with ambient air or pure oxygen: a meta-analysis.
BACKGROUND: It is discussed whether depressed newborn infants should be resuscitated with room air or 100% O2. OBJECTIVE: To perform a systematic review and meta-analysis including studies that report resuscitation of depressed newly born infants with 21 or 100% O2. METHODS: Inclusion criterion was randomized or pseudo-randomized, blinded or not, studies of depressed newborn infants resuscitated with either 21 or 100% O2. The literature was searched in Medline/Pubmed/EMBASE and The Cochrane library databases. All identified studies were included. RESULTS: Five studies fulfilled the inclusion criterion in which 881 infants were resuscitated with 21% O2 and 856 with 100% O2. Neonatal mortality was 8.0 vs. 13.0% in the 21 and 100% O2 groups respectively, OR 0.57, 95% CI 0.42-0.78. In term infants neonatal mortality was 5.9% in the 21% O2 group and 9.8% in the 100% O2 group, OR 0.59, 95% CI 0.40-0.87. The figures for the premature infants were very similar. In infants with 1-min Apgar score <4, OR for neonatal mortality was 0.81 (95% CI 0.54-1.21). Apgar score at 5 min and heart rate at 90 s were significantly higher, and time to first breath significantly earlier in infants given 21% O2 compared with 100% O2. CONCLUSIONS: A systematic review and meta-analysis demonstrated that neonatal mortality is significantly reduced when depressed newly born infants are resuscitated with ambient air instead of pure oxygen. For infants with low 1-min Apgar score (<4), no significant difference in neonatal mortality was found. Recovery was faster in infants resuscitated with 21% O2 than 100% O2.
Air↗