PEDIATRICS Vol. 119 No. 4 April 2007, pp. 790-796 (doi:10.1542/peds.2006-2200)
SPECIAL ARTICLE |
Executive Summary of the Workshop on Oxygen in Neonatal Therapies: Controversies and Opportunities for Research
a Pregnancy and Perinatology Branch, Center for Developmental Biology and Perinatal Medicine, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
b Department of Pediatrics, University of Miami College of Medicine, Miami, Florida
 |
ABSTRACT |
|---|
 TOP ABSTRACT BIOLOGICAL FEATURES OF OXYGEN:...PRACTICAL ASPECTS OF OXYGEN...RESUSCITATION AND OXYGENCONCLUSIONSREFERENCES |
|---|
One of the most complex areas in perinatal/neonatal medicine is the use of oxygen in neonatal therapies. To address the knowledge gaps that preclude optimal, evidence-based care in this critical field of perinatal medicine, the National Institute of Child Health and Human Development organized a workshop, Oxygen in Neonatal Therapies: Controversies and Opportunities for Research, in August 2005. The information presented at the workshop included basic and translational oxygen research; a review of completed, ongoing, and planned clinical trials; oxygen administration for neonatal resuscitation; and a review of the collaborative home infant monitoring evaluation study. This article provides a summary of the discussions, focusing on major knowledge gaps, with prioritized suggestions for studies in this area.
Key Words: bronchopulmonary dysplasia • intensive care • neonatal resuscitation • oxygen • retinopathy of prematurity • ventilation
Abbreviations: ROP—retinopathy of prematurity • CHIME—collaborative home infant monitoring evaluation • BOOST—Benefits of Oxygen Saturation Targeting Study • ROS—reactive oxygen species
In the 1890s, Thomas Morgan Rotch, a pioneer US pediatrician, administered oxygen to premature infants in small doses as a stimulant, often combining it with brandy as a second stimulant.1 By the middle 1930s, "routine" oxygen therapy piped into incubators had become common. After 8 decades of regular use, however, large knowledge gaps remain concerning oxygen therapy for newborn infants. Even the definition of "appropriate oxygenation" is not clear. New concerns have emerged about the use of supplemental oxygen for resuscitation. The proper concentration of administered oxygen, especially for extremely preterm infants, remains to be established. Therefore, although we know many short- and long-term risks of hypoxia, the goal of using oxygen safely to combat hypoxia remains to be achieved. To complicate matters, the evolution and course of disorders such as retinopathy of prematurity (ROP), bronchopulmonary dysplasia, and persistent pulmonary hypertension of the newborn may be influenced both by deficiency and excess of administered oxygen and by systemic hypoxia and hyperoxia.
To address the complex issues related to oxygen therapy, the National Institute of Child Health and Human Development organized a workshop in 2005, Oxygen in Neonatal Therapies: Controversies and Opportunities for Research. The invited experts reviewed the current evidence for care practices and identified knowledge gaps. They addressed the biological features of oxygen therapy, the consequences of deficient and excess oxygen, data from the collaborative home infant monitoring evaluation (CHIME) study, and practical aspects of oxygen use for newborns. This meeting summary may help future investigators plan for innovative research and clinicians develop evidence-based practice strategies, while appreciating the limits of our current knowledge on this complex topic.
|
BIOLOGICAL FEATURES OF OXYGEN: BASIC AND TRANSLATIONAL OXYGEN RESEARCH |
|---|
|
TOPABSTRACTBIOLOGICAL FEATURES OF OXYGEN:...PRACTICAL ASPECTS OF OXYGEN...RESUSCITATION AND OXYGENCONCLUSIONSREFERENCES |
|---|
Blood flow and oxygen content are integrated intimately to meet the metabolic needs of tissues. Hypoxia refers to low oxygen content or partial pressure in the blood or in inspired air. Hyperoxia is defined as an excess of oxygen content in the blood or inspired air. Just as lack of blood flow or hypoxia, on either an acute or chronic basis, can lead to poor tissue oxygenation and injury, acute or chronic hyperoxia can lead to oxygen-induced cellular and tissue injury. The following is a summary of the research discussed. The gaps in knowledge and opportunities for basic and translational research identified by the participants are summarized in Table 1.
|
Several investigators are attempting to characterize the nature of tolerance and susceptibility to low and high concentrations of oxygen. Haddad2 showed that Drosophila melanogaster flies can sustain complete anoxia for up to 5 hours without morphologic abnormalities and continue to engage in complex behavior, such as mating, flying, and seeing. Phenotypic evaluation of anoxia-sensitive D melanogaster by using behavioral and physiologic assays and genomic markers or elements of the reactive oxygen species (ROS) systems were used in the model. For evaluation of the effects of long-term chronic hypoxia, exposure to lower ambient oxygen levels can occur over several generations of D melanogaster, for assessment of offspring under conditions of hypoxia or demonstration of genes whose expression is increased or decreased under conditions of chronic hypoxia. Three genes have been found to be downregulated by 5% oxygen, namely, ubiquitin ligase, peptidase,3 and oxidase.4 Trehalose-6-phosphate synthase synthesizes trehalose, a disaccharide found to be protective against stress, including oxidative injury.5 Overexpression of trehalose-6-phosphate synthase in D melanogaster enhances resistance to low oxygen conditions. Although genes have been identified as mediators of hypoxic tolerance, much work needs to be done to translate these findings into clinical applications in higher species and to develop therapeutic modalities for oxidant-related diseases6 (Table 1).
ROS can have profound effects on lung tissues.7 ROS can lead to protein modification, DNA base modification, and strand scission. Increased proliferation of type II pneumocytes and fibroblasts, alterations in the surfactant system (synthesis, function, and clearance), and stimulation of inflammatory cells and cytokines are attributable to ROS. Lung hyperoxia can lead to increased collagen deposition, endothelial cell damage, and apoptotic cell death.8 Elevations of growth factors (transforming growth factor-ß, fibroblast growth factor, and insulin-like growth factor) and increased matrix metalloproteinases have been observed in the presence of ROS. In vivo experiments have demonstrated that ROS cause decreased cell proliferation and alveolarization in neonatal animals and decreased microvascular density.9 Research gaps and opportunities are listed in Table 1.
Newborn animals have better tolerance to hyperoxia than adults because of their ability to increase antioxidant defense mechanisms when exposed to oxygen.10 The activity of antioxidant enzymes and other antioxidant mechanisms is generally lower in premature animals and humans than in their term counterparts.11 Maturation of the antioxidant system parallels maturation of the surfactant system. Prenatal glucocorticoid therapy also increases antioxidant enzyme responses and survival rates for oxygen-exposed premature animals.
Premature infants are more vulnerable to oxygen toxicity because of decreased levels of antioxidant enzymes, including superoxide dismutase, glutathione peroxidase, and catalase. Premature infants have decreased levels of antioxidant vitamins A, E, and C and decreased amounts of the trace elements zinc, copper, and iron. Strategies that have been proposed to decrease oxygen toxicity in premature infants include reduction of oxygen exposure, antioxidants (including vitamin A, vitamin E, glutathione, trace elements, lipids, and inositol), and antioxidant enzymes. Identified gaps and opportunities are listed in Table 1.
Hyperoxia and hypoxia have been implicated in retinal injury in preterm infants. Preterm birth results in exposure of the infant to a higher ambient oxygen concentration ex utero, as opposed to in utero. This relative hyperoxia after preterm birth results in slowing, cessation, and sometimes regression of retinal vasculature development. Over time, the retina grows in thickness without concurrent blood vessel growth. Ultimately, hypoxia occurs at the tissue level, causing an increase in the release of angiogenic growth factors (such as vascular endothelial growth factor) and resulting in an overgrowth of vessels or ROP.12
It has been long recognized that acute hypoxia is a powerful stimulus for cerebral vasodilation. However, the responses of fetal and neonatal cerebral circulation seem to be considerably different from those seen in older age groups. Some factors that seem to affect cerebral vascular responses include the severity and acuteness of hypoxia, speed of acclimatization, maturation and postnatal age, and systemic blood pressure and cardiac output. Acute hypoxia promotes adenosine release, leading to a dual effect. Through adenosine's action on neuronal A1 receptors, fetal cerebral oxygen consumption is depressed; at the same time, through activation of A2 receptors on cerebral arteries, vasodilation is achieved. The latter accounts for approximately one half of the vasodilation observed in response to hypoxia in the fetus. Much of the adenosine-independent vasodilatory response to hypoxia is mediated through the release of nitric oxide and opioids, and a small fraction of the vasodilatory effect is attributable to the direct effect of hypoxia on cerebral arteries, through a vascular endothelial effect. During acclimatization to chronic hypoxia, fetal cerebral blood flow tends to normalize, especially if cardiac output is not compromised. However, severe, prolonged, uncompensated chronic hypoxia (lack of oxygen over time, without mechanisms to offset the process) in the fetus can produce significant changes in brain structure and function, increased incidence of intracranial hemorrhage, and periventricular leukomalacia. Pearce and colleagues13–15 showed that fetal cerebrovascular adaptations to chronic hypoxia seem prioritized to conserve energy while preserving basic contractility. More research is needed in the areas listed in Table 1. Similar to hypoxia, hyperoxia can lead to a complex set of responses in the brain. Increased minute ventilation, leading to a decrease in PCO2,16 leads to reductions in cerebral blood flow. Therefore, a combination of hyperoxia and hypocapnea has been shown to increase the risk of brain injury after intrapartum asphyxia.17 Vannucci et al18 showed that, in an hypoxic/ischemic encephalopathy rat model, mild hypercarbia could be neuroprotective. Systemic effects of hyperoxia can produce increased plasma insulin levels, increased glucagon levels, diminished myocardial contractility, and reduced myocardial relaxation.19 These effects may be mediated by central neural actions on sympathetic and hypothalamic hormonal regulation, rather than just peripheral actions of oxygen. Hyperoxia results in responses from forebrain, limbic, and cerebellar sites,20 which have the potential to modify autonomic and hormonal output21 (Table 1).
Hypoxia combined with anemia can affect oxygen content profoundly and thus reduce levels of oxygen delivered to the tissues, which in turn can affect growth. Severe anemia has been shown to cause neonatal growth failure.22 Although fetal growth occurs optimally at PaO2 levels of 35 to 40 mm Hg (levels much lower than those seen postnatally), there are important differences in oxygen physiologic features between fetal and postnatal life. Some of these differences include higher hemoglobin concentrations, greater proportions of fetal hemoglobin having steeper oxygen dissociation characteristics (enabling uptake of more oxygen from the placenta and release of more oxygen at the tissues), differences in oxygen consumption, and fetal levels of activity. There are also differences in placental transfer of nutrients, compared with the postnatal period. The complexities of oxygen physiologic features in the transition from fetal life through the newborn period highlight the need for more research, as outlined in Table 1.
|
PRACTICAL ASPECTS OF OXYGEN THERAPY: CLINICAL TRIALS |
|---|
|
TOPABSTRACTBIOLOGICAL FEATURES OF OXYGEN:...PRACTICAL ASPECTS OF OXYGEN...RESUSCITATION AND OXYGENCONCLUSIONSREFERENCES |
|---|
Oxygen is used widely in neonatal care. Many issues regarding its use represent outstanding gaps in knowledge and research questions to optimize clinical care. Table 1 summarizes major questions regarding the clinical use of oxygen.
Clinical trials that have been conducted to test the role of supplemental oxygen for ROP include the Supplemental Therapy With Oxygen to Prevent ROP Trial23 and the Benefits of Oxygen Saturation Targeting Study (BOOST).24 The Supplemental Therapy With Oxygen to Prevent ROP Trial23 tested the hypothesis that, among premature infants with prethreshold ROP in 
1 eye, supplemental oxygen given to maintain 96% to 99% saturation (determined through pulse oximetry), in contrast to conventional levels of 89% to 94% saturation, would reduce the rate of progression to threshold ROP. A secondary hypothesis was that supplemental oxygen would also improve the infants' growth. Six hundred forty-nine children were enrolled, with an average gestational age at birth of 25.4 weeks and an average postmenstrual age of 35.4 ± 2.5 weeks (range: 30–48 weeks). The progression of ROP from prethreshold to threshold disease was not reduced by supplemental oxygen. A posthoc subgroup analysis showed that infants with no plus disease, defined as posterior pole dilation/tortuosity, at the time of enrollment had less progression to threshold with supplemental oxygen. There were no differences with respect to infant growth in the 2 groups. Supplemental oxygen increased adverse pulmonary events during treatment and during follow-up monitoring through a corrected age of 3 months.
BOOST24 was designed to determine whether 1 of 2 oxygen saturation target ranges (pulse oximetry saturation of 91%–95% or 95%–98%) begun at postmenstrual age of 32 weeks would improve growth and development at a corrected age of 1 year. A total of 358 infants were enrolled. There were no differences in outcomes between the 2 target saturation groups, with respect to growth (assessed as weight, height, and head circumference) or major developmental abnormalities. Analysis of secondary outcomes showed an increased number of oxygen days and older postmenstrual age at oxygen discontinuation for the higher target saturation group (target saturation of 95%–98%). The authors stated that the optimal oxygen saturation range for preterm infants soon after birth should be determined with a large trial.24
Existing gaps in the area of oxygen administration, oxygen saturation, and toxicity are summarized in Table 1. Trials to determine target saturation ranges are ongoing and under development. The following trials have the same design for the oxygen saturation arm. The Surfactant, Positive Airway Pressure, Pulse Oximetry Randomized Trial is being conducted in the National Institute of Child Health and Human Development Neonatal Research Network.25 A factorial design has been developed to enroll infants to 4 possible strategies, as shown in Table 2.
|
The hypotheses being tested are that early continuous positive airway pressure and permissive ventilation can increase survival rates without an increase in bronchopulmonary dysplasia rates and that lower saturation targets (85%–89%) can increase survival rates without severe ROP (threshold disease or disease requiring surgical intervention). Infants between 240/7 weeks and 2767 weeks of gestation are eligible for enrollment by 2 hours of age. As of April 30, 2006, 276 of the needed 1300 infants had been enrolled.
Funded by the National Health and Medical Research Council in Australia, BOOST II26 is a randomized, double-blind trial that will evaluate 2 ranges of oxygen saturation (85%–90% and 91%–95%) to determine whether development, vision, and health assessment are affected at 2 years of age. The primary study outcomes include severe ROP (stage III or higher), major disability, and death. Children will be enrolled by 24 hours of life and be of gestational age of <28 weeks. At the time of this writing, BOOST II has begun enrollment.
The US Pulse Oximetry Saturation Trial for Prevention of ROP under development27 will enroll children by 24 hours of age into 2 saturation arms (85%–89% and 91%–95%). The study will enroll 1525 children by 24 hours of age at <28 weeks of gestation. The primary study outcomes are ROP, pulmonary morbidity, severe disability at 24 months, and death. The hypothesis of this study is that children assigned randomly to the lower saturation arm should have less severe ROP and less pulmonary morbidity with no increase in the combined outcome of death or severe disability at a corrected age of 24 months. A prospective meta-analysis has been proposed to combine the resultant data from the Surfactant, Positive Airway Pressure, Pulse Oximetry Randomized Trial, BOOST II, and the Pulse Oximetry Saturation Trial for Prevention of ROP to examine moderate but important effects that may be detected with the large number of patients.
|
RESUSCITATION AND OXYGEN |
|---|
|
TOPABSTRACTBIOLOGICAL FEATURES OF OXYGEN:...PRACTICAL ASPECTS OF OXYGEN...RESUSCITATION AND OXYGENCONCLUSIONSREFERENCES |
|---|
Immediate use of oxygen for resuscitation in the neonatal period has been a long-standing practice. A recent Cochrane review evaluated air versus oxygen at birth for infants.28 The value of routine use of high inspired oxygen concentrations for resuscitation has been questioned recently, and many scientists have suggested that room air can be as effective as and perhaps safer than higher concentrations of oxygen during resuscitation. The rationale in favor of the use of room air use for resuscitation is that infants resuscitated with room air have earlier spontaneous respiration and 100% oxygen exposure can increase oxidative injury.29 Furthermore, a study of the surviving infants in the Collaborative Perinatal Project30 suggested a weak association between exposure to higher concentrations of oxygen for >3 minutes during resuscitation and later childhood cancer. Because of major limitations, such as selection bias and early death as a competing outcome, the conclusions of this study should be considered speculative. However, on the basis of a systematic review of 5 studies that compared room air versus oxygen for resuscitation of term infants, the authors concluded that resuscitation using room air resulted in a reduction in the neonatal mortality rate (8% vs 13%), higher 5-minute Apgar scores (6.6 vs 6.45), faster heart rate at 90 seconds of age (116 vs 111 beats per minute), and faster time to first breath (1.8 vs 2.3 minutes).31
Despite the optimistic conclusion regarding the value of room air for resuscitation based on the meta-analyses, some limitations of the latter should be noted, including a lack of blinding in many studies, exclusion of apparent stillbirths, leading to lower prevalence of infants with severe asphyxia, and lack of validation of these studies in diverse intensive care settings around the world. Issues involving the use of oxygen for neonatal resuscitation are summarized in Table 1.
It should be noted that oxygen use in neonatal resuscitation has garnered much interest in commentaries.32–35 The expert panel at the workshop discussed the advantages and disadvantages of resuscitation using room air versus oxygen. The International Liaison Committee on Resuscitation recommendations for pediatric and neonatal advanced life support have since been published and state the following.
There is insufficient information to recommend for or against the use of any specific inspired oxygen concentration during and immediately after resuscitation from cardiac arrest. Until additional evidence is published, we support health care providers' use of 100% oxygen during resuscitation (when available). Once circulation is restored, providers should monitor oxygen saturation and wean inspired oxygen while ensuring adequate oxygen delivery.36
Additional International Liaison Committee on Resuscitation recommendations for neonatal resuscitation state the following.
There is currently insufficient evidence to specify the concentration of oxygen to be used at the initiation of resuscitation. ... Once adequate ventilation is established, if the heart rate remains low, there is no evidence to support or refute a change in the oxygen concentration that was initiated. ... Supplementary oxygen should be considered for infants with persistent central cyanosis. Some have advocated adjusting the oxygen supply according to pulse oximetry measurements to avoid hyperoxia, but there is insufficient evidence to determine the appropriate oximetry goal because observations are confounded by the gradual increase in oxyhemoglobin saturation that normally occurs following birth.37
In summary, appropriate use of oxygen during resuscitation is an area in need of additional study (Table 1). The CHIME study was set up to determine whether preterm infants, infants with sibling sudden infant death syndrome, and infants who have had a life-threatening event are at greater risk for cardiorespiratory events than are healthy term infants.38 Extreme events (defined as apnea for 30 seconds, heart rate of <60 beats per minute for 10 seconds at postconceptional age of 
44 weeks' postconceptional age, or heart rate of <50 beats per minutes at postconceptional age of >44 weeks) were common for preterm infants. The increased risk for these events among preterm infants diminished by postconceptional age of 43 weeks, and it was concluded that these events are not likely to be immediate precursors to sudden infant death syndrome. The CHIME study also collected information on oxygen saturation levels, as measured with pulse oximetry. Among the two thirds of extreme events with high-quality pulse oximetry recordings, the degree of hypoxemia increased with increasing duration of apnea or bradycardia. In addition to storing waveforms associated with cardiorespiratory events, the CHIME monitor automatically stored 3 minutes of recordings every hour. Oxygen saturations ranged from 97% to 100% during periods of regular breathing. There were, however, well-documented periods of saturation decreases to <90% for 66% of the infants in the first 5 weeks of life. These decreases in saturation were usually brief (<5 seconds) but could last for >10 seconds (7% of events).39 Acute decreases in saturation occurred for 50% of infants. Most of these events (79%) were associated with periodic breathing and were more likely to occur during side or supine sleeping.
Areas identified throughout the meeting as opportunities to advance technology for oxygen monitoring are summarized in Table 1. Measurements of oxygenation at the tissue level, oxygen feedback systems, and feedback systems from pulse oximeters to maintain constant oxygenation were identified as areas for technology development.
|
CONCLUSIONS |
|---|
|
TOPABSTRACTBIOLOGICAL FEATURES OF OXYGEN:...PRACTICAL ASPECTS OF OXYGEN...RESUSCITATION AND OXYGENCONCLUSIONSREFERENCES |
|---|
A significant number of gaps and opportunities for research were identified (Table 1). The workshop participants observed that presently there is a lack of information on the effects of varying oxygen levels on organ development as a whole. They also noted that there is a need for data on interventions to prevent and to treat hypoxic and hyperoxic injury. Studies are needed to provide evidence-based information to assist clinicians in using oxygen appropriately for newborn infants. Critical areas in need of urgent study include the use of oxygen during resuscitation and appropriately targeting oxygen saturations for a wide variety of newborn infants. In addition, it is important to obtain more information on the short- and long-term outcomes related to oxygen therapy.
|
ACKNOWLEDGMENTS |
|---|
The following invited scientists participated in the conference: Judy L. Aschner, MD, Department of Pediatrics/Division of Neonatology, Vanderbilt University Medical Center (Nashville, TN); Lisa Askie, PhD, MPH, New South Wales Centre for Perinatal Health Services Research, University of Sydney (Sydney, Australia); Eduardo Bancalari, MD, Department of Pediatrics, Division of Neonatology, University of Miami School of Medicine (Miami, FL); Mary Anne Berberich, PhD, National Heart, Lung, and Blood Institute (Bethesda, MD); Waldemar A. Carlo, MD, Department of Pediatrics, University of Alabama at Birmingham (Birmingham, AL); Charlotte Catz, MD, National Institute of Child Health and Human Development (Bethesda, MD); Cynthia H. Cole, MD, MPH, Department of Neonatology, Beth Israel Deaconess Medical Center; Michael Corwin, PhD, Department of Epidemiology, Boston University; Maria Delivoria-Papadopoulous, MD, Department of Pediatrics, St Christopher's Hospital for Children; Mary C. Demory, Public Outreach and Education Program, Office of Rare Diseases, National Institutes of Health; Neil N. Finer, MD, Department of Pediatrics/Neonatology, University of California, San Diego, Medical Center; Stephen C. Groft, Pharm. D, Office of Rare Diseases, National Institutes of Health; Gabriel G. Haddad, MD, Department of Pediatrics, Albert Einstein College of Medicine Montefiore Medical Center (Bronx, NY); James Hanson, MD, Center for Developmental Biology and Perinatal Medicine, National Institute of Child Health and Human Development; Ronald Harper, PhD, Department of Neurobiology, University of California, Los Angeles; William W. Hay, Jr, MD, Perinatal Research Center, University of Colorado Health Sciences Center (Aurora, CO); Carl E. Hunt, MD, National Center for Sleep Disorders Research, National Heart, Lung, and Blood Institute; John Kattwinkel, MD, Department of Pediatrics, University of Virginia School of Medicine (Charlottesville, VA); Edward E. Lawson, MD, Division of Neonatology, Johns Hopkins Medical Institutions (Baltimore, MD); George Lister, MD, Department of Pediatrics, University of Texas Southwestern Medical Center (Dallas, TX); Susan K. McCune, MD, Food and Drug Administration (Rockville, MD); Paivi Miskala, MD, National Eye Institute; William Pearce, MD, Physiology and Pharmacology, Center for Perinatal Biology, Loma Linda University School of Medicine (Loma Linda, CA); Jeffrey M. Perlman, MB, ChB, New York Presbyterian Hospital, Weil Medical College (New York, NY); Dale L. Phelps, MD, Department of Pediatrics, University of Rochester (Rochester, NY); Ola Didrik Saugstad, MD, Department of Pediatric Research, Rikshospitalet (Oslo, Norway); Michael E. Speer, MD, Department of Pediatrics, Baylor College of Medicine (Houston, TX); Giovanna M. Spinella, MD, Office of Rare Diseases, National Institutes of Health; Ann R. Stark, MD, Section of Neonatology, Baylor College of Medicine, Texas Children's Hospital; William Tarnow-Mordi, MD, Neonatal Medicine, University of Sydney, Westmead Hospital and the Children's Hospital at Westmead (Sydney, Australia); Marian Willinger, PhD, Pregnancy and Perinatology Branch, Center for Developmental Biology and Perinatal Medicine, National Institute of Child Health and Human Development.
|
FOOTNOTES |
|---|
Accepted Nov 28, 2006.
Address correspondence to Rosemary D. Higgins, MD, Pregnancy and Perinatology Branch, Center for Developmental Biology and Perinatal Medicine, NICHD, NIH, 6100 Executive Blvd, Room 4B03B, MSC 7510, Bethesda, MD 20892. E-mail: higginsr{at}mail.nih.gov
Financial Disclosure: Dr Bancalari received a license agreement for respiratory equipment and an educational grant for a postgraduate education conference from Viasys Healthcare.
|
REFERENCES |
|---|
|
TOPABSTRACTBIOLOGICAL FEATURES OF OXYGEN:...PRACTICAL ASPECTS OF OXYGEN...RESUSCITATION AND OXYGENCONCLUSIONSREFERENCES |
|---|
- Baker JP. Machine in the Nursery: Incubator Technology and the Origin of Newborn Intensive Care. Baltimore, MD: Johns Hopkins University Press; 1996:132 –133
- Haddad GG. Tolerance to low O2: lessons from invertebrate genetic models.
Exp Physiol. 2006;91
:277
–282
[Abstract/Free Full Text] - Ryu J, Vicencio AG, Yeager ME, Kashgarian M, Haddad GG, Eickelberg O. Differential expression of matrix metalloproteinases and their inhibitors in human and mouse lung development. Thromb Haemost. 2005;94 :175 –183[Web of Science][Medline]
- Lai JCK, White BK, Buerstatte CR, Haddad GG, Novotny EJ, Behar KL. Chronic hypoxia in development selectively alters the activities of key enzymes of glucose oxidative metabolism in brain regions. Neurochem Res. 2003;28 :933 –940[CrossRef][Web of Science][Medline]
- Chen Q, Behar KL, Xu T, Fan C, Haddad GG. Expression of Drosophila trehalose-phosphatase synthase in HEK-293 cells increases hypoxia tolerance.
J Biol Chem. 2003;278
:49113
–49118
[Abstract/Free Full Text] - Chen Q, Haddad GG. Role of trehalose phosphate synthase and trehalose during hypoxia: from flies to mammals.
J Exp Biol. 2004;207
:3125
–3129
[Abstract/Free Full Text] - Frank L. Developmental aspects of experimental pulmonary oxygen toxicity. Free Radical Biol Med. 1991;11 :463 –494[CrossRef][Web of Science][Medline]
- Thibeault DW, Mabry SM, Ekekezie II, Zhang X, Truog WE. Collagen scaffolding during development and its deformation with chronic lung disease.
Pediatrics. 2003;111
:766
–776
[Abstract/Free Full Text] - Coalson JJ. Pathology of new bronchopulmonary dysplasia. Semin Neonatol. 2003;8 :73 –81[CrossRef][Medline]
- Frank L, Groseclose EE. Preparation for birth into an O2-rich environment: the antioxidant enzymes in the developing rabbit lung. Pediatr Res. 1984;18 :240 –244[Web of Science][Medline]
- Frank L, Sosenko IR. Failure of premature rabbits to increase antioxidant enzymes during hyperoxic exposure: increased susceptibility to pulmonary oxygen toxicity compared to term rabbits. Pediatr Res. 1991;29 :292 –296[Web of Science][Medline]
- Smith LEH. IGF-1 and retinopathy of prematurity in the preterm infant. Biol Neonate. 2005;88 :237 –244[CrossRef][Web of Science][Medline]
- Longo LD, Pearce WJ. Fetal cerebrovascular acclimatization responses to high-altitude, long-term hypoxia: a model for prenatal programming of adult disease?
Am J Physiol Regul Integr Comp Physiol. 2005;288
:R16
–R24
[Abstract/Free Full Text] - Angeles DM, Williams J, Zhang L, Pearce WJ. Acute hypoxia modulates 5-HT receptor density and agonist affinity in fetal and ovine carotid arteries. Am J Physiol Heart Circ Physiol. 2000;279 :H502–H510
- Williams JM, Pearce WJ. Age-dependent modulation of endothelium-dependent vasodilatation by chronic hypoxia in ovine cranial arteries.
J Appl Physiol. 2006;100
:225
–232
[Abstract/Free Full Text] - Mulkey DH, Henderson RA, Putnam RW, Dean JB. Hyperbaric oxygen and chemical oxidants stimulate CO2/H+-sensitive neurons in rat brain stem slices.
J Appl Physiol. 2003;95
:910
–921
[Abstract/Free Full Text] - Klinger G, Beyene J, Shah P, Perlman M. Do hyperoxaemia and hypocapnea add to the risk of brain injury after intrapartum asphyxia?
Arch Dis Child Fetal Neonatal Ed. 2005;90
:F49
–F52
[Abstract/Free Full Text] - Vannucci RC, Towfighi J, Heitjan DF, Brucklacher RM. Carbon dioxide protects the perinatal brain from hypoxic-ischemic damage: an experimental study in the immature rat.
Pediatrics. 1995;95
:868
–874
[Abstract/Free Full Text] - Bandali KS, Belanger MP, Wittnich C. Hyperoxia causes oxygen free radical-mediated membrane injury and alters myocardial function and hemodynamics in the newborn. Am J Physiol Heart Circ Physiol. 2004;287 :H553—H559
- Woo MA, Macey PM, Macey KE, et al. FMRI responses to hyperoxia in congenital central hypoventilation syndrome. Pediatr Res. 2005;57 :510 –518[CrossRef][Web of Science][Medline]
- Harper RM, Macey PM, Woo MA, et al. Hypercapnic exposure in congenital hypoventilation syndromes reveals CNS respiratory control mechanisms.
J Neurophysiol. 2005;93
:1647
–1658
[Abstract/Free Full Text] - Stockman JA, Graeber JE, Clark DA, McClellan K, Garcia JF, Kavey RE. Anemia of prematurity: determinants of erythropoietin response. J Pediatr. 1984;105 :786 –792[CrossRef][Web of Science][Medline]
- STOP-ROP Multicenter Study Group. Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity (STOP-ROP), a randomized, controlled trial, part I: primary outcomes.
Pediatrics. 2000;105
:295
–310
[Abstract/Free Full Text] - Askie LM, Henderson-Smart DJ, Irwig L, Simpson JM. Oxygen-saturation targets and outcomes in extremely preterm infants.
N Engl J Med. 2003;349
:959
–967
[Abstract/Free Full Text] - National Institutes of Health. Continuous positive airway pressure (CPAP) versus surfactant, and a lower versus a higher oxygen saturation in 24 to 27 week preterm infants. Available at: www.clinicaltrials.gov/ct/show/NCT00233324?order=2. Accessed January 31, 2007
- National Health and Medical Research Council Clinical Trials Centre. Benefits of Oxygen Saturation Targeting, trial II. Available at: www.ctc.usyd.edu.au/trials/other_trials/boost.htm. Accessed January 31, 2007
- Cole CH, Wright KW, Tarnow-Mordi W, Phelps DL. Resolving our uncertainty about oxygen therapy.
Pediatrics. 2003;112
:1415
–1419
[Free Full Text] - Tan A, Schulze A, O'Donnell CP, Davis PG. Air versus oxygen for resuscitation of infants at birth. Cochrane Database Syst Rev. 2005;(2):CD002273
- Saugstad OD. Room air resuscitation: two decades of neonatal research. Early Hum Dev. 2005;81 :111 –116[CrossRef][Web of Science][Medline]
- Spector LG, Klebanoff MA, Feusner JH, Georfieff MK, Ross JA. Childhood cancer following neonatal oxygen supplementation. J Pediatr. 2005;147 :27 –31[CrossRef][Web of Science][Medline]
- Saugstad OD, Ramji S, Vento M. Resuscitation of depressed newborn infants with ambient air or pure oxygen: a meta-analysis. Biol Neonate. 2005;87 :27 –34[CrossRef][Web of Science][Medline]
- Saugstad OD. Resuscitation with pure oxygen at birth: is it time for a change? J Matern Fetal Neonat Med. 2004;15 :73 –74[CrossRef]
- Paneth N. The evidence mounts against use of pure oxygen in newborn resuscitation. J Pediatr. 2005;147 :4 –6[CrossRef][Web of Science][Medline]
- Sola A, Deulofeut R. Oxygen and oxygenation in the delivery room. J Pediatr. 2006;148 :564 –565[Web of Science][Medline]
- Saugstad OD, Ramji S, Vento M. Oxygen for newborn resuscitation: how much is enough?
Pediatrics. 2006;118
:789
–792
[Free Full Text] - International Liaison Committee on Resuscitation. The International Liaison Committee on Resuscitation (ILCOR) consensus on science with treatment recommendations for pediatric and neonatal patients: pediatric basic and advanced life support. Pediatrics. 2006;117(5) . Available at: www.pediatrics.org/cgi/content/full/117/5/e955
- International Liaison Committee on Resuscitation. The International Liaison Committee on Resuscitation (ILCOR) consensus on science with treatment recommendations for pediatric and neonatal patients: neonatal resuscitation. Pediatrics. 2006;117(5) . Available at: www.pediatrics.org/cgi/content/full/117/5/e978
- Ramanathan R, Corwin MJ, Hunt CE, et al. Cardiorespiratory events recorded on home monitors: comparison of healthy infants with those at increased risk for SIDS.
JAMA. 2001;285
:2199
–2207
[Abstract/Free Full Text] - Hunt CE, Hufford DR, Bourguignon C, Oess MA. Home documented monitoring of cardiorespiratory pattern and oxygen saturation in healthy infants. Pediatr Res. 1996;39 :216 –222[Web of Science][Medline]
PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics
CiteULike 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  I M Balfour-Lynn, D J Field, P Gringras, B Hicks, E Jardine, R C Jones, A G Magee, R A Primhak, M P Samuels, N J Shaw, et al. BTS guidelines for home oxygen in children Thorax, August 1, 2009; 64(Suppl_2): ii1 - ii26. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
